Resting-State Pallidal-Cortical Oscillatory Couplings in Patients With Predominant Phasic and Tonic Dystonia.

PubMed

Yokochi, Fusako; Kato, Kenji; Iwamuro, Hirokazu; Kamiyama, Tsutomu; Kimura, Katsuo; Yugeta, Akihiro; Okiyama, Ryoichi; Taniguchi, Makoto; Kumada, Satoko; Ushiba, Junichi

2018-01-01

Pallidal deep brain stimulation (DBS) improves the symptoms of dystonia. The improvement processes of dystonic movements (phasic symptoms) and tonic symptoms differ. Phasic symptoms improve rapidly after starting DBS treatment, but tonic symptoms improve gradually. This difference implies distinct neuronal mechanisms for phasic and tonic symptoms in the underlying cortico-basal ganglia neuronal network. Phasic symptoms are related to the pallido-thalamo-cortical pathway. The pathway related to tonic symptoms has been assumed to be different from that for phasic symptoms. In the present study, local field potentials of the globus pallidus internus (GPi) and globus pallidus externus (GPe) and electroencephalograms from the motor cortex (MCx) were recorded in 19 dystonia patients to analyze the differences between the two types of symptoms. The 19 patients were divided into two groups, 10 with predominant phasic symptoms (phasic patients) and 9 with predominant tonic symptoms (tonic patients). To investigate the distinct features of oscillations and functional couplings across the GPi, GPe, and MCx by clinical phenotype, power and coherence were calculated over the delta (2-4 Hz), theta (5-7 Hz), alpha (8-13 Hz), and beta (14-35 Hz) frequencies. In phasic patients, the alpha spectral peaks emerged in the GPi oscillatory activities, and alpha GPi coherence with the GPe and MCx was higher than in tonic patients. On the other hand, delta GPi oscillatory activities were prominent, and delta GPi-GPe coherence was significantly higher in tonic than in phasic patients. However, there was no significant delta coherence between the GPi/GPe and MCx in tonic patients. These results suggest that different pathophysiological cortico-pallidal oscillations are related to tonic and phasic symptoms.

Central control of cardiorespiratory interactions in fish.

PubMed

Taylor, Edwin W; Leite, Cleo A C; Levings, Jennifer J

2009-01-01

Fish control the relative flow rates of water and blood over the gills in order to optimise respiratory gas exchange. As both flows are markedly pulsatile, close beat-to-beat relationships can be predicted. Cardiorespiratory interactions in fish are controlled primarily by activity in the parasympathetic nervous system that has its origin in cardiac vagal preganglionic neurons. Recordings of efferent activity in the cardiac vagus include units firing in respiration-related bursts. Bursts of electrical stimuli delivered peripherally to the cardiac vagus or centrally to respiratory branches of cranial nerves can recruit the heart over a range of frequencies. So, phasic, efferent activity in cardiac vagi, that in the intact fish are respiration-related, can cause heart rate to be modulated by the respiratory rhythm. In elasmobranch fishes this phasic activity seems to arise primarily from central feed-forward interactions with respiratory motor neurones that have overlapping distributions with cardiac neurons in the brainstem. In teleost fish, they arise from increased levels of efferent vagal activity arising from reflex stimulation of chemoreceptors and mechanoreceptors in the orobranchial cavity. However, these differences are largely a matter of emphasis as both groups show elements of feed-forward and feed-back control of cardiorespiratory interactions.

Validation of an integrated software for the detection of rapid eye movement sleep behavior disorder.

PubMed

Frauscher, Birgit; Gabelia, David; Biermayr, Marlene; Stefani, Ambra; Hackner, Heinz; Mitterling, Thomas; Poewe, Werner; Högl, Birgit

2014-10-01

Rapid eye movement sleep without atonia (RWA) is the polysomnographic hallmark of REM sleep behavior disorder (RBD). To partially overcome the disadvantages of manual RWA scoring, which is time consuming but essential for the accurate diagnosis of RBD, we aimed to validate software specifically developed and integrated with polysomnography for RWA detection against the gold standard of manual RWA quantification. Academic referral center sleep laboratory. Polysomnographic recordings of 20 patients with RBD and 60 healthy volunteers were analyzed. N/A. Motor activity during REM sleep was quantified manually and computer assisted (with and without artifact detection) according to Sleep Innsbruck Barcelona (SINBAR) criteria for the mentalis ("any," phasic, tonic electromyographic [EMG] activity) and the flexor digitorum superficialis (FDS) muscle (phasic EMG activity). Computer-derived indices (with and without artifact correction) for "any," phasic, tonic mentalis EMG activity, phasic FDS EMG activity, and the SINBAR index ("any" mentalis + phasic FDS) correlated well with the manually derived indices (all Spearman rhos 0.66-0.98). In contrast with computerized scoring alone, computerized scoring plus manual artifact correction (median duration 5.4 min) led to a significant reduction of false positives for "any" mentalis (40%), phasic mentalis (40.6%), and the SINBAR index (41.2%). Quantification of tonic mentalis and phasic FDS EMG activity was not influenced by artifact correction. The computer algorithm used here appears to be a promising tool for REM sleep behavior disorder detection in both research and clinical routine. A short check for plausibility of automatic detection should be a basic prerequisite for this and all other available computer algorithms. © 2014 Associated Professional Sleep Societies, LLC.

NS309 decreases rat detrusor smooth muscle membrane potential and phasic contractions by activating SK3 channels

PubMed Central

Parajuli, Shankar P; Hristov, Kiril L; Soder, Rupal P; Kellett, Whitney F; Petkov, Georgi V

2013-01-01

Background and Purpose Overactive bladder (OAB) is often associated with abnormally increased detrusor smooth muscle (DSM) contractions. We used NS309, a selective and potent opener of the small or intermediate conductance Ca2+-activated K+ (SK or IK, respectively) channels, to evaluate how SK/IK channel activation modulates DSM function. Experimental Approach We employed single-cell RT-PCR, immunocytochemistry, whole cell patch-clamp in freshly isolated rat DSM cells and isometric tension recordings of isolated DSM strips to explore how the pharmacological activation of SK/IK channels with NS309 modulates DSM function. Key Results We detected SK3 but not SK1, SK2 or IK channels expression at both mRNA and protein levels by RT-PCR and immunocytochemistry in DSM single cells. NS309 (10 μM) significantly increased the whole cell SK currents and hyperpolarized DSM cell resting membrane potential. The NS309 hyperpolarizing effect was blocked by apamin, a selective SK channel inhibitor. NS309 inhibited the spontaneous phasic contraction amplitude, force, frequency, duration and tone of isolated DSM strips in a concentration-dependent manner. The inhibitory effect of NS309 on spontaneous phasic contractions was blocked by apamin but not by TRAM-34, indicating no functional role of the IK channels in rat DSM. NS309 also significantly inhibited the pharmacologically and electrical field stimulation-induced DSM contractions. Conclusions and Implications Our data reveal that SK3 channel is the main SK/IK subtype in rat DSM. Pharmacological activation of SK3 channels with NS309 decreases rat DSM cell excitability and contractility, suggesting that SK3 channels might be potential therapeutic targets to control OAB associated with detrusor overactivity. PMID:23145946

An enquiry into the mechanism by which substance P facilitates the phasic longitudinal contractions of the rabbit ileum

PubMed Central

Holzer, Peter

1982-01-01

1. The effect of substance P on the phasic longitudinal contractions of the isolated rabbit ileum has been investigated. The contractions were recorded isotonically. Substance P in concentrations below those which cause tonic contraction (0·2-2 nM) increased the height of the phasic contractions in a concentration-dependent fashion without affecting their frequency (8-12/min). 2. The effect of substance P was inhibited by verapamil, ouabain, noradrenaline, and isoprenaline, but was unaffected by tetrodotoxin, atropine, D-2-ala,5-metenkephalin, somatostatin, and vasoactive intestinal polypeptide. 3. Tetraethylammonium, which blocks voltage-dependent K+ channels, enhanced the phasic contractile activity of the rabbit ileum in a manner quite similar to substance P, but the maximal response to tetraethylammonium was larger than that to substance P. 4. The effect of matched concentrations of substance P and tetraethylammonium, which enhanced the phasic contractions to a similar extent, was investigated at various concentrations of K+, Na+, Ca2+ and Cl- in the bathing medium. Both substance P and tetraethylammonium lost their ability to enhance the phasic contractions when K+ was omitted from the medium or when its concentration therein was increased by a factor of 4, or when the NaCl concentration was reduced to less than 10%. The relative increase in phasic contractile activity evoked by substance P was smaller than that evoked by tetraethylammonium when more than 90% of the Cl- was replaced with propionate. 5. Noradrenaline, in a concentration which just abolished the spontaneous phasic contractions (200-300 nM), reduced the enhancing effect of substance P on the phasic activity by 40-50%, but did not influence the effect of tetraethylammonium. 6. These results indicate that substance P enhances the phasic longitudinal contractions of the isolated rabbit ileum by a direct action on the smooth muscle cells and that this effect is brought about by facilitation of the myogenically controlled action potential discharges in the ileum. Circumstantial evidence suggests that the underlying ionic mechanism of action of substance P is a decrease in K+ and Cl- conductances. ImagesFig. 1Fig. 2Fig. 5Fig. 7 PMID:6180164

ANO1 in intramuscular interstitial cells of Cajal plays a key role in the generation of slow waves and tone in the internal anal sphincter

PubMed Central

Hannah, E. E.; Zhu, M. H.; Lyle, H. E.; Rock, J. R.; Sanders, K. M.; Ward, S. M.; Keef, K. D.

2017-01-01

Key points The internal anal sphincter develops tone important for maintaining high anal pressure and continence. Controversy exists regarding the mechanisms underlying tone development.We examined the hypothesis that tone depends upon electrical slow waves (SWs) initiated in intramuscular interstitial cells of Cajal (ICC‐IM) by activation of Ca2+‐activated Cl− channels (ANO1, encoded by Ano1) and voltage‐dependent L‐type Ca2+ channels (CavL, encoded by Cacna1c).Measurement of membrane potential and contraction indicated that ANO1 and CavL have a central role in SW generation, phasic contractions and tone, independent of stretch.ANO1 expression was examined in wildtype and Ano1/+egfp mice with immunohistochemical techniques. Ano1 and Cacna1c expression levels were examined by quantitative PCR in fluorescence‐activated cell sorting.ICC‐IM were the predominant cell type expressing ANO1 and the most likely candidate for SW generation. SWs in ICC‐IM are proposed to conduct to smooth muscle where Ca2+ entry via CavL results in phasic activity that sums to produce tone. Abstract The mechanism underlying tone generation in the internal anal sphincter (IAS) is controversial. We examined the hypothesis that tone depends upon generation of electrical slow waves (SWs) initiated in intramuscular interstitial cells of Cajal (ICC‐IM) by activation of Ca2+‐activated Cl− channels (encoded by Ano1) and voltage‐dependent L‐type Ca2+ channels (encoded by Cacna1c). Phasic contractions and tone in the IAS were nearly abolished by ANO1 and CavL antagonists. ANO1 antagonists also abolished SWs as well as transient depolarizations that persisted after addition of CavL antagonists. Tone development in the IAS did not require stretch of muscles, and the sensitivity of contraction to ANO1 antagonists was the same in stretched versus un‐stretched muscles. ANO1 expression was examined in wildtype and Ano1/+egfp mice with immunohistochemical techniques. Dual labelling revealed that ANO1 expression could be resolved in ICC but not smooth muscle cells (SMCs) in the IAS and rectum. Ano1, Cacna1c and Kit gene expression were the same in extracts of IAS and rectum muscles. In IAS cells isolated with fluorescence‐activated cell sorting, Ano1 expression was 26.5‐fold greater in ICC than in SMCs while Cacna1c expression was only 2‐fold greater in SMCs than in ICC. These data support a central role for ANO1 and CavL in the generation of SWs and tone in the IAS. ICC‐IM are the probable cellular candidate for ANO1 currents and SW generation. We propose that ANO1 and CavL collaborate to generate SWs in ICC‐IM followed by conduction to adjacent SMCs where phasic calcium entry through CavL sums to produce tone. PMID:28054347

Tonic and phasic co-variation of peripheral arousal indices in infants

PubMed Central

Wass, S.V.; de Barbaro, K.; Clackson, K.

2015-01-01

Tonic and phasic differences in peripheral autonomic nervous system (ANS) indicators strongly predict differences in attention and emotion regulation in developmental populations. However, virtually all previous research has been based on individual ANS measures, which poses a variety of conceptual and methodlogical challenges to comparing results across studies. Here we recorded heart rate, electrodermal activity (EDA), pupil size, head movement velocity and peripheral accelerometry concurrently while a cohort of 37 typical 12-month-old infants completed a mixed assessment battery lasting approximately 20 min per participant. We analysed covariation of these autonomic indices in three ways: first, tonic (baseline) arousal; second, co-variation in spontaneous (phasic) changes during testing; third, phasic co-variation relative to an external stimulus event. We found that heart rate, head velocity and peripheral accelerometry showed strong positive co-variation across all three analyses. EDA showed no co-variation in tonic activity levels but did show phasic positive co-variation with other measures, that appeared limited to sections of high but not low general arousal. Tonic pupil size showed significant positive covariation, but phasic pupil changes were inconsistent. We conclude that: (i) there is high covariation between autonomic indices in infants, but that EDA may only be sensitive at extreme arousal levels, (ii) that tonic pupil size covaries with other indices, but does not show predicted patterns of phasic change and (iii) that motor activity appears to be a good proxy measure of ANS activity. The strongest patterns of covariation were observed using epoch durations of 40 s per epoch, although significant covariation between indices was also observed using shorter epochs (1 and 5 s). PMID:26316360

Tonic or Phasic Stimulation of Dopaminergic Projections to Prefrontal Cortex Causes Mice to Maintain or Deviate from Previously Learned Behavioral Strategies

PubMed Central

Ellwood, Ian T.; Patel, Tosha; Wadia, Varun; Lee, Anthony T.; Liptak, Alayna T.

2017-01-01

Dopamine neurons in the ventral tegmental area (VTA) encode reward prediction errors and can drive reinforcement learning through their projections to striatum, but much less is known about their projections to prefrontal cortex (PFC). Here, we studied these projections and observed phasic VTA–PFC fiber photometry signals after the delivery of rewards. Next, we studied how optogenetic stimulation of these projections affects behavior using conditioned place preference and a task in which mice learn associations between cues and food rewards and then use those associations to make choices. Neither phasic nor tonic stimulation of dopaminergic VTA–PFC projections elicited place preference. Furthermore, substituting phasic VTA–PFC stimulation for food rewards was not sufficient to reinforce new cue–reward associations nor maintain previously learned ones. However, the same patterns of stimulation that failed to reinforce place preference or cue–reward associations were able to modify behavior in other ways. First, continuous tonic stimulation maintained previously learned cue–reward associations even after they ceased being valid. Second, delivering phasic stimulation either continuously or after choices not previously associated with reward induced mice to make choices that deviated from previously learned associations. In summary, despite the fact that dopaminergic VTA–PFC projections exhibit phasic increases in activity that are time locked to the delivery of rewards, phasic activation of these projections does not necessarily reinforce specific actions. Rather, dopaminergic VTA–PFC activity can control whether mice maintain or deviate from previously learned cue–reward associations. SIGNIFICANCE STATEMENT Dopaminergic inputs from ventral tegmental area (VTA) to striatum encode reward prediction errors and reinforce specific actions; however, it is currently unknown whether dopaminergic inputs to prefrontal cortex (PFC) play similar or distinct roles. Here, we used bulk Ca2+ imaging to show that unexpected rewards or reward-predicting cues elicit phasic increases in the activity of dopaminergic VTA–PFC fibers. However, in multiple behavioral paradigms, we failed to observe reinforcing effects after stimulation of these fibers. In these same experiments, we did find that tonic or phasic patterns of stimulation caused mice to maintain or deviate from previously learned cue–reward associations, respectively. Therefore, although they may exhibit similar patterns of activity, dopaminergic inputs to striatum and PFC can elicit divergent behavioral effects. PMID:28739583

The impact of luminance on tonic and phasic pupillary responses to sustained cognitive load.

PubMed

Peysakhovich, Vsevolod; Vachon, François; Dehais, Frédéric

2017-02-01

Pupillary reactions independent of light conditions have been linked to cognition for a long time. However, the light conditions can impact the cognitive pupillary reaction. Previous studies underlined the impact of luminance on pupillary reaction, but it is still unclear how luminance modulates the sustained and transient components of pupillary reaction - tonic pupil diameter and phasic pupil response. In the present study, we investigated the impact of the luminance on these two components under sustained cognitive load. Fourteen participants performed a novel working memory task combining mathematical computations with a classic n-back task. We studied both tonic pupil diameter and phasic pupil response under low (1-back) and high (2-back) working memory load and two luminance levels (gray and white). We found that the impact of working memory load on the tonic pupil diameter was modulated by the level of luminance, the increase in tonic pupil diameter with the load being larger under lower luminance. In contrast, the smaller phasic pupil response found under high load remained unaffected by luminance. These results showed that luminance impacts the cognitive pupillary reaction - tonic pupil diameter (phasic pupil response) being modulated under sustained (respectively, transient) cognitive load. These findings also support the relationship between the locus-coeruleus system, presumably functioning in two firing modes - tonic and phasic - and the pupil diameter. We suggest that the tonic pupil diameter tracks the tonic activity of the locus-coeruleus while phasic pupil response reflects its phasic activity. Besides, the designed novel cognitive paradigm allows the simultaneous manipulation of sustained and transient components of the cognitive load and is useful for dissociating the effects on the tonic pupil diameter and phasic pupil response. Copyright © 2016 Elsevier B.V. All rights reserved.

Ethanol modulates the VR-1 variant amiloride-insensitive salt taste receptor. I. Effect on TRC volume and Na+ flux.

PubMed

Lyall, Vijay; Heck, Gerard L; Phan, Tam-Hao T; Mummalaneni, Shobha; Malik, Shahbaz A; Vinnikova, Anna K; DeSimone, John A

2005-06-01

The effect of ethanol on the amiloride- and benzamil (Bz)-insensitive salt taste receptor was investigated by the measurement of intracellular Na(+) activity ([Na(+)](i)) in polarized rat fungiform taste receptor cells (TRCs) using fluorescence imaging and by chorda tympani (CT) taste nerve recordings. CT responses were monitored during lingual stimulation with ethanol solutions containing NaCl or KCl. CT responses were recorded in the presence of Bz (a specific blocker of the epithelial Na(+) channel [ENaC]) or the vanilloid receptor-1 (VR-1) antagonists capsazepine or SB-366791, which also block the Bz-insensitive salt taste receptor, a VR-1 variant. CT responses were recorded at 23 degrees C or 42 degrees C (a temperature at which the VR-1 variant salt taste receptor activity is maximally enhanced). In the absence of permeable cations, ethanol induced a transient decrease in TRC volume, and stimulating the tongue with ethanol solutions without added salt elicited only transient phasic CT responses that were insensitive to elevated temperature or SB-366791. Preshrinking TRCs in vivo with hypertonic mannitol (0.5 M) attenuated the magnitude of the phasic CT response, indicating that in the absence of mineral salts, transient phasic CT responses are related to the ethanol-induced osmotic shrinkage of TRCs. In the presence of mineral salts, ethanol increased the Bz-insensitive apical cation flux in TRCs without a change in cell volume, increased transepithelial electrical resistance across the tongue, and elicited CT responses that were similar to salt responses, consisting of both a transient phasic component and a sustained tonic component. Ethanol increased the Bz-insensitive NaCl CT response. This effect was further enhanced by elevating the temperature from 23 degrees C to 42 degrees C, and was blocked by SB-366791. We conclude that in the presence of mineral salts, ethanol modulates the Bz-insensitive VR-1 variant salt taste receptor.

Ventral tegmental ionotropic glutamate receptor stimulation of nucleus accumbens tonic dopamine efflux blunts hindbrain-evoked phasic neurotransmission: implications for dopamine dysregulation disorders.

PubMed

Tye, S J; Miller, A D; Blaha, C D

2013-11-12

Activation of glutamate receptors within the ventral tegmental area (VTA) stimulates extrasynaptic (basal) dopamine release in terminal regions, including the nucleus accumbens (NAc). Hindbrain inputs from the laterodorsal tegmental nucleus (LDT) are critical for elicitation of phasic VTA dopamine cell activity and consequent transient dopamine release. This study investigated the role of VTA ionotropic glutamate receptor (iGluR) stimulation on both basal and LDT electrical stimulation-evoked dopamine efflux in the NAc using in vivo chronoamperometry and fixed potential amperometry in combination with stearate-graphite paste and carbon fiber electrodes, respectively. Intra-VTA infusion of the iGluR agonists (±)-α-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA; 1 μg/μl) or N-methyl-d-aspartic acid (NMDA; 2 μg/μl) enhanced basal NAc dopamine efflux. This iGluR-mediated potentiation of basal dopamine efflux was paralleled by an attenuation of LDT-evoked transient NAc dopamine efflux, suggesting that excitation of basal activity effectively inhibited the capacity of hindbrain afferents to elicit transient dopamine efflux. In line with this, post-NMDA infusion of the dopamine D2 autoreceptor (D2R) agonist quinpirole (1 μg/μl; intra-VTA) partially recovered NMDA-mediated attenuation of LDT-evoked NAc dopamine, while concurrently attenuating NMDA-mediated potentiation of basal dopamine efflux. Post-NMDA infusion of quinpirole (1 μg/μl) alone attenuated basal and LDT-evoked dopamine efflux. Taken together, these data reveal that hyperstimulation of basal dopamine transmission can stunt hindbrain burst-like stimulation-evoked dopamine efflux. Inhibitory autoreceptor mechanisms within the VTA help to partially recover the magnitude of phasic dopamine efflux, highlighting the importance of both iGluRs and D2 autoreceptors in maintaining the functional balance of tonic and phasic dopamine neurotransmission. Dysregulation of this balance may have important implications for disorders of dopamine dysregulation such as attention deficit hyperactivity disorder. Copyright © 2013 IBRO. Published by Elsevier Ltd. All rights reserved.

Specific Diurnal EMG Activity Pattern Observed in Occlusal Collapse Patients: Relationship between Diurnal Bruxism and Tooth Loss Progression

PubMed Central

Kawakami, Shigehisa; Kumazaki, Yohei; Manda, Yosuke; Oki, Kazuhiro; Minagi, Shogo

2014-01-01

Aim The role of parafunctional masticatory muscle activity in tooth loss has not been fully clarified. This study aimed to reveal the characteristic activity of masseter muscles in bite collapse patients while awake and asleep. Materials and Methods Six progressive bite collapse patients (PBC group), six age- and gender-matched control subjects (MC group), and six young control subjects (YC group) were enrolled. Electromyograms (EMG) of the masseter muscles were continuously recorded with an ambulatory EMG recorder while patients were awake and asleep. Diurnal and nocturnal parafunctional EMG activity was classified as phasic, tonic, or mixed using an EMG threshold of 20% maximal voluntary clenching. Results Highly extended diurnal phasic activity was observed only in the PBC group. The three groups had significantly different mean diurnal phasic episodes per hour, with 13.29±7.18 per hour in the PBC group, 0.95±0.97 per hour in the MC group, and 0.87±0.98 per hour in the YC group (p<0.01). ROC curve analysis suggested that the number of diurnal phasic episodes might be used to predict bite collapsing tooth loss. Conclusion Extensive bite loss might be related to diurnal masticatory muscle parafunction but not to parafunction during sleep. Clinical Relevance: Scientific rationale for study Although mandibular parafunction has been implicated in stomatognathic system breakdown, a causal relationship has not been established because scientific modalities to evaluate parafunctional activity have been lacking. Principal findings This study used a newly developed EMG recording system that evaluates masseter muscle activity throughout the day. Our results challenge the stereotypical idea of nocturnal bruxism as a strong destructive force. We found that diurnal phasic masticatory muscle activity was most characteristic in patients with progressive bite collapse. Practical implications The incidence of diurnal phasic contractions could be used for the prognostic evaluation of stomatognathic system stability. PMID:25010348

Eye movements and abducens motoneuron behavior after cholinergic activation of the nucleus reticularis pontis caudalis.

PubMed

Márquez-Ruiz, Javier; Escudero, Miguel

2010-11-01

the aim of this work was to characterize eye movements and abducens (ABD) motoneuron behavior after cholinergic activation of the nucleus reticularis pontis caudalis (NRPC). six female adult cats were prepared for chronic recording of eye movements (using the scleral search-coil technique), electroencephalography, electromyography, ponto-geniculo-occipital (PGO) waves in the lateral geniculate nucleus, and ABD motoneuron activities after microinjections of the cholinergic agonist carbachol into the NRPC. unilateral microinjections of carbachol in the NRPC induced tonic and phasic phenomena in the oculomotor system. Tonic effects consisted of ipsiversive rotation to the injected side, convergence, and downward rotation of the eyes. Phasic effects consisted of bursts of rhythmic rapid eye movements directed contralaterally to the injected side along with PGO-like waves in the lateral geniculate and ABD nuclei. Although tonic effects were dependent on the level of drowsiness, phasic effects were always present and appeared along with normal saccades when the animal was vigilant. ABD motoneurons showed phasic activities associated with ABD PGO-like waves during bursts of rapid eye movements, and tonic and phasic activities related to eye position and velocity during alertness. the cholinergic activation of the NRPC induces oculomotor phenomena that are somewhat similar to those described during REM sleep. A precise comparison of the dynamics and timing of the eye movements further suggests that a temporal organization of both NRPCs is needed to reproduce the complexity of the oculomotor behavior during REM sleep.

Phasic Contractions of the Mouse Vagina and Cervix at Different Phases of the Estrus Cycle and during Late Pregnancy

PubMed Central

Gravina, Fernanda S.; van Helden, Dirk F.; Kerr, Karen P.; de Oliveira, Ramatis B.; Jobling, Phillip

2014-01-01

Background/Aims The pacemaker mechanisms activating phasic contractions of vaginal and cervical smooth muscle remain poorly understood. Here, we investigate properties of pacemaking in vaginal and cervical tissues by determining whether: 1) functional pacemaking is dependent on the phase of the estrus cycle or pregnancy; 2) pacemaking involves Ca2+ release from sarcoplasmic/endoplasmic reticulum Ca2+-ATPase (SERCA) -dependent intracellular Ca2+ stores; and 3) c-Kit and/or vimentin immunoreactive ICs have a role in pacemaking. Methodology/Principal Findings Vaginal and cervical contractions were measured in vitro, as was the distribution of c-Kit and vimentin positive interstitial cells (ICs). Cervical smooth muscle was spontaneously active in estrus and metestrus but quiescent during proestrus and diestrus. Vaginal smooth muscle was normally quiescent but exhibited phasic contractions in the presence of oxytocin or the K+ channel blocker tetraethylammonium (TEA) chloride. Spontaneous contractions in the cervix and TEA-induced phasic contractions in the vagina persisted in the presence of cyclopiazonic acid (CPA), a blocker of the SERCA that refills intracellular SR Ca2+ stores, but were inhibited in low Ca2+ solution or in the presence of nifedipine, an inhibitor of L-type Ca2+channels. ICs were found in small numbers in the mouse cervix but not in the vagina. Conclusions/Significance Cervical smooth muscle strips taken from mice in estrus, metestrus or late pregnancy were generally spontaneously active. Vaginal smooth muscle strips were normally quiescent but could be induced to exhibit phasic contractions independent on phase of the estrus cycle or late pregnancy. Spontaneous cervical or TEA-induced vaginal phasic contractions were not mediated by ICs or intracellular Ca2+ stores. Given that vaginal smooth muscle is normally quiescent then it is likely that increases in hormones such as oxytocin, as might occur through sexual stimulation, enhance the effectiveness of such pacemaking until phasic contractile activity emerges. PMID:25337931

Phasic contractions of the mouse vagina and cervix at different phases of the estrus cycle and during late pregnancy.

PubMed

Gravina, Fernanda S; van Helden, Dirk F; Kerr, Karen P; de Oliveira, Ramatis B; Jobling, Phillip

2014-01-01

The pacemaker mechanisms activating phasic contractions of vaginal and cervical smooth muscle remain poorly understood. Here, we investigate properties of pacemaking in vaginal and cervical tissues by determining whether: 1) functional pacemaking is dependent on the phase of the estrus cycle or pregnancy; 2) pacemaking involves Ca2+ release from sarcoplasmic/endoplasmic reticulum Ca2+-ATPase (SERCA) -dependent intracellular Ca2+ stores; and 3) c-Kit and/or vimentin immunoreactive ICs have a role in pacemaking. Vaginal and cervical contractions were measured in vitro, as was the distribution of c-Kit and vimentin positive interstitial cells (ICs). Cervical smooth muscle was spontaneously active in estrus and metestrus but quiescent during proestrus and diestrus. Vaginal smooth muscle was normally quiescent but exhibited phasic contractions in the presence of oxytocin or the K+ channel blocker tetraethylammonium (TEA) chloride. Spontaneous contractions in the cervix and TEA-induced phasic contractions in the vagina persisted in the presence of cyclopiazonic acid (CPA), a blocker of the SERCA that refills intracellular SR Ca2+ stores, but were inhibited in low Ca2+ solution or in the presence of nifedipine, an inhibitor of L-type Ca2+channels. ICs were found in small numbers in the mouse cervix but not in the vagina. Cervical smooth muscle strips taken from mice in estrus, metestrus or late pregnancy were generally spontaneously active. Vaginal smooth muscle strips were normally quiescent but could be induced to exhibit phasic contractions independent on phase of the estrus cycle or late pregnancy. Spontaneous cervical or TEA-induced vaginal phasic contractions were not mediated by ICs or intracellular Ca2+ stores. Given that vaginal smooth muscle is normally quiescent then it is likely that increases in hormones such as oxytocin, as might occur through sexual stimulation, enhance the effectiveness of such pacemaking until phasic contractile activity emerges.

Design, Simulation and Experimental Evaluation of Tri-Phasic Piezoelectric Composite Transducers

NASA Astrophysics Data System (ADS)

Tamez, Juan Pedro

Piezoelectric ceramics exhibit excellent piezoelectric and dielectric properties that is the basis of practically all transducers and piezoelectric devices, but their inherent properties, such as brittleness, non-ductility and poor shapeability may limit their applications in areas such as vibration sensing, impact detection, structural health monitoring and other reinforced structures and energy harvesting. To compensate for such limitations, the 1-3 piezoelectric composites transducers have become the material of choice for many high performance ultrasound transducers since it was invented in the late 1970's [ref. Newnham/Cross]. Extensive studies on 1-3 composites have been performed since then to improve the performance of a transducer by modifying their electromechanical coupling, bandwidth, quality factor, and flexibility and by reducing or eliminating the cross talk, i.e., induced noise between the active piezoelectric elements, especially in high power and low frequency applications. These fundamental issues, their possible solutions and their wide impact underline the motivation of the current work in this dissertation report. The motivation for this dissertation was to study and provide a foundation to designing multiphasic piezoelectric transducers that could be useful for multitude of applications. The goal was to improve the 1-3 diphasic composite transducer by eliminating the cross talk between the active piezoelectric elements while maintaining and improving the figures of merit of the design. To achieve the ultimate goal, the steps outlined below were followed: i. Understanding the theoretical and mathematical modeling for tri-phasic piezoelectric composite. ii. Implement Finite Element Analysis (FEA) and simulations of tri-phasic piezoelectric composites where the different active piezoelectric material PZT-5H and PMN-30%PT is surrounded by a vacuum phase that is enclosed by a hexagonal polymer walls. iii. Propose a redesign of the tri-phasic transducer to improve the Figures of Merit (FOM) for non-destructive evaluation (NDE) applications. iv. Explore the performance of the diphasic and tri-phasic transducer for energy harvesting applications. v. Perform analysis and quantification of the transducers in a laboratory environment to analyze their performance for Non-Destructive Testing (NDE) using pulse echo acoustics and Electro-Mechanical Impedance (EMI) measurements. The findings of this research are reported in this dissertation indicate that the measured piezoelectric properties of the fabricated tri-phasic transducers are in good agreement with those of the predicted designs. The simulation of the designed transducer has acoustic energy channeled in the d33 mode at resonance, with weak or no shear mode cross talk behavior from the other modes. The mechanical displacements measured were large and highly aligned along polar direction consistent with d33 mode. This implies that multiphasic piezoelectric transducer performs as a single device with improved mechanical and electrical response for sensing, actuation or single device transducer applications. Testing in a laboratory environment demonstrated that they can be highly useful for both the contact and air coupled noncontact Non-Destructive Evaluation (NDE) and nondestructive testing (NDT) applications.

Phasic action of the tensor muscle modulates the calling song in cicadas

PubMed

Fonseca; Hennig

1996-01-01

The effect of tensor muscle contraction on sound production by the tymbal was investigated in three species of cicadas (Tettigetta josei, Tettigetta argentata and Tympanistalna gastrica). All species showed a strict time correlation between the activity of the tymbal motoneurone and the discharge of motor units in the tensor nerve during the calling song. Lesion of the tensor nerve abolished the amplitude modulation of the calling song, but this modulation was restored by electrical stimulation of the tensor nerve or by mechanically pushing the tensor sclerite. Electrical stimulation of the tensor nerve at frequencies higher than 30­40 Hz changed the sound amplitude. In Tett. josei and Tett. argentata there was a gradual increase in sound amplitude with increasing frequency of tensor nerve stimulation, while in Tymp. gastrica there was a sudden reduction in sound amplitude at stimulation frequencies higher than 30 Hz. This contrasting effect in Tymp. gastrica was due to a bistable tymbal frame. Changes in sound pulse amplitude were positively correlated with changes in the time lag measured from tymbal motoneurone stimulation to the sound pulse. The tensor muscle acted phasically because electrical stimulation of the tensor nerve during a time window (0­10 ms) before electrical stimulation of the tymbal motoneurone was most effective in eliciting amplitude modulations. In all species, the tensor muscle action visibly changed the shape of the tymbal. Despite the opposite effects of the tensor muscle on sound pulse amplitude observed between Tettigetta and Tympanistalna species, the tensor muscle of both acts by modulating the shape of the tymbal, which changes the force required for the tymbal muscle to buckle the tymbal.

Control of Phasic Firing by a Background Leak Current in Avian Forebrain Auditory Neurons

PubMed Central

Dagostin, André A.; Lovell, Peter V.; Hilscher, Markus M.; Mello, Claudio V.; Leão, Ricardo M.

2015-01-01

Central neurons express a variety of neuronal types and ion channels that promote firing heterogeneity among their distinct neuronal populations. Action potential (AP) phasic firing, produced by low-threshold voltage-activated potassium currents (VAKCs), is commonly observed in mammalian brainstem neurons involved in the processing of temporal properties of the acoustic information. The avian caudomedial nidopallium (NCM) is an auditory area analogous to portions of the mammalian auditory cortex that is involved in the perceptual discrimination and memorization of birdsong and shows complex responses to auditory stimuli We performed in vitro whole-cell patch-clamp recordings in brain slices from adult zebra finches (Taeniopygia guttata) and observed that half of NCM neurons fire APs phasically in response to membrane depolarizations, while the rest fire transiently or tonically. Phasic neurons fired APs faster and with more temporal precision than tonic and transient neurons. These neurons had similar membrane resting potentials, but phasic neurons had lower membrane input resistance and time constant. Surprisingly phasic neurons did not express low-threshold VAKCs, which curtailed firing in phasic mammalian brainstem neurons, having similar VAKCs to other NCM neurons. The phasic firing was determined not by VAKCs, but by the potassium background leak conductances, which was more prominently expressed in phasic neurons, a result corroborated by pharmacological, dynamic-clamp, and modeling experiments. These results reveal a new role for leak currents in generating firing diversity in central neurons. PMID:26696830

Basal activity of voltage-gated Ca(2+) channels controls the IP3-mediated contraction by α(1)-adrenoceptor stimulation of mouse aorta segments.

PubMed

Leloup, Arthur J; Van Hove, Cor E; De Meyer, Guido R Y; Schrijvers, Dorien M; Fransen, Paul

2015-08-05

α1-Adrenoceptor stimulation of mouse aorta causes intracellular Ca(2+) release from sarcoplasmic reticulum Ca(2+) stores via stimulation of inositoltriphosphate (IP3) receptors. It is hypothesized that this Ca(2+) release from the contractile and IP3-sensitive Ca(2+) store is under the continuous dynamic control of time-independent basal Ca(2+) influx via L-type voltage-gated Ca(2+) channels (LCC) residing in their window voltage range. Mouse aortic segments were α1-adrenoceptor stimulated with phenylephrine in the absence of external Ca(2+) (0Ca) to measure phasic isometric contractions. They gradually decreased with time in 0Ca, were inhibited with 2-aminoethoxydiphenyl borate, and declined with previous membrane potential hyperpolarization (levcromakalim) or with previous inhibition of LCC (diltiazem). Former basal stimulation of LCC with depolarization (15 mM K(+)) or with BAY K8644 increased the subsequent phasic contractions by phenylephrine in 0Ca. Although exogenous NO (diethylamine NONOate) reduced the phasic contractions by phenylephrine, stimulation of endothelial cells with acetylcholine in 0Ca failed to attenuate these phasic contractions. Finally, inhibition of the basal release of NO with N(Ω)-nitro-L-arginine methyl ester also attenuated the phasic contractions by phenylephrine. Results indicated that α1-adrenoceptor stimulation with phenylephrine causes phasic contractions, which are controlled by basal LCC and endothelial NO synthase activity. Endothelial NO release by acetylcholine was absent in 0Ca. Given the growing interest in the active regulation of arterial compliance, the dependence of contractile SR Ca(2+) store-refilling in basal conditions on the activity of LCC and basal eNOS may contribute to a more thorough understanding of physiological mechanisms leading to arterial stiffness. Copyright © 2015. Published by Elsevier B.V.

Characterization of REM sleep without atonia in patients with narcolepsy and idiopathic hypersomnia using AASM scoring manual criteria.

PubMed

DelRosso, Lourdes M; Chesson, Andrew L; Hoque, Romy

2013-07-15

The AASM Manual for the Scoring of Sleep and Associated Events (Manual) has provided standardized definitions for tonic and phasic REM sleep without atonia (RSWA). This study used Manual criteria to characterize REM sleep in patients with narcolepsy and idiopathic hypersomnia (IH). A retrospective review of PSG data from ICSD-2 defined patients with narcolepsy or IH, performed by two board certified sleep medicine physicians. Data compiled included REM sleep epochs and the presence in REM sleep of epochs scored as sustained muscle activity (tonic), and excessive transient muscle activity (phasic) as defined by Manual criteria. PSG data from 8 narcolepsy patients (mean age: 27.5 years; age range: 11-55) showed mean ± standard deviation values for: total REM sleep epochs 205 ± 46.1; RSWA/ phasic epochs 56.1 ± 25.4; and RSWA/tonic epochs 15.0 ± 10.7. PSG data from 8 IH patients (mean age: 33.1 years; age range: 20-57) showed mean ± standard deviation values of total REM sleep epochs 163.8 ± 67.9; RSWA/phasic epochs 6.2 ± 3.5; and RSWA/tonic epochs 0.2 ± 0.4. Comparison revealed intergroup differences in phasic REM sleep (p < 0.01) and tonic REM sleep (p < 0.01) were significantly increased in narcoleptics compared to IH. Our retrospective analysis showed that RSWA phasic activity and RSWA tonic activity are significantly increased in patients meeting ICSD-2 criteria for narcolepsy compared to patients meeting ICSD-2 criteria for IH. This robust difference, with further validation, could be useful as electrophysiological criteria differentiating the two disorders and understanding the physiological differences.

Dehydration-induced modulation of κ-opioid inhibition of vasopressin neurone activity

PubMed Central

Scott, Victoria; Bishop, Valerie R; Leng, Gareth; Brown, Colin H

2009-01-01

Dehydration increases vasopressin (antidiuretic hormone) secretion from the posterior pituitary gland to reduce water loss in the urine. Vasopressin secretion is determined by action potential firing in vasopressin neurones, which can exhibit continuous, phasic (alternating periods of activity and silence), or irregular activity. Autocrine κ-opioid inhibition contributes to the generation of activity patterning of vasopressin neurones under basal conditions and so we used in vivo extracellular single unit recording to test the hypothesis that changes in autocrine κ-opioid inhibition drive changes in activity patterning of vasopressin neurones during dehydration. Dehydration increased the firing rate of rat vasopressin neurones displaying continuous activity (from 7.1 ± 0.5 to 9.0 ± 0.6 spikes s−1) and phasic activity (from 4.2 ± 0.7 to 7.8 ± 0.9 spikes s−1), but not those displaying irregular activity. The dehydration-induced increase in phasic activity was via an increase in intraburst firing rate. The selective κ-opioid receptor antagonist nor-binaltorphimine increased the firing rate of phasic neurones in non-dehydrated rats (from 3.4 ± 0.8 to 5.3 ± 0.6 spikes s−1) and dehydrated rats (from 6.4 ± 0.5 to 9.1 ± 1.2 spikes s−1), indicating that κ-opioid feedback inhibition of phasic bursts is maintained during dehydration. In a separate series of experiments, prodynorphin mRNA expression was increased in vasopressin neurones of hyperosmotic rats, compared to hypo-osmotic rats. Hence, it appears that dynorphin expression in vasopressin neurones undergoes dynamic changes in proportion to the required secretion of vasopressin so that, even under stimulated conditions, autocrine feedback inhibition of vasopressin neurones prevents over-excitation. PMID:19822541

The actions of isoprenaline and mirabegron in the isolated whole rat and guinea pig bladder.

PubMed

Persyn, Sara; De Wachter, Stefan; Wyndaele, Jean-Jacques; Eastham, Jane; Gillespie, James

2016-07-01

β3-adrenoceptor agonists influence overactive bladder in humans and animal models. However, data is emerging that the mode of action of these drugs is complex. The present study explored the actions of the β3-adrenergic agonist mirabegron and the non-selective agonist isoprenaline on the contractile systems in the rat and guinea pig bladder. Intravesical pressure was measured in isolated whole bladders from female adult animals. In both species spontaneous contractile activity was observed. The muscarinic agonist arecaidine produced complex responses consisting of an initial transient pressure rise followed by complex phasic activity. Three contractile elements were identified: intrinsic micro-contractile activity, initial transient response and steady state phasic activity. The intrinsic and steady state activity could be further divided into a baseline pressure with superimposed phasic activity. The effects of isoprenaline and mirabegron were investigated on these elements. In the rat, the micro-contractile activity could be completely inhibited by isoprenaline (full agonist). The arecaidine-induced initial and steady state baseline pressures were partially reduced, while the phasic activity was little affected. In the guinea pig, both the arecaidine-induced baseline pressure and the phasic activity were affected by isoprenaline. Mirabegron didn't produce significant inhibitory effects in any of the contractile elements in either species. These results show that complex contractile systems operate in the rat and guinea pig bladder that can be modulated by β1/β2-adrenoceptor mechanisms. No evidence was obtained for any β3-dependent regulation of contraction. These data support similar data in humans. Therefore the primary site of therapeutic action of β3-adrenergic agonists remains unknown. Copyright © 2016 Elsevier B.V. All rights reserved.

Receptor units responding to movement in the octopus mantle.

PubMed

Boyle, P R

1976-08-01

1. A preparation of the mantle of Octopus which is inverted over a solid support and which exposes the stellate ganglion and associated nerves is described. 2. Afferent activity can be recorded from stellar nerves following electrical stimulation of the pallial nerve. The latency and frequency of the phasic sensory response is correlated with the contraction of the mantle musculature. 3. It is proposed that receptors cells located in the muscle, and their activity following mantle contraction, form part of a sensory feedback system in the mantle. Large, multipolar nerve cells that were found between the two main layers of circular muscle in the mantle could be such receptors.

Neural breathing patterns in preterm newborns supported with non-invasive neurally adjusted ventilatory assist.

PubMed

García-Muñoz Rodrigo, Fermín; Urquía Martí, Lourdes; Galán Henríquez, Gloria; Rivero Rodríguez, Sonia; Hernández Gómez, Alberto

2018-06-18

To characterize the neural breathing pattern in preterm infants supported with non-invasive neurally adjusted ventilatory assist (NIV-NAVA). Single-center prospective observational study. The electrical activity of the diaphragm (EAdi) was periodically recorded in 30-second series with the Edi catheter and the Servo-n software (Maquet, Solna, Sweden) in preterm infants supported with NIV-NAVA. The EAdi Peak , EAdi Min , EAdi Tonic , EAdi Phasic , neural inspiratory, and expiratory times (nTi and nTe) and the neural respiratory rate (nRR) were calculated. EAdi curves were generated by Excel for visual examination and classified according to the predominant pattern. 291 observations were analyzed in 19 patients with a mean GA of 27.3 weeks (range 24-36 weeks), birth weight 1028 g (510-2945 g), and a median (IQR) postnatal age of 18 days (4-27 days). The distribution of respiratory patterns was phasic without tonic activity 61.9%, phasic with basal tonic activity 18.6, tonic burst 3.8%, central apnea 7.9%, and mixed pattern 7.9%. In addition, 12% of the records showed apneas of >10 seconds, and 50.2% one or more "sighs", defined as breaths with an EAdi Peak and/or nTi greater than twice the average EAdi Peak and/or nTi of the recording. Neural times were measurable in 252 observations. The nTi was, median (IQR): 279 ms (253-285 ms), the nTe 764 ms (642-925 ms), and the nRR 63 bpm (51-70), with a great intra and inter-subjects variability. The neural breathing patterns in preterm infants supported with NIV-NAVA are quite variable and are characterized by the presence of significant tonic activity. Central apneas and sighs are common in this group of patients. The nTi seems to be shorter than the mechanical Ti commonly used in assisted ventilation.

Phasic spike patterning in rat supraoptic neurones in vivo and in vitro

PubMed Central

Sabatier, Nancy; Brown, Colin H; Ludwig, Mike; Leng, Gareth

2004-01-01

In vivo, most vasopressin cells of the hypothalamic supraoptic nucleus fire action potentials in a ‘phasic’ pattern when the systemic osmotic pressure is elevated, while most oxytocin cells fire continuously. The phasic firing pattern is believed to arise as a consequence of intrinsic activity-dependent changes in membrane potential, and these have been extensively studied in vitro. Here we analysed the discharge patterning of supraoptic nucleus neurones in vivo, to infer the characteristics of the post-spike sequence of hyperpolarization and depolarization from the observed spike patterning. We then compared patterning in phasic cells in vivo and in vitro, and we found systematic differences in the interspike interval distributions, and in other statistical parameters that characterized activity patterns within bursts. Analysis of hazard functions (probability of spike initiation as a function of time since the preceding spike) revealed that phasic firing in vitro appears consistent with a regenerative process arising from a relatively slow, late depolarizing afterpotential that approaches or exceeds spike threshold. By contrast, in vivo activity appears to be dominated by stochastic rather than deterministic mechanisms, and appears consistent with a relatively early and fast depolarizing afterpotential that modulates the probability that random synaptic input exceeds spike threshold. Despite superficial similarities in the phasic firing patterns observed in vivo and in vitro, there are thus fundamental differences in the underlying mechanisms. PMID:15146047

Tonic and Phasic Receptor Neurons in the Vertebrate Olfactory Epithelium

PubMed Central

Madrid, Rodolfo; Sanhueza, Magdalena; Alvarez, Osvaldo; Bacigalupo, Juan

2003-01-01

Olfactory receptor neurons (ORNs) respond to odorants with characteristic patterns of action potentials that are relevant for odor coding. Prolonged odorant exposures revealed three populations of dissociated toad ORNs, which were mimicked by depolarizing currents: tonic (TN, displaying sustained firing, 49% of 102 cells), phasic (PN, exhibiting brief action potential trains, 36%) and intermediate neurons (IN, generating trains longer than PN, 15%). We studied the biophysical properties underlying the differences between TNs and PNs, the most extreme cases among ORNs. TNs and PNs possessed similar membrane capacitances (∼4 pF), but they differed in resting potential (−82 versus −64 mV), input resistance (4.2 versus 2.9 GΩ) and unspecific current, Iu (TNs: 0 < Iu ≤ 1 pA/pF; and PNs: Iu > 1 pA/pF). Firing behavior did not correlate with differences in voltage-gated conductances. We developed a mathematical model that accurately simulates tonic and phasic patterns. Whole cell recordings from rat ORNs in fragments (∼4 mm2) of olfactory epithelium showed that such a tissue normally contains tonic and phasic receptor neurons, suggesting that this feature is common across a wide range of vertebrates. Our findings show that the individual passive electrical properties can govern the firing patterns of ORNs. PMID:12770919

Revealing the functional neuroanatomy of intrinsic alertness using fMRI: methodological peculiarities.

PubMed

Clemens, Benjamin; Zvyagintsev, Mikhail; Sack, Alexander T; Sack, Alexander; Heinecke, Armin; Willmes, Klaus; Sturm, Walter

2011-01-01

Clinical observations and neuroimaging data revealed a right-hemisphere fronto-parietal-thalamic-brainstem network for intrinsic alertness, and additional left fronto-parietal activity during phasic alertness. The primary objective of this fMRI study was to map the functional neuroanatomy of intrinsic alertness as precisely as possible in healthy participants, using a novel assessment paradigm already employed in clinical settings. Both the paradigm and the experimental design were optimized to specifically assess intrinsic alertness, while at the same time controlling for sensory-motor processing. The present results suggest that the processing of intrinsic alertness is accompanied by increased activity within the brainstem, thalamus, anterior cingulate gyrus, right insula, and right parietal cortex. Additionally, we found increased activation in the left hemisphere around the middle frontal gyrus (BA 9), the insula, the supplementary motor area, and the cerebellum. Our results further suggest that rather minute aspects of the experimental design may induce aspects of phasic alertness, which in turn might lead to additional brain activation in left-frontal areas not normally involved in intrinsic alertness. Accordingly, left BA 9 activation may be related to co-activation of the phasic alertness network due to the switch between rest and task conditions functioning as an external warning cue triggering the phasic alertness network. Furthermore, activation of the intrinsic alertness network during fixation blocks due to enhanced expectancy shortly before the switch to the task block might, when subtracted from the task block, lead to diminished activation in the typical right hemisphere intrinsic alertness network. Thus, we cautiously suggest that--as a methodological artifact--left frontal activations might show up due to phasic alertness involvement and intrinsic alertness activations might be weakened due to contrasting with fixation blocks, when assessing the functional neuroanatomy of intrinsic alertness with a block design in fMRI studies.

Revealing the Functional Neuroanatomy of Intrinsic Alertness Using fMRI: Methodological Peculiarities

PubMed Central

Clemens, Benjamin; Zvyagintsev, Mikhail; Sack, Alexander; Heinecke, Armin; Willmes, Klaus; Sturm, Walter

2011-01-01

Clinical observations and neuroimaging data revealed a right-hemisphere fronto-parietal-thalamic-brainstem network for intrinsic alertness, and additional left fronto-parietal activity during phasic alertness. The primary objective of this fMRI study was to map the functional neuroanatomy of intrinsic alertness as precisely as possible in healthy participants, using a novel assessment paradigm already employed in clinical settings. Both the paradigm and the experimental design were optimized to specifically assess intrinsic alertness, while at the same time controlling for sensory-motor processing. The present results suggest that the processing of intrinsic alertness is accompanied by increased activity within the brainstem, thalamus, anterior cingulate gyrus, right insula, and right parietal cortex. Additionally, we found increased activation in the left hemisphere around the middle frontal gyrus (BA 9), the insula, the supplementary motor area, and the cerebellum. Our results further suggest that rather minute aspects of the experimental design may induce aspects of phasic alertness, which in turn might lead to additional brain activation in left-frontal areas not normally involved in intrinsic alertness. Accordingly, left BA 9 activation may be related to co-activation of the phasic alertness network due to the switch between rest and task conditions functioning as an external warning cue triggering the phasic alertness network. Furthermore, activation of the intrinsic alertness network during fixation blocks due to enhanced expectancy shortly before the switch to the task block might, when subtracted from the task block, lead to diminished activation in the typical right hemisphere intrinsic alertness network. Thus, we cautiously suggest that – as a methodological artifact – left frontal activations might show up due to phasic alertness involvement and intrinsic alertness activations might be weakened due to contrasting with fixation blocks, when assessing the functional neuroanatomy of intrinsic alertness with a block design in fMRI studies. PMID:21984928

The main source of ambient GABA responsible for tonic inhibition in the mouse hippocampus

PubMed Central

Glykys, Joseph; Mody, Istvan

2007-01-01

The extracellular space of the brain contains γ-aminobutyric acid (GABA) that activates extrasynaptic GABAA receptors mediating tonic inhibition. The source of this GABA is uncertain: it could be overspill of vesicular release, non-vesicular leakage, reverse transport, dying cells or glia. Using a novel approach, we simultaneously measured phasic and tonic inhibitory currents and assessed their correlation. Enhancing or diminishing vesicular GABA release in hippocampal neurons caused highly correlated changes in the two inhibitions. During high-frequency phasic inhibitory bursts, tonic current was also enhanced as shown by simulating the summation of IPSCs and by recordings in knockout mice devoid of tonic inhibitory current. When vesicular release was reduced by blocking action potentials or the vesicular GABA transporter, phasic and tonic currents decreased in a correlated fashion. Our results are consistent with most of hippocampal tonic inhibitory current being mediated by GABA released from the very vesicles responsible for activating phasic inhibition. PMID:17525114

The main source of ambient GABA responsible for tonic inhibition in the mouse hippocampus.

PubMed

Glykys, Joseph; Mody, Istvan

2007-08-01

The extracellular space of the brain contains gamma-aminobutyric acid (GABA) that activates extrasynaptic GABA(A) receptors mediating tonic inhibition. The source of this GABA is uncertain: it could be overspill of vesicular release, non-vesicular leakage, reverse transport, dying cells or glia. Using a novel approach, we simultaneously measured phasic and tonic inhibitory currents and assessed their correlation. Enhancing or diminishing vesicular GABA release in hippocampal neurons caused highly correlated changes in the two inhibitions. During high-frequency phasic inhibitory bursts, tonic current was also enhanced as shown by simulating the summation of IPSCs and by recordings in knockout mice devoid of tonic inhibitory current. When vesicular release was reduced by blocking action potentials or the vesicular GABA transporter, phasic and tonic currents decreased in a correlated fashion. Our results are consistent with most of hippocampal tonic inhibitory current being mediated by GABA released from the very vesicles responsible for activating phasic inhibition.

Discharge patterns of human genioglossus motor units during arousal from sleep.

PubMed

Wilkinson, Vanessa; Malhotra, Atul; Nicholas, Christian L; Worsnop, Christopher; Jordan, Amy S; Butler, Jane E; Saboisky, Julian P; Gandevia, Simon C; White, David P; Trinder, John

2010-03-01

Single motor unit recordings of the human genioglossus muscle reveal motor units with a variety of discharge patterns. Integrated multiunit electromyographic recordings of genioglossus have demonstrated an abrupt increase in the muscle's activity at arousal from sleep. The aim of the present study was to determine the effect of arousal from sleep on the activity of individual motor units as a function of their particular discharge pattern. Genioglossus activity was measured using intramuscular fine-wire electrodes inserted via a percutaneous approach. Arousals from sleep were identified using the ASDA criterion and the genioglossus electromyogram recordings analyzed for single motor unit activity. Sleep research laboratory. Sleep and respiratory data were collected in 8 healthy subjects (6 men). 138 motor units were identified during prearousalarousal sleep: 25% inspiratory phasic, 33% inspiratory tonic, 4% expiratory phasic, 3% expiratory tonic, and 35% tonic. At arousal from sleep inspiratory phasic units significantly increased the proportion of a breath over which they were active, but did not appreciably increase their rate of firing. 80 new units were identified at arousals, 75% were inspiratory, many of which were active for only 1 or 2 breaths. 22% of units active before arousal, particularly expiratory and tonic units, stopped at the arousal. Increased genioglossus muscle activity at arousal from sleep is primarily due to recruitment of inspiratory phasic motor units. Further, activity within the genioglossus motoneuron pool is reorganized at arousal as, in addition to recruitment, approximately 20% of units active before arousals stopped firing.

Noise-enhanced coding in phasic neuron spike trains.

PubMed

Ly, Cheng; Doiron, Brent

2017-01-01

The stochastic nature of neuronal response has lead to conjectures about the impact of input fluctuations on the neural coding. For the most part, low pass membrane integration and spike threshold dynamics have been the primary features assumed in the transfer from synaptic input to output spiking. Phasic neurons are a common, but understudied, neuron class that are characterized by a subthreshold negative feedback that suppresses spike train responses to low frequency signals. Past work has shown that when a low frequency signal is accompanied by moderate intensity broadband noise, phasic neurons spike trains are well locked to the signal. We extend these results with a simple, reduced model of phasic activity that demonstrates that a non-Markovian spike train structure caused by the negative feedback produces a noise-enhanced coding. Further, this enhancement is sensitive to the timescales, as opposed to the intensity, of a driving signal. Reduced hazard function models show that noise-enhanced phasic codes are both novel and separate from classical stochastic resonance reported in non-phasic neurons. The general features of our theory suggest that noise-enhanced codes in excitable systems with subthreshold negative feedback are a particularly rich framework to study.

Gravitational and Dynamic Components of Muscle Torque Underlie Tonic and Phasic Muscle Activity during Goal-Directed Reaching.

PubMed

Olesh, Erienne V; Pollard, Bradley S; Gritsenko, Valeriya

2017-01-01

Human reaching movements require complex muscle activations to produce the forces necessary to move the limb in a controlled manner. How gravity and the complex kinetic properties of the limb contribute to the generation of the muscle activation pattern by the central nervous system (CNS) is a long-standing and controversial question in neuroscience. To tackle this issue, muscle activity is often subdivided into static and phasic components. The former corresponds to posture maintenance and transitions between postures. The latter corresponds to active movement production and the compensation for the kinetic properties of the limb. In the present study, we improved the methodology for this subdivision of muscle activity into static and phasic components by relating them to joint torques. Ten healthy subjects pointed in virtual reality to visual targets arranged to create a standard center-out reaching task in three dimensions. Muscle activity and motion capture data were synchronously collected during the movements. The motion capture data were used to calculate postural and dynamic components of active muscle torques using a dynamic model of the arm with 5 degrees of freedom. Principal Component Analysis (PCA) was then applied to muscle activity and the torque components, separately, to reduce the dimensionality of the data. Muscle activity was also reconstructed from gravitational and dynamic torque components. Results show that the postural and dynamic components of muscle torque represent a significant amount of variance in muscle activity. This method could be used to define static and phasic components of muscle activity using muscle torques.

Gravitational and Dynamic Components of Muscle Torque Underlie Tonic and Phasic Muscle Activity during Goal-Directed Reaching

PubMed Central

Olesh, Erienne V.; Pollard, Bradley S.; Gritsenko, Valeriya

2017-01-01

Human reaching movements require complex muscle activations to produce the forces necessary to move the limb in a controlled manner. How gravity and the complex kinetic properties of the limb contribute to the generation of the muscle activation pattern by the central nervous system (CNS) is a long-standing and controversial question in neuroscience. To tackle this issue, muscle activity is often subdivided into static and phasic components. The former corresponds to posture maintenance and transitions between postures. The latter corresponds to active movement production and the compensation for the kinetic properties of the limb. In the present study, we improved the methodology for this subdivision of muscle activity into static and phasic components by relating them to joint torques. Ten healthy subjects pointed in virtual reality to visual targets arranged to create a standard center-out reaching task in three dimensions. Muscle activity and motion capture data were synchronously collected during the movements. The motion capture data were used to calculate postural and dynamic components of active muscle torques using a dynamic model of the arm with 5 degrees of freedom. Principal Component Analysis (PCA) was then applied to muscle activity and the torque components, separately, to reduce the dimensionality of the data. Muscle activity was also reconstructed from gravitational and dynamic torque components. Results show that the postural and dynamic components of muscle torque represent a significant amount of variance in muscle activity. This method could be used to define static and phasic components of muscle activity using muscle torques. PMID:29018339

Distinct changes in evoked and resting globus pallidus activity in early and late Parkinson's disease experimental models.

PubMed

Zold, Camila L; Larramendy, Celia; Riquelme, Luis A; Murer, M Gustavo

2007-09-01

The main clinical manifestations of Parkinson's disease are caused by alterations of basal ganglia activity that are tied in with the progressive loss of mesencephalic dopaminergic neurons. Recent theoretical and modeling studies have suggested that changes in resting neuronal activity occurred later in the course of the disease than those evoked by phasic cortical input. However, there is no empirical support for this proposal. Here we report a marked increase in the responsiveness of globus pallidus neurons to electrical motor cortex stimulation, in the absence of noticeable changes in resting activity, in anesthetized rats that had consistently shown a deficit in forelimb use during behavioral testing before the experiments, and had approximately 45% dopamine neurons spared in the substantia nigra. Pallidal neurons were also over-responsive to motor cortex stimulation and lost spatial selectivity for cortical inputs in rats with extensive nigrostriatal damage. After partial lesions, over-responsiveness was mainly due to an increased proportion of neurons showing excitatory responses, while extensive lesions led to an increased likelihood of inhibitory responding neurons. Changes in resting neuronal activity, comprising pauses disrupting tonic discharge, occurred across different global brain states, including an activated condition which shares similarities with natural patterns of cortical activity seen in awake states and rapid eye-movement sleep, but only after massive nigrostriatal degeneration. These results suggest that a loss of functional segregation and an abnormal temporal encoding of phasic cortical inputs by globus pallidus neurons may contribute to inducing early motor impairment in Parkinson's disease.

Electrical conduction disturbance effects on dynamic changes of functional mitral regurgitation.

PubMed

Fukuda, Shota; Grimm, Richard; Song, Jong-Min; Kihara, Takashi; Daimon, Masao; Agler, Deborah A; Wilkoff, Bruce L; Natale, Andrea; Thomas, James D; Shiota, Takahiro

2005-12-20

The aim of this study was to investigate the relationship between dynamics of functional mitral regurgitation (MR) and the degree of electrical conduction disturbance, and to evaluate the impact of cardiac resynchronization therapy (CRT) on MR severity and its phasic pattern. Mechanisms of phasic changes of functional MR, which may be determined by annulus dilation and tethering of the leaflet, remain unclear. Transthoracic two-dimensional echocardiography was performed in 60 patients with functional MR. A biventricular pacemaker was implanted in 19 patients. The mitral annulus area (MAA) and the tenting area (TA) were measured from apical views. The MR volume and fraction were assessed by the quantitative pulsed Doppler method. Instantaneous regurgitation flow rate was measured by proximal flow convergence method. A dynamic change in MR flow rate was evaluated by frame-by-frame analysis throughout systole. A phasic pattern with two peaks at early- and late-systole and decrease in mid-systole was noticed in 57 patients. The early-systolic peak of MR was larger than the late-systolic peak (128.4 +/- 64.3 ml/s vs. 73.9 +/- 55.1 ml/s, p < 0.001). The ratio of flow rate at these two peaks correlated with QRS duration (r = 0.55, p < 0.001). Early-systolic flow rate reduced after CRT (143.9 +/- 60.8 ml/s to 90.7 +/- 54.1 ml/s, p < 0.05), but late-systolic flow rate did not (61.5 +/- 55.0 ml/s to 51.2 +/- 40.9 ml/s, p = NS). A similar pattern was observed for TA, whereas MAA did not change after CRT. Biphasic pattern was found in functional MR, and the ratio of flow rate at two peaks correlated with QRS duration. The CRT decreased regurgitation flow volume by reducing early-systolic MR but not late-systolic MR, resulting in the change in phasic pattern of functional MR.

Night-to-night variability of muscle tone, movements, and vocalizations in patients with REM sleep behavior disorder.

PubMed

Cygan, Fanny; Oudiette, Delphine; Leclair-Visonneau, Laurène; Leu-Semenescu, Smaranda; Arnulf, Isabelle

2010-12-15

The video-polysomnographic criteria of REM sleep behavior disorder (RBD) have not been well described. We evaluated the between-night reproducibility of phasic and tonic enhanced muscle activity during REM sleep as well as the associated behaviors and vocalizations of the patients. Fifteen patients with clinical RBD underwent two consecutive video-polysomnographies. The amount of excessive phasic and tonic chin muscle activity during REM sleep was measured in 15 patients in 3-sec mini-epochs. The time spent with motor (minor, major, complex, and scenic) or vocal (sounds, mumblings, and comprehensible speeches) events was measured in 7 patients during REM sleep. There was a good between-night agreement for tonic (Spearman rho = 0.55, p = 0.03; Kendall tau = 0.48, p = 0.01) but not for phasic (rho = 0.47, p = 0.1; tau = 0.31, p = 0.1) excessive chin muscle activity. On the video and audio recordings, the minor RBD behaviors tended to occur more frequently during the second night than the first, whereas the patients spoke longer during the first than the second night. The excessive tonic activity during REM sleep is a reliable marker of RBD. It could represent the extent of dysfunction in the permissive atonia systems. In contrast, the more variable phasic activity and motor/vocal events could be more dependent on dream content (executive systems).

The area postrema (AP) and the parabrachial nucleus (PBN) are important sites for salmon calcitonin (sCT) to decrease evoked phasic dopamine release in the nucleus accumbens (NAc).

PubMed

Whiting, Lynda; McCutcheon, James E; Boyle, Christina N; Roitman, Mitchell F; Lutz, Thomas A

2017-07-01

The pancreatic hormone amylin and its agonist salmon calcitonin (sCT) act via the area postrema (AP) and the lateral parabrachial nucleus (PBN) to reduce food intake. Investigations of amylin and sCT signaling in the ventral tegmental area (VTA) and nucleus accumbens (NAc) suggest that the eating inhibitory effect of amylin is, in part, mediated through the mesolimbic 'reward' pathway. Indeed, administration of the sCT directly to the VTA decreased phasic dopamine release (DA) in the NAc. However, it is not known if peripheral amylin modulates the mesolimbic system directly or whether this occurs via the AP and PBN. To determine whether and how peripheral amylin or sCT affect mesolimbic reward circuitry we utilized fast scan cyclic voltammetry under anesthesia to measure phasic DA release in the NAc evoked by electrical stimulation of the VTA in intact, AP lesioned and bilaterally PBN lesioned rats. Amylin (50μg/kg i.p.) did not change phasic DA responses compared to saline control rats. However, sCT (50μg/kg i.p.) decreased evoked DA release to VTA-stimulation over 1h compared to saline treated control rats. Further investigations determined that AP and bilateral PBN lesions abolished the ability of sCT to suppress evoked phasic DA responses to VTA-stimulation. These findings implicate the AP and the PBN as important sites for peripheral sCT to decrease evoked DA release in the NAc and suggest that these nuclei may influence hedonic and motivational processes to modulate food intake. Copyright © 2017 Elsevier Inc. All rights reserved.

Locus coeruleus phasic discharge is essential for stimulus-induced gamma oscillations in the prefrontal cortex.

PubMed

Neves, Ricardo M; van Keulen, Silvia; Yang, Mingyu; Logothetis, Nikos K; Eschenko, Oxana

2018-03-01

The locus coeruleus (LC) noradrenergic (NE) neuromodulatory system is critically involved in regulation of neural excitability via its diffuse ascending projections. Tonic NE release in the forebrain is essential for maintenance of vigilant states and increases the signal-to-noise ratio of cortical sensory responses. The impact of phasic NE release on cortical activity and sensory processing is less explored. We previously reported that LC microstimulation caused a transient desynchronization of population activity in the medial prefrontal cortex (mPFC), similar to noxious somatosensory stimuli. The LC receives nociceptive information from the medulla and therefore may mediate sensory signaling to its forebrain targets. Here we performed extracellular recordings in LC and mPFC while presenting noxious stimuli in urethane-anesthetized rats. A brief train of foot shocks produced a robust phasic response in the LC and a transient change in the mPFC power spectrum, with the strongest modulation in the gamma (30-90 Hz) range. The LC phasic response preceded prefrontal gamma power increase, and cortical modulation was proportional to the LC excitation. We also quantitatively characterized distinct cortical states and showed that sensory responses in both LC and mPFC depend on the ongoing cortical state. Finally, cessation of the LC firing by bilateral local iontophoretic injection of clonidine, an α 2 -adrenoreceptor agonist, completely eliminated sensory responses in the mPFC without shifting cortex to a less excitable state. Together, our results suggest that the LC phasic response induces gamma power increase in the PFC and is essential for mediating sensory information along an ascending noxious pathway. NEW & NOTEWORTHY Our study shows linear relationships between locus coeruleus phasic excitation and the amplitude of gamma oscillations in the prefrontal cortex. Results suggest that the locus coeruleus phasic response is essential for mediating sensory information along an ascending noxious pathway.

Low concentrations of niflumic acid enhance basal spontaneous and carbachol-induced contractions of the detrusor.

PubMed

Lam, Wai Ping; Tang, Hong Chai; Zhang, Xin; Leung, Ping Chung; Yew, David Tai Wai; Liang, Willmann

2014-02-01

The urinary bladder expresses Ca(2+)-activated Cl(-) channels (CACC), but its physiological role in governing contractility remains to be defined. The CACC modulator niflumic acid (NFA) is widely used despite the variable results arisen from different drug concentrations used. This study was designed to examine the effects of NFA at low concentrations on detrusor strip contractility. Rat detrusor strips with mucosa-intact (+MU) and mucosa-denuded (-MU) were prepared in transverse (Tr) and longitudinal (Lg) with respect to the bladder orientation. Isometric force measurements were made at baseline (for spontaneous phasic contractile activity) and during drug stimulation (by carbachol, CCh) with and without NFA. NFA (1 and 10 μmol/L) pretreatment enhanced CCh-induced contractions more in +MU than -MU strips with no selectivity on contractile direction. For spontaneous phasic contractions, NFA-treated strips in the Tr direction showed increased phasic amplitude, while phasic frequency was unchanged. The findings suggest low concentrations of NFA having a potentiating effect on detrusor contractions that was sensitive to the MU and contractile direction.

Rhythm and amplitude of rhythmic masticatory muscle activity during sleep in bruxers - comparison with gum chewing.

PubMed

Matsuda, Shinpei; Yamaguchi, Taihiko; Mikami, Saki; Okada, Kazuki; Gotouda, Akihito; Sano, Kazuo

2016-07-01

The aim of this study was to elucidate characteristics of rhythmic masticatory muscle activity (RMMA) during sleep by comparing masseteric EMG (electromyogram) activities of RMMA with gum chewing. The parts of five or more consecutive phasic bursts in RMMA of 23 bruxers were analyzed. Wilcoxon signed-rank test for matched pairs and Spearman's correlation coefficient by the rank test were used for statistical analysis. Root mean square value of RMMA phasic burst was smaller than that during gum chewing, but correlates to that of gum chewing. The cycle of RMMA was longer than that of gum chewing due to the longer burst duration of RMMA, and variation in the cycles of RMMA was wider. These findings suggest that the longer but smaller EMG burst in comparison with gum chewing is one of the characteristics of RMMA. The relation between size of RMMA phasic bursts and gum chewing is also suggested.

Brain regions engaged by part- and whole-task performance in a video game: a model-based test of the decomposition hypothesis.

PubMed

Anderson, John R; Bothell, Daniel; Fincham, Jon M; Anderson, Abraham R; Poole, Ben; Qin, Yulin

2011-12-01

Part- and whole-task conditions were created by manipulating the presence of certain components of the Space Fortress video game. A cognitive model was created for two-part games that could be combined into a model that performed the whole game. The model generated predictions both for behavioral patterns and activation patterns in various brain regions. The activation predictions concerned both tonic activation that was constant in these regions during performance of the game and phasic activation that occurred when there was resource competition. The model's predictions were confirmed about how tonic and phasic activation in different regions would vary with condition. These results support the Decomposition Hypothesis that the execution of a complex task can be decomposed into a set of information-processing components and that these components combine unchanged in different task conditions. In addition, individual differences in learning gains were predicted by individual differences in phasic activation in those regions that displayed highest tonic activity. This individual difference pattern suggests that the rate of learning of a complex skill is determined by capacity limits.

Role of rho-kinase (ROCK) in tonic but not phasic contraction in the frog stomach smooth muscle.

PubMed

Sahin, Leyla; Cevik, Ozge Selin; Koyuncu, Dilan Deniz; Buyukafsar, Kansu

2018-04-01

Rho/Rho-kinase (ROCK) signaling has extensively been shown to take part in mammalian smooth muscle contractions in response to diverse agents yet its role in the contraction of amphibian smooth muscle has not been investigated. Therefore, we aimed to explore any role of this pathway in the contractions of frog stomach smooth. The strips were prepared and suspended in organ baths filled with Ringer solution. Changes in the circular strips of the frog stomach muscle length were recorded isotonically with a force transducer in organ baths. Carbachol (CCh) exerted both phasic and tonic contractions. In contrast, atropin abolished all types of contractions by CCh. The phasic contractions were suppressed by a Ca 2+ channel blocker, nifedipine but not by the ROCK inhibitor, Y-27632. However, the tonic contractions were markedly attenuated by Y-27632. Selective M 1 receptor blocker, pirenzepin, selective M 3 receptor blocker and DAMP had no effects on CCh-elicited contractions. On the other hand, selective M 2 receptor blocker, AF-DX suppressed all types of contractile activity by CCh. These data suggest that M 2 receptor activation could mainly mediate CCh-induced phasic and tonic contractions, and ROCK seems to be involved in the CCh-induced tonic but not phasic contractions of the frog stomach smooth muscle. Copyright © 2018 Elsevier Inc. All rights reserved.

Endoscopic manometry of the sphincter of Oddi in sphincterotomized patients.

PubMed

Ugljesić, M; Bulajić, M; Milosavljević, T; Stimec, B

1995-01-01

Endoscopic sphincterotomy (ES) of the sphincter of Oddi (SO) has been accepted as an effective method in extraction of common bile duct stones in postcholecystectomy patients. The purpose of this study was to examine the completeness of the performed ES and observe the post sphincterotomy pancreatic duct sphincter (PDS) activity using endoscopic manometry. Activity of the sphincter of Oddi was examined in 15 sphincterotomized patients using endoscopic manometry one to 2.5 years after endoscopic sphincterotomy for choledocholithiasis. In eight patients absence of choledochoduodenal gradient, baseline pressure and the sphincter of Oddi phasic activity up to 2.5 years after endoscopic sphincterotomy indicated a complete sphincterotomy. In seven patients with incomplete endoscopic sphincterotomy, manometry exhibited either a lower choledochoduodenal gradient and baseline pressure without phasic activity of the sphincter of Oddi (three patients), a sphincter of Oddi activity without choledochoduodenal gradient (one patient), or a complete restitution of the sphincter of Oddi activity 1 to 2 years after endoscopic sphincterotomy (three patients). In five patients, with complete endoscopic sphincterotomy, measurements of pancreatic sphincter activity showed lower values of the pancreatic ductal pressure and baseline pressure, while the pancreatic sphincter phasic activity was equal to that found in the control group. Endoscopic manometry is method which enables us to test the completeness of endoscopic sphincterotomy and to follow the restitution of the phasic contractile function of the sphincter. Manometric findings reveal pancreatic sphincter in most patients as a separate sphincteric entity, the function of which is reduced but not eliminated by a complete endoscopic sphincterotomy.

Electromyographic activity of the hyoepiglotticus muscle and control of epiglottis position in horses.

PubMed

Holcombe, Susan J; Cornelisse, Cornelis J; Berney, Cathy; Robinson, N Edward

2002-12-01

To determine whether the hyoepiglotticus muscle has respiratory-related electromyographic activity and whether electrical stimulation of this muscle changes the position and conformation of the epiglottis, thereby altering dimensions of the aditus laryngis. 6 Standardbred horses. Horses were anesthetized, and a bipolar fine-wire electrode was placed in the hyoepiglotticus muscle of each horse. Endoscopic images of the nasopharynx and larynx were recorded during electrical stimulation of the hyoepiglotticus muscle in standing, unsedated horses. Dorsoventral length and area of the aditus laryngis were measured on images obtained before and during electrical stimulation. Electromyographic activity of the hyoepiglotticus muscle and nasopharyngeal pressures were measured while horses exercised on a treadmill at 50, 75, 90, and 100% of the speed that produced maximum heart rate. Electrical stimulation of the hyoepiglotticus muscle changed the shape of the epiglottis, displaced it ventrally, and significantly increased the dorsoventral length and area of the aditus laryngis. The hyoepiglotticus muscle had inspiratory activity that increased significantly with treadmill speed as a result of an increase in phasic and tonic activity. Expiratory activity of the hyoepiglotticus muscle did not change with treadmill speed in 4 of 6 horses. Findings reported here suggest that contraction of the hyoepiglotticus muscle increases dimensions of the airway in horses by depressing the epiglottis ventrally during intense breathing efforts. The hyoepiglotticus muscle may be an important muscle for dilating the airway in horses, and contraction of the hyoepiglotticus muscle may induce conformational changes in the epiglottis.

Rhythmic activities of hypothalamic magnocellular neurons: autocontrol mechanisms.

PubMed

Richard, P; Moos, F; Dayanithi, G; Gouzènes, L; Sabatier, N

1997-12-01

Electrophysiological recordings in lactating rats show that oxytocin (OT) and vasopressin (AVP) neurons exhibit specific patterns of activities in relation to peripheral stimuli: periodic bursting firing for OT neurons during suckling, phasic firing for AVP neurons during hyperosmolarity (systemic injection of hypertonic saline). These activities are autocontrolled by OT and AVP released somato-dentritically within the hypothalamic magnocellular nuclei. In vivo, OT enhances the amplitude and frequency of bursts, an effect accompanied with an increase in basal firing rate. However, the characteristics of firing change as facilitation proceeds: the spike patterns become very irregular with clusters of spikes spaced by long silences; the firing rate is highly variable and clearly oscillates before facilitated bursts. This unstable behaviour dramatically decreases during intense tonic activation which temporarily interrupts bursting, and could therefore be a prerequisite for bursting. In vivo, the effects of AVP depend on the initial firing pattern of AVP neurons: AVP excites weakly active neurons (increasing duration of active periods and decreasing silences), inhibits highly active neurons, and does not affect neurons with intermediate phasic activity. AVP brings the entire population of AVP neurons to discharge with a medium phasic activity characterised by periods of firing and silence lasting 20-40 s, a pattern shown to optimise the release of AVP from the neurohypophysis. Each of the peptides (OT or AVP) induces an increase in intracellular Ca2+ concentration, specifically in the neurons containing either OT or AVP respectively. OT evokes the release of Ca2+ from IP3-sensitive intracellular stores. AVP induces an influx of Ca2+ through voltage-dependent Ca2+ channels of T-, L- and N-types. We postulate that the facilitatory autocontrol of OT and AVP neurons could be mediated by Ca2+ known to play a key role in the control of the patterns of phasic neurons.

[Functional significance of high-frequency components of brain electrical activity in the processes of gestalt formation].

PubMed

Dumenko, V N

2002-01-01

A review. Current views of the so-called binding problem, which considers hypothetical mechanisms of perception of sensory stimuli and formation of their corresponding Gestalts (internal images) are discussed. The mechanism of intensification of synchronized reactions of cortical electrical activity in the gamma band frequency (30-80 Hz) is the basis of the most popular point of view of "binding". The article considers the evidence for the functional significance of the high-frequency components exceeding the gamma-range (to 200 Hz) obtained by the author, the origin of these oscillations, and conditions of their focal derivation. The problem of "binding" and stages of instrumental conditioning (a stimulus, perception of the stimulus, and its transformation into a signal) as well as significance of the context in learning and formation of tonic states ensuring the realization of phasic reactions is discussed. Forms of "binding" at the final stage of conditioning (selective attention) are considered. The question is posed as to whether "binding" is exhausted only by the mechanisms of synchronization of activities of large neuronal populations and only in the frequencies of the gamma range.

Brain Regions Engaged by Part- and Whole-task Performance in a Video Game: A Model-based Test of the Decomposition Hypothesis

PubMed Central

Anderson, John R.; Bothell, Daniel; Fincham, Jon M.; Anderson, Abraham R.; Poole, Ben; Qin, Yulin

2013-01-01

Part- and whole-task conditions were created by manipulating the presence of certain components of the Space Fortress video game. A cognitive model was created for two-part games that could be combined into a model that performed the whole game. The model generated predictions both for behavioral patterns and activation patterns in various brain regions. The activation predictions concerned both tonic activation that was constant in these regions during performance of the game and phasic activation that occurred when there was resource competition. The model’s predictions were confirmed about how tonic and phasic activation in different regions would vary with condition. These results support the Decomposition Hypothesis that the execution of a complex task can be decomposed into a set of information-processing components and that these components combine unchanged in different task conditions. In addition, individual differences in learning gains were predicted by individual differences in phasic activation in those regions that displayed highest tonic activity. This individual difference pattern suggests that the rate of learning of a complex skill is determined by capacity limits. PMID:21557648

Age differences in gain- and loss-motivated attention.

PubMed

Williams, Ryan S; Biel, Anna Lena; Dyson, Benjamin J; Spaniol, Julia

2017-02-01

Adaptive gain theory (Aston-Jones & Cohen, 2005) suggests that the phasic release of norepinephrine (NE) to cortical areas reflects changes in the utility of ongoing tasks. In the context of aging, this theory raises interesting questions, given that the motivations of older adults differ from those of younger adults. According to socioemotional selectivity theory (Carstensen, Isaacowitz, & Charles, 1999), aging is associated with greater emphasis on emotion-regulation goals, leading older adults to prioritize positive over negative information. This suggests that the phasic release of NE in response to threatening stimuli may be diminished in older adults. In the present study, younger adults (aged 18-34years) and older adults (60-82years) completed the Attention Network Test (ANT), modified to include an incentive manipulation. A behavioral index of attentional alerting served as a marker of phasic arousal. For younger adults, this marker correlated with the effect of both gain and loss incentives on performance. For older adults, in contrast, the correlation between phasic arousal and incentive sensitivity held for gain incentives only. These findings suggest that the enlistment of phasic NE activity may be specific to approach-oriented motivation in older adults. Copyright © 2016. Published by Elsevier Inc.

Age differences in high frequency phasic heart rate variability and performance response to increased executive function load in three executive function tasks

PubMed Central

Byrd, Dana L.; Reuther, Erin T.; McNamara, Joseph P. H.; DeLucca, Teri L.; Berg, William K.

2015-01-01

The current study examines similarity or disparity of a frontally mediated physiological response of mental effort among multiple executive functioning tasks between children and adults. Task performance and phasic heart rate variability (HRV) were recorded in children (6 to 10 years old) and adults in an examination of age differences in executive functioning skills during periods of increased demand. Executive load levels were varied by increasing the difficulty levels of three executive functioning tasks: inhibition (IN), working memory (WM), and planning/problem solving (PL). Behavioral performance decreased in all tasks with increased executive demand in both children and adults. Adults’ phasic high frequency HRV was suppressed during the management of increased IN and WM load. Children’s phasic HRV was suppressed during the management of moderate WM load. HRV was not suppressed during either children’s or adults’ increasing load during the PL task. High frequency phasic HRV may be most sensitive to executive function tasks that have a time-response pressure, and simply requiring performance on a self-paced task requiring frontal lobe activation may not be enough to generate HRV responsitivity to increasing demand. PMID:25798113

Altered impulse activity modifies synaptic physiology and mitochondria in crayfish phasic motor neurons.

PubMed

Nguyen, P V; Atwood, H L

1994-12-01

1. Crayfish phasic motor synapses produce large initial excitatory postsynaptic potentials (EPSPs) that fatigue rapidly during high-frequency stimulation. Periodic in vivo stimulation of an identified phasic abdominal extensor motor neuron (axon 3) induced long-term adaptation (LTA) of neuromuscular transmission: initial EPSP amplitude became smaller and synaptic depression was significantly reduced. We tested the hypothesis that activity-induced synaptic fatigue-resistance seen during LTA was dependent upon, or correlated with, mitochondrial oxidative competence. 2. Periodic unilateral conditioning stimulation of axon 3 entering each of two adjacent homologous abdominal segments (segments 2 and 3) increased the synaptic stamina in both "conditioned" axons; mean final EPSP amplitudes, recorded after 20 min of 5-Hz test stimulation, were significantly larger than those measured with the same protocol from contralateral unstimulated axons. 3. During 5-Hz test stimulation of the conditioned axon 3 of segment 3, acute superfusion with 0.8 mM dinitrophenol or 20 mM sodium azide [inhibitors of oxidative adenosinetriphosphate (ATP) synthesis] produced increased synaptic depression. Drug-free saline superfusion of the conditioned axon 3 of segment 2 in these same animals did not affect the increased synaptic fatigue resistance seen in this segment. Thus both successful induction (in axon 3 of saline-perfused segment 2) and attenuation (in axon 3 of drug-perfused segment 3) of the increased synaptic stamina can be demonstrated with this twin-segment conditioning protocol. 4. Confocal microscopic imaging of mitochondrial rhodamine-123 (Rh123) fluorescence was used to assess relative oxidative competence of conditioned and unconditioned phasic axons. Conditioned phasic axons showed significantly higher mean mitochondrial Rh123 fluorescence than contralateral unstimulated axons. In the same preparations that showed increased postconditioning Rh123 fluorescence, the synaptic fatigue resistance measured from conditioned axon 3 was also significantly greater than that recorded from contralateral unstimulated axon 3. 5. Axotomy of the phasic extensor nerve root (containing axon 3), before in vivo conditioning stimulation of its decentralized segment, prevented induction of both the increased synaptic stamina in axon 3 and the enhanced mitochondrial fluorescence in decentralized motor axons of the nerve root. Hence, induction of both changes requires axonal transport of materials between the soma and the motor synapses of axon 3. 5. Axotomy of the phasic extensor nerve root (containing axon 3), before in vivo conditioning stimulation of its decentralized segment, Prevented induction of both the increased synaptic stamina in axon 3 and the enhanced mitochondrial fluorescence in decentralized motor axons of the nerve root Hence, induction of both changes requires axonal transport of materials between the soma and the motor synapses of axon 3 6. Because mitochondrial Rh123 fluorescence is primarily dependent upon the oxidative activity of these organelles, our findings suggest that conditioning stimulation of phasic extensor axon 3 increases its mitochondrial oxidative competence and that the enhanced synaptic stamina seen during LTA in axon 3 is correlated with, and dependent upon, oxidative activity.(ABSTRACT TRUNCATED AT 400 WORDS)

An Integrative Perspective on the Role of Dopamine in Schizophrenia

PubMed Central

Maia, Tiago V.; Frank, Michael J.

2017-01-01

We propose that schizophrenia involves a combination of decreased phasic dopamine responses for relevant stimuli and increased spontaneous phasic dopamine release. Using insights from computational reinforcement-learning models and basic-science studies of the dopamine system, we show that each of these two disturbances contributes to a specific symptom domain and explains a large set of experimental findings associated with that domain. Reduced phasic responses for relevant stimuli help to explain negative symptoms and provide a unified explanation for the following experimental findings in schizophrenia, most of which have been shown to correlate with negative symptoms: reduced learning from rewards; blunted activation of the ventral striatum, midbrain, and other limbic regions for rewards and positive prediction errors; blunted activation of the ventral striatum during reward anticipation; blunted autonomic responding for relevant stimuli; blunted neural activation for aversive outcomes and aversive prediction errors; reduced willingness to expend effort for rewards; and psychomotor slowing. Increased spontaneous phasic dopamine release helps to explain positive symptoms and provides a unified explanation for the following experimental findings in schizophrenia, most of which have been shown to correlate with positive symptoms: aberrant learning for neutral cues (assessed with behavioral and autonomic responses), and aberrant, increased activation of the ventral striatum, midbrain, and other limbic regions for neutral cues, neutral outcomes, and neutral prediction errors. Taken together, then, these two disturbances explain many findings in schizophrenia. We review evidence supporting their co-occurrence and consider their differential implications for the treatment of positive and negative symptoms. PMID:27452791

Bi-phasic regulation of glycogen content in astrocytes via Cav-1/PTEN/PI3K/AKT/GSK-3β pathway by fluoxetine.

PubMed

Bai, Qiufang; Song, Dan; Gu, Li; Verkhratsky, Alexei; Peng, Liang

2017-04-01

Here, we present the data indicating that chronic treatment with fluoxetine regulates Cav-1/PTEN/PI3K/AKT/GSK-3β signalling pathway and glycogen content in primary cultures of astrocytes with bi-phasic concentration dependence. At lower concentrations, fluoxetine downregulates gene expression of Cav-1, decreases membrane content of PTEN, increases activity of PI3K/AKT, and elevates GSK-3β phosphorylation thus suppressing its activity. At higher concentrations, fluoxetine acts in an inverse fashion. As expected, fluoxetine at lower concentrations increased while at higher concentrations decreased glycogen content in astrocytes. Our findings indicate that bi-phasic regulation of glycogen content via Cav-1/PTEN/PI3K/AKT/GSK-3β pathway by fluoxetine may be responsible for both therapeutic and side effects of the drug.

The effect of four-phasic versus three-phasic contrast media injection protocols on extravasation rate in coronary CT angiography: a randomized controlled trial.

PubMed

Karády, Júlia; Panajotu, Alexisz; Kolossváry, Márton; Szilveszter, Bálint; Jermendy, Ádám L; Bartykowszki, Andrea; Károlyi, Mihály; Celeng, Csilla; Merkely, Béla; Maurovich-Horvat, Pál

2017-11-01

Contrast media (CM) extravasation is a well-known complication of CT angiography (CTA). Our prospective randomized control study aimed to assess whether a four-phasic CM administration protocol reduces the risk of extravasation compared to the routinely used three-phasic protocol in coronary CTA. Patients referred to coronary CTA due to suspected coronary artery disease were included in the study. All patients received 400 mg/ml iomeprol CM injected with dual-syringe automated injector. Patients were randomized into a three-phasic injection-protocol group, with a CM bolus of 85 ml followed by 40 ml of 75%:25% saline/CM mixture and 30 ml saline chaser bolus; and a four-phasic injection-protocol group, with a saline pacer bolus of 10 ml injected at a lower flow rate before the three-phasic protocol. 2,445 consecutive patients were enrolled (mean age 60.6 ± 12.1 years; females 43.6%). Overall rate of extravasation was 0.9% (23/2,445): 1.4% (17/1,229) in the three-phasic group and 0.5% (6/1,216) in the four-phasic group (p = 0.034). Four-phasic CM administration protocol is easy to implement in the clinical routine at no extra cost. The extravasation rate is reduced by 65% with the application of the four-phasic protocol compared to the three-phasic protocol in coronary CTA. • Four-phasic CM injection-protocol reduces extravasation rate by 65% compared to three-phasic. • The saline pacer bolus substantially reduces the risk of CM extravasation. • The implementation of four-phasic injection-protocol is at no cost.

How are tonic and phasic cardiovascular changes related to central motor command?

PubMed

Jennings, J R; van der Molen, M W; Brock, K; Somsen, R J

1993-07-01

We examined the influence of central motor command on heart rate, respiration, and peripheral vascular activity. Central command was enhanced or reduced using tendon vibration. Muscle tension was held constant permitting the examination of variation in central command. Experiment 1 demonstrated in 13 college-aged males an enhancement of heart rate and vascular responses to an isometric, extensor contraction when vibration of the flexor tendon was added. Experiment 2 asked whether changes in central command interacted with phasic cardiovascular changes such as stimulus-linked anticipatory cardiac deceleration. Twenty college-aged males performed either an isometric flexor or extensor contraction with or without flexor tendon vibration. As expected, vibration enhanced cardiovascular change with extensor contraction more than with flexor contraction. Relative to control contractions, however, the flexor change was not an absolute decrease in cardiovascular change. More importantly, tendon vibration failed to alter phasic cardiovascular changes. Force and central commands for force induce cardiovascular change, but this change seems independent of phasic changes induced by the anticipation and processing of environmental stimuli.

Orienting, emotion, and memory: phasic and tonic variation in heart rate predicts memory for emotional pictures in men.

PubMed

Abercrombie, Heather C; Chambers, Andrea S; Greischar, Lawrence; Monticelli, Roxanne M

2008-11-01

Arousal-related processes associated with heightened heart rate (HR) predict memory enhancement, especially for emotionally arousing stimuli. In addition, phasic HR deceleration reflects "orienting" and sensory receptivity during perception of stimuli. We hypothesized that both tonic elevations in HR as well as phasic HR deceleration during viewing of pictures would be associated with deeper encoding and better subsequent memory for stimuli. Emotional pictures are more memorable and cause greater HR deceleration than neutral pictures. Thus, we predicted that the relations between cardiac activity and memory enhancement would be most pronounced for emotionally-laden compared to neutral pictures. We measured HR in 53 males during viewing of unpleasant, neutral, and pleasant pictures, and tested memory for the pictures two days later. Phasic HR deceleration during viewing of individual pictures was greater for subsequently remembered than forgotten pictures across all three emotion categories. Elevated mean HR across the entire encoding epoch also predicted better memory performance, but only for emotionally arousing pictures. Elevated mean HR and phasic HR deceleration were associated, such that individuals with greater tonic HR also showed greater HR decelerations during picture viewing, but only for emotionally arousing pictures. Results suggest that tonic elevations in HR are associated both with greater orienting and heightened memory for emotionally arousing stimuli.

Orienting, emotion, and memory: Phasic and tonic variation in heart rate predicts memory for emotional pictures in men

PubMed Central

Abercrombie, Heather C.; Chambers, Andrea S.; Greischar, Lawrence; Monticelli, Roxanne M.

2008-01-01

Arousal-related processes associated with heightened heart rate (HR) predict memory enhancement, especially for emotionally arousing stimuli. In addition, phasic HR deceleration reflects “orienting” and sensory receptivity during perception of stimuli. We hypothesized that both tonic elevations in HR as well as phasic HR deceleration during viewing of pictures would be associated with deeper encoding and better subsequent memory for stimuli. Emotional pictures are more memorable and cause greater HR deceleration than neutral pictures. Thus, we predicted that the relations between cardiac activity and memory enhancement would be most pronounced for emotionally-laden compared to neutral pictures. We measured HR in 53 males during viewing of unpleasant, neutral, and pleasant pictures, and tested memory for the pictures two days later. Phasic HR deceleration during viewing of individual pictures was greater for subsequently remembered than forgotten pictures across all three emotion categories. Elevated mean HR across the entire encoding epoch also predicted better memory performance, but only for emotionally arousing pictures. Elevated mean HR and phasic HR deceleration were associated, such that individuals with greater tonic HR also showed greater HR decelerations during picture viewing, but only for emotionally arousing pictures. Results suggest that tonic elevations in HR are associated both with greater orienting and heightened memory for emotionally arousing stimuli. PMID:18755284

Eye position modulates the electromyographic responses of neck muscles to electrical stimulation of the superior colliculus in the alert cat.

PubMed

Hadjidimitrakis, K; Moschovakis, A K; Dalezios, Y; Grantyn, A

2007-05-01

Rapid gaze shifts are often accomplished with coordinated movements of the eyes and head, the relative amplitude of which depends on the starting position of the eyes. The size of gaze shifts is determined by the superior colliculus (SC) but additional processing in the lower brain stem is needed to determine the relative contributions of eye and head components. Models of eye-head coordination often assume that the strength of the command sent to the head controllers is modified by a signal indicative of the eye position. Evidence in favor of this hypothesis has been recently obtained in a study of phasic electromyographic (EMG) responses to stimulation of the SC in head-restrained monkeys (Corneil et al. in J Neurophysiol 88:2000-2018, 2002b). Bearing in mind that the patterns of eye-head coordination are not the same in all species and because the eye position sensitivity of phasic EMG responses has not been systematically investigated in cats, in the present study we used cats to address this issue. We stimulated electrically the intermediate and deep layers of the caudal SC in alert cats and recorded the EMG responses of neck muscles with horizontal and vertical pulling directions. Our data demonstrate that phasic, short latency EMG responses can be modulated by the eye position such that they increase as the eye occupies more and more eccentric positions in the pulling direction of the muscle tested. However, the influence of the eye position is rather modest, typically accounting for only 10-50% of the variance of EMG response amplitude. Responses evoked from several SC sites were not modulated by the eye position.

Electrical Stimulation of the Primate Lateral Habenula Suppresses Saccadic Eye Movement through a Learning Mechanism

PubMed Central

Matsumoto, Masayuki; Hikosaka, Okihide

2011-01-01

The lateral habenula (LHb) is a brain structure which represents negative motivational value. Neurons in the LHb are excited by unpleasant events such as reward omission and aversive stimuli, and transmit these signals to midbrain dopamine neurons which are involved in learning and motivation. However, it remains unclear whether these phasic changes in LHb neuronal activity actually influence animal behavior. To answer this question, we artificially activated the LHb by electrical stimulation while monkeys were performing a visually guided saccade task. In one block of trials, saccades to one fixed direction (e.g., right direction) were followed by electrical stimulation of the LHb while saccades to the other direction (e.g., left direction) were not. The direction-stimulation contingency was reversed in the next block. We found that the post-saccadic stimulation of the LHb increased the latencies of saccades in subsequent trials. Notably, the increase of the latency occurred gradually as the saccade was repeatedly followed by the stimulation, suggesting that the effect of the post-saccadic stimulation was accumulated across trials. LHb stimulation starting before saccades, on the other hand, had no effect on saccade latency. Together with previous studies showing LHb activation by reward omission and aversive stimuli, the present stimulation experiment suggests that LHb activity contributes to learning to suppress actions which lead to unpleasant events. PMID:22039537

An Integrative Perspective on the Role of Dopamine in Schizophrenia.

PubMed

Maia, Tiago V; Frank, Michael J

2017-01-01

We propose that schizophrenia involves a combination of decreased phasic dopamine responses for relevant stimuli and increased spontaneous phasic dopamine release. Using insights from computational reinforcement-learning models and basic-science studies of the dopamine system, we show that each of these two disturbances contributes to a specific symptom domain and explains a large set of experimental findings associated with that domain. Reduced phasic responses for relevant stimuli help to explain negative symptoms and provide a unified explanation for the following experimental findings in schizophrenia, most of which have been shown to correlate with negative symptoms: reduced learning from rewards; blunted activation of the ventral striatum, midbrain, and other limbic regions for rewards and positive prediction errors; blunted activation of the ventral striatum during reward anticipation; blunted autonomic responding for relevant stimuli; blunted neural activation for aversive outcomes and aversive prediction errors; reduced willingness to expend effort for rewards; and psychomotor slowing. Increased spontaneous phasic dopamine release helps to explain positive symptoms and provides a unified explanation for the following experimental findings in schizophrenia, most of which have been shown to correlate with positive symptoms: aberrant learning for neutral cues (assessed with behavioral and autonomic responses), and aberrant, increased activation of the ventral striatum, midbrain, and other limbic regions for neutral cues, neutral outcomes, and neutral prediction errors. Taken together, then, these two disturbances explain many findings in schizophrenia. We review evidence supporting their co-occurrence and consider their differential implications for the treatment of positive and negative symptoms. Copyright © 2016 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.

Theta and gamma coordination of hippocampal networks during waking and rapid eye movement sleep.

PubMed

Montgomery, Sean M; Sirota, Anton; Buzsáki, György

2008-06-25

Rapid eye movement (REM) sleep has been considered a paradoxical state because, despite the high behavioral threshold to arousing perturbations, gross physiological patterns in the forebrain resemble those of waking states. To understand how intrahippocampal networks interact during REM sleep, we used 96 site silicon probes to record from different hippocampal subregions and compared the patterns of activity during waking exploration and REM sleep. Dentate/CA3 theta and gamma synchrony was significantly higher during REM sleep compared with active waking. In contrast, gamma power in CA1 and CA3-CA1 gamma coherence showed significant decreases in REM sleep. Changes in unit firing rhythmicity and unit-field coherence specified the local generation of these patterns. Although these patterns of hippocampal network coordination characterized the more common tonic periods of REM sleep (approximately 95% of total REM), we also detected large phasic bursts of local field potential power in the dentate molecular layer that were accompanied by transient increases in the firing of dentate and CA1 neurons. In contrast to tonic REM periods, phasic REM epochs were characterized by higher theta and gamma synchrony among the dentate, CA3, and CA1 regions. These data suggest enhanced dentate processing, but limited CA3-CA1 coordination during tonic REM sleep. In contrast, phasic bursts of activity during REM sleep may provide windows of opportunity to synchronize the hippocampal trisynaptic loop and increase output to cortical targets. We hypothesize that tonic REM sleep may support off-line mnemonic processing, whereas phasic bursts of activity during REM may promote memory consolidation.

Night-to-Night Variability of Muscle Tone, Movements, and Vocalizations in Patients with REM Sleep Behavior Disorder

PubMed Central

Cygan, Fanny; Oudiette, Delphine; Leclair-Visonneau, Laurène; Leu-Semenescu, Smaranda; Arnulf, Isabelle

2010-01-01

Objectives: The video-polysomnographic criteria of REM sleep behavior disorder (RBD) have not been well described. We evaluated the between-night reproducibility of phasic and tonic enhanced muscle activity during REM sleep as well as the associated behaviors and vocalizations of the patients. Methods: Fifteen patients with clinical RBD underwent two consecutive video-polysomnographies. The amount of excessive phasic and tonic chin muscle activity during REM sleep was measured in 15 patients in 3-sec mini-epochs. The time spent with motor (minor, major, complex, and scenic) or vocal (sounds, mumblings, and comprehensible speeches) events was measured in 7 patients during REM sleep. Results: There was a good between-night agreement for tonic (Spearman rho = 0.55, p = 0.03; Kendall tau = 0.48, p = 0.01) but not for phasic (rho = 0.47, p = 0.1; tau = 0.31, p = 0.1) excessive chin muscle activity. On the video and audio recordings, the minor RBD behaviors tended to occur more frequently during the second night than the first, whereas the patients spoke longer during the first than the second night. Conclusion: The excessive tonic activity during REM sleep is a reliable marker of RBD. It could represent the extent of dysfunction in the permissive atonia systems. In contrast, the more variable phasic activity and motor/vocal events could be more dependent on dream content (executive systems). Citation: Cygan F; Oudiette D; Leclair-Visonneau L; Leu-Semenescu S; Arnulf I. Night-to-night variability of muscle tone, movements, and vocalizations in patients with REM sleep behavior disorder. J Clin Sleep Med 2010;6(6):551-555. PMID:21206543

Unraveling Synaptic GCaMP Signals: Differential Excitability and Clearance Mechanisms Underlying Distinct Ca2+ Dynamics in Tonic and Phasic Excitatory, and Aminergic Modulatory Motor Terminals in Drosophila

PubMed Central

Xing, Xiaomin

2018-01-01

Abstract GCaMP is an optogenetic Ca2+ sensor widely used for monitoring neuronal activities but the precise physiological implications of GCaMP signals remain to be further delineated among functionally distinct synapses. The Drosophila neuromuscular junction (NMJ), a powerful genetic system for studying synaptic function and plasticity, consists of tonic and phasic glutamatergic and modulatory aminergic motor terminals of distinct properties. We report a first simultaneous imaging and electric recording study to directly contrast the frequency characteristics of GCaMP signals of the three synapses for physiological implications. Different GCaMP variants were applied in genetic and pharmacological perturbation experiments to examine the Ca2+ influx and clearance processes underlying the GCaMP signal. Distinct mutational and drug effects on GCaMP signals indicate differential roles of Na+ and K+ channels, encoded by genes including paralytic (para), Shaker (Sh), Shab, and ether-a-go-go (eag), in excitability control of different motor terminals. Moreover, the Ca2+ handling properties reflected by the characteristic frequency dependence of the synaptic GCaMP signals were determined to a large extent by differential capacity of mitochondria-powered Ca2+ clearance mechanisms. Simultaneous focal recordings of synaptic activities further revealed that GCaMPs were ineffective in tracking the rapid dynamics of Ca2+ influx that triggers transmitter release, especially during low-frequency activities, but more adequately reflected cytosolic residual Ca2+ accumulation, a major factor governing activity-dependent synaptic plasticity. These results highlight the vast range of GCaMP response patterns in functionally distinct synaptic types and provide relevant information for establishing basic guidelines for the physiological interpretations of presynaptic GCaMP signals from in situ imaging studies. PMID:29464198

Activity alterations in the bed nucleus of the stria terminalis and amygdala during threat anticipation in generalized anxiety disorder

PubMed Central

Brinkmann, Leonie; Bruchmann, Maximilian; Becker, Michael P I; Tupak, Sara; Herrmann, Martin J; Straube, Thomas

2017-01-01

Abstract Sustained anticipatory anxiety is central to Generalized Anxiety Disorder (GAD). During anticipatory anxiety, phasic threat responding appears to be mediated by the amygdala, while sustained threat responding seems related to the bed nucleus of the stria terminalis (BNST). Although sustained anticipatory anxiety in GAD patients was proposed to be associated with BNST activity alterations, firm evidence is lacking. We aimed to explore temporal characteristics of BNST and amygdala activity during threat anticipation in GAD patients. Nineteen GAD patients and nineteen healthy controls (HC) underwent functional magnetic resonance imaging (fMRI) during a temporally unpredictable threat anticipation paradigm. We defined phasic and a systematic variation of sustained response models for blood oxygen level-dependent responses during threat anticipation, to disentangle temporally dissociable involvement of the BNST and the amygdala. GAD patients relative to HC responded with increased phasic amygdala activity to onset of threat anticipation and with elevated sustained BNST activity that was delayed relative to the onset of threat anticipation. Both the amygdala and the BNST displayed altered responses during threat anticipation in GAD patients, albeit with different time courses. The results for the BNST activation hint towards its role in sustained threat responding, and contribute to a deeper understanding of pathological sustained anticipatory anxiety in GAD. PMID:28981839

Motor-Behavioral Episodes in REM Sleep Behavior Disorder and Phasic Events During REM Sleep

PubMed Central

Manni, Raffaele; Terzaghi, Michele; Glorioso, Margaret

2009-01-01

Study Objectives: To investigate if sudden-onset motor-behavioral episodes in REM sleep behavior disorder (RBD) are associated with phasic events of REM sleep, and to explore the potential meaning of such an association. Design: Observational review analysis. Setting: Tertiary sleep center. Patients: Twelve individuals (11 males; mean age 67.6 ± 7.4 years) affected by idiopathic RBD, displaying a total of 978 motor-behavioral episodes during nocturnal in-laboratory video-PSG. Interventions: N/A Measurements and Results: The motor activity displayed was primitive in 69.1% and purposeful/semi-purposeful in 30.9% of the motor-behavioral episodes recorded. Sleeptalking was significantly more associated with purposeful/semi-purposeful motor activity than crying and/or incomprehensible muttering (71.0% versus 21.4%, P < 0.005). In 58.2% of the motor-behavioral episodes, phasic EEG-EOG events (rapid eye movements [REMs], α bursts, or sawtooth waves [STWs]) occurred simultaneously. Each variable (REMs, STWs, α bursts) was associated more with purposeful/semi-purposeful than with primitive movements (P < 0.05). Conclusions: Motor-behavioral episodes in RBD were significantly more likely to occur in association with phasic than with tonic periods of REM sleep. The presence of REMs, α bursts and STWs was found to be more frequent in more complex episodes. We hypothesize that motor-behavioral episodes in RBD are likely to occur when the brain, during REM sleep, is in a state of increased instability (presence of α bursts) and experiencing stronger stimulation of visual areas (REMs). Citation: Manni R; Terzaghi M; Glorioso M. Motor-behavioral episodes in REM sleep behavior disorder and phasic events during REM sleep. SLEEP 2009;32(2):241–245. PMID:19238811

Use of fast-scan cyclic voltammetry to assess phasic dopamine release in rat models of early postpartum maternal behavior and neglect.

PubMed

Shnitko, Tatiana A; Mace, Kyla D; Sullivan, Kaitlin M; Martin, W Kyle; Andersen, Elizabeth H; Williams Avram, Sarah K; Johns, Josephine M; Robinson, Donita L

2017-12-01

Maternal behavior (MB) is a complex response to infant cues, orchestrated by postpartum neurophysiology. Although mesolimbic dopamine contributes toward MB, little is known about real-time dopamine fluctuations during the postpartum period. Thus, we used fast-scan cyclic voltammetry to measure individual dopamine transients in the nucleus accumbens of early postpartum rats and compared them with dopamine transients in virgins and in postpartum females exposed to cocaine during pregnancy, which is known to disrupt MB. We hypothesized that dopamine transients are normally enhanced postpartum and support MB. In anesthetized rats, electrically evoked dopamine release was larger and clearance was faster in postpartum females than in virgins and gestational cocaine exposure blocked the change in clearance. In awake rats, control mothers showed more dopamine transients than cocaine-exposed mothers during MB. Salient pup-produced stimuli may contribute toward differences in maternal phasic dopamine by evoking dopamine transients; supporting the feasibility of this hypothesis, urine composition (glucose, ketones, and leukocytes) differed between unexposed and cocaine-exposed infants. These data, resulting from the novel application of fast-scan cyclic voltammetry to models of MB, support the hypothesis that phasic dopamine signaling is enhanced postpartum. Future studies with additional controls can delineate which aspects of gestational cocaine reduce dopamine clearance and transient frequency.

Frequency dependence of excitation-contraction of multicellular smooth muscle preparations: the relevance to bipolar electrosurgery.

PubMed

Vladimirova, Irina A; Lankin, Yuri N; Philyppov, Igor B; Sushiy, Lyudmyla F; Shuba, Yaroslav M

2014-01-01

Bipolar electrosurgical tissue welding uses forceps-like electrodes for grasping the tissues and delivering high-frequency electric current (HFEC) to produce local heat, desiccation, and protein denaturation, resulting in the fusion of the contacting tissues. Although in this technique no electric current is flowing through the whole body to cause electric injury, depending on the frequency of applied energy, it may produce local excitation of intramural nerves, which can propagate beyond the surgical site potentially causing harmful effects. The effects of varying frequency of HFEC on tissue excitability in bipolar electrosurgical modality were studied in vitro using electric field stimulation (EFS) method on multicellular smooth muscle strips of rat vas deferens. Contractile response to 5-s-long sine wave EFS train was taken as the measure of excitation of intramural nerves. EFS-induced contraction consisted of phasic and tonic components. The amplitude of both components decreased with increasing frequency, with tonic component disappearing at about 10 kHz and phasic component at about 50 kHz. Because components of EFS-induced contraction depend on different neurotransmitters, this indicates that various neurotransmitter systems are characterized by distinct frequency dependence, but above 50 kHz they all become inactivated. Bipolar electrosurgical sealing of porcine gut showed no difference in the structure of seal area at HFEC of 67 and 533 kHz. EFS frequency of 50 kHz represents the upper limit for excitation. HFEC above 50 kHz is safe to use for bipolar electrosurgical tissue welding without concerns of excitation propagating beyond the surgical site. Copyright © 2014 Elsevier Inc. All rights reserved.

Multi-phasic bi-directional chemotactic responses of the growth cone

PubMed Central

Naoki, Honda; Nishiyama, Makoto; Togashi, Kazunobu; Igarashi, Yasunobu; Hong, Kyonsoo; Ishii, Shin

2016-01-01

The nerve growth cone is bi-directionally attracted and repelled by the same cue molecules depending on the situations, while other non-neural chemotactic cells usually show uni-directional attraction or repulsion toward their specific cue molecules. However, how the growth cone differs from other non-neural cells remains unclear. Toward this question, we developed a theory for describing chemotactic response based on a mathematical model of intracellular signaling of activator and inhibitor. Our theory was first able to clarify the conditions of attraction and repulsion, which are determined by balance between activator and inhibitor, and the conditions of uni- and bi-directional responses, which are determined by dose-response profiles of activator and inhibitor to the guidance cue. With biologically realistic sigmoidal dose-responses, our model predicted tri-phasic turning response depending on intracellular Ca2+ level, which was then experimentally confirmed by growth cone turning assays and Ca2+ imaging. Furthermore, we took a reverse-engineering analysis to identify balanced regulation between CaMKII (activator) and PP1 (inhibitor) and then the model performance was validated by reproducing turning assays with inhibitions of CaMKII and PP1. Thus, our study implies that the balance between activator and inhibitor underlies the multi-phasic bi-directional turning response of the growth cone. PMID:27808115

Urothelium-dependent and urothelium-independent detrusor contractility mediated by nitric oxide synthase and cyclooxygenase inhibition.

PubMed

Santoso, Aneira Gracia Hidayat; Lo, Wan Ning; Liang, Willmann

2011-04-01

The urothelium has been implicated in regulating detrusor smooth muscle contractility but the identity of the putative urothelium-derived inhibitory factor remains unconfirmed. There was inconclusive evidence on the role of nitric oxide synthase (NOS) and cyclooxygenase (COX) in mediating detrusor contractions. This study examined varying regulation by NOS and COX in transverse and longitudinal carbachol (CCh)-induced and unstimulated phasic contractions. Rat detrusor strips with the urothelium-intact (+UE) and urothelium-denuded (-UE) were isolated in both transverse and longitudinal directions. Isometric tension of the detrusor strips was recorded both during stimulation with CCh and at the unstimulated state. In the unstimulated state, phasic contractile activity was measured. Tension recordings were made with and without the NOS inhibitor N(ω)-nitro-L-arginine methyl ester (L-NAME) and COX inhibitor indomethacin (Indo). Only transverse +UE strips responded convincingly to L-NAME and Indo treatment, generating larger CCh-induced contractions. In unstimulated tissues, L-NAME treatment increased phasic amplitude in -UE strips only. Indo treatment failed to elicit any change in the amplitude but suppressed frequency of the phasic activity in transverse +UE strips. There was no significant Indo-mediated change in other strips. The data suggested heterogeneity in the regulation of directional detrusor contractility via NOS- and COX-associated mechanisms. Copyright © 2011 Wiley-Liss, Inc.

Contact heat-evoked temporal summation: tonic versus repetitive-phasic stimulation.

PubMed

Granot, Michal; Granovsky, Yelena; Sprecher, Elliot; Nir, Rony-Reuven; Yarnitsky, David

2006-06-01

Temporal summation (TS) is usually evoked by repetitive mechanical or electrical stimuli, and less commonly by tonic heat pain. The present study aimed to examine the TS induction by repetitive-phasic versus tonic heat pain stimuli. Using 27 normal volunteers, we compared the extent of summation by three calculation methods: start-to-end pain rating difference, percent change, and double-logarithmic regression of successive ratings along the stimulation. Subjects were tested twice, and the reliability of each of the paradigms was obtained. In addition, personality factors related to pain catastrophizing and anxiety level were also correlated with the psychophysical results. Both paradigms induced significant TS, with similar increases for the repetitive-phasic and the tonic paradigms, as measured on 0-100 numerical pain scale (from 52.9+/-11.7 to 80.2+/-15.5, p<0.001; and from 38.5+/-13.3 to 75.8+/-18.3, p<0.001, respectively). The extent of summation was significantly correlated between the two paradigms, when calculated by absolute change (r=0.543, p=0.004) and by regression (r=0.438, p=0.025). Session-to-session variability was similar for both paradigms, relatively large, yet not biased. As with other psychophysical parameters, this poses some limitations on TS assessment in individual patients over time. The extent of TS induced by both paradigms was found to be associated with anxiety level and pain catastrophizing. Despite some dissimilarity between the repetitive-phasic and the tonic paradigms, the many similarities suggest that the two represent a similar physiological process, even if not precisely the same. Future clinical applications of these tests will determine the clinical relevance of the TS paradigms presented in this study.

High-definition spatiotemporal mapping of contractile activity in the isolated proximal colon of the rabbit.

PubMed

Lentle, Roger G; Janssen, Patrick W M; Asvarujanon, Patchana; Chambers, Paul; Stafford, Kevin J; Hemar, Yacine

2008-03-01

Four types of contractile activity were identified and characterised in the isolated triple haustrated proximal colon of the rabbit using high-definition spatiotemporal mapping techniques. Mass peristalses were hexamethonium-sensitive deep circular contractions with associated taenial longitudinal contractile activity that occurred irregularly and propagated rapidly aborad, preceded by a zone of local lumen distension. They were sufficiently sustained for each event to occupy the length of the isolated colonic segment and the contraction persisted longer orally than aborally, the difference being more pronounced when lumen contents were viscous. Haustra were bounded by deep even-spaced ring contractions that progressed slowly aborad (haustral progression). Haustral formation and progression were hexamethonium-sensitive and coordinated across intertaenial domains. Ripples were hexamethonium-resistant phasic circular contractions that propagated predominantly orad at varying rates. In the presence of haustra, they were uncoordinated across intertaenial domains but were more coordinated when haustra were absent. Fast phasic contractions were relatively shallow hexamethonium-resistant contractions that propagated rapidly in a predominantly aborad direction. Fast phasic circular contractions were accompanied by taenial longitudinal muscle contractions which increased in amplitude prior to a mass peristaltic event and following the administration of hexamethonium. On the basis of the concurrence and interaction of these contractile activities, we hypothesise that dual pacemakers are present with fast phasic contractions being modulated by the interstitial cells of Cajal in the Auerbach's plexus (ICC-MY) while ripples are due to the submucosal ICC (ICC-SM). Further, that ICC-SM mediate the enteric motor neurons that generate haustral progression, while the intramuscular ICC (ICC-IM) mediate mass peristalsis. The orad movement of watery fluid was possibly due to ripples in the absence of haustra.

Objective Measurement of Clinical Competency in Surgical Education Using Electrodermal Activity.

PubMed

Quick, Jacob A; Bukoski, Alex D; Doty, Jennifer; Bennett, Bethany J; Crane, Megan; Barnes, Stephen L

Within the realm of surgical education, there is a need for objective means to determine surgical competence and resident readiness to operate independently. We propose a novel, objective method of assessing resident confidence and clinical competence based on measurement of electrodermal activity (EDA) during live surgical procedures. We hypothesized that with progressive training, EDA responses to the stress of performing surgery would exhibit decline, elucidating an objective correlate of clinical competence. EDA was measured using galvanic skin response sensors worn by residents performing laparoscopic cholecystectomy on sequential live human patients over an 8-month period. Baseline, phasic (peak) and tonic EDA responses were measured as a fractional change from baseline. University of Missouri, Columbia, Missouri, an academic tertiary care facility. Fourteen categorical general surgery residents and 5 faculty surgeons were voluntarily enrolled and participated through completion. Tonic fractional change (FC TONIC ) was highest in PGY3 residents compared with postgraduate year (PGY) 1 and 2 residents (7.199 vs. 2.100, p = 0.004, 95% CI: 8.58-1.61 and PGY4 and 5 residents (7.199 vs. 2.079, p = 0.002, 95% CI: 8.38-0.29). Phasic fractional change in EDA (FC PHASIC ) exhibited a progressive decline across resident training levels, with PGY1 and 2 residents having the highest response, and faculty displaying the lowest FC PHASIC responses. Statistical differences were seen between FC PHASIC faculty and PGY4 and 5 (3.596 vs. 6.180, p = 0.004, 95% CI: 0.80-4.36), PGY4 and 5, and PGY3 (6.180 vs. 15.998, p = 0.003, 95% CI: 3.33-16.3), as well as among all residents and faculty (13.057 vs. 3.596, p = 0.004, 95% CI: 15.8-3.1). Phasic EDA changes decrease with increasing clinical competence. For those participants with the lowest and highest levels of competence, tonic EDA changes are minimal. Tonic EDA changes follow an inverse-U shape with differing levels of clinical competence. Copyright © 2017 Association of Program Directors in Surgery. Published by Elsevier Inc. All rights reserved.

An integrative theory of the phasic and tonic modes of dopamine modulation in the prefrontal cortex.

PubMed

Dreher, Jean-Claude; Burnod, Yves

2002-01-01

This paper presents a model of both tonic and phasic dopamine (DA) effects on maintenance of working memory representations in the prefrontal cortex (PFC). The central hypothesis is that DA modulates the efficacy of inputs to prefrontal pyramidal neurons to prevent interferences for active maintenance. Phasic DA release, due to DA neurons discharges, acts at a short time-scale (a few seconds), while the tonic mode of DA release, independent of DA neurons firing, acts at a long time-scale (a few minutes). The overall effect of DA modulation is modeled as a threshold restricting incoming inputs arriving on PFC neurons. Phasic DA release temporary increases this threshold while tonic DA release progressively increases the basal level of this threshold. Thus, unlike the previous gating theory of phasic DA release, proposing that it facilitates incoming inputs at the time of their arrival, the effect of phasic DA release is supposed to restrict incoming inputs during a period of time after DA neuron discharges. The model links the cellular and behavioral levels during performance of a working memory task. It allows us to understand why a critical range of DA D1 receptors stimulation is required for optimal working memory performance and how D1 receptor agonists (respectively antagonists) increase perseverations (respectively distractability). Finally, the model leads to several testable predictions, including that the PFC regulates DA neurons firing rate to adapt to the delay of the task and that increase in tonic DA release may either improve or decrease performance, depending on the level of DA receptors stimulation at the beginning of the task.

Activity alterations in the bed nucleus of the stria terminalis and amygdala during threat anticipation in generalized anxiety disorder.

PubMed

Buff, Christine; Brinkmann, Leonie; Bruchmann, Maximilian; Becker, Michael P I; Tupak, Sara; Herrmann, Martin J; Straube, Thomas

2017-11-01

Sustained anticipatory anxiety is central to Generalized Anxiety Disorder (GAD). During anticipatory anxiety, phasic threat responding appears to be mediated by the amygdala, while sustained threat responding seems related to the bed nucleus of the stria terminalis (BNST). Although sustained anticipatory anxiety in GAD patients was proposed to be associated with BNST activity alterations, firm evidence is lacking. We aimed to explore temporal characteristics of BNST and amygdala activity during threat anticipation in GAD patients. Nineteen GAD patients and nineteen healthy controls (HC) underwent functional magnetic resonance imaging (fMRI) during a temporally unpredictable threat anticipation paradigm. We defined phasic and a systematic variation of sustained response models for blood oxygen level-dependent responses during threat anticipation, to disentangle temporally dissociable involvement of the BNST and the amygdala. GAD patients relative to HC responded with increased phasic amygdala activity to onset of threat anticipation and with elevated sustained BNST activity that was delayed relative to the onset of threat anticipation. Both the amygdala and the BNST displayed altered responses during threat anticipation in GAD patients, albeit with different time courses. The results for the BNST activation hint towards its role in sustained threat responding, and contribute to a deeper understanding of pathological sustained anticipatory anxiety in GAD. © The Author (2017). Published by Oxford University Press.

Dynamin phosphorylation controls optimization of endocytosis for brief action potential bursts

PubMed Central

Armbruster, Moritz; Messa, Mirko; Ferguson, Shawn M; De Camilli, Pietro; Ryan, Timothy A

2013-01-01

Modulation of synaptic vesicle retrieval is considered to be potentially important in steady-state synaptic performance. Here we show that at physiological temperature endocytosis kinetics at hippocampal and cortical nerve terminals show a bi-phasic dependence on electrical activity. Endocytosis accelerates for the first 15–25 APs during bursts of action potential firing, after which it slows with increasing burst length creating an optimum stimulus for this kinetic parameter. We show that activity-dependent acceleration is only prominent at physiological temperature and that the mechanism of this modulation is based on the dephosphorylation of dynamin 1. Nerve terminals in which dynamin 1 and 3 have been replaced with dynamin 1 harboring dephospho- or phospho-mimetic mutations in the proline-rich domain eliminate the acceleration phase by either setting endocytosis at an accelerated state or a decelerated state, respectively. DOI: http://dx.doi.org/10.7554/eLife.00845.001 PMID:23908769

Dopamine Dynamics during Continuous Intracranial Self-Stimulation: Effect of Waveform on Fast-Scan Cyclic Voltammetry Data

PubMed Central

2016-01-01

The neurotransmitter dopamine is heavily implicated in intracranial self-stimulation (ICSS). Many drugs of abuse that affect ICSS behavior target the dopaminergic system, and optogenetic activation of dopamine neurons is sufficient to support self-stimulation. However, the patterns of phasic dopamine release during ICSS remain unclear. Early ICSS studies using fast-scan cyclic voltammetry (FSCV) rarely observed phasic dopamine release, which led to the surprising conclusion that it is dissociated from ICSS. However, several advances in the sensitivity (i.e., the use of waveforms with extended anodic limits) and analysis (i.e., principal component regression) of FSCV measurements have made it possible to detect smaller, yet physiologically relevant, dopamine release events. Therefore, this study revisits phasic dopamine release during ICSS using these tools. It was found that the anodic limit of the voltammetric waveform has a substantial effect on the patterns of dopamine release observed during continuous ICSS. While data collected with low anodic limits (i.e., +1.0 V) support the disappearance of phasic dopamine release observed in previous investigation, the use of high anodic limits (+1.3 V, +1.4 V) allows for continual detection of dopamine release throughout ICSS. However, the +1.4 V waveform lacks the ability to resolve narrowly spaced events, with the best balance of temporal resolution and sensitivity provided by the +1.3 V waveform. Ultimately, it is revealed that the amplitude of phasic dopamine release decays but does not fully disappear during continuous ICSS. PMID:27548680

Dopamine Dynamics during Continuous Intracranial Self-Stimulation: Effect of Waveform on Fast-Scan Cyclic Voltammetry Data.

PubMed

Rodeberg, Nathan T; Johnson, Justin A; Bucher, Elizabeth S; Wightman, R Mark

2016-11-16

The neurotransmitter dopamine is heavily implicated in intracranial self-stimulation (ICSS). Many drugs of abuse that affect ICSS behavior target the dopaminergic system, and optogenetic activation of dopamine neurons is sufficient to support self-stimulation. However, the patterns of phasic dopamine release during ICSS remain unclear. Early ICSS studies using fast-scan cyclic voltammetry (FSCV) rarely observed phasic dopamine release, which led to the surprising conclusion that it is dissociated from ICSS. However, several advances in the sensitivity (i.e., the use of waveforms with extended anodic limits) and analysis (i.e., principal component regression) of FSCV measurements have made it possible to detect smaller, yet physiologically relevant, dopamine release events. Therefore, this study revisits phasic dopamine release during ICSS using these tools. It was found that the anodic limit of the voltammetric waveform has a substantial effect on the patterns of dopamine release observed during continuous ICSS. While data collected with low anodic limits (i.e., +1.0 V) support the disappearance of phasic dopamine release observed in previous investigation, the use of high anodic limits (+1.3 V, +1.4 V) allows for continual detection of dopamine release throughout ICSS. However, the +1.4 V waveform lacks the ability to resolve narrowly spaced events, with the best balance of temporal resolution and sensitivity provided by the +1.3 V waveform. Ultimately, it is revealed that the amplitude of phasic dopamine release decays but does not fully disappear during continuous ICSS.

The use of in-flight foot pressure as a countermeasure to neuromuscular degradation

NASA Technical Reports Server (NTRS)

Layne, C. S.; Mulavara, A. P.; Pruett, C. J.; McDonald, P. V.; Kozlovskaya, I. B.; Bloomberg, J. J.

1998-01-01

The purpose of this study was to determine whether applying foot pressure to unrestrained subjects during space flight could enhance the neuromuscular activation associated with rapid arm movements. Four men performed unilateral arm raises while wearing--or not wearing--specially designed boots during a 81- or 115-day space flight. Arm acceleration and surface EMG were obtained from selected lower limb and trunk muscles. Pearson r coefficients were used to evaluate similarity in phasic patterns between the two in-flight conditions. In-flight data also were magnitude normalized to the mean voltage value of the muscle activation waveforms obtained during the no-foot-pressure condition to facilitate comparison of activation amplitude between the two in-flight conditions. Foot pressure enhanced neuromuscular activation and somewhat modified the phasic features of the neuromuscular activation during the arm raises.

Latencies in BOLD response during visual attention processes.

PubMed

Kellermann, Thilo; Reske, Martina; Jansen, Andreas; Satrapi, Peyman; Shah, N Jon; Schneider, Frank; Habel, Ute

2011-04-22

One well-investigated division of attentional processes focuses on alerting, orienting and executive control, which can be assessed applying the attentional network test (ANT). The goal of the present study was to add further knowledge about the temporal dynamics of relevant neural correlates. As a right hemispheric dominance for alerting and orienting has previously been reported for intrinsic but not for phasic alertness, we additionally addressed a potential impact of this lateralization of attention by employing a lateralized version of the ANT, capturing phasic alertness processes. Sixteen healthy subjects underwent event-related functional magnetic resonance imaging (fMRI) while performing the ANT. Analyses of BOLD magnitude replicated the engagement of a fronto-parietal network in the attentional subsystems. The amplitudes of the attentional contrasts interacted with visual field presentation in the sense that the thalamus revealed a greater involvement for spatially cued items presented in the left visual field. Comparisons of BOLD latencies in visual cortices, first, verified faster BOLD responses following contra-lateral stimulus presentation. Second and more importantly, we identified attention-modulated activation in secondary visual and anterior cingulate cortices. Results are discussed in terms of bottom-up and lateralization processes. Although intrinsic and phasic alertness are distinct cognitive processes, we propose that neural substrates of intrinsic alertness may be accessed by phasic alertness provided that the attention-dominant (i.e., the right) hemisphere is activated directly by a warning stimulus. Copyright © 2011 Elsevier B.V. All rights reserved.

Amphetamine Elicits Opposing Actions on Readily Releasable and Reserve Pools for Dopamine

PubMed Central

Covey, Dan P.; Juliano, Steven A.; Garris, Paul A.

2013-01-01

Amphetamine, a highly addictive drug with therapeutic efficacy, exerts paradoxical effects on the fundamental communication modes employed by dopamine neurons in modulating behavior. While amphetamine elevates tonic dopamine signaling by depleting vesicular stores and driving non-exocytotic release through reverse transport, this psychostimulant also activates phasic dopamine signaling by up-regulating vesicular dopamine release. We hypothesized that these seemingly incongruent effects arise from amphetamine depleting the reserve pool and enhancing the readily releasable pool. This novel hypothesis was tested using in vivo voltammetry and stimulus trains of varying duration to access different vesicular stores. We show that amphetamine actions are stimulus dependent in the dorsal striatum. Specifically, amphetamine up-regulated vesicular dopamine release elicited by a short-duration train, which interrogates the readily releasable pool, but depleted release elicited by a long-duration train, which interrogates the reserve pool. These opposing actions of vesicular dopamine release were associated with concurrent increases in tonic and phasic dopamine responses. A link between vesicular depletion and tonic signaling was supported by results obtained for amphetamine in the ventral striatum and cocaine in both striatal sub-regions, which demonstrated augmented vesicular release and phasic signals only. We submit that amphetamine differentially targeting dopamine stores reconciles the paradoxical activation of tonic and phasic dopamine signaling. Overall, these results further highlight the unique and region-distinct cellular mechanisms of amphetamine and may have important implications for its addictive and therapeutic properties. PMID:23671560

Quantitative assessment of isolated rapid eye movement (REM) sleep without atonia without clinical REM sleep behavior disorder: clinical and research implications.

PubMed

Sasai-Sakuma, Taeko; Frauscher, Birgit; Mitterling, Thomas; Ehrmann, Laura; Gabelia, David; Brandauer, Elisabeth; Inoue, Yuichi; Poewe, Werner; Högl, Birgit

2014-09-01

Rapid eye movement (REM) sleep without atonia (RWA) is observed in some patients without a clinical history of REM sleep behavior disorder (RBD). It remains unknown whether these patients meet the refined quantitative electromyographic (EMG) criteria supporting a clinical RBD diagnosis. We quantitatively evaluated EMG activity and investigated its overnight distribution in patients with isolated qualitative RWA. Fifty participants with an incidental polysomnographic finding of RWA (isolated qualitative RWA) were included. Tonic, phasic, and 'any' EMG activity during REM sleep on PSG were quantified retrospectively. Referring to the quantitative cut-off values for a polysomnographic diagnosis of RBD, 7/50 (14%) and 6/50 (12%) of the patients showed phasic and 'any' EMG activity in the mentalis muscle above the respective cut-off values. No patient was above the cut-off value for tonic EMG activity or phasic EMG activity in the anterior tibialis muscles. Patients with RWA above the cut-off value showed higher amounts of RWA during later REM sleep periods. This is the first study showing that some subjects with incidental RWA meet the refined quantitative EMG criteria for a diagnosis of RBD. Future longitudinal studies must investigate whether this subgroup with isolated qualitative RWA is at an increased risk of developing fully expressed RBD and/or neurodegenerative disease. Copyright © 2014 Elsevier B.V. All rights reserved.

Quantitative differences among EMG activities of muscles innervated by subpopulations of hypoglossal and upper spinal motoneurons during non-REM sleep - REM sleep transitions: a window on neural processes in the sleeping brain.

PubMed

Rukhadze, I; Kamani, H; Kubin, L

2011-12-01

In the rat, a species widely used to study the neural mechanisms of sleep and motor control, lingual electromyographic activity (EMG) is minimal during non-rapid eye movement (non-REM) sleep and then phasic twitches gradually increase after the onset of REM sleep. To better characterize the central neural processes underlying this pattern, we quantified EMG of muscles innervated by distinct subpopulations of hypoglossal motoneurons and nuchal (N) EMG during transitions from non-REM sleep to REM sleep. In 8 chronically instrumented rats, we recorded cortical EEG, EMG at sites near the base of the tongue where genioglossal and intrinsic muscle fibers predominate (GG-I), EMG of the geniohyoid (GH) muscle, and N EMG. Sleep-wake states were identified and EMGs quantified relative to their mean levels in wakefulness in successive 10 s epochs. During non-REM sleep, the average EMG levels differed among the three muscles, with the order being N>GH>GG-I. During REM sleep, due to different magnitudes of phasic twitches, the order was reversed to GG-I>GH>N. GG-I and GH exhibited a gradual increase of twitching that peaked at 70-120 s after the onset of REM sleep and then declined if the REM sleep episode lasted longer. We propose that a common phasic excitatory generator impinges on motoneuron pools that innervate different muscles, but twitching magnitudes are different due to different levels of tonic motoneuronal hyperpolarization. We also propose that REM sleep episodes of average durations are terminated by intense activity of the central generator of phasic events, whereas long REM sleep episodes end as a result of a gradual waning of the tonic disfacilitatory and inhibitory processes.

Association between patterns of jaw motor activity during sleep and clinical signs and symptoms of sleep bruxism.

PubMed

Yoshida, Yuya; Suganuma, Takeshi; Takaba, Masayuki; Ono, Yasuhiro; Abe, Yuka; Yoshizawa, Shuichiro; Sakai, Takuro; Yoshizawa, Ayako; Nakamura, Hirotaka; Kawana, Fusae; Baba, Kazuyoshi

2017-08-01

The aim of this study was to investigate the association between patterns of jaw motor activity during sleep and clinical signs and symptoms of sleep bruxism. A total of 35 university students and staff members participated in this study after providing informed consent. All participants were divided into either a sleep bruxism group (n = 21) or a control group (n = 14), based on the following clinical diagnostic criteria: (1) reports of tooth-grinding sounds for at least two nights a week during the preceding 6 months by their sleep partner; (2) presence of tooth attrition with exposed dentin; (3) reports of morning masticatory muscle fatigue or tenderness; and (4) presence of masseter muscle hypertrophy. Video-polysomnography was performed in the sleep laboratory for two nights. Sleep bruxism episodes were measured using masseter electromyography, visually inspected and then categorized into phasic or tonic episodes. Phasic episodes were categorized further into episodes with or without grinding sounds as evaluated by audio signals. Sleep bruxism subjects with reported grinding sounds had a significantly higher total number of phasic episodes with grinding sounds than subjects without reported grinding sounds or controls (Kruskal-Wallis/Steel-Dwass tests; P < 0.05). Similarly, sleep bruxism subjects with tooth attrition exhibited significantly longer phasic burst durations than those without or controls (Kruskal-Wallis/Steel-Dwass tests; P < 0.05). Furthermore, sleep bruxism subjects with morning masticatory muscle fatigue or tenderness exhibited significantly longer tonic burst durations than those without or controls (Kruskal-Wallis/Steel-Dwass tests; P < 0.05). These results suggest that each clinical sign and symptom of sleep bruxism represents different aspects of jaw motor activity during sleep. © 2016 European Sleep Research Society.

Decoding brain state transitions in the pedunculopontine nucleus: cooperative phasic and tonic mechanisms

PubMed Central

Petzold, Anne; Valencia, Miguel; Pál, Balázs; Mena-Segovia, Juan

2015-01-01

Cholinergic neurons of the pedunculopontine nucleus (PPN) are most active during the waking state. Their activation is deemed to cause a switch in the global brain activity from sleep to wakefulness, while their sustained discharge may contribute to upholding the waking state and enhancing arousal. Similarly, non-cholinergic PPN neurons are responsive to brain state transitions and their activation may influence some of the same targets of cholinergic neurons, suggesting that they operate in coordination. Yet, it is not clear how the discharge of distinct classes of PPN neurons organize during brain states. Here, we monitored the in vivo network activity of PPN neurons in the anesthetized rat across two distinct levels of cortical dynamics and their transitions. We identified a highly structured configuration in PPN network activity during slow-wave activity that was replaced by decorrelated activity during the activated state (AS). During the transition, neurons were predominantly excited (phasically or tonically), but some were inhibited. Identified cholinergic neurons displayed phasic and short latency responses to sensory stimulation, whereas the majority of non-cholinergic showed tonic responses and remained at high discharge rates beyond the state transition. In vitro recordings demonstrate that cholinergic neurons exhibit fast adaptation that prevents them from discharging at high rates over prolonged time periods. Our data shows that PPN neurons have distinct but complementary roles during brain state transitions, where cholinergic neurons provide a fast and transient response to sensory events that drive state transitions, whereas non-cholinergic neurons maintain an elevated firing rate during global activation. PMID:26582977

Phasic and tonic neuron ensemble codes for stimulus-environment conjunctions in the lateral entorhinal cortex.

PubMed

Pilkiw, Maryna; Insel, Nathan; Cui, Younghua; Finney, Caitlin; Morrissey, Mark D; Takehara-Nishiuchi, Kaori

2017-07-06

The lateral entorhinal cortex (LEC) is thought to bind sensory events with the environment where they took place. To compare the relative influence of transient events and temporally stable environmental stimuli on the firing of LEC cells, we recorded neuron spiking patterns in the region during blocks of a trace eyeblink conditioning paradigm performed in two environments and with different conditioning stimuli. Firing rates of some neurons were phasically selective for conditioned stimuli in a way that depended on which room the rat was in; nearly all neurons were tonically selective for environments in a way that depended on which stimuli had been presented in those environments. As rats moved from one environment to another, tonic neuron ensemble activity exhibited prospective information about the conditioned stimulus associated with the environment. Thus, the LEC formed phasic and tonic codes for event-environment associations, thereby accurately differentiating multiple experiences with overlapping features.

Sleep Apnea and Left Atrial Phasic Function in Heart Failure With Reduced Ejection Fraction.

PubMed

Haruki, Nobuhiko; Tsang, Wendy; Thavendiranathan, Paaladinesh; Woo, Anna; Tomlinson, George; Logan, Alexander G; Bradley, T Douglas; Floras, John S

2016-12-01

The study aim was to determine whether phasic left atrial (LA) function of patients with heart failure with reduced ejection fraction differs between those with obstructive sleep apnea (OSA) and central sleep apnea (CSA). Participation in the Adaptive Servo Ventilation for Therapy of Sleep Apnea in Heart Failure (ADVENT-HF) trial requires 2-dimensional echocardiographic documentation of left ventricular ejection fraction ≤ 45% and a polysomnographic apnea hypopnea index (AHI) ≥ 15 events per hour. Of initial enrollees, we identified 132 patients in sinus rhythm (82 with predominantly OSA and 50 with CSA). To determine LA reservoir (expansion index; EI), conduit (passive emptying index; PEI), and booster function (active emptying index), we blindly quantified maximum and minimum LA volume and LA volume before atrial contraction. Each of EI (P = 0.004), PEI (P < 0.001), and active emptying index (P = 0.045) was less in participants with CSA compared with those with OSA, whereas average left ventricular ejection fraction and LA and left ventricular volumes were similar. Multivariable analysis identified an independent relationship between central AHI and LA EI (P = 0.040) and PEI (P = 0.005). In contrast, the obstructive AHI was unrelated to any LA phasic index, and slopes relating central AHI to EI and PEI differed significantly from corresponding relationships with obstructive AHI (P = 0.018; P = 0.006). In these ADVENT-HF patients with heart failure with reduced ejection fraction, all 3 components of LA phasic function (reservoir, conduit, and contractile) were significantly reduced in those with CSA compared with participants with OSA. The severity of CSA, but not OSA associated inversely and independently with LA reservoir and conduit function. Impaired LA phasic function might be consequent to or could exacerbate CSA. Copyright © 2016 Canadian Cardiovascular Society. Published by Elsevier Inc. All rights reserved.

Electrical and magnetic properties of nano-sized magnesium ferrite

NASA Astrophysics Data System (ADS)

T, Smitha; X, Sheena; J, Binu P.; Mohammed, E. M.

2015-02-01

Nano-sized magnesium ferrite was synthesized using sol-gel techniques. Structural characterization was done using X-ray diffractometer and Fourier Transform Infrared Spectrometer. Vibration Sample Magnetometer was used to record the magnetic measurements. XRD analysis reveals the prepared sample is single phasic without any impurity. Particle size calculation shows the average crystallite size of the sample is 19nm. FTIR analysis confirmed spinel structure of the prepared samples. Magnetic measurement study shows that the sample is ferromagnetic with high degree of isotropy. Hysterisis loop was traced at temperatures 100K and 300K. DC electrical resistivity measurements show semiconducting nature of the sample.

Context-dependent modulation of alphabetagamma and alphabetadelta GABA A receptors by penicillin: implications for phasic and tonic inhibition.

PubMed

Feng, Hua-Jun; Botzolakis, Emmanuel J; Macdonald, Robert L

2009-01-01

Penicillin, an open-channel blocker of GABA(A) receptors, was recently reported to inhibit phasic, but not tonic, currents in hippocampal neurons. To distinguish between isoform-specific and context-dependent modulation as possible explanations for this selectivity, the effects of penicillin were evaluated on recombinant GABA(A) receptors expressed in HEK293T cells. When co-applied with saturating GABA, penicillin decreased peak amplitude, induced rebound, and prolonged deactivation of currents evoked from both synaptic and extrasynaptic receptor isoforms. However, penicillin had isoform-specific effects on the extent of desensitization, reflecting its ability to differentially modulate peak (non-equilibrium) and residual (near-equilibrium) currents. This suggested that the context of activation could determine the apparent sensitivity of a given receptor isoform to penicillin. To test this hypothesis, we explored the ability of penicillin to modulate synaptic and extrasynaptic isoform currents that were activated under more physiologically relevant conditions. Interestingly, while currents evoked from synaptic isoforms under phasic conditions (transient activation by a saturating concentration of GABA) were substantially inhibited by penicillin, currents evoked from extrasynaptic isoforms under tonic conditions (prolonged application by a sub-saturating concentration of GABA) were minimally affected. We therefore concluded that the reported inability of penicillin to modulate tonic currents could not simply be attributed to insensitivity of extrasynaptic receptors, but rather, reflected an inability to modulate these receptors in their native context of activation.

Repeated noxious stimulation of the skin enhances cutaneous pain perception of migraine patients in-between attacks: clinical evidence for continuous sub-threshold increase in membrane excitability of central trigeminovascular neurons.

PubMed

Weissman-Fogel, Irit; Sprecher, Elliot; Granovsky, Yelena; Yarnitsky, David

2003-08-01

Recent clinical studies showed that acute migraine attacks are accompanied by increased periorbital and bodily skin sensitivity to touch, heat and cold. Parallel pre-clinical studies showed that the underlying mechanism is sensitization of primary nociceptors and central trigeminovascular neurons. The present study investigates the sensory state of neuronal pathways that mediate skin pain sensation in migraine patients in between attacks. The assessments of sensory perception included (a) mechanical and thermal pain thresholds of the periorbital area, electrical pain threshold of forearm skin, (b) pain scores to phasic supra-threshold stimuli in the same modalities and areas as above, and (c) temporal summation of pain induced by applying noxious tonic heat pain and brief trains of noxious mechanical and electrical pulses to the above skin areas. Thirty-four pain-free migraine patients and 28 age- and gender-matched controls were studied. Patients did not differ from controls in their pain thresholds for heat (44+/-2.6 vs. 44.6+/-1.9 degrees C), and electrical (4.8+/-1.6 vs. 4.3+/-1.6 mA) stimulation, and in their pain scores for supra-threshold phasic stimuli for all modalities. They did, however, differ in their pain threshold for mechanical stimulation, just by one von Frey filament (P=0.01) and in their pain scores of the temporal summation tests. Increased summation of pain was found in migraineurs for repeated mechanical stimuli (delta visual analog scale (VAS) +2.32+/-0.73 in patients vs. +0.16+/-0.83 in controls, P=0.05) and repeated electrical stimuli (delta VAS +3.83+/-1.91 vs -3.79+/-2.31, P=0.01). Increased summation corresponded with more severe clinical parameters of migraine and tended to depend on interval since last migraine attack. The absence of clinically or overt laboratory expressed allodynia suggests that pain pathways are not sensitized in the pain-free migraine patients. Nevertheless, the increased temporal summation, and the slight decrease in mechanical pain thresholds, suggest that central nociceptive neurons do express activation-dependent plasticity. These findings may point to an important pathophysiological change in membrane properties of nociceptive neurons of migraine patients; a change that may hold a key to more effective prophylactic treatment.

The control of locomotor frequency by excitation and inhibition

PubMed Central

Li, Wen-Chang; Moult, Peter R

2012-01-01

Every type of neural rhythm has its own operational range of frequency. Neuronal mechanisms underlying rhythms at different frequencies, however, are poorly understood. We use a simple aquatic vertebrate, the two day old Xenopus tadpole, to investigate how the brainstem and spinal circuits generate swimming rhythms of different speeds. We first determined that the basic motor output pattern was not altered with varying swimming frequencies. The firing reliability of different types of rhythmic neuron involved in swimming was then analysed. The results showed that there was a drop in the firing reliability in some inhibitory interneurons when fictive swimming slowed. We have recently established that premotor excitatory interneurons (descending interneurons; dINs) are critical in rhythmically driving activity in the swimming circuit. Voltage-clamp recordings from dINs showed higher frequency swimming correlated with stronger background excitation and phasic inhibition, but did not correlate with phasic excitation. Two parallel mechanisms have been proposed for tadpole swimming maintenance: post-inhibition rebound firing and NMDA receptor (NMDAR) dependent pace-maker firing in dINs. Rebound tests in dINs in this study showed that greater background depolarization and phasic inhibition led to faster rebound firing. Higher depolarization was previously shown to accelerate dIN pace-maker firing in the presence of NMDA. Here we show that enhancing dIN background excitation during swimming speeds up fictive swimming frequency whilst weakening phasic inhibition without changing background excitation slows down swimming rhythms. We conclude that both strong background excitation and phasic inhibition can promote faster tadpole swimming. PMID:22553028

Evidence for P(2)-purinoceptors contribution in H(2)O(2)-induced contraction of rat aorta in the absence of endothelium.

PubMed

Shen, J Z; Zheng, X F; Kwan, C Y

2000-08-18

H(2)O(2) can contract many arteries, however the underlying mechanisms are not fully understood. This study aims to test whether H(2)O(2)-induced vasoconstriction could be functionally attributed to the activation of P(2)-purinoceptors in rat aorta and to explore its possible signaling mechanisms. Isometric tension recording of H(2)O(2) and ATP-induced contractions of rat aortic rings were compared in the absence or presence of various pharmacological tools to identify their possible common signaling pathways. Both H(2)O(2) and ATP induced transient phasic contractions in a concentration-dependent manner (1-1000 microM). Removal of endothelium potentiated the contractile responses to H(2)O(2) and to ATP. H(2)O(2) (30 microM)-induced phasic contraction could be abolished by catalase (800 U/ml), but not affected by SOD (150 U/ml), DMSO (5 mM) and apyrase (5 U/ml), suggesting no involvement of O(2)(-), hydroxyl free radicals and ATP release. Also, several receptor antagonists including phentolamine, atropine, methysergide and chlorpheniramine (each 3 microM) were without effect on H(2)O(2) (30 microM)-induced phasic contraction, suggesting no involvement of typical neurotransmitter release. However, both H(2)O(2) (30 microM) and ATP (1 mM)-induced phasic contractions not only presented homologous desensitization, but also showed heterogeneous desensitization. Furthermore, the phasic contractions in response to H(2)O(2) (30 microM) or ATP (100 microM) could be inhibited or abolished in a concentration dependent manner by RB-2 and suramin (10-100 microM), two widely used P(2)-purinoceptor antagonists, with only partial inhibition by Evans blue (300 microM), a moderately selective P(2x) receptor blocker, or by alpha-beta-methylene-ATP (100 microM), a selective P(2x) receptor desensitizer. On the other hand, both H(2)O(2) (30 microM) and ATP (100 microM)-induced phasic contractions were also attenuated, to different degree, by inhibitors of several enzymes including PLC, PKC, PLA(2) and cyclooxygenase. Lastly, removal of extracellular Ca(2+) or pretreatment with procaine (10 mM) and dantrolene (30 microM), two putative intracellular Ca(2+) release blockers, or with Ni(2+) (100 microM) and tetrandrine (5 microM), two Ca(2+) channel blockers, all significantly inhibited H(2)O(2) and ATP-induced contractions. However, nifedipine (1 microM), a voltage-dependent L-type Ca(2+) channel blocker, was without effect. Our results demonstrate that H(2)O(2)-induced phasic contraction of rat aorta involves, at least in part, the activation of P(2)-purinoceptors in the aortic smooth muscle cells

Dopaminergic circuitry and risk/reward decision making: implications for schizophrenia.

PubMed

Stopper, Colin M; Floresco, Stan B

2015-01-01

Abnormal reinforcement learning and representations of reward value are present in schizophrenia, and these impairments can manifest as deficits in risk/reward decision making. These abnormalities may be due in part to dopaminergic dysfunction within cortico-limbic-striatal circuitry. Evidence from studies with laboratory animal have revealed that normal DA activity within different nodes of these circuits is critical for mediating dissociable processes that can refine decision biases. Moreover, both phasic and tonic dopamine transmission appear to play separate yet complementary roles in these processes. Tonic dopamine release within the prefrontal cortex and nucleus accumbens, serves as a "running rate-meter" of reward and reflects contextual information such as reward uncertainty and overt choice behavior. On the other hand, manipulations of outcome-related phasic dopamine bursts and dips suggest these signals provide rapid feedback to allow for quick adjustments in choice as reward contingencies change. The lateral habenula is a key input to the DA system that phasic signals is necessary for expressing subjective decision biases; as suppression of activity within this nucleus leads to catastrophic impairments in decision making and random patterns of choice behavior. As schizophrenia is characterized by impairments in using positive and negative feedback to appropriately guide decision making, these findings suggest that these deficits in these processes may be mediated, at least in part, by abnormalities in both tonic and phasic dopamine transmission. © The Author 2014. Published by Oxford University Press on behalf of the Maryland Psychiatric Research Center. All rights reserved. For permissions, please email: journals.permissions@oup.com.

Delayed mirror visual feedback presented using a novel mirror therapy system enhances cortical activation in healthy adults.

PubMed

Lee, Hsin-Min; Li, Ping-Chia; Fan, Shih-Chen

2015-07-11

Mirror visual feedback (MVF) generated in mirror therapy (MT) with a physical mirror promotes the recovery of hemiparetic limbs in patients with stroke, but is limited in that it cannot provide an asymmetric mode for bimanual coordination training. Here, we developed a novel MT system that can manipulate the MVF to resolve this issue. The aims of this pilot study were to examine the feasibility of delayed MVF on MT and to establish its effects on cortical activation in order to understand how it can be used for clinical applications in the future. Three conditions (no MVF, MVF, and 2-s delayed MVF) presented via our digital MT system were evaluated for their time-course effects on cortical activity by event-related desynchronization (ERD) of mu rhythm electroencephalography (EEG) during button presses in 18 healthy adults. Phasic ERD areas, defined as the areas of the relative ERD curve that were below the reference level and within -2-0 s (P0), 0-2 s (P1), and 2-4 s (P2) of the button press, were used. The overall (P0 to P2) and phasic ERD areas were higher when MVF was provided compared to when MVF was not provided for all EEG channels (C3, Cz, and C4). Phasic ERD areas in the P2 phase only increased during the delayed-MVF condition. Significant enhancement of cortical activation in the mirror neuron system and an increase in attention to the unseen limb may play major roles in the response to MVF during MT. In comparison to the no MVF condition, the higher phasic ERD areas that were observed during the P1 phase in the delayed-MVF condition indicate that the image of the still hand may have enhanced the cortical activation that occurred in response to the button press. This study is the first to achieve delayed MVF for upper-limb MT. Our approach confirms previous findings regarding the effects of MVF on cortical activation and contributes additional evidence supporting the use of this method in the future for upper-limb motor training in patients with stroke.

A Computational Model of the Ionic Currents, Ca2+ Dynamics and Action Potentials Underlying Contraction of Isolated Uterine Smooth Muscle

PubMed Central

Tong, Wing-Chiu; Choi, Cecilia Y.; Karche, Sanjay; Holden, Arun V.; Zhang, Henggui; Taggart, Michael J.

2011-01-01

Uterine contractions during labor are discretely regulated by rhythmic action potentials (AP) of varying duration and form that serve to determine calcium-dependent force production. We have employed a computational biology approach to develop a fuller understanding of the complexity of excitation-contraction (E-C) coupling of uterine smooth muscle cells (USMC). Our overall aim is to establish a mathematical platform of sufficient biophysical detail to quantitatively describe known uterine E-C coupling parameters and thereby inform future empirical investigations of physiological and pathophysiological mechanisms governing normal and dysfunctional labors. From published and unpublished data we construct mathematical models for fourteen ionic currents of USMCs: currents (L- and T-type), current, an hyperpolarization-activated current, three voltage-gated currents, two -activated current, -activated current, non-specific cation current, - exchanger, - pump and background current. The magnitudes and kinetics of each current system in a spindle shaped single cell with a specified surface area∶volume ratio is described by differential equations, in terms of maximal conductances, electrochemical gradient, voltage-dependent activation/inactivation gating variables and temporal changes in intracellular computed from known fluxes. These quantifications are validated by the reconstruction of the individual experimental ionic currents obtained under voltage-clamp. Phasic contraction is modeled in relation to the time constant of changing . This integrated model is validated by its reconstruction of the different USMC AP configurations (spikes, plateau and bursts of spikes), the change from bursting to plateau type AP produced by estradiol and of simultaneous experimental recordings of spontaneous AP, and phasic force. In summary, our advanced mathematical model provides a powerful tool to investigate the physiological ionic mechanisms underlying the genesis of uterine electrical E-C coupling of labor and parturition. This will furnish the evolution of descriptive and predictive quantitative models of myometrial electrogenesis at the whole cell and tissue levels. PMID:21559514

Attenuating GABAA Receptor Signaling in Dopamine Neurons Selectively Enhances Reward Learning and Alters Risk Preference in Mice

PubMed Central

Parker, Jones G.; Wanat, Matthew J.; Soden, Marta E.; Ahmad, Kinza; Zweifel, Larry S.; Bamford, Nigel S.; Palmiter, Richard D.

2011-01-01

Phasic dopamine transmission encodes the value of reward-predictive stimuli and influences both learning and decision-making. Altered dopamine signaling is associated with psychiatric conditions characterized by risky choices such as pathological gambling. These observations highlight the importance of understanding how dopamine neuron activity is modulated. While excitatory drive onto dopamine neurons is critical for generating phasic dopamine responses, emerging evidence suggests that inhibitory signaling also modulates these responses. To address the functional importance of inhibitory signaling in dopamine neurons, we generated mice lacking the β3 subunit of the GABAA receptor specifically in dopamine neurons (β3-KO mice) and examined their behavior in tasks that assessed appetitive learning, aversive learning, and risk preference. Dopamine neurons in midbrain slices from β3-KO mice exhibited attenuated GABA-evoked inhibitory post-synaptic currents. Furthermore, electrical stimulation of excitatory afferents to dopamine neurons elicited more dopamine release in the nucleus accumbens of β3-KO mice as measured by fast-scan cyclic voltammetry. β3-KO mice were more active than controls when given morphine, which correlated with potential compensatory upregulation of GABAergic tone onto dopamine neurons. β3-KO mice learned faster in two food-reinforced learning paradigms, but extinguished their learned behavior normally. Enhanced learning was specific for appetitive tasks, as aversive learning was unaffected in β3-KO mice. Finally, we found that β3-KO mice had enhanced risk preference in a probabilistic selection task that required mice to choose between a small certain reward and a larger uncertain reward. Collectively, these findings identify a selective role for GABAA signaling in dopamine neurons in appetitive learning and decision-making. PMID:22114279

Mathematical Model Of Nerve/Muscle Interaction

NASA Technical Reports Server (NTRS)

Hannaford, Blake

1990-01-01

Phasic Excitation/Activation (PEA) mathematical model simulates short-term nonlinear dynamics of activation and control of muscle by nerve. Includes electronic and mechanical elements. Is homeomorphic at level of its three major building blocks, which represent motoneuron, dynamics of activation of muscle, and mechanics of muscle.

Phasic and tonic neuron ensemble codes for stimulus-environment conjunctions in the lateral entorhinal cortex

PubMed Central

Pilkiw, Maryna; Insel, Nathan; Cui, Younghua; Finney, Caitlin; Morrissey, Mark D; Takehara-Nishiuchi, Kaori

2017-01-01

The lateral entorhinal cortex (LEC) is thought to bind sensory events with the environment where they took place. To compare the relative influence of transient events and temporally stable environmental stimuli on the firing of LEC cells, we recorded neuron spiking patterns in the region during blocks of a trace eyeblink conditioning paradigm performed in two environments and with different conditioning stimuli. Firing rates of some neurons were phasically selective for conditioned stimuli in a way that depended on which room the rat was in; nearly all neurons were tonically selective for environments in a way that depended on which stimuli had been presented in those environments. As rats moved from one environment to another, tonic neuron ensemble activity exhibited prospective information about the conditioned stimulus associated with the environment. Thus, the LEC formed phasic and tonic codes for event-environment associations, thereby accurately differentiating multiple experiences with overlapping features. DOI: http://dx.doi.org/10.7554/eLife.28611.001 PMID:28682237

Integrated wireless fast-scan cyclic voltammetry recording and electrical stimulation for reward-predictive learning in awake, freely moving rats

NASA Astrophysics Data System (ADS)

Li, Yu-Ting; Wickens, Jeffery R.; Huang, Yi-Ling; Pan, Wynn H. T.; Chen, Fu-Yu Beverly; Chen, Jia-Jin Jason

2013-08-01

Objective. Fast-scan cyclic voltammetry (FSCV) is commonly used to monitor phasic dopamine release, which is usually performed using tethered recording and for limited types of animal behavior. It is necessary to design a wireless dopamine sensing system for animal behavior experiments. Approach. This study integrates a wireless FSCV system for monitoring the dopamine signal in the ventral striatum with an electrical stimulator that induces biphasic current to excite dopaminergic neurons in awake freely moving rats. The measured dopamine signals are unidirectionally transmitted from the wireless FSCV module to the host unit. To reduce electrical artifacts, an optocoupler and a separate power are applied to isolate the FSCV system and electrical stimulator, which can be activated by an infrared controller. Main results. In the validation test, the wireless backpack system has similar performance in comparison with a conventional wired system and it does not significantly affect the locomotor activity of the rat. In the cocaine administration test, the maximum electrically elicited dopamine signals increased to around 230% of the initial value 20 min after the injection of 10 mg kg-1 cocaine. In a classical conditioning test, the dopamine signal in response to a cue increased to around 60 nM over 50 successive trials while the electrically evoked dopamine concentration decreased from about 90 to 50 nM in the maintenance phase. In contrast, the cue-evoked dopamine concentration progressively decreased and the electrically evoked dopamine was eliminated during the extinction phase. In the histological evaluation, there was little damage to brain tissue after five months chronic implantation of the stimulating electrode. Significance. We have developed an integrated wireless voltammetry system for measuring dopamine concentration and providing electrical stimulation. The developed wireless FSCV system is proven to be a useful experimental tool for the continuous monitoring of dopamine levels during animal learning behavior studies of freely moving rats.

Integrated wireless fast-scan cyclic voltammetry recording and electrical stimulation for reward-predictive learning in awake, freely moving rats.

PubMed

Li, Yu-Ting; Wickens, Jeffery R; Huang, Yi-Ling; Pan, Wynn H T; Chen, Fu-Yu Beverly; Chen, Jia-Jin Jason

2013-08-01

Fast-scan cyclic voltammetry (FSCV) is commonly used to monitor phasic dopamine release, which is usually performed using tethered recording and for limited types of animal behavior. It is necessary to design a wireless dopamine sensing system for animal behavior experiments. This study integrates a wireless FSCV system for monitoring the dopamine signal in the ventral striatum with an electrical stimulator that induces biphasic current to excite dopaminergic neurons in awake freely moving rats. The measured dopamine signals are unidirectionally transmitted from the wireless FSCV module to the host unit. To reduce electrical artifacts, an optocoupler and a separate power are applied to isolate the FSCV system and electrical stimulator, which can be activated by an infrared controller. In the validation test, the wireless backpack system has similar performance in comparison with a conventional wired system and it does not significantly affect the locomotor activity of the rat. In the cocaine administration test, the maximum electrically elicited dopamine signals increased to around 230% of the initial value 20 min after the injection of 10 mg kg(-1) cocaine. In a classical conditioning test, the dopamine signal in response to a cue increased to around 60 nM over 50 successive trials while the electrically evoked dopamine concentration decreased from about 90 to 50 nM in the maintenance phase. In contrast, the cue-evoked dopamine concentration progressively decreased and the electrically evoked dopamine was eliminated during the extinction phase. In the histological evaluation, there was little damage to brain tissue after five months chronic implantation of the stimulating electrode. We have developed an integrated wireless voltammetry system for measuring dopamine concentration and providing electrical stimulation. The developed wireless FSCV system is proven to be a useful experimental tool for the continuous monitoring of dopamine levels during animal learning behavior studies of freely moving rats.

Orienting of attention, pupil size, and the norepinephrine system.

PubMed

Gabay, Shai; Pertzov, Yoni; Henik, Avishai

2011-01-01

This research examined a novel suggestion regarding the involvement of the locus coeruleus-norepinephrine (LC-NE) system in orienting reflexive (exogenous) attention. A common procedure for studying exogenous orienting of attention is Posner's cuing task. Importantly, one can manipulate the required level of target processing by changing task requirements, which, in turn, can elicit a different time course of inhibition of return (IOR). An easy task (responding to target location) produces earlier onset IOR, whereas a demanding task (responding to target identity) produces later onset IOR. Aston-Jones and Cohen (Annual Review of Neuroscience, 28, 403-450, 2005) presented a theory suggesting two different modes of LC activity: tonic and phasic. Accordingly, we suggest that in the more demanding task, the LC-NE system is activated in phasic mode, and in the easier task, it is activated in tonic mode. This, in turn, influences the appearance of IOR. We examined this suggestion by measuring participants' pupil size, which has been demonstrated to correlate with the LC-NE system, while they performed cuing tasks. We found a response-locked phasic dilation of the pupil in the discrimination task, as compared with the localization task, which may reflect different firing modes of the LC-NE system during the two tasks. We also demonstrated a correlation between pupil size at the time of cue presentation and magnitude of IOR.

Context-Dependent Modulation of αβγ and αβγ GABAA Receptors by Penicillin: Implications for Phasic and Tonic Inhibition

PubMed Central

Feng, Hua-Jun; Botzolakis, Emmanuel J.; Macdonald, Robert L.

2009-01-01

Summary Penicillin, an open-channel blocker of GABAA receptors, was recently reported to inhibit phasic, but not tonic, currents in hippocampal neurons. To distinguish between isoform-specific and context-dependent modulation as possible explanations for this selectivity, the effects of penicillin were evaluated on recombinant GABAA receptors expressed in HEK293T cells. When co-applied with saturating GABA, penicillin decreased peak amplitude, induced rebound, and prolonged deactivation of currents evoked from both synaptic and extrasynaptic receptor isoforms. However, penicillin had isoform-specific effects on the extent of desensitization, reflecting its ability to differentially modulate peak (non-equilibrium) and residual (near-equilibrium) currents. This suggested that the context of activation could determine the apparent sensitivity of a given receptor isoform to penicillin. To test this hypothesis, we explored the ability of penicillin to modulate synaptic and extrasynaptic isoforms that were activated under more physiologically relevant conditions. Interestingly, while currents evoked from synaptic isoforms under phasic conditions (transient activation by a saturating concentration of GABA) were substantially inhibited by penicillin, currents evoked from extrasynaptic isoforms under tonic conditions (prolonged application by a sub-saturating concentration of GABA) were minimally affected. We therefore concluded that the reported inability of penicillin to modulate tonic currents could not simply be attributed to insensitivity of extrasynaptic receptors, but rather, reflected an inability to modulate these receptors in their native context of activation. PMID:18775733

Central GLP-1 receptor activation modulates cocaine-evoked phasic dopamine signaling in the nucleus accumbens core.

PubMed

Fortin, Samantha M; Roitman, Mitchell F

2017-07-01

Drugs of abuse increase the frequency and magnitude of brief (1-3s), high concentration (phasic) dopamine release events in terminal regions. These are thought to be a critical part of drug reinforcement and ultimately the development of addiction. Recently, metabolic regulatory peptides, including the satiety signal glucagon-like peptide-1 (GLP-1), have been shown to modulate cocaine reward-driven behavior and sustained dopamine levels after cocaine administration. Here, we use fast-scan cyclic voltammetry (FSCV) to explore GLP-1 receptor (GLP-1R) modulation of dynamic dopamine release in the nucleus accumbens (NAc) during cocaine administration. We analyzed dopamine release events in both the NAc shell and core, as these two subregions are differentially affected by cocaine and uniquely contribute to motivated behavior. We found that central delivery of the GLP-1R agonist Exendin-4 suppressed the induction of phasic dopamine release events by intravenous cocaine. This effect was selective for dopamine signaling in the NAc core. Suppression of phasic signaling in the core by Exendin-4 could not be attributed to interference with cocaine binding to one of its major substrates, the dopamine transporter, as cocaine-induced increases in reuptake were unaffected. The results suggest that GLP-1R activation, instead, exerts its suppressive effects by altering dopamine release - possibly by suppressing the excitability of dopamine neurons. Given the role of NAc core dopamine in the generation of conditioned responses based on associative learning, suppression of cocaine-induced dopamine signaling in this subregion by GLP-1R agonism may decrease the reinforcing properties of cocaine. Thus, GLP-1Rs remain viable targets for the treatment and prevention of cocaine seeking, taking and relapse. Copyright © 2017 Elsevier Inc. All rights reserved.

Quantitative differences among EMG activities of muscles innervated by subpopulations of hypoglossal and upper spinal motoneurons during non-REM sleep - REM sleep transitions: a window on neural processes in the sleeping brain

PubMed Central

RUKHADZE, I.; KAMANI, H.; KUBIN, L.

2017-01-01

In the rat, a species widely used to study the neural mechanisms of sleep and motor control, lingual electromyographic activity (EMG) is minimal during non-rapid eye movement (non-REM) sleep and then phasic twitches gradually increase after the onset of REM sleep. To better characterize the central neural processes underlying this pattern, we quantified EMG of muscles innervated by distinct subpopulations of hypoglossal motoneurons and nuchal (N) EMG during transitions from non-REM sleep to REM sleep. In 8 chronically instrumented rats, we recorded cortical EEG, EMG at sites near the base of the tongue where genioglossal and intrinsic muscle fibers predominate (GG-I), EMG of the geniohyoid (GH) muscle, and N EMG. Sleep-wake states were identified and EMGs quantified relative to their mean levels in wakefulness in successive 10 s epochs. During non-REM sleep, the average EMG levels differed among the three muscles, with the order being N > GH > GG-I. During REM sleep, due to different magnitudes of phasic twitches, the order was reversed to GG-I > GH > N. GG-I and GH exhibited a gradual increase of twitching that peaked at 70–120 s after the onset of REM sleep and then declined if the REM sleep episode lasted longer. We propose that a common phasic excitatory generator impinges on motoneuron pools that innervate different muscles, but twitching magnitudes are different due to different levels of tonic motoneuronal hyperpolarization. We also propose that REM sleep episodes of average durations are terminated by intense activity of the central generator of phasic events, whereas long REM sleep episodes end as a result of a gradual waning of the tonic disfacilitatory and inhibitory processes. PMID:22205596

Waveform generation in the weakly electric fish Gymnotus coropinae (Hoedeman): the electric organ and the electric organ discharge.

PubMed

Castelló, María E; Rodríguez-Cattáneo, Alejo; Aguilera, Pedro A; Iribarne, Leticia; Pereira, Ana Carolina; Caputi, Angel A

2009-05-01

This article deals with the electric organ and its discharge in Gymnotus coropinae, a representative species of one of the three main clades of the genus. Three regions with bilateral symmetry are described: (1) subopercular (medial and lateral columns of complex shaped electrocytes); (2) abdominal (medial and lateral columns of cuboidal and fusiform electrocytes); and (3) main [four columns, one dorso-lateral (containing fusiform electrocytes) and three medial (containing cuboidal electrocytes)]. Subopercular electrocytes are all caudally innervated whereas two of the medial subopercular ones are also rostrally innervated. Fusiform electrocytes are medially innervated at the abdominal portion, and at their rostral and caudal poles at the main portion. Cuboidal electrocytes are always caudally innervated. The subopercular portion generates a slow head-negative wave (V(1r)) followed by a head-positive spike (V(3r)). The abdominal and main portions generate a fast tetra-phasic complex (V(2345ct)). Since subopercular components prevail in the near field and the rest in the far field, time coincidence of V(3r) with V(2) leads to different waveforms depending on the position of the receiver. This confirms the splitting hypothesis of communication and exploration channels based on the different timing, frequency band and reach of the regional waveforms. The following hypothesis is compatible with the observed anatomo-functional organization: V(1r) corresponds to the rostral activation of medial subopercular electrocytes and V(3r) to the caudal activation of all subopercular electrocytes; V(2), and part of V(3ct), corresponds to the successive activation of the rostral and caudal poles of dorso-lateral fusiform electrocytes; and V(345ct) is initiated in the caudal face of cuboidal electrocytes by synaptic activation (V(3ct)) and it is completed (V(45ct)) by the successive activation of rostral and caudal faces by the action currents evoked in the opposite face.

Human primary motor cortex is both activated and stabilized during observation of other person's phasic motor actions.

PubMed

Hari, Riitta; Bourguignon, Mathieu; Piitulainen, Harri; Smeds, Eero; De Tiège, Xavier; Jousmäki, Veikko

2014-01-01

When your favourite athlete flops over the high-jump bar, you may twist your body in front of the TV screen. Such automatic motor facilitation, 'mirroring' or even overt imitation is not always appropriate. Here, we show, by monitoring motor-cortex brain rhythms with magnetoencephalography (MEG) in healthy adults, that viewing intermittent hand actions of another person, in addition to activation, phasically stabilizes the viewer's primary motor cortex, with the maximum of half a second after the onset of the seen movement. Such a stabilization was evident as enhanced cortex-muscle coherence at 16-20 Hz, despite signs of almost simultaneous suppression of rolandic rhythms of approximately 7 and 15 Hz as a sign of activation of the sensorimotor cortex. These findings suggest that inhibition suppresses motor output during viewing another person's actions, thereby withholding unintentional imitation.

Electrodermal Activity of Undersocialized Aggressive Children: A Pilot Study.

ERIC Educational Resources Information Center

Schmidt, Katalin; And Others

1985-01-01

Investigated the electrodermal activity (EDA) of a small group of prepubertal children suffering from a severe form of undersocialized aggressive conduct disorder (CD). The EDA profile of the CD children resembled that of the adult sociopath on phasic measures only. (RH)

Transient inhibition and long-term facilitation of locomotion by phasic optogenetic activation of serotonin neurons

PubMed Central

Correia, Patrícia A; Lottem, Eran; Banerjee, Dhruba; Machado, Ana S; Carey, Megan R; Mainen, Zachary F

2017-01-01

Serotonin (5-HT) is associated with mood and motivation but the function of endogenous 5-HT remains controversial. Here, we studied the impact of phasic optogenetic activation of 5-HT neurons in mice over time scales from seconds to weeks. We found that activating dorsal raphe nucleus (DRN) 5-HT neurons induced a strong suppression of spontaneous locomotor behavior in the open field with rapid kinetics (onset ≤1 s). Inhibition of locomotion was independent of measures of anxiety or motor impairment and could be overcome by strong motivational drive. Repetitive place-contingent pairing of activation caused neither place preference nor aversion. However, repeated 15 min daily stimulation caused a persistent increase in spontaneous locomotion to emerge over three weeks. These results show that 5-HT transients have strong and opposing short and long-term effects on motor behavior that appear to arise from effects on the underlying factors that motivate actions. DOI: http://dx.doi.org/10.7554/eLife.20975.001 PMID:28193320

Discharge properties of upper airway motor units during wakefulness and sleep.

PubMed

Trinder, John; Jordan, Amy S; Nicholas, Christian L

2014-01-01

Upper airway muscle motoneurons, as assessed at the level of the motor unit, have a range of different discharge patterns, varying as to whether their activity is modulated in phase with the respiratory cycle, are predominantly inspiratory or expiratory, or are phasic as opposed to tonic. Two fundamental questions raised by this observation are: how are synaptic inputs from premotor neurons distributed over motoneurons to achieve these different discharge patterns; and how do different discharge patterns contribute to muscle function? We and others have studied the behavior of genioglossus (GG) and tensor palatini (TP) single motor units at transitions from wakefulness to sleep (sleep onset), from sleep to wakefulness (arousal from sleep), and during hypercapnia. Results indicate that decreases or increases in GG and TP muscle activity occur as a consequence of derecruitment or recruitment, respectively, of phasic and tonic inspiratory-modulated motoneurons, with only minor changes in rate coding. Further, sleep-wake state and chemical inputs to this "inspiratory system" appear to be mediated through the respiratory pattern generator. In contrast, phasic and tonic expiratory units and units with a purely tonic pattern, the "tonic system," are largely unaffected by sleep-wake state, and are only weakly influenced by chemical stimuli and the respiratory cycle. We speculate that the "inspiratory system" produces gross changes in upper airway muscle activity in response to changes in respiratory drive, while the "tonic system" fine tunes airway configuration with activity in this system being determined by local mechanical conditions. © 2014 Elsevier B.V. All rights reserved.

Regional influence of cocaine on evoked dopamine release in the nucleus accumbens core: A role for the caudal brainstem.

PubMed

Gerth, Ashlynn I; Alhadeff, Amber L; Grill, Harvey J; Roitman, Mitchell F

2017-01-15

Cocaine increases dopamine concentration in the nucleus accumbens through competitive binding to the dopamine transporter (DAT). However, it also increases the frequency of dopamine release events, a finding that cannot be explained by action at the DAT alone. Rather, this effect may be mediated by cocaine-induced modulation of brain regions that project to dopamine neurons. To explore regional contributions of cocaine to dopamine signaling, we administered cocaine to the lateral or fourth ventricles and compared the effects on dopamine release in the nucleus accumbens evoked by electrical stimulation of the ventral tegmental area to that of systemically-delivered cocaine. Stimulation trains caused a sharp rise in dopamine followed by a slower return to baseline. The magnitude of dopamine release ([DA]max) as well as the latency to decay to fifty percent of the maximum (t(1/2); index of DAT activity) by each stimulation train were recorded. All routes of cocaine delivery caused an increase in [DA]max; only systemic cocaine caused an increase in t(1/2). Importantly, these data are the first to show that hindbrain (fourth ventricle)-delivered cocaine modulates phasic dopamine signaling. Fourth ventricular cocaine robustly increased cFos immunoreactivity in the nucleus of the solitary tract (NTS), suggesting a neural substrate for hindbrain cocaine-mediated effects on [DA]max. Together, the data demonstrate that cocaine-induced effects on phasic dopamine signaling are mediated via actions throughout the brain including the hindbrain. Copyright © 2016 The Authors. Published by Elsevier B.V. All rights reserved.

Stimulation of the hydrolytic stage for biogas production from cattle manure in an electrochemical bioreactor.

PubMed

Samani, Saeed; Abdoli, Mohammad Ali; Karbassi, Abdolreza; Amin, Mohammad Mehdi

Electrical current in the hydrolytic phase of the biogas process might affect biogas yield. In this study, four 1,150 mL single membrane-less chamber electrochemical bioreactors, containing two parallel titanium plates were connected to the electrical source with voltages of 0, -0.5, -1 and -1.5 V, respectively. Reactor 1 with 0 V was considered as a control reactor. The trend of biogas production was precisely checked against pH, oxidation reduction potential and electrical power at a temperature of 37 ± 0.5°C amid cattle manure as substrate for 120 days. Biogas production increased by voltage applied to Reactors 2 and 3 when compared with the control reactor. In addition, the electricity in Reactors 2 and 3 caused more biogas production than Reactor 4. Acetogenic phase occurred more quickly in Reactor 3 than in the other reactors. The obtained results from Reactor 4 were indicative of acidogenic domination and its continuous behavior under electrical stimulation. The results of the present investigation clearly revealed that phasic electrical current could enhance the efficiency of biogas production.

Differential effects of phasic and tonic alerting on the efficiency of executive attention.

PubMed

Asanowicz, Dariusz; Marzecová, Anna

2017-05-01

The study examined how alerting and executive attention interact in a task involving conflict resolution. We proposed a tentative scenario in which an initial exogenous phasic alerting phase is followed by an endogenous tonic alerting phase, and hypothesized that these two processes may have distinct effects on conflict resolution. Phasic alerting was expected to increase the conflict, whereas tonic alerting was expected to decrease the conflict. Three experiments were conducted using different variants of the flanker task with visual alerting cues and varied cue-target intervals (SOA), to differentiate between effects of phasic alerting (short SOA) and tonic alerting (long SOA). The results showed that phasic alerting consistently decreased the efficiency of conflict resolution indexed by response time and accuracy, whereas tonic alerting increased the accuracy of conflict resolution, but at a cost in the speed of processing the conflict. The third experiment additionally showed that the effects of phasic alerting may be modulated by the psychophysical strength of alerting cues. Discussed are possible mechanisms that could account for the observed interactions between alerting and conflict resolution, as well as some discrepancies between the current and previous studies. Copyright © 2017 Elsevier B.V. All rights reserved.

A Neurocomputational model of tonic and phasic dopamine in action selection: A comparison with cognitive deficits in Parkinson’s disease

PubMed Central

Guthrie, M.; Myers, C.E.; Gluck, M.A.

2015-01-01

The striatal dopamine signal has multiple facets; tonic level, phasic rise and fall, and variation of the phasic rise/fall depending on the expectation of reward/punishment. We have developed a network model of the striatal direct pathway using an ionic current level model of the medium spiny neuron that incorporates currents sensitive to changes in the tonic level of dopamine. The model neurons in the network learn action selection based on a novel set of mathematical rules that incorporate the phasic change in the dopamine signal. This network model is capable of learning to perform a sequence learning task that in humans is thought to be dependent on the basal ganglia. When both tonic and phasic levels of dopamine are decreased, as would be expected in unmedicated Parkinson’s disease (PD), the model reproduces the deficits seen in a human PD group off medication. When the tonic level is increased to normal, but with reduced phasic increases and decreases in response to reward and punishment respectively, as would be expected in PD medicated with L-Dopa, the model again reproduces the human data. These findings support the view that the cognitive dysfunctions seen in Parkinson’s disease are not solely due to either the decreased tonic level of dopamine or to the decreased responsiveness of the phasic dopamine signal to reward and punishment, but to a combination of the two factors that varies dependent on disease stage and medication status. PMID:19162084

Phasic-to-tonic shift in trunk muscle activity relative to walking during low-impact weight bearing exercise

NASA Astrophysics Data System (ADS)

Caplan, Nick; Gibbon, Karl; Hibbs, Angela; Evetts, Simon; Debuse, Dorothée

2014-11-01

The aim of this study was to investigate the influence of an exercise device, designed to improve the function of lumbopelvic muscles via low-impact weight-bearing exercise, on electromyographic (EMG) activity of lumbopelvic, including abdominal muscles. Surface EMG activity was collected from lumbar multifidus (LM), erector spinae (ES), internal oblique (IO), external oblique (EO) and rectus abdominis (RA) during overground walking (OW) and exercise device (EX) conditions. During walking, most muscles showed peaks in activity which were not seen during EX. Spinal extensors (LM, ES) were more active in EX. Internal oblique and RA were less active in EX. In EX, LM and ES were active for longer than during OW. Conversely, EO and RA were active for a shorter duration in EX than OW. The exercise device showed a phasic-to-tonic shift in activation of both local and global lumbopelvic muscles and promoted increased activation of spinal extensors in relation to walking. These features could make the exercise device a useful rehabilitative tool for populations with lumbopelvic muscle atrophy and dysfunction, including those recovering from deconditioning due to long-term bed rest and microgravity in astronauts.

Relaxation of Isolated Ventricular Cardiomyocytes by a Voltage-Dependent Process

NASA Astrophysics Data System (ADS)

Bridge, John H. B.; Spitzer, Kenneth W.; Ershler, Philip R.

1988-08-01

Cell contraction and relaxation were measured in single voltage-clamped guinea pig cardiomyocytes to investigate the contribution of sarcolemmal Na+-Ca2+ exchange to mechanical relaxation. Cells clamped from -80 to 0 millivolts displayed initial phasic and subsequent tonic contractions; caffeine reduced or abolished the phasic and enlarged the tonic contraction. The rate of relaxation from tonic contractions was steeply voltage-dependent and was significantly slowed in the absence of a sarcolemmal Na+ gradient. Tonic contractions elicited in the absence of a Na+ gradient promptly relaxed when external Na+ was applied, reflecting activation of Na+-Ca2+ exchange. It appears that a voltage-dependent Na+-Ca2+ exchange can rapidly mechanically relax mammalian heart muscle.

Simultaneous characterizations of reflex and nonreflex dynamic and static changes in spastic hemiparesis

PubMed Central

Chung, Sun G.; Ren, Yupeng; Liu, Lin; Roth, Elliot J.; Rymer, W. Zev

2013-01-01

This study characterizes tonic and phasic stretch reflex and stiffness and viscosity changes associated with spastic hemiparesis. Perturbations were applied to the ankle of 27 hemiparetic and 36 healthy subjects under relaxed or active contracting conditions. A nonlinear delay differential equation model characterized phasic and tonic stretch reflex gains, elastic stiffness, and viscous damping. Tendon reflex was characterized with reflex gain and threshold. Reflexively, tonic reflex gain was increased in spastic ankles at rest (P < 0.038) and was not regulated with muscle contraction, indicating impaired tonic stretch reflex. Phasic-reflex gain in spastic plantar flexors was higher and increased faster with plantar flexor contraction (P < 0.012) than controls (P < 0.023) and higher in dorsi-flexors at lower torques (P < 0.038), primarily because of its increase at rest (P = 0.045), indicating exaggerated phasic stretch reflex especially in more spastic plantar flexors, which showed higher phasic stretch reflex gain than dorsi-flexors (P < 0.032). Spasticity was associated with increased tendon reflex gain (P = 0.002) and decreased threshold (P < 0.001). Mechanically, stiffness in spastic ankles was higher than that in controls across plantar flexion/dorsi-flexion torque levels (P < 0.032), and the more spastic plantar flexors were stiffer than dorsi-flexors at comparable torques (P < 0.031). Increased stiffness in spastic ankles was mainly due to passive stiffness increase (P < 0.001), indicating increased connective tissues/shortened fascicles. Viscous damping in spastic ankles was increased across the plantar flexion torque levels and at lower dorsi-flexion torques, reflecting increased passive viscous damping (P = 0.033). The more spastic plantar flexors showed higher viscous damping than dorsi-flexors at comparable torque levels (P < 0.047). Simultaneous characterizations of reflex and nonreflex changes in spastic hemiparesis may help to evaluate and treat them more effectively. PMID:23636726

Force estimation from ensembles of Golgi tendon organs

NASA Astrophysics Data System (ADS)

Mileusnic, M. P.; Loeb, G. E.

2009-06-01

Golgi tendon organs (GTOs) located in the skeletal muscles provide the central nervous system with information about muscle tension. The ensemble firing of all GTO receptors in the muscle has been hypothesized to represent a reliable measure of the whole muscle force but the precision and accuracy of that information are largely unknown because it is impossible to record activity simultaneously from all GTOs in a muscle. In this study, we combined a new mathematical model of force sampling and transduction in individual GTOs with various models of motor unit (MU) organization and recruitment simulating various normal, pathological and neural prosthetic conditions. Our study suggests that in the intact muscle the ensemble GTO activity accurately encodes force information according to a nonlinear, monotonic relationship that has its steepest slope for low force levels and tends to saturate at the highest force levels. The relationship between the aggregate GTO activity and whole muscle tension under some pathological conditions is similar to one seen in the intact muscle during rapidly modulated, phasic excitation of the motor pool (typical for many natural movements) but quite different when the muscle is activated slowly or held at a given force level. Substantial deviations were also observed during simulated functional electrical stimulation.

Behavioral and Brain Measures of Phasic Alerting Effects on Visual Attention.

PubMed

Wiegand, Iris; Petersen, Anders; Finke, Kathrin; Bundesen, Claus; Lansner, Jon; Habekost, Thomas

2017-01-01

In the present study, we investigated effects of phasic alerting on visual attention in a partial report task, in which half of the displays were preceded by an auditory warning cue. Based on the computational Theory of Visual Attention (TVA), we estimated parameters of spatial and non-spatial aspects of visual attention and measured event-related lateralizations (ERLs) over visual processing areas. We found that the TVA parameter sensory effectiveness a , which is thought to reflect visual processing capacity, significantly increased with phasic alerting. By contrast, the distribution of visual processing resources according to task relevance and spatial position, as quantified in parameters top-down control α and spatial bias w index , was not modulated by phasic alerting. On the electrophysiological level, the latencies of ERLs in response to the task displays were reduced following the warning cue. These results suggest that phasic alerting facilitates visual processing in a general, unselective manner and that this effect originates in early stages of visual information processing.

The Brain Circuitry Underlying the Temporal Evolution of Nausea in Humans

PubMed Central

Sheehan, James D.; Kim, Jieun; LaCount, Lauren T.; Park, Kyungmo; Kaptchuk, Ted J.; Rosen, Bruce R.; Kuo, Braden

2013-01-01

Nausea is a universal human experience. It evolves slowly over time, and brain mechanisms underlying this evolution are not well understood. Our functional magnetic resonance imaging (fMRI) approach evaluated brain activity contributing to and arising from increasing motion sickness. Subjects rated transitions to increasing nausea, produced by visually induced vection within the fMRI environment. We evaluated parametrically increasing brain activity 1) precipitating increasing nausea and 2) following transition to stronger nausea. All subjects demonstrated visual stimulus–associated activation (P < 0.01) in primary and extrastriate visual cortices. In subjects experiencing motion sickness, increasing phasic activity preceding nausea was found in amygdala, putamen, and dorsal pons/locus ceruleus. Increasing sustained response following increased nausea was found in a broader network including insular, anterior cingulate, orbitofrontal, somatosensory and prefrontal cortices. Moreover, sustained anterior insula activation to strong nausea was correlated with midcingulate activation (r = 0.87), suggesting a closer linkage between these specific regions within the brain circuitry subserving nausea perception. Thus, while phasic activation in fear conditioning and noradrenergic brainstem regions precipitates transition to strong nausea, sustained activation following this transition occurs in a broader interoceptive, limbic, somatosensory, and cognitive network, reflecting the multiple dimensions of this aversive commonly occurring symptom. PMID:22473843

The brain circuitry underlying the temporal evolution of nausea in humans.

PubMed

Napadow, Vitaly; Sheehan, James D; Kim, Jieun; Lacount, Lauren T; Park, Kyungmo; Kaptchuk, Ted J; Rosen, Bruce R; Kuo, Braden

2013-04-01

Nausea is a universal human experience. It evolves slowly over time, and brain mechanisms underlying this evolution are not well understood. Our functional magnetic resonance imaging (fMRI) approach evaluated brain activity contributing to and arising from increasing motion sickness. Subjects rated transitions to increasing nausea, produced by visually induced vection within the fMRI environment. We evaluated parametrically increasing brain activity 1) precipitating increasing nausea and 2) following transition to stronger nausea. All subjects demonstrated visual stimulus-associated activation (P < 0.01) in primary and extrastriate visual cortices. In subjects experiencing motion sickness, increasing phasic activity preceding nausea was found in amygdala, putamen, and dorsal pons/locus ceruleus. Increasing sustained response following increased nausea was found in a broader network including insular, anterior cingulate, orbitofrontal, somatosensory and prefrontal cortices. Moreover, sustained anterior insula activation to strong nausea was correlated with midcingulate activation (r = 0.87), suggesting a closer linkage between these specific regions within the brain circuitry subserving nausea perception. Thus, while phasic activation in fear conditioning and noradrenergic brainstem regions precipitates transition to strong nausea, sustained activation following this transition occurs in a broader interoceptive, limbic, somatosensory, and cognitive network, reflecting the multiple dimensions of this aversive commonly occurring symptom.

Phasic Dopaminergic Signaling and the Presymptomatic Phase of Parkinson’s Disease

DTIC Science & Technology

2005-07-01

provides an ambient , steady- state level of extracellular dopamine, whereas phasic signaling results in a transient increase (i.e., a short-lived...certain ambient extracellular level of dopamine is essential for movement to occur [116]. Phasic signaling involves synchronized high frequency firing of...microdialysis. A measurement of the ambient level of dopamine by microdialysis in animal studies shows that extracellular dopamine levels are normal

A computational model of the ionic currents, Ca2+ dynamics and action potentials underlying contraction of isolated uterine smooth muscle.

PubMed

Tong, Wing-Chiu; Choi, Cecilia Y; Kharche, Sanjay; Karche, Sanjay; Holden, Arun V; Zhang, Henggui; Taggart, Michael J

2011-04-29

Uterine contractions during labor are discretely regulated by rhythmic action potentials (AP) of varying duration and form that serve to determine calcium-dependent force production. We have employed a computational biology approach to develop a fuller understanding of the complexity of excitation-contraction (E-C) coupling of uterine smooth muscle cells (USMC). Our overall aim is to establish a mathematical platform of sufficient biophysical detail to quantitatively describe known uterine E-C coupling parameters and thereby inform future empirical investigations of physiological and pathophysiological mechanisms governing normal and dysfunctional labors. From published and unpublished data we construct mathematical models for fourteen ionic currents of USMCs: Ca2+ currents (L- and T-type), Na+ current, an hyperpolarization-activated current, three voltage-gated K+ currents, two Ca2+-activated K+ current, Ca2+-activated Cl current, non-specific cation current, Na+-Ca2+ exchanger, Na+-K+ pump and background current. The magnitudes and kinetics of each current system in a spindle shaped single cell with a specified surface area:volume ratio is described by differential equations, in terms of maximal conductances, electrochemical gradient, voltage-dependent activation/inactivation gating variables and temporal changes in intracellular Ca2+ computed from known Ca2+ fluxes. These quantifications are validated by the reconstruction of the individual experimental ionic currents obtained under voltage-clamp. Phasic contraction is modeled in relation to the time constant of changing [Ca2+]i. This integrated model is validated by its reconstruction of the different USMC AP configurations (spikes, plateau and bursts of spikes), the change from bursting to plateau type AP produced by estradiol and of simultaneous experimental recordings of spontaneous AP, [Ca2+]i and phasic force. In summary, our advanced mathematical model provides a powerful tool to investigate the physiological ionic mechanisms underlying the genesis of uterine electrical E-C coupling of labor and parturition. This will furnish the evolution of descriptive and predictive quantitative models of myometrial electrogenesis at the whole cell and tissue levels.

Serotonergic neurons signal reward and punishment on multiple timescales

PubMed Central

Cohen, Jeremiah Y; Amoroso, Mackenzie W; Uchida, Naoshige

2015-01-01

Serotonin's function in the brain is unclear. One challenge in testing the numerous hypotheses about serotonin's function has been observing the activity of identified serotonergic neurons in animals engaged in behavioral tasks. We recorded the activity of dorsal raphe neurons while mice experienced a task in which rewards and punishments varied across blocks of trials. We ‘tagged’ serotonergic neurons with the light-sensitive protein channelrhodopsin-2 and identified them based on their responses to light. We found three main features of serotonergic neuron activity: (1) a large fraction of serotonergic neurons modulated their tonic firing rates over the course of minutes during reward vs punishment blocks; (2) most were phasically excited by punishments; and (3) a subset was phasically excited by reward-predicting cues. By contrast, dopaminergic neurons did not show firing rate changes across blocks of trials. These results suggest that serotonergic neurons signal information about reward and punishment on multiple timescales. DOI: http://dx.doi.org/10.7554/eLife.06346.001 PMID:25714923

Assessing the temporal aspects of attention and its correlates in aging and chronic stroke patients.

PubMed

Shalev, Nir; Humphreys, Glyn; Demeyere, Nele

2016-11-01

Temporal dynamics of attention have been in the spotlight of research since the earliest days of cognitive psychology. Typically, researchers describe two different aspects of the temporal fluctuations of attention: one is in intervals of milliseconds (phasic alertness), and the other over minutes or even hours (tonic alertness or sustained attention). In order to evaluate individual capacities for sustained attention and phasic alertness, most studies rely on variations of the Continuous Performance Task (CPT). Indices of sustained attention and phasic alertness are typically based on reaction times to targets; phasic alertness is related to the change in reaction times following a cue, and sustained attention is related to variability of reaction times during the task. In the following study, we attempted to establish a new approach for studying sustained attention and phasic alertness, not reliant solely on reaction time measures. We developed a new variation of the CPT with conjunctive feature targets and forward and backward masking to induce a higher variability in accuracy. This allowed us to assess an individual's ability to maintain the same level of sensitivity to targets (d-prime) across a ten minute period on the task as an index for sustained attention. We also assessed reaction times as a function of previous trial type, and suggest previous trial RT benefit might be a marker for an individual's phasic alertness. We demonstrated the use of this task with healthy aging controls and stroke survivors. As a demonstration of external validity of the novel paradigm, we present a correlation between how individual performance drops over time and individual reports of distractibility in everyday life on the Cognitive Failures Questionnaire. In addition, we found significant differences between the patient and control groups in our proposed marker of phasic alertness. We discuss the implications of our study for current assessment tools, as well as general differences in phasic alertness between clinical and neurologically unimpaired groups. Copyright © 2016 Elsevier Ltd. All rights reserved.

Relationship between regional myocardial blood flow and thallium-201 distribution in the presence of coronary artery stenosis and dipyridamole-induced vasodilation.

PubMed Central

Mays, A E; Cobb, F R

1984-01-01

This study assesses the relationship between the distribution of thallium-201 and myocardial blood flow during coronary vasodilation induced by intravenous dipyridamole in canine models of partial and complete coronary artery stenosis. 10 dogs were chronically instrumented with catheters in the left atrium and aorta and with a balloon occluder and electromagnetic flow probe on the proximal left circumflex coronary artery. Regional myocardial blood flow was measured during control conditions with radioisotope-labeled microspheres, and the phasic reactive hyperemic response to a 20-s transient occlusion was then recorded. Dipyridamole was then infused intravenously until phasic coronary blood flow increased to match peak hyperemic values. The left circumflex coronary artery was either partially occluded to reduce phasic blood flow to control values (group 1) or it was completely occluded (group 2), and thallium-201 and a second microsphere label were injected. 5 min later, the animals were sacrificed, the left ventricle was sectioned into 1-2-g samples, and thallium-201 activity and regional myocardial blood flow were measured. Curvilinear regression analyses between thallium-201 localization and myocardial blood flow during dipyridamole infusion demonstrated a slightly better fit to a second- as compared with a first-order model, indicating a slight roll-off of thallium activity as myocardial blood flow increases. During the dipyridamole infusion, the increases in phasic blood flow, the distributions of regional myocardial blood flow, and the relationships between thallium-201 localization and regional blood flow were comparable to values previously observed in exercising dogs with similar occlusions. These data provide basic validation that supports the use of intravenous dipyridamole and thallium-201 as an alternative to exercise stress and thallium-201 for evaluating the effects of coronary occlusive lesions on the distribution of regional myocardial blood flow. PMID:6715540

Roles of Na(+)/Ca(2+) exchanger isoforms NCX1 and NCX2 in motility in mouse ileum.

PubMed

Nishiyama, Kazuhiro; Azuma, Yasu-Taka; Morioka, Ai; Yoshida, Natsuho; Teramoto, Midori; Tanioka, Kohta; Kita, Satomi; Hayashi, Satomi; Nakajima, Hidemitsu; Iwamoto, Takahiro; Takeuchi, Tadayoshi

2016-10-01

The Na(+)/Ca(2+) exchanger (NCX) is a plasma membrane transporter that is involved in regulating intracellular Ca(2+) concentrations in various tissues. The physiological roles by which NCX influences gastrointestinal motility are incompletely understood, although its role in the heart, brain, and kidney has been widely investigated. In this study, we focused on the functions of the NCX isoforms, NCX1 and NCX2, in the motility of the ileum in the gastrointestinal tract. We investigated the response to electric field stimulation (EFS) in the longitudinal smooth muscle of the ileum obtained from wild-type mice (WT), NCX1-heterozygote knockout mice (NCX1 HET), NCX2 HET and smooth muscle-specific NCX1.3 transgenic mice (NCX1.3 Tg). EFS induced a phasic contraction that persisted during EFS and a tonic contraction that occurred after the end of EFS. We found that the amplitudes of the phasic and tonic contractions were significantly smaller in NCX2 HET, but not in NCX1 HET, compared to WT. Moreover, the magnitudes of acetylcholine (ACh)- and substance P (SP)-induced contractions of NCX2 HET, but not of NCX1 HET, were smaller compared to WT. In contrast, the amplitudes of the phasic and tonic contractions were greater in NCX1.3 Tg compared to WT. Similar to EFS, the magnitude of ACh-induced contraction was greater in NCX1.3 Tg than in WT. Taken together, our findings indicated that NCX1 and NCX2 play important roles in ileal motility and suggest that NCX1 and NCX2 regulate the motility in the ileum by controlling the sensitivity of smooth muscles to ACh and SP.

Eyelid Opening with Trigeminal Proprioceptive Activation Regulates a Brainstem Arousal Mechanism.

PubMed

Matsuo, Kiyoshi; Ban, Ryokuya; Hama, Yuki; Yuzuriha, Shunsuke

2015-01-01

Eyelid opening stretches mechanoreceptors in the supratarsal Müller muscle to activate the proprioceptive fiber supplied by the trigeminal mesencephalic nucleus. This proprioception induces reflex contractions of the slow-twitch fibers in the levator palpebrae superioris and frontalis muscles to sustain eyelid and eyebrow positions against gravity. The cell bodies of the trigeminal proprioceptive neurons in the mesencephalon potentially make gap-junctional connections with the locus coeruleus neurons. The locus coeruleus is implicated in arousal and autonomic function. Due to the relationship between arousal, ventromedial prefrontal cortex, and skin conductance, we assessed whether upgaze with trigeminal proprioceptive evocation activates sympathetically innervated sweat glands and the ventromedial prefrontal cortex. Specifically, we examined whether 60° upgaze induces palmar sweating and hemodynamic changes in the prefrontal cortex in 16 subjects. Sweating was monitored using a thumb-mounted perspiration meter, and prefrontal cortex activity was measured with 45-channel, functional near-infrared spectroscopy (fNIRS) and 2-channel NIRS at Fp1 and Fp2. In 16 subjects, palmar sweating was induced by upgaze and decreased in response to downgaze. Upgaze activated the ventromedial prefrontal cortex with an accumulation of integrated concentration changes in deoxyhemoglobin, oxyhemoglobin, and total hemoglobin levels in 12 subjects. Upgaze phasically and degree-dependently increased deoxyhemoglobin level at Fp1 and Fp2, whereas downgaze phasically decreased it in 16 subjects. Unilateral anesthetization of mechanoreceptors in the supratarsal Müller muscle used to significantly reduce trigeminal proprioceptive evocation ipsilaterally impaired the increased deoxyhemoglobin level by 60° upgaze at Fp1 or Fp2 in 6 subjects. We concluded that upgaze with strong trigeminal proprioceptive evocation was sufficient to phasically activate sympathetically innervated sweat glands and appeared to induce rapid oxygen consumption in the ventromedial prefrontal cortex and to rapidly produce deoxyhemoglobin to regulate physiological arousal. Thus, eyelid opening with trigeminal proprioceptive evocation may activate the ventromedial prefrontal cortex via the mesencephalic trigeminal nucleus and locus coeruleus.

Eyelid Opening with Trigeminal Proprioceptive Activation Regulates a Brainstem Arousal Mechanism

PubMed Central

Matsuo, Kiyoshi; Ban, Ryokuya; Hama, Yuki; Yuzuriha, Shunsuke

2015-01-01

Eyelid opening stretches mechanoreceptors in the supratarsal Müller muscle to activate the proprioceptive fiber supplied by the trigeminal mesencephalic nucleus. This proprioception induces reflex contractions of the slow-twitch fibers in the levator palpebrae superioris and frontalis muscles to sustain eyelid and eyebrow positions against gravity. The cell bodies of the trigeminal proprioceptive neurons in the mesencephalon potentially make gap-junctional connections with the locus coeruleus neurons. The locus coeruleus is implicated in arousal and autonomic function. Due to the relationship between arousal, ventromedial prefrontal cortex, and skin conductance, we assessed whether upgaze with trigeminal proprioceptive evocation activates sympathetically innervated sweat glands and the ventromedial prefrontal cortex. Specifically, we examined whether 60° upgaze induces palmar sweating and hemodynamic changes in the prefrontal cortex in 16 subjects. Sweating was monitored using a thumb-mounted perspiration meter, and prefrontal cortex activity was measured with 45-channel, functional near-infrared spectroscopy (fNIRS) and 2-channel NIRS at Fp1 and Fp2. In 16 subjects, palmar sweating was induced by upgaze and decreased in response to downgaze. Upgaze activated the ventromedial prefrontal cortex with an accumulation of integrated concentration changes in deoxyhemoglobin, oxyhemoglobin, and total hemoglobin levels in 12 subjects. Upgaze phasically and degree-dependently increased deoxyhemoglobin level at Fp1 and Fp2, whereas downgaze phasically decreased it in 16 subjects. Unilateral anesthetization of mechanoreceptors in the supratarsal Müller muscle used to significantly reduce trigeminal proprioceptive evocation ipsilaterally impaired the increased deoxyhemoglobin level by 60° upgaze at Fp1 or Fp2 in 6 subjects. We concluded that upgaze with strong trigeminal proprioceptive evocation was sufficient to phasically activate sympathetically innervated sweat glands and appeared to induce rapid oxygen consumption in the ventromedial prefrontal cortex and to rapidly produce deoxyhemoglobin to regulate physiological arousal. Thus, eyelid opening with trigeminal proprioceptive evocation may activate the ventromedial prefrontal cortex via the mesencephalic trigeminal nucleus and locus coeruleus. PMID:26244675

Do intensity ratings and skin conductance responses reliably discriminate between different stimulus intensities in experimentally induced pain?

PubMed

Breimhorst, Markus; Sandrock, Stephan; Fechir, Marcel; Hausenblas, Nadine; Geber, Christian; Birklein, Frank

2011-01-01

The present study addresses the question whether pain-intensity ratings and skin conductance responses (SCRs) are able to detect different intensities of phasic painful stimuli and to determine the reliability of this discrimination. For this purpose, 42 healthy participants of both genders were assigned to either electrical, mechanical, or laser heat-pain stimulation (each n = 14). A whole range of single brief painful stimuli were delivered on the right volar forearm of the dominant hand in a randomized order. Pain-intensity ratings and SCRs were analyzed. Using generalizability theory, individual and gender differences were the main contributors to the variability of both intensity ratings and SCRs. Most importantly, we showed that pain-intensity ratings are a reliable measure for the discrimination of different pain stimulus intensities in the applied modalities. The reliability of SCR was adequate when mechanical and heat stimuli were tested but failed for the discrimination of electrical stimuli. Further studies are needed to reveal the reason for this lack of accuracy for SCRs when applying electrical pain stimuli. Our study could help researchers to better understand the relationship between pain and activation of the sympathetic nervous system. Pain researchers are furthermore encouraged to consider individual and gender differences when measuring pain intensity and the concomitant SCRs in experimental settings. Copyright © 2011 American Pain Society. Published by Elsevier Inc. All rights reserved.

Norepinephrine ignites local hot spots of neuronal excitation: How arousal amplifies selectivity in perception and memory

PubMed Central

Mather, Mara; Clewett, David; Sakaki, Michiko; Harley, Carolyn W.

2018-01-01

Long Abstract Existing brain-based emotion-cognition theories fail to explain arousal’s ability to both enhance and impair cognitive processing. In the Glutamate Amplifies Noradrenergic Effects (GANE) model outlined in this paper, we propose that arousal-induced norepinephrine (NE) released from the locus coeruleus (LC) biases perception and memory in favor of salient, high priority representations at the expense of lower priority representations. This increase in gain under phasic arousal occurs via synaptic self-regulation of NE based on glutamate levels. When the LC is phasically active, elevated levels of glutamate at the site of prioritized representations increase local NE release, creating “NE hot spots.” At these local hot spots, glutamate and NE release are mutually enhancing and amplify activation of prioritized representations. This excitatory effect contrasts with widespread NE suppression of weaker representations via lateral and auto-inhibitory processes. On a broader scale, hot spots increase oscillatory synchronization across neural ensembles transmitting high priority information. Furthermore, key brain structures that detect or pre-determine stimulus priority interact with phasic NE release to preferentially route such information through large-scale functional brain networks. A surge of NE before, during or after encoding enhances synaptic plasticity at sites of high glutamate activity, triggering local protein synthesis processes that enhance selective memory consolidation. Together, these noradrenergic mechanisms increase perceptual and memory selectivity under arousal. Beyond explaining discrepancies in the emotion-cognition literature, GANE reconciles and extends previous influential theories of LC neuromodulation by highlighting how NE can produce such different outcomes in processing based on priority. PMID:26126507

Left atrial phasic function and heart rate variability in asymptomatic diabetic patients.

PubMed

Tadic, Marijana; Vukomanovic, Vladan; Cuspidi, Cesare; Suzic-Lazic, Jelena; Stanisavljevic, Dejana; Celic, Vera

2017-03-01

We evaluated left atrial (LA) phasic function and heart rate variability (HRV) in asymptomatic diabetic patients, and the relationship between HRV indices and LA phasic function assessed by volumes and speckle tracking imaging. This cross-sectional study included 55 asymptomatic patients with type 2 diabetes and 50 healthy controls without cardiovascular risk factors. All study subjects underwent laboratory analyses, complete two-dimensional echocardiography examination (2DE) and 24-h Holter monitoring. Maximum, minimum LA and pre-A LA volumes and volume indexes are significantly higher in diabetic patients. Total and passive LA emptying fractions (EF), representing the LA reservoir and conduit function, are significantly lower in diabetic subjects. Active LA EF, the parameter of the LA booster pump function, is compensatory increased in diabetic patients. Similar results were obtained by 2DE strain analysis. Cardiac autonomic function, assessed by HRV, is significantly deteriorated in diabetic patients. Time and frequency-domain HRV measures are significantly lower in diabetic subjects than in controls. HbA1c, LV mass index and HRV are associated with total LA EF and longitudinal LA strain independently of age, body mass index and LV diastolic function in the whole study population. LA phasic function and cardiac autonomic nervous system assessed by HRV are impacted by diabetes. HbA1c and HRV are independently associated with LA reservoir function evaluated by volumetric and strain methods in the whole study population. This study emphasizes the importance of determination of LA function and HRV as important markers of preclinical cardiac damage and autonomic function impairment in diabetic patients.

Molecular expression and pharmacological evidence for a functional role of kv7 channel subtypes in Guinea pig urinary bladder smooth muscle.

PubMed

Afeli, Serge A Y; Malysz, John; Petkov, Georgi V

2013-01-01

Voltage-gated Kv7 (KCNQ) channels are emerging as essential regulators of smooth muscle excitability and contractility. However, their physiological role in detrusor smooth muscle (DSM) remains to be elucidated. Here, we explored the molecular expression and function of Kv7 channel subtypes in guinea pig DSM by RT-PCR, qRT-PCR, immunohistochemistry, electrophysiology, and isometric tension recordings. In whole DSM tissue, mRNAs for all Kv7 channel subtypes were detected in a rank order: Kv7.1~Kv7.2Kv7.3~Kv7.5Kv7.4. In contrast, freshly-isolated DSM cells showed mRNA expression of: Kv7.1~Kv7.2Kv7.5Kv7.3~Kv7.4. Immunohistochemical confocal microscopy analyses of DSM, conducted by using co-labeling of Kv7 channel subtype-specific antibodies and α-smooth muscle actin, detected protein expression for all Kv7 channel subtypes, except for the Kv7.4, in DSM cells. L-364373 (R-L3), a Kv7.1 channel activator, and retigabine, a Kv7.2-7.5 channel activator, inhibited spontaneous phasic contractions and the 10-Hz electrical field stimulation (EFS)-induced contractions of DSM isolated strips. Linopiridine and XE991, two pan-Kv7 (effective at Kv7.1-Kv7.5 subtypes) channel inhibitors, had opposite effects increasing DSM spontaneous phasic and 10 Hz EFS-induced contractions. EFS-induced DSM contractions generated by a wide range of stimulation frequencies were decreased by L-364373 (10 µM) or retigabine (10 µM), and increased by XE991 (10 µM). Retigabine (10 µM) induced hyperpolarization and inhibited spontaneous action potentials in freshly-isolated DSM cells. In summary, Kv7 channel subtypes are expressed at mRNA and protein levels in guinea pig DSM cells. Their pharmacological modulation can control DSM contractility and excitability; therefore, Kv7 channel subtypes provide potential novel therapeutic targets for urinary bladder dysfunction.

Store-operated Ca²⁺ entry and depolarization explain the anomalous behaviour of myometrial SR: effects of SERCA inhibition on electrical activity, Ca²⁺ and force.

PubMed

Noble, Debbie; Borysova, Lyudmyla; Wray, Susan; Burdyga, Theodor

2014-09-01

In the myometrium SR Ca(2+) depletion promotes an increase in force but unlike several other smooth muscles, there is no Ca(2+) sparks-STOCs coupling mechanism to explain this. Given the importance of the control of contractility for successful parturition, we have examined, in pregnant rat myometrium, the effects of SR Ca(2+)-ATPase (SERCA) inhibition on the temporal relationship between action potentials, Ca(2+) transients and force. Simultaneous recording of electrical activity, calcium and force showed that SERCA inhibition, by cyclopiazonic acid (CPA 20 μM), caused time-dependent changes in excitability, most noticeably depolarization and elevations of baseline [Ca(2+)]i and force. At the onset of these changes there was a prolongation of the bursts of action potentials and a corresponding series of Ca(2+) spikes, which increased the amplitude and duration of contractions. As the rise of baseline Ca(2+) and depolarization continued a point was reached when electrical and Ca(2+) spikes and phasic contractions ceased, and a maintained, tonic force and Ca(2+) was produced. Lanthanum, a non-selective blocker of store-operated Ca(2+) entry, but not the L-type Ca(2+) channel blocker nifedipine (1-10 μM), could abolish the maintained force and calcium. Application of the agonist, carbachol, produced similar effects to CPA, i.e. depolarization, elevation of force and calcium. A brief, high concentration of carbachol, to cause SR Ca(2+) depletion without eliciting receptor-operated channel opening, also produced these results. The data obtained suggest that in pregnant rats SR Ca(2+) release is coupled to marked Ca(2+) entry, via store operated Ca(2+) channels, leading to depolarization and enhanced electrical and mechanical activity. Copyright © 2014. Published by Elsevier Ltd.

Normative Irritability in Youth: Developmental Findings From the Great Smoky Mountains Study.

PubMed

Copeland, William E; Brotman, Melissa A; Costello, E Jane

2015-08-01

The goal of this study is to examine the developmental epidemiology of normative irritability and its tonic and phasic components in a longitudinal community sample of youth. Eight waves of data from the prospective, community Great Smoky Mountains Study (6,674 assessments of 1,420 participants) were used, covering children in the community 9 to 16 years of age. Youth and 1 parent were interviewed using the Child and Adolescent Psychiatric Assessment to assess tonic (touchy/easily annoyed, irritable mood, angry or resentful) and phasic (temper tantrums or anger outbursts) components of irritability, including frequency, duration, onset, and cross-context variability. At any given point in childhood/adolescence, 51.4% (standard error [SE] = 1.4) of participants reported phasic irritability, 28.3% (SE = 1.2) reported tonic irritability, and 22.8% (SE = 1.1) reported both. These prevalence levels decreased with age but did not vary by sex. The overlap between tonic and phasic irritability was high (odds ratio = 5.8, 95% CI = 3.3-10.5, p < .0001), with little evidence of tonic occurring without phasic irritability. Both tonic and phasic irritability predicted one another over time, supporting both heterotypic and homotypic continuity. Low levels of either tonic or phasic irritability increased risk for disrupted functioning including service use, school suspensions, parental burden, and emotional symptoms both concurrently and at 1-year follow-up. Irritability is relatively common, decreases with age but does not vary by sex, and at almost any level is associated with increased risk of disrupted functioning. Its relative components frequently overlap, although irritable outbursts are more common than irritable mood. Irritability appears to be a high-priority transdiagnostic marker for screening children in need of clinical attention. Copyright © 2015 American Academy of Child and Adolescent Psychiatry. All rights reserved.

Ethanol modulates the VR-1 variant amiloride-insensitive salt taste receptor. II. Effect on chorda tympani salt responses.

PubMed

Lyall, Vijay; Heck, Gerard L; Phan, Tam-Hao T; Mummalaneni, Shobha; Malik, Shahbaz A; Vinnikova, Anna K; Desimone, John A

2005-06-01

The effect of ethanol on the amiloride- and benzamil (Bz)-insensitive salt taste receptor was investigated by direct measurement of intracellular Na(+) activity ([Na(+)](i)) using fluorescence imaging in polarized fungiform taste receptor cells (TRCs) and by chorda tympani (CT) taste nerve recordings. CT responses to KCl and NaCl were recorded in Sprague-Dawley rats, and in wild-type (WT) and vanilloid receptor-1 (VR-1) knockout mice (KO). CT responses were monitored in the presence of Bz, a specific blocker of the epithelial Na(+) channel (ENaC). CT responses were also recorded in the presence of agonists (resiniferatoxin and elevated temperature) and antagonists (capsazepine and SB-366791) of VR-1 that similarly modulate the Bz-insensitive VR-1 variant salt taste receptor. In the absence of mineral salts, ethanol induced a transient decrease in TRC volume and elicited only transient phasic CT responses. In the presence of mineral salts, ethanol increased the apical cation flux in TRCs without a change in volume, increased transepithelial electrical resistance across the tongue, and elicited CT responses that were similar to salt responses, consisting of both a phasic component and a sustained tonic component. At concentrations <50%, ethanol enhanced responses to KCl and NaCl, while at ethanol concentrations >50%, those CT responses were inhibited. Resiniferatoxin and elevated temperature increased the sensitivity of the CT response to ethanol in salt-containing media, and SB-366791 inhibited the effect of ethanol, resiniferatoxin, and elevated temperature on the CT responses to mineral salts. VR-1 KO mice demonstrated no Bz-insensitive CT response to NaCl and no sensitivity to ethanol. We conclude that ethanol increases salt taste sensitivity by its direct action on the Bz-insensitive VR-1 variant salt taste receptor.

No Evidence for Ionotropic Pheromone Transduction in the Hawkmoth Manduca sexta.

PubMed

Nolte, Andreas; Gawalek, Petra; Koerte, Sarah; Wei, HongYing; Schumann, Robin; Werckenthin, Achim; Krieger, Jürgen; Stengl, Monika

2016-01-01

Insect odorant receptors (ORs) are 7-transmembrane receptors with inverse membrane topology. They associate with the conserved ion channel Orco. As chaperon, Orco maintains ORs in cilia and, as pacemaker channel, Orco controls spontaneous activity in olfactory receptor neurons. Odorant binding to ORs opens OR-Orco receptor ion channel complexes in heterologous expression systems. It is unknown, whether this also occurs in vivo. As an alternative to this ionotropic transduction, experimental evidence is accumulating for metabotropic odor transduction, implicating that insect ORs couple to G-proteins. Resulting second messengers gate various ion channels. They generate the sensillum potential that elicits phasic-tonic action potentials (APs) followed by late, long-lasting pheromone responses. Because it is still unclear how and when Orco opens after odor-OR-binding, we used tip recordings to examine in vivo the effects of the Orco antagonist OLC15 and the amilorides MIA and HMA on bombykal transduction in the hawkmoth Manduca sexta. In contrast to OLC15 both amilorides decreased the pheromone-dependent sensillum potential amplitude and the frequency of the phasic AP response. Instead, OLC15 decreased spontaneous activity, increased latencies of phasic-, and decreased frequencies of late, long-lasting pheromone responses Zeitgebertime-dependently. Our results suggest no involvement for Orco in the primary transduction events, in contrast to amiloride-sensitive channels. Instead of an odor-gated ionotropic receptor, Orco rather acts as a voltage- and apparently second messenger-gated pacemaker channel controlling the membrane potential and hence threshold and kinetics of the pheromone response.

The Dopamine Prediction Error: Contributions to Associative Models of Reward Learning

PubMed Central

Nasser, Helen M.; Calu, Donna J.; Schoenbaum, Geoffrey; Sharpe, Melissa J.

2017-01-01

Phasic activity of midbrain dopamine neurons is currently thought to encapsulate the prediction-error signal described in Sutton and Barto’s (1981) model-free reinforcement learning algorithm. This phasic signal is thought to contain information about the quantitative value of reward, which transfers to the reward-predictive cue after learning. This is argued to endow the reward-predictive cue with the value inherent in the reward, motivating behavior toward cues signaling the presence of reward. Yet theoretical and empirical research has implicated prediction-error signaling in learning that extends far beyond a transfer of quantitative value to a reward-predictive cue. Here, we review the research which demonstrates the complexity of how dopaminergic prediction errors facilitate learning. After briefly discussing the literature demonstrating that phasic dopaminergic signals can act in the manner described by Sutton and Barto (1981), we consider how these signals may also influence attentional processing across multiple attentional systems in distinct brain circuits. Then, we discuss how prediction errors encode and promote the development of context-specific associations between cues and rewards. Finally, we consider recent evidence that shows dopaminergic activity contains information about causal relationships between cues and rewards that reflect information garnered from rich associative models of the world that can be adapted in the absence of direct experience. In discussing this research we hope to support the expansion of how dopaminergic prediction errors are thought to contribute to the learning process beyond the traditional concept of transferring quantitative value. PMID:28275359

NRMRL EVALUATES ACTIVE AND SEMI-PASSIVE TECHNOLOGIES FOR TREATING ACID MINE DRAINAGE

EPA Science Inventory

Two-page article describing three SITE demonstration projects underway on the Leviathan mine site in California. BiPhasic lime treatment, lime treatment lagoons and compost free BioReactors are being evaluated as innovative technologies for treating acid mine drainage.

The Roles of Phasic and Tonic Dopamine in Tic Learning and Expression.

PubMed

Maia, Tiago V; Conceição, Vasco A

2017-09-15

Tourette syndrome (TS) prominently involves dopaminergic disturbances, but the precise nature of those disturbances has remained elusive. A substantial body of empirical work and recent computational models have characterized the specific roles of phasic and tonic dopamine (DA) in action learning and selection, respectively. Using insights from this work and models, we suggest that TS involves increases in both phasic and tonic DA, which produce increased propensities for tic learning and expression, respectively. We review the evidence from reinforcement-learning and habit-learning studies in TS, which supports the idea that TS involves increased phasic DA responses; we also review the evidence that tics engage the habit-learning circuitry. On the basis of these findings, we suggest that tics are exaggerated, maladaptive, and persistent motor habits reinforced by aberrant, increased phasic DA responses. Increased tonic DA amplifies the tendency to execute learned tics and also provides a fertile ground of motor hyperactivity for tic learning. We review evidence suggesting that antipsychotics may counter both the increased propensity for tic expression, by increasing excitability in the indirect pathway, and the increased propensity for tic learning, by shifting plasticity in the indirect pathway toward long-term potentiation (and possibly also through more complex mechanisms). Finally, we review evidence suggesting that low doses of DA agonists that effectively treat TS decrease both phasic and tonic DA, thereby also reducing the propensity for both tic learning and tic expression, respectively. Copyright © 2017 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.

Enhanced phasic GABA inhibition during the repair phase of stroke: a novel therapeutic target.

PubMed

Hiu, Takeshi; Farzampour, Zoya; Paz, Jeanne T; Wang, Eric Hou Jen; Badgely, Corrine; Olson, Andrew; Micheva, Kristina D; Wang, Gordon; Lemmens, Robin; Tran, Kevin V; Nishiyama, Yasuhiro; Liang, Xibin; Hamilton, Scott A; O'Rourke, Nancy; Smith, Stephen J; Huguenard, John R; Bliss, Tonya M; Steinberg, Gary K

2016-02-01

Ischaemic stroke is the leading cause of severe long-term disability yet lacks drug therapies that promote the repair phase of recovery. This repair phase of stroke occurs days to months after stroke onset and involves brain remapping and plasticity within the peri-infarct zone. Elucidating mechanisms that promote this plasticity is critical for the development of new therapeutics with a broad treatment window. Inhibiting tonic (extrasynaptic) GABA signalling during the repair phase was reported to enhance functional recovery in mice suggesting that GABA plays an important function in modulating brain repair. While tonic GABA appears to suppress brain repair after stroke, less is known about the role of phasic (synaptic) GABA during the repair phase. We observed an increase in postsynaptic phasic GABA signalling in mice within the peri-infarct cortex specific to layer 5; we found increased numbers of α1 receptor subunit-containing GABAergic synapses detected using array tomography, and an associated increased efficacy of spontaneous and miniature inhibitory postsynaptic currents in pyramidal neurons. Furthermore, we demonstrate that enhancing phasic GABA signalling using zolpidem, a Food and Drug Administration (FDA)-approved GABA-positive allosteric modulator, during the repair phase improved behavioural recovery. These data identify potentiation of phasic GABA signalling as a novel therapeutic strategy, indicate zolpidem's potential to improve recovery, and underscore the necessity to distinguish the role of tonic and phasic GABA signalling in stroke recovery. © The Author (2015). Published by Oxford University Press on behalf of the Guarantors of Brain.

Enhanced phasic GABA inhibition during the repair phase of stroke: a novel therapeutic target

PubMed Central

Paz, Jeanne T.; Wang, Eric Hou Jen; Badgely, Corrine; Olson, Andrew; Micheva, Kristina D.; Wang, Gordon; Lemmens, Robin; Tran, Kevin V.; Nishiyama, Yasuhiro; Liang, Xibin; Hamilton, Scott A.; O’Rourke, Nancy; Smith, Stephen J.; Huguenard, John R.; Bliss, Tonya M.

2016-01-01

Abstract Ischaemic stroke is the leading cause of severe long-term disability yet lacks drug therapies that promote the repair phase of recovery. This repair phase of stroke occurs days to months after stroke onset and involves brain remapping and plasticity within the peri-infarct zone. Elucidating mechanisms that promote this plasticity is critical for the development of new therapeutics with a broad treatment window. Inhibiting tonic (extrasynaptic) GABA signalling during the repair phase was reported to enhance functional recovery in mice suggesting that GABA plays an important function in modulating brain repair. While tonic GABA appears to suppress brain repair after stroke, less is known about the role of phasic (synaptic) GABA during the repair phase. We observed an increase in postsynaptic phasic GABA signalling in mice within the peri-infarct cortex specific to layer 5; we found increased numbers of α1 receptor subunit-containing GABAergic synapses detected using array tomography, and an associated increased efficacy of spontaneous and miniature inhibitory postsynaptic currents in pyramidal neurons. Furthermore, we demonstrate that enhancing phasic GABA signalling using zolpidem, a Food and Drug Administration (FDA)-approved GABA-positive allosteric modulator, during the repair phase improved behavioural recovery. These data identify potentiation of phasic GABA signalling as a novel therapeutic strategy, indicate zolpidem’s potential to improve recovery, and underscore the necessity to distinguish the role of tonic and phasic GABA signalling in stroke recovery. PMID:26685158

Current source density analysis of the hippocampal theta rhythm: associated sustained potentials and candidate synaptic generators.

PubMed

Brankack, J; Stewart, M; Fox, S E

1993-07-02

Single-electrode depth profiles of the hippocampal EEG were made in urethane-anesthetized rats and rats trained in an alternating running/drinking task. Current source density (CSD) was computed from the voltage as a function of depth. A problem inherent to AC-coupled profiles was eliminated by incorporating sustained potential components of the EEG. 'AC' profiles force phasic current sinks to alternate with current sources at each lamina, changing the magnitude and even the sign of the computed membrane current. It was possible to include DC potentials in the profiles from anesthetized rats by using glass micropipettes for recording. A method of 'subtracting' profiles of the non-theta EEG from theta profiles was developed as an approach to including sustained potentials in recordings from freely-moving animals implanted with platinum electrodes. 'DC' profiles are superior to 'AC' profiles for analysis of EEG activity because 'DC'-CSD values can be considered correct in sign and more closely represent the actual membrane current magnitudes. Since hippocampal inputs are laminated, CSD analysis leads to straightforward predictions of the afferents involved. Theta-related activity in afferents from entorhinal neurons, hippocampal interneurons and ipsi- and contralateral hippocampal pyramids all appear to contribute to sources and sinks in CA1 and the dentate area. The largest theta-related generator was a sink at the fissure, having both phasic and tonic components. This sink may reflect activity in afferents from the lateral entorhinal cortex. The phase of the dentate mid-molecular sink suggests that medial entorhinal afferents drive the theta-related granule and pyramidal cell firing. The sustained components may be simply due to different average rates of firing during theta rhythm than during non-theta EEG in afferents whose firing rates are also phasically modulated.

Pulmonary arterial distension and vagal afferent nerve activity in anaesthetized dogs.

PubMed

Moore, Jonathan P; Hainsworth, Roger; Drinkhill, Mark J

2004-03-16

Distension of the main pulmonary artery and its bifurcation are known to result in a reflex vasoconstriction and increased respiratory drive; however, these responses are observed at abnormally high distending pressures. In this study we recorded afferent activity from pulmonary arterial baroreceptors to investigate their stimulus-response characteristics and to determine whether they are influenced by physiological changes in intrathoracic pressure. In chloralose-anaesthetized dogs, a cardiopulmonary bypass was established, the pulmonary trunk and its main branches were vascularly isolated and perfused with venous blood at pulsatile pressures designed to simulate the normal pulmonary arterial pressure waveform. Afferent slips of a cervical vagus were dissected and nerve fibres identified that displayed discharge patterns with characteristics expected from pulmonary arterial baroreceptors. Recordings were obtained with (a) chest open (b) chest closed and resealed, and (c) with phasic negative intrathoracic pressures in the resealed chest. Pressure-discharge characteristics obtained in the open-chest animals indicated that the threshold pulmonary pressure (corresponding to 5% of the overall response) was 17.1 +/- 2.9 and the inflexion point of the curve was 29.2 +/- 3.3 mmHg (mean +/-S.E.M). In closed-chest animals the threshold and inflexion pressures were reduced to 12.0 +/- 1.7 and 20.7 +/- 1.8 mmHg. Application of phasic negative intrathoracic pressures further reduced the threshold and inflexion pressures to 9.5 +/- 1.2 mmHg (P < 0.05 vs. open) and 14.7 +/- 0.8 mmHg (P < 0.003 vs. open and P < 0.02 vs. atmospheric). These results indicate that under physiological conditions, with closed-chest and phasic negative intrathoracic pressure changes similar to those associated with normal breathing, activity from pulmonary baroreceptors is obtained at physiological pulmonary arterial pressures in intact animals.

Low amplitude rhythmic contraction frequency in human detrusor strips correlates with phasic intravesical pressure waves.

PubMed

Colhoun, Andrew F; Speich, John E; Cooley, Lauren F; Bell, Eugene D; Barbee, R Wayne; Guruli, Georgi; Ratz, Paul H; Klausner, Adam P

2017-08-01

Low amplitude rhythmic contractions (LARC) occur in detrusor smooth muscle and may play a role in storage disorders such as overactive bladder and detrusor overactivity. The purpose of this study was to determine whether LARC frequencies identified in vitro from strips of human urinary bladder tissue correlate with in vivo LARC frequencies, visualized as phasic intravesical pressure (p ves ) waves during urodynamics (UD). After IRB approval, fresh strips of human urinary bladder were obtained from patients. LARC was recorded with tissue strips at low tension (<2 g) and analyzed by fast Fourier transform (FFT) to identify LARC signal frequencies. Blinded UD tracings were retrospectively reviewed for signs of LARC on the p ves tracing during filling and were analyzed via FFT. Distinct LARC frequencies were identified in 100% of tissue strips (n = 9) obtained with a mean frequency of 1.97 ± 0.47 cycles/min (33 ± 8 mHz). Out of 100 consecutive UD studies reviewed, 35 visually displayed phasic p ves waves. In 12/35 (34%), real p ves signals were present that were independent of abdominal activity. Average UD LARC frequency was 2.34 ± 0.36 cycles/min (39 ± 6 mHz) which was similar to tissue LARC frequencies (p = 0.50). A majority (83%) of the UD cohort with LARC signals also demonstrated detrusor overactivity. During UD, a subset of patients displayed phasic p ves waves with a distinct rhythmic frequency similar to the in vitro LARC frequency quantified in human urinary bladder tissue strips. Further refinements of this technique may help identify subsets of individuals with LARC-mediated storage disorders.

Corrugator activity confirms immediate negative affect in surprise

PubMed Central

Topolinski, Sascha; Strack, Fritz

2015-01-01

The emotion of surprise entails a complex of immediate responses, such as cognitive interruption, attention allocation to, and more systematic processing of the surprising stimulus. All these processes serve the ultimate function to increase processing depth and thus cognitively master the surprising stimulus. The present account introduces phasic negative affect as the underlying mechanism responsible for this switch in operating mode. Surprising stimuli are schema-discrepant and thus entail cognitive disfluency, which elicits immediate negative affect. This affect in turn works like a phasic cognitive tuning switching the current processing mode from more automatic and heuristic to more systematic and reflective processing. Directly testing the initial elicitation of negative affect by surprising events, the present experiment presented high and low surprising neutral trivia statements to N = 28 participants while assessing their spontaneous facial expressions via facial electromyography. High compared to low surprising trivia elicited higher corrugator activity, indicative of negative affect and mental effort, while leaving zygomaticus (positive affect) and frontalis (cultural surprise expression) activity unaffected. Future research shall investigate the mediating role of negative affect in eliciting surprise-related outcomes. PMID:25762956

Corrugator activity confirms immediate negative affect in surprise.

PubMed

Topolinski, Sascha; Strack, Fritz

2015-01-01

The emotion of surprise entails a complex of immediate responses, such as cognitive interruption, attention allocation to, and more systematic processing of the surprising stimulus. All these processes serve the ultimate function to increase processing depth and thus cognitively master the surprising stimulus. The present account introduces phasic negative affect as the underlying mechanism responsible for this switch in operating mode. Surprising stimuli are schema-discrepant and thus entail cognitive disfluency, which elicits immediate negative affect. This affect in turn works like a phasic cognitive tuning switching the current processing mode from more automatic and heuristic to more systematic and reflective processing. Directly testing the initial elicitation of negative affect by surprising events, the present experiment presented high and low surprising neutral trivia statements to N = 28 participants while assessing their spontaneous facial expressions via facial electromyography. High compared to low surprising trivia elicited higher corrugator activity, indicative of negative affect and mental effort, while leaving zygomaticus (positive affect) and frontalis (cultural surprise expression) activity unaffected. Future research shall investigate the mediating role of negative affect in eliciting surprise-related outcomes.

Surface EMG crosstalk during phasic involuntary muscle activation in the nociceptive withdrawal reflex.

PubMed

Frahm, Ken S; Jensen, Michael B; Farina, Dario; Andersen, Ole K

2012-08-01

The human nociceptive withdrawal reflex is typically assessed using surface electromyography (sEMG). Based on sEMG, the reflex receptive field (RRF) can be mapped. However, EMG crosstalk can cause erroneous results in the RRF determination. Single differential (SD) vs. double differential (DD) surface EMG were evaluated. Different electrode areas and inter-electrode-distances (IED) were evaluated. The reflexes were elicited by electrical stimulation of the sole of the foot. EMG was obtained from both tibialis anterior (TA) and soleus (SOL) using both surface and intramuscular EMG (iEMG). The amount of crosstalk was significantly higher in SD recordings than in DD recordings (P < 0.05). Crosstalk increased when electrode measuring area increased (P < 0.05) and when IED increased (P < 0.05). Reflex detection sensitivity decreases with increasing measuring area and increasing IED. These results stress that for determination of RRF and similar tasks, DD recordings should be applied. Copyright © 2012 Wiley Periodicals, Inc.

Dynamic risk control by human nucleus accumbens

PubMed Central

Lopez-Sosa, Fernando; Gonzalez-Rosa, Javier Jesus; Galarza, Ana; Avecillas, Josue; Pineda-Pardo, Jose Angel; Lopez-Ibor, Juan José; Reneses, Blanca; Barcia, Juan Antonio

2015-01-01

Real-world decisions about reward often involve a complex counterbalance of risk and value. Although the nucleus accumbens has been implicated in the underlying neural substrate, its criticality to human behaviour remains an open question, best addressed with interventional methodology that probes the behavioural consequences of focal neural modulation. Combining a psychometric index of risky decision-making with transient electrical modulation of the nucleus accumbens, here we reveal profound, highly dynamic alteration of the relation between probability of reward and choice during therapeutic deep brain stimulation in four patients with treatment-resistant psychiatric disease. Short-lived phasic electrical stimulation of the region of the nucleus accumbens dynamically altered risk behaviour, transiently shifting the psychometric function towards more risky decisions only for the duration of stimulation. A critical, on-line role of human nucleus accumbens in dynamic risk control is thereby established. PMID:26428667

Control of Vertebrate Respiration and Locomotion: A Brief Account.

ERIC Educational Resources Information Center

Feldman, Jack L.; Grillner, Sten

1983-01-01

Areas considered in this discussion include: activation/modulation of movement; control of motoneuronal discharge by excitation/inhibition; neural generation of movement synergies (considering interaction of central/peripheral elements, phasic gating of reflex effects, and neuronal organization of central pattern generators); protean nature of…

Bidirectional Modulation of Substantia Nigra Activity by Motivational State

PubMed Central

Rossi, Mark A.; Fan, David; Barter, Joseph W.; Yin, Henry H.

2013-01-01

A major output nucleus of the basal ganglia is the substantia nigra pars reticulata, which sends GABAergic projections to brainstem and thalamic nuclei. The GABAergic (GABA) neurons are reciprocally connected with nearby dopaminergic neurons, which project mainly to the basal ganglia, a set of subcortical nuclei critical for goal-directed behaviors. Here we examined the impact of motivational states on the activity of GABA neurons in the substantia nigra pars reticulata and the neighboring dopaminergic (DA) neurons in the pars compacta. Both types of neurons show short-latency bursts to a cue predicting a food reward. As mice became sated by repeated consumption of food pellets, one class of neurons reduced cue-elicited firing, whereas another class of neurons progressively increased firing. Extinction or pre-feeding just before the test session dramatically reduced the phasic responses and their motivational modulation. These results suggest that signals related to the current motivational state bidirectionally modulate behavior and the magnitude of phasic response of both DA and GABA neurons in the substantia nigra. PMID:23936522

Tamping Ramping: Algorithmic, Implementational, and Computational Explanations of Phasic Dopamine Signals in the Accumbens

PubMed Central

Lloyd, Kevin; Dayan, Peter

2015-01-01

Substantial evidence suggests that the phasic activity of dopamine neurons represents reinforcement learning’s temporal difference prediction error. However, recent reports of ramp-like increases in dopamine concentration in the striatum when animals are about to act, or are about to reach rewards, appear to pose a challenge to established thinking. This is because the implied activity is persistently predictable by preceding stimuli, and so cannot arise as this sort of prediction error. Here, we explore three possible accounts of such ramping signals: (a) the resolution of uncertainty about the timing of action; (b) the direct influence of dopamine over mechanisms associated with making choices; and (c) a new model of discounted vigour. Collectively, these suggest that dopamine ramps may be explained, with only minor disturbance, by standard theoretical ideas, though urgent questions remain regarding their proximal cause. We suggest experimental approaches to disentangling which of the proposed mechanisms are responsible for dopamine ramps. PMID:26699940

The hypothalamic slice approach to neuroendocrinology.

PubMed

Hatton, G I

1983-07-01

The magnocellular peptidergic cells of the supraoptic and paraventricular nuclei comprise much of what is known as the hypothalamo-neurohypophysial system and is involved in several functions, including body fluid balance, parturition and lactation. While we have learned much from experiments in vivo, they have not produced a clear understanding of some of the crucial features associated with the functioning of this system. In particular, questions relating to the osmosensitivity of magnocellular neurones and the mechanism(s) by which their characteristic firing patterns are generated have not been answered using the older approaches. Electrophysiological studies with brain slices present direct evidence for osmosensitivity, and perhaps even osmoreceptivity, of magnocellular neurones. Other evidence indicates that the phasic bursting patterns of activity associated with vasopressin-releasing neurones (a) occur in the absence of patterned chemical synaptic input, (b) may be modulated by electrotonic conduction across gap junctions connecting magnocellular neurones and (c) are likely to be generated by endogenous membrane currents. These results make untenable the formerly held idea that phasic bursting activity is dependent upon recurrent synaptic inhibition.

Association between left atrial phasic conduit function and early atrial fibrillation recurrence in patients undergoing electrical cardioversion.

PubMed

Degiovanni, Anna; Boggio, Enrico; Prenna, Eleonora; Sartori, Chiara; De Vecchi, Federica; Marino, Paolo N

2018-04-01

Diastolic dysfunction promotes atrial fibrillation (AF) inducing left atrial (LA) remodeling, with chamber dilation and fibrosis. Predominance of LA phasic conduit (LAC) function should reflect not only chamber alterations but also underlying left ventricular (LV) filling impairment. Thus, LAC was tested as possible predictor of early AF relapse after electrical cardioversion (EC). 96 consecutive patients, who underwent EC for persistent non-valvular AF, were prospectively enrolled. Immediately after successful EC (3 h ± 15 min), an echocardiographic apical four-chamber view was acquired with transmitral velocities, annular tissue Doppler and simultaneous LV and LA three-dimensional full-volume datasets. Then, from LA-LV volumetric curves we computed LAC as: [(LV maximum - LV minimum) - (LA maximum - LA minimum) volume], expressed as % LV stroke volume. LA pump, immediately post-EC, was assumed and verified as being negligible. Sinus rhythm persistence at 1 month was checked with ECG-Holter monitoring. At 1 month 62 patients were in sinus rhythm and 34 in AF. AF patients presented pre-EC higher E/é values (p = 0.012), no major LA volume differences (p = NS), but a stiffer LV cavity (p = 0.012) for a comparable LV capacitance (p = 0.461). Conduit contributed more (p < 0.001) to LV stroke volume in AF subpopulation. Multiple regression revealed LAC as the most significant AF predictor (p = 0.013), even after correction for biometric characteristics and pharmacotherapy (p = 0.008). Our data suggest that LAC larger contribution to LV filling soon after EC reflects LA-LV stiffening, which skews atrioventricular interaction leading to AF perpetuation and makes conduit dominance a powerful predictor of early AF recurrence.

Adolescent binge-like alcohol alters sensitivity to acute alcohol effects on dopamine release in the nucleus accumbens of adult rats

PubMed Central

Shnitko, Tatiana A.; Spear, Linda P.; Robinson, Donita L.

2015-01-01

Rationale Early onset of alcohol drinking has been associated with alcohol abuse in adulthood. The neurobiology of this phenomenon is unclear, but mesolimbic dopamine pathways, which are dynamic during adolescence, may play a role. Objectives We investigated the impact of adolescent binge-like alcohol on phasic dopaminergic neurotransmission during adulthood. Methods Rats received intermittent intragastric ethanol, water or nothing during adolescence. In adulthood, electrically-evoked dopamine release and subsequent uptake were measured in the nucleus accumbens core at baseline and after acute challenge of ethanol or saline. Results Adolescent ethanol exposure did not alter basal measures of evoked dopamine release or uptake. Ethanol challenge dose-dependently decreased the amplitude of evoked dopamine release in rats by 30–50% in control groups, as previously reported, but did not alter evoked release in ethanol-exposed animals. To address the mechanism by which ethanol altered dopamine signaling, the evoked signals were modeled to estimate dopamine efflux per impulse and the velocity of the dopamine transporter. Dopamine uptake was slower in all exposure groups after ethanol challenge compared to saline, while dopamine efflux per pulse of electrical stimulation was reduced by ethanol only in ethanol-naive rats. Conclusions The results demonstrate that exposure to binge levels of ethanol during adolescence blunts the effect of ethanol challenge to reduce the amplitude of phasic dopamine release in adulthood. Large dopamine transients may result in more extracellular dopamine after alcohol challenge in adolescent-exposed rats, and may be one mechanism by which alcohol is more reinforcing in people who initiated drinking at an early age. PMID:26487039

Patterns of sarcomere activation, temperature dependence, and effect of ryanodine in chemically skinned cardiac fibers

PubMed Central

1986-01-01

Functionally skinned and electrochemically shunted myocytes were prepared by perfusing rat hearts with collagenase in order to obtain a technically improved measurement of sarcomere dynamics and to evaluate the role of sarcoplasmic reticulum in situ with respect to contractile activation. In the presence of micromolar calcium, the myocytes exhibited phasic and propagated contraction waves beginning at one end and proceeding along the myocyte. Beating rates, the propagation velocity of the activation wave, and single sarcomere shortening and relaxation velocities were obtained by manual or automated analysis of 16-mm film recorded at 170 frames/s from a camera attached to a microscope that was equipped with a temperature-controlled stage. In parallel experiments, calcium accumulation by the sarcoplasmic reticulum of the myocytes in situ was measured by direct isotopic tracer methods. The frequency (10-38 min-1) of spontaneous contractions, the velocity (1.9-7.4 microns . s-1) of sarcomere shortening, and the velocity (1.7-6.8 microns . s-1) of sarcomere relaxation displayed identical temperature dependences (Q10 = 2.2), which are similar to that of the calcium pump of sarcoplasmic reticulum and are consistent with a rate limit imposed by enzyme-catalyzed mechanisms on all these parameters. On the other hand, the velocity (77- 159 microns . s-1) of sequential sarcomere activation displayed a lower temperature dependence (Q10 = 1.5), which is consistent with a diffusion-limited and self-propagating release of calcium from one sarcomere to the other. The phasic contractile activity of the dissociated myocytes was inhibited by 10(-8)-10(6) M ryanodine (and not by myolemmal calcium blockers) under conditions in which calcium accumulation by sarcoplasmic reticulum in situ was demonstrated to proceed optimally. The effect of ryanodine is attributed to an interaction of this drug with sarcotubular structures, producing inhibition of calcium release from the sarcoplasmic reticulum. The consequent lack of sarcomere activation underlines the role of sarcoplasmic reticulum uptake and release in the phasic contractile activation of the electrochemically shunted myocytes. PMID:3522803

Phasic vs Sustained Fear in Rats and Humans: Role of the Extended Amygdala in Fear vs Anxiety

PubMed Central

Davis, Michael; Walker, David L; Miles, Leigh; Grillon, Christian

2010-01-01

Data will be reviewed using the acoustic startle reflex in rats and humans based on our attempts to operationally define fear vs anxiety. Although the symptoms of fear and anxiety are very similar, they also differ. Fear is a generally adaptive state of apprehension that begins rapidly and dissipates quickly once the threat is removed (phasic fear). Anxiety is elicited by less specific and less predictable threats, or by those that are physically or psychologically more distant. Thus, anxiety is a more long-lasting state of apprehension (sustained fear). Rodent studies suggest that phasic fear is mediated by the amygdala, which sends outputs to the hypothalamus and brainstem to produce symptoms of fear. Sustained fear is also mediated by the amygdala, which releases corticotropin-releasing factor, a stress hormone that acts on receptors in the bed nucleus of the stria terminalis (BNST), a part of the so-called ‘extended amygdala.' The amygdala and BNST send outputs to the same hypothalamic and brainstem targets to produce phasic and sustained fear, respectively. In rats, sustained fear is more sensitive to anxiolytic drugs. In humans, symptoms of clinical anxiety are better detected in sustained rather than phasic fear paradigms. PMID:19693004

Do β3-adrenergic receptors play a role in guinea pig detrusor smooth muscle excitability and contractility?

PubMed Central

Afeli, Serge A. Y.; Hristov, Kiril L.

2012-01-01

In many species, β3-adrenergic receptors (β3-ARs) have been reported to play a primary role in pharmacologically induced detrusor smooth muscle (DSM) relaxation. However, their role in guinea pig DSM remains controversial. The aim of this study was to investigate whether β3-ARs are expressed in guinea pig DSM and to evaluate how BRL37344 and L-755,507, two selective β3-AR agonists, modulate guinea pig DSM excitability and contractility. We used a combined experimental approach including RT-PCR, patch-clamp electrophysiology, and isometric DSM tension recordings. β3-AR mRNA message was detected in freshly isolated guinea pig DSM single cells. BRL37344 but not L-755,507 caused a slight decrease in DSM spontaneous phasic contraction amplitude and frequency in a concentration-dependent manner. In the presence of atropine (1 μM), only the spontaneous phasic contractions frequency was inhibited by BRL37344 at higher concentrations. Both BRL37344 and L-755,507 significantly decreased DSM carbachol-induced phasic and tonic contractions in a concentration-dependent manner. However, only BRL37344 inhibitory effect was partially antagonized by SR59230A (10 μM), a β3-AR antagonist. In the presence of atropine, BRL37344 and L-755,507 had no inhibitory effect on electrical field stimulation-induced contractions. Patch-clamp experiments showed that BRL37344 (100 μM) did not affect the DSM cell resting membrane potential and K+ conductance. Although β3-ARs are expressed at the mRNA level, they play a minor to no role in guinea pig DSM spontaneous contractility without affecting cell excitability. However, BRL37344 and L-755,507 have pronounced inhibitory effects on guinea pig DSM carbachol-induced contractions. The study outlines important DSM β3-ARs species differences. PMID:21993887

Smartphone application for multi-phasic interventional trials in psychiatry: Technical design of a smart server.

PubMed

Zhang, Melvyn W B; Ho, Roger C M

2017-01-01

Smartphones and their accompanying applications are currently widely utilized in various healthcare interventions. Prior to the deployment of these tools for healthcare intervention, typically, proof of concept feasibility studies, as well as randomized trials are conducted to determine that these tools are efficacious prior to their actual implementation. In the field of psychiatry, most of the current interventions seek to compare smartphone based intervention against conventional care. There remains a paucity of research evaluating different forms of interventions using a single smartphone application. In the field of nutrition, there has been recent pioneering research demonstrating how a multi-phasic randomized controlled trial could be conducted using a single smartphone application. Despite the innovativeness of the previous smartphone conceptualization, there remains a paucity of technical information underlying the conceptualization that would support a multi-phasic interventional trial. It is thus the aim of the current technical note to share insights into an innovative server design that would enable the delivery of multi-phasic trials.

Dynamic modulation of decision biases by brainstem arousal systems.

PubMed

de Gee, Jan Willem; Colizoli, Olympia; Kloosterman, Niels A; Knapen, Tomas; Nieuwenhuis, Sander; Donner, Tobias H

2017-04-11

Decision-makers often arrive at different choices when faced with repeated presentations of the same evidence. Variability of behavior is commonly attributed to noise in the brain's decision-making machinery. We hypothesized that phasic responses of brainstem arousal systems are a significant source of this variability. We tracked pupil responses (a proxy of phasic arousal) during sensory-motor decisions in humans, across different sensory modalities and task protocols. Large pupil responses generally predicted a reduction in decision bias. Using fMRI, we showed that the pupil-linked bias reduction was (i) accompanied by a modulation of choice-encoding pattern signals in parietal and prefrontal cortex and (ii) predicted by phasic, pupil-linked responses of a number of neuromodulatory brainstem centers involved in the control of cortical arousal state, including the noradrenergic locus coeruleus. We conclude that phasic arousal suppresses decision bias on a trial-by-trial basis, thus accounting for a significant component of the variability of choice behavior.

Dynamic modulation of decision biases by brainstem arousal systems

PubMed Central

de Gee, Jan Willem; Colizoli, Olympia; Kloosterman, Niels A; Knapen, Tomas; Nieuwenhuis, Sander; Donner, Tobias H

2017-01-01

Decision-makers often arrive at different choices when faced with repeated presentations of the same evidence. Variability of behavior is commonly attributed to noise in the brain’s decision-making machinery. We hypothesized that phasic responses of brainstem arousal systems are a significant source of this variability. We tracked pupil responses (a proxy of phasic arousal) during sensory-motor decisions in humans, across different sensory modalities and task protocols. Large pupil responses generally predicted a reduction in decision bias. Using fMRI, we showed that the pupil-linked bias reduction was (i) accompanied by a modulation of choice-encoding pattern signals in parietal and prefrontal cortex and (ii) predicted by phasic, pupil-linked responses of a number of neuromodulatory brainstem centers involved in the control of cortical arousal state, including the noradrenergic locus coeruleus. We conclude that phasic arousal suppresses decision bias on a trial-by-trial basis, thus accounting for a significant component of the variability of choice behavior. DOI: http://dx.doi.org/10.7554/eLife.23232.001 PMID:28383284

Sampling phasic dopamine signaling with fast-scan cyclic voltammetry in awake behaving rats

PubMed Central

Fortin, SM; Cone, JJ; Ng-Evans, S; McCutcheon, JE; Roitman, MF

2015-01-01

Fast-scan cyclic voltammetry (FSCV) is an electrochemical technique which permits the in vivo measurement of extracellular fluctuations in multiple chemical species. The technique is frequently utilized to sample sub-second (phasic) concentration changes of the neurotransmitter dopamine in awake and behaving rats. Phasic dopamine signaling is implicated in reinforcement, goal-directed behavior, and locomotion and FSCV has been used to investigate how rapid changes in striatal dopamine concentration contribute to these and other behaviors. This unit describes the instrumentation and construction, implantation, and use of necessary components required to sample and analyze dopamine concentration changes in awake rats with FSCV. PMID:25559005

Effects of dietary tryptophan and phenylalanine-tyrosine depletion on phasic alertness in healthy adults - A pilot study.

PubMed

Hildebrand, Patricia; Königschulte, Werner; Gaber, Tilman Jakob; Bubenzer-Busch, Sarah; Helmbold, Katrin; Biskup, Caroline Sarah; Langen, Karl-Josef; Fink, Gereon Rudolf; Zepf, Florian Daniel

2015-01-01

The synthesis of the neurotransmitters serotonin (5-HT) and dopamine (DA) in the brain can be directly altered by dietary manipulation of their relevant precursor amino acids (AA). There is evidence that altered serotonergic and dopaminergic neurotransmission are both associated with impaired attentional control. Specifically, phasic alertness is one specific aspect of attention that has been linked to changes in 5-HT and DA availability in different neurocircuitries related to attentional processes. The present study investigated the impact of short-term reductions in central nervous system 5-HT and DA synthesis, which was achieved by dietary depletion of the relevant precursor AA, on phasic alertness in healthy adult volunteers; body weight-adapted dietary tryptophan and phenylalanine-tyrosine depletion (PTD) techniques were used. The study employed a double-blind between-subject design. Fifty healthy male and female subjects were allocated to three groups in a randomized and counterbalanced manner and received three different dietary challenge conditions: acute tryptophan depletion (ATD, for the depletion of 5-HT; N=16), PTD (for the depletion of DA; N=17), and a balanced AA load (BAL; N=17), which served as a control condition. Three hours after challenge intake (ATD/PTD/BAL), phasic alertness was assessed using a standardized test battery for attentional performance (TAP). Blood samples for AA level analyses were obtained at baseline and 360 min after the challenge intake. Overall, there were no significant differences in phasic alertness for the different challenge conditions. Regarding PTD administration, a positive correlation between the reaction times and the DA-related depletion magnitude was detected via the lower plasma tyrosine levels and the slow reaction times of the first run of the task. In contrast, higher tryptophan concentrations were associated with slower reaction times in the fourth run of the task in the same challenge group. The present study is the first to demonstrate preliminary data that support an association between decreased central nervous system DA synthesis, which was achieved by dietary depletion strategies, and slower reaction times in specific runs of a task designed to assess phasic alertness in healthy adult volunteers; these findings are consistent with previous evidence that links phasic alertness with dopaminergic neurotransmission. A lack of significant differences between the three groups could be due to compensatory mechanisms and the limited sample size, as well as the dietary challenge procedures administered to healthy participants and the strict exclusion criteria used. The potential underlying neurochemical processes related to phasic alertness should be the subject of further investigations.

The effect of phasic auditory alerting on visual perception.

PubMed

Petersen, Anders; Petersen, Annemarie Hilkjær; Bundesen, Claus; Vangkilde, Signe; Habekost, Thomas

2017-08-01

Phasic alertness refers to a short-lived change in the preparatory state of the cognitive system following an alerting signal. In the present study, we examined the effect of phasic auditory alerting on distinct perceptual processes, unconfounded by motor components. We combined an alerting/no-alerting design with a pure accuracy-based single-letter recognition task. Computational modeling based on Bundesen's Theory of Visual Attention was used to examine the effect of phasic alertness on visual processing speed and threshold of conscious perception. Results show that phasic auditory alertness affects visual perception by increasing the visual processing speed and lowering the threshold of conscious perception (Experiment 1). By manipulating the intensity of the alerting cue, we further observed a positive relationship between alerting intensity and processing speed, which was not seen for the threshold of conscious perception (Experiment 2). This was replicated in a third experiment, in which pupil size was measured as a physiological marker of alertness. Results revealed that the increase in processing speed was accompanied by an increase in pupil size, substantiating the link between alertness and processing speed (Experiment 3). The implications of these results are discussed in relation to a newly developed mathematical model of the relationship between levels of alertness and the speed with which humans process visual information. Copyright © 2017 Elsevier B.V. All rights reserved.

Molecular Expression and Pharmacological Evidence for a Functional Role of Kv7 Channel Subtypes in Guinea Pig Urinary Bladder Smooth Muscle

PubMed Central

Afeli, Serge A. Y.; Malysz, John; Petkov, Georgi V.

2013-01-01

Voltage-gated Kv7 (KCNQ) channels are emerging as essential regulators of smooth muscle excitability and contractility. However, their physiological role in detrusor smooth muscle (DSM) remains to be elucidated. Here, we explored the molecular expression and function of Kv7 channel subtypes in guinea pig DSM by RT-PCR, qRT-PCR, immunohistochemistry, electrophysiology, and isometric tension recordings. In whole DSM tissue, mRNAs for all Kv7 channel subtypes were detected in a rank order: Kv7.1~Kv7.2Kv7.3~Kv7.5Kv7.4. In contrast, freshly-isolated DSM cells showed mRNA expression of: Kv7.1~Kv7.2Kv7.5Kv7.3~Kv7.4. Immunohistochemical confocal microscopy analyses of DSM, conducted by using co-labeling of Kv7 channel subtype-specific antibodies and α-smooth muscle actin, detected protein expression for all Kv7 channel subtypes, except for the Kv7.4, in DSM cells. L-364373 (R-L3), a Kv7.1 channel activator, and retigabine, a Kv7.2-7.5 channel activator, inhibited spontaneous phasic contractions and the 10-Hz electrical field stimulation (EFS)-induced contractions of DSM isolated strips. Linopiridine and XE991, two pan-Kv7 (effective at Kv7.1-Kv7.5 subtypes) channel inhibitors, had opposite effects increasing DSM spontaneous phasic and 10 Hz EFS-induced contractions. EFS-induced DSM contractions generated by a wide range of stimulation frequencies were decreased by L-364373 (10 µM) or retigabine (10 µM), and increased by XE991 (10 µM). Retigabine (10 µM) induced hyperpolarization and inhibited spontaneous action potentials in freshly-isolated DSM cells. In summary, Kv7 channel subtypes are expressed at mRNA and protein levels in guinea pig DSM cells. Their pharmacological modulation can control DSM contractility and excitability; therefore, Kv7 channel subtypes provide potential novel therapeutic targets for urinary bladder dysfunction. PMID:24073284

Tonic signaling from O2 sensors sets neural circuit activity and behavioral state

PubMed Central

Busch, Karl Emanuel; Laurent, Patrick; Soltesz, Zoltan; Murphy, Robin Joseph; Faivre, Olivier; Hedwig, Berthold; Thomas, Martin; Smith, Heather L.; de Bono, Mario

2012-01-01

Tonic receptors convey stimulus duration and intensity and are implicated in homeostatic control. However, how tonic homeostatic signals are generated, and how they reconfigure neural circuits and modify animal behavior is poorly understood. Here we show that C. elegans O2-sensing neurons are tonic receptors that continuously signal ambient [O2] to set the animal’s behavioral state. Sustained signalling relies on a Ca2+ relay involving L-type voltage-gated Ca2+ channels, the ryanodine and the IP3 receptors. Tonic activity evokes continuous neuropeptide release, which helps elicit the enduring behavioral state associated with high [O2]. Sustained O2 receptor signalling is propagated to downstream neural circuits, including the hub interneuron RMG. O2 receptors evoke similar locomotory states at particular [O2], regardless of previous d[O2]/dt. However, a phasic component of the URX receptors’ response to high d[O2]/dt, as well as tonic-to-phasic transformations in downstream interneurons, enable transient reorientation movements shaped by d[O2]/dt. Our results highlight how tonic homeostatic signals can generate both transient and enduring behavioral change. PMID:22388961

The Relevance of Interoception in Chronic Tinnitus: Analyzing Interoceptive Sensibility and Accuracy

PubMed Central

Lau, Pia; Miesen, Miriam; Wunderlich, Robert; Stein, Alwina; Engell, Alva; Gerlach, Alexander L.; Junghöfer, Markus; Ehring, Thomas

2015-01-01

In order to better understand tinnitus and distress associated with tinnitus, psychological variables such as emotional and cognitive processing are a central element in theoretical models of this debilitating condition. Interoception, that is, the perception of internal processes, may be such a psychological factor relevant to tinnitus. Against this background, 20 participants suffering from chronic tinnitus and 20 matched healthy controls were tested with questionnaires, assessing interoceptive sensibility, and participated in two tasks, assessing interoceptive accuracy: the Schandry task, a heartbeat estimation assignment, and a skin conductance fluctuations perception task assessing the participants' ability to perceive phasic increases in sympathetic activation were used. To test stress reactivity, a construct tightly connected to tinnitus onset, we also included a stress induction. No differences between the groups were found for interoceptive accuracy and sensibility. However, the tinnitus group tended to overestimate the occurrence of phasic activation. Loudness of the tinnitus was associated with reduced interoceptive performance under stress. Our results indicate that interoceptive sensibility and accuracy do not play a significant role in tinnitus. However, tinnitus might be associated with a tendency to overestimate physical changes. PMID:26583114

A Physiological Approach to the Study of Human Information Processing.

ERIC Educational Resources Information Center

Fletcher, James E.

Soviet neuropsychologist Sokolov's notions of tonic and phasic orienting responses and of defense responses are examined for relevance to individual information processing. The phasic orienting response provides an index to attention and to information demands generated by the cerebral cortex. The sum of orienting responses elicted by a message…

An open-source LabVIEW application toolkit for phasic heart rate analysis in psychophysiological research.

PubMed

Duley, Aaron R; Janelle, Christopher M; Coombes, Stephen A

2004-11-01

The cardiovascular system has been extensively measured in a variety of research and clinical domains. Despite technological and methodological advances in cardiovascular science, the analysis and evaluation of phasic changes in heart rate persists as a way to assess numerous psychological concomitants. Some researchers, however, have pointed to constraints on data analysis when evaluating cardiac activity indexed by heart rate or heart period. Thus, an off-line application toolkit for heart rate analysis is presented. The program, written with National Instruments' LabVIEW, incorporates a variety of tools for off-line extraction and analysis of heart rate data. Current methods and issues concerning heart rate analysis are highlighted, and how the toolkit provides a flexible environment to ameliorate common problems that typically lead to trial rejection is discussed. Source code for this program may be downloaded from the Psychonomic Society Web archive at www.psychonomic.org/archive/.

Temporally Coordinated Deep Brain Stimulation in the Dorsal and Ventral Striatum Synergistically Enhances Associative Learning.

PubMed

Katnani, Husam A; Patel, Shaun R; Kwon, Churl-Su; Abdel-Aziz, Samer; Gale, John T; Eskandar, Emad N

2016-01-04

The primate brain has the remarkable ability of mapping sensory stimuli into motor behaviors that can lead to positive outcomes. We have previously shown that during the reinforcement of visual-motor behavior, activity in the caudate nucleus is correlated with the rate of learning. Moreover, phasic microstimulation in the caudate during the reinforcement period was shown to enhance associative learning, demonstrating the importance of temporal specificity to manipulate learning related changes. Here we present evidence that extends upon our previous finding by demonstrating that temporally coordinated phasic deep brain stimulation across both the nucleus accumbens and caudate can further enhance associative learning. Monkeys performed a visual-motor associative learning task and received stimulation at time points critical to learning related changes. Resulting performance revealed an enhancement in the rate, ceiling, and reaction times of learning. Stimulation of each brain region alone or at different time points did not generate the same effect.

Pyloric motor response to central and peripheral nitric oxide in the ferret.

PubMed

Lingenfelser, T; Blackshaw, L A; Sun, W M; Dent, J

1997-09-01

This study has investigated the relative importance of central nervous and peripheral nitroxidergic mechanisms in the control of pyloric motility. In 10 urethane-anaesthetized ferrets, drugs were administered directly to the CNS via a 0.5-mm-diameter cannula inserted into the 4th ventricle, approximately at the obex. Drugs were also given directly to the upper GI tract by close intra-arterial (i.a.) injection at the coeliac axis. Antropyloroduodenal pressures were recorded with a five-channel sleeve/sidehole micromanometric assembly (1.35 x 1.75 mm o.d.), which was introduced via the duodenum. Pyloric motility was stimulated throughout the main part of each study with a continuous i.v. infusion of CCK-8 (30 pmol min-1). This infusion produced an immediate and sustained increase in tonic and phasic pyloric activity, and sustained abolition of antral pressure waves. CCK-8 also induced a duodenal motor response, but this was short-lived (11.4 +/- 7.9 min). Coeliac axis injection of the NO donor S-nitroso-N-acetyl-penicillamine (SNAP) decreased phasic pyloric activity (from 330 +/- 35 to 148 +/- 21 mmHg min-1 after SNAP 5 micrograms, P < 0.01). By comparison central SNAP administration over the same dose range had no effect on CCK-stimulated pyloric motlity. Inhibition of endogenous NO synthase with L-Nitro Arginine Methyl Ester (L-NAME, 100 mg kg-1 close i.a.) caused a marked increase of phase pyloric motor activity from 349 +/- 59 to 1044 +/- 140 mmHg min-1 (P < 0.01). In addition, SNAP caused marked stimulation of pyloric tone from 2.6 +/- 0.5 to 13.1 +/- 2.8 mmHg (P < 0.01). Central nervous administration of L-NAME caused modest enhancement of phasic pyloric activity (248 +/- 31 to 283 +/- 32 mmHg min-1 P < 0.05) and pyloric tone (2.6 +/- 0.5 to 3.7 +/- 0.7 mmHg, P < 0.05). Our data indicate that motor activity of the ferret pylorus is potently modulated by NO released within the upper gut. Additionally, there is potential for modulation of pyloric motility by central nervous system production of NO.

Color-Change Detection Activity in the Primate Superior Colliculus.

PubMed

Herman, James P; Krauzlis, Richard J

2017-01-01

The primate superior colliculus (SC) is a midbrain structure that participates in the control of spatial attention. Previous studies examining the role of the SC in attention have mostly used luminance-based visual features (e.g., motion, contrast) as the stimuli and saccadic eye movements as the behavioral response, both of which are known to modulate the activity of SC neurons. To explore the limits of the SC's involvement in the control of spatial attention, we recorded SC neuronal activity during a task using color, a visual feature dimension not traditionally associated with the SC, and required monkeys to detect threshold-level changes in the saturation of a cued stimulus by releasing a joystick during maintained fixation. Using this color-based spatial attention task, we found substantial cue-related modulation in all categories of visually responsive neurons in the intermediate layers of the SC. Notably, near-threshold changes in color saturation, both increases and decreases, evoked phasic bursts of activity with magnitudes as large as those evoked by stimulus onset. This change-detection activity had two distinctive features: activity for hits was larger than for misses, and the timing of change-detection activity accounted for 67% of joystick release latency, even though it preceded the release by at least 200 ms. We conclude that during attention tasks, SC activity denotes the behavioral relevance of the stimulus regardless of feature dimension and that phasic event-related SC activity is suitable to guide the selection of manual responses as well as saccadic eye movements.

Sampling phasic dopamine signaling with fast-scan cyclic voltammetry in awake, behaving rats.

PubMed

Fortin, S M; Cone, J J; Ng-Evans, S; McCutcheon, J E; Roitman, M F

2015-01-05

Fast-scan cyclic voltammetry (FSCV) is an electrochemical technique that permits the in vivo measurement of extracellular fluctuations in multiple chemical species. The technique is frequently utilized to sample sub-second (phasic) concentration changes of the neurotransmitter dopamine in awake and behaving rats. Phasic dopamine signaling is implicated in reinforcement, goal-directed behavior, and locomotion, and FSCV has been used to investigate how rapid changes in striatal dopamine concentration contribute to these and other behaviors. This unit describes the instrumentation and construction, implantation, and use of components required to sample and analyze dopamine concentration changes in awake rats with FSCV. Copyright © 2015 John Wiley & Sons, Inc.

Neuroethology and life history adaptations of the elasmobranch electric sense.

PubMed

Sisneros, Joseph A; Tricas, Timothy C

2002-01-01

The electric sense of elasmobranch fishes (sharks and rays) is an important sensory modality known to mediate the detection of bioelectric stimuli. Although the best known function for the use of the elasmobranch electric sense is prey detection, relatively few studies have investigated other possible biological functions. Here, we review recent studies that demonstrate the elasmobranch electrosensory system functions in a wide number of behavioral contexts including social, reproductive and anti-predator behaviors. Recent work on non-electrogenic stingrays demonstrates that the electric sense is used during reproduction and courtship for conspecific detection and localization. Electrogenic skates may use their electrosensory encoding capabilities and electric organ discharges for communication during social and reproductive interactions. The electric sense may also be used to detect and avoid predators during early life history stages in many elasmobranch species. Embryonic clearnose skates demonstrate a ventilatory freeze response when a weak low-frequency electric field is imposed upon the egg capsule. Peak frequency sensitivity of the peripheral electrosensory system in embryonic skates matches the low frequencies of phasic electric stimuli produced by natural fish egg-predators. Neurophysiology experiments reveal that electrosensory tuning changes across the life history of a species and also seasonally due to steroid hormone changes during the reproductive season. We argue that the ontogenetic and seasonal variation in electrosensory tuning represent an adaptive electrosensory plasticity that may be common to many elasmobranchs to enhance an individual's fitness throughout its life history.

Development of a closed-loop system for tremor suppression in patients with Parkinson's disease.

PubMed

Xu, F L; Hao, M Z; Xu, S Q; Hu, Z X; Xiao, Q; Lan, N

2016-08-01

More than 70% of patients suffering Parkinson's disease (PD) exhibit resting tremor in their extremities, hampering their ability to perform daily activities. Based on our earlier studies on corticospinal transmission of tremor signals [10,11], we hypothesize that cutaneous afferents evoked by surface stimulation can produce an inhibitory effect on propriospinal neurons (PN), which in turn will suppress tremor signals passing through the PN. This paper presents the development of a closed-loop system for tremor suppression by transcutaneous electrical nerve stimulation (TENS) of sensory fibers beneath the skin. The closed-loop system senses EMGs of forearm muscles, and detects rhythmic bursting in the EMG signal. When a tremor is detected by the system, a command signal triggers a stimulator to output a train of bi-phasic, current regulated pulses to a pair of surface electrodes. The stimulation electrode is placed on the dorsal hand skin near the metacarpophalangeal joint of index finger, which is innervated by the superficial radial nerve that projects an inhibitory afferent to PNs of forearm muscles. We tested the closed-loop system in 3 normal subjects to verify the algorithm and in 2 tremor dominated PD subjects for feasibility of tremor detecting and suppression. Preliminary results indicate that the closed-loop system can detect tremor in all subjects, and tremor in PD patients was suppressed significantly by electrical stimulation of cutaneous afferents.

Phasic dopamine as a prediction error of intrinsic and extrinsic reinforcements driving both action acquisition and reward maximization: a simulated robotic study.

PubMed

Mirolli, Marco; Santucci, Vieri G; Baldassarre, Gianluca

2013-03-01

An important issue of recent neuroscientific research is to understand the functional role of the phasic release of dopamine in the striatum, and in particular its relation to reinforcement learning. The literature is split between two alternative hypotheses: one considers phasic dopamine as a reward prediction error similar to the computational TD-error, whose function is to guide an animal to maximize future rewards; the other holds that phasic dopamine is a sensory prediction error signal that lets the animal discover and acquire novel actions. In this paper we propose an original hypothesis that integrates these two contrasting positions: according to our view phasic dopamine represents a TD-like reinforcement prediction error learning signal determined by both unexpected changes in the environment (temporary, intrinsic reinforcements) and biological rewards (permanent, extrinsic reinforcements). Accordingly, dopamine plays the functional role of driving both the discovery and acquisition of novel actions and the maximization of future rewards. To validate our hypothesis we perform a series of experiments with a simulated robotic system that has to learn different skills in order to get rewards. We compare different versions of the system in which we vary the composition of the learning signal. The results show that only the system reinforced by both extrinsic and intrinsic reinforcements is able to reach high performance in sufficiently complex conditions. Copyright © 2013 Elsevier Ltd. All rights reserved.

A tonic heat test stimulus yields a larger and more reliable conditioned pain modulation effect compared to a phasic heat test stimulus

PubMed Central

Lie, Marie Udnesseter; Matre, Dagfinn; Hansson, Per; Stubhaug, Audun; Zwart, John-Anker; Nilsen, Kristian Bernhard

2017-01-01

Abstract Introduction: The interest in conditioned pain modulation (CPM) as a clinical tool for measuring endogenously induced analgesia is increasing. There is, however, large variation in the CPM methodology, hindering comparison of results across studies. Research comparing different CPM protocols is needed in order to obtain a standardized test paradigm. Objectives: The aim of the study was to assess whether a protocol with phasic heat stimuli as test-stimulus is preferable to a protocol with tonic heat stimulus as test-stimulus. Methods: In this experimental crossover study, we compared 2 CPM protocols with different test-stimulus; one with tonic test-stimulus (constant heat stimulus of 120-second duration) and one with phasic test-stimuli (3 heat stimulations of 5 seconds duration separated by 10 seconds). Conditioning stimulus was a 7°C water bath in parallel with the test-stimulus. Twenty-four healthy volunteers were assessed on 2 occasions with minimum 1 week apart. Differences in the magnitude and test–retest reliability of the CPM effect in the 2 protocols were investigated with repeated-measures analysis of variance and by relative and absolute reliability indices. Results: The protocol with tonic test-stimulus induced a significantly larger CPM effect compared to the protocol with phasic test-stimuli (P < 0.001). Fair and good relative reliability was found with the phasic and tonic test-stimuli, respectively. Absolute reliability indices showed large intraindividual variability from session to session in both protocols. Conclusion: The present study shows that a CPM protocol with a tonic test-stimulus is preferable to a protocol with phasic test-stimuli. However, we emphasize that one should be cautious to use the CPM effect as biomarker or in clinical decision making on an individual level due to large intraindividual variability. PMID:29392240

Neural correlates of the behavioral-autonomic interaction response to potentially threatening stimuli

PubMed Central

Farrow, Tom F. D.; Johnson, Naomi K.; Hunter, Michael D.; Barker, Anthony T.; Wilkinson, Iain D.; Woodruff, Peter W. R.

2013-01-01

Subjective assessment of emotional valence is typically associated with both brain activity and autonomic arousal. Accurately assessing emotional salience is particularly important when perceiving threat. We sought to characterize the neural correlates of the interaction between behavioral and autonomic responses to potentially threatening visual and auditory stimuli. Twenty-five healthy male subjects underwent fMRI scanning whilst skin conductance responses (SCR) were recorded. One hundred and eighty pictures, sentences, and sounds were assessed as “harmless” or “threatening.” Individuals' stimulus-locked, phasic SCRs and trial-by-trial behavioral assessments were entered as regressors into a flexible factorial design to establish their separate autonomic and behavioral neural correlates, and convolved to examine psycho-autonomic interaction (PAI) effects. Across all stimuli, “threatening,” compared with “harmless” behavioral assessments were associated with mainly frontal and precuneus activation with specific within-modality activations including bilateral parahippocampal gyri (pictures), bilateral anterior cingulate cortex (ACC) and frontal pole (sentences), and right Heschl's gyrus and bilateral temporal gyri (sounds). Across stimulus modalities SCRs were associated with activation of parieto-occipito-thalamic regions, an activation pattern which was largely replicated within-modality. In contrast, PAI analyses revealed modality-specific activations including right fusiform/parahippocampal gyrus (pictures), right insula (sentences), and mid-cingulate gyrus (sounds). Phasic SCR activity was positively correlated with an individual's propensity to assess stimuli as “threatening.” SCRs may modulate cognitive assessments on a “harmless–threatening” dimension, thereby modulating affective tone and hence behavior. PMID:23335893

Phorbol 12,13-dibutyrate-induced protein kinase C activation triggers sustained contracture in human myometrium in vitro.

PubMed

Massenavette, Laurence; Paul, Wilène; Corriveau, Stéphanie; Pasquier, Jean-Charles; Rousseau, Éric

2017-09-01

Although physiologic transition from rhythmic contractions to uterine retraction postpartum remains a poorly understood process, it has been shown that the latter is essential in the prevention of hemorrhage and its negative consequences. To investigate the transition from oscillatory contractions to tonic contracture in human myometrium after delivery, a mechanism purported to facilitate postpartum hemostasis. Protein kinase C (PKC) plays a key regulatory role in human uterine contractions because it can prevent dephosphorylation of regulatory proteins and sensitize the contractile machinery to low Ca 2+ . Thus, activation of PKC by phorbol 12,13-dibutyrate (PDBu) may act as a strong uterotonic agent. Uterine biopsies were obtained from consenting women undergoing elective caesarian delivery at term without labor (N = 19). Isometric tension measurements were performed on uterine strips (n = 114). The amplitudes and area under the curve of phasic contractions and tonic responses were measured and compared. A total of 1 μM PDBu was added to the isolated organ baths, and maximal tension of the uterine contracture was determined in the absence and presence of either 1 μM of staurosporine, 100 nM nifedipine, or 10 μM cyclopiazonic acid to assess the role of PKC and calcium sensitivity on uterine contractility. On the addition of PDBu on either basal or oxytocin-induced activity, consistent contractures were obtained concomitant with complete inhibition of phasic contractions. After a 30-minute incubation period, the mean amplitude of the PDBu-induced tone represented 65.3% of the amplitude of spontaneous contraction. Staurosporine, a protein kinase inhibitor, induced a 91.9% inhibition of PDBu contractures, a process not affected by nifedipine or cyclopiazonic acid, thus indicating that this mechanism is largely Ca 2+ independent. Pharmacologic activation of PKC leads to a significant contracture of the myometrium. Together, these data suggest that the up-regulation of PKC plays a physiologic role in the modulation of uterine contracture after delivery. A switch from phasic to strong tonic contractions potentially may facilitate postpartum hemostasis. Copyright © 2017 Elsevier Inc. All rights reserved.

Pramipexole enhances disadvantageous decision-making: Lack of relation to changes in phasic dopamine release.

PubMed

Pes, Romina; Godar, Sean C; Fox, Andrew T; Burgeno, Lauren M; Strathman, Hunter J; Jarmolowicz, David P; Devoto, Paola; Levant, Beth; Phillips, Paul E; Fowler, Stephen C; Bortolato, Marco

2017-03-01

Pramipexole (PPX) is a high-affinity D 2 -like dopamine receptor agonist, used in the treatment of Parkinson's disease (PD) and restless leg syndrome. Recent evidence indicates that PPX increases the risk of problem gambling and impulse-control disorders in vulnerable patients. Although the molecular bases of these complications remain unclear, several authors have theorized that PPX may increase risk propensity by activating presynaptic dopamine receptors in the mesolimbic system, resulting in the reduction of dopamine release in the nucleus accumbens (NAcc). To test this possibility, we subjected rats to a probability-discounting task specifically designed to capture the response to disadvantageous options. PPX enhanced disadvantageous decision-making at a dose (0.3 mg/kg/day, SC) that reduced phasic dopamine release in the NAcc. To test whether these modifications in dopamine efflux were responsible for the observed neuroeconomic deficits, PPX was administered in combination with the monoamine-depleting agent reserpine (RES), at a low dose (1 mg/kg/day, SC) that did not affect baseline locomotor and operant responses. Contrary to our predictions, RES surprisingly exacerbated the effects of PPX on disadvantageous decision-making, even though it failed to augment PPX-induced decreases in phasic dopamine release. These results collectively suggest that PPX impairs the discounting of probabilistic losses and that the enhancement in risk-taking behaviors secondary to this drug may be dissociated from dynamic changes in mesolimbic dopamine release. Copyright © 2016 Elsevier Ltd. All rights reserved.

Neural Mechanisms Supporting Acquired Phasic Dopamine Responses in Learning: An Integrative Synthesis

PubMed Central

Hazy, Thomas E.; Frank, Michael J.; O’Reilly, Randall C.

2010-01-01

What biological mechanisms underlie the reward-predictive firing properties of midbrain dopaminergic neurons, and how do they relate to the complex constellation of empirical findings understood as Pavlovian and instrumental conditioning? We previously presented PVLV, a biologically-inspired Pavlovian learning algorithm accounting for DA activity in terms of two interrelated systems: a primary value (PV) system, which governs how DA cells respond to a US (reward) and; a learned value (LV) system, which governs how DA cells respond to a CS. Here, we provide a more extensive review of the biological mechanisms supporting phasic DA firing and their relation to the spate of Pavlovian conditioning phenomena and their sensitivity to focal brain lesions. We further extend the model by incorporating a new NV (novelty value) component reflecting the ability of novel stimuli to trigger phasic DA firing, providing “novelty bonuses” which encourages exploratory working memory updating and in turn speeds learning in trace conditioning and other working memory-dependent paradigms. The evolving PVLV model builds upon insights developed in many earlier computational models, especially reinforcement learning models based on the ideas of Sutton and Barto, biological models, and the psychological model developed by Savastano and Miller. The PVLV framework synthesizes these various approaches, overcoming important shortcomings of each by providing a coherent and specific mapping to much of the relevant empirical data at both the micro- and macro-levels, and examines their relevance for higher order cognitive functions. PMID:19944716

Ponto-geniculo-occipital-wave suppression amplifies lateral geniculate nucleus cell-size changes in monocularly deprived kittens.

PubMed

Shaffery, J P; Roffwarg, H P; Speciale, S G; Marks, G A

1999-04-12

We have previously shown that during the post-natal critical period of development of the cat visual system, 1 week of instrumental rapid eye movement (REM) sleep deprivation (IRSD) during 2 weeks of monocular deprivation (MD) results in significant amplification of the effects of solely the 2-week MD on cell-size in the binocular segment of the lateral geniculate nucleus (LGN) [36,40]. In this study, we examined whether elimination of ponto-geniculo-occipital (PGO)-wave phasic activity in the LGN during REM sleep (REMS), rather than suppression of all REMS state-related activity, would similarly yield enhanced plasticity effects on cell-size in LGN. PGO-activity was eliminated in LGN by bilateral pontomesencephalic lesions [8,32]. This method of removing phasic activation at the level of the LGN preserved sleep and wake proportions as well as the tonic activities (low voltage, fast frequency ECoG and low amplitude EMG) that characterize REM sleep. The lesions were performed in kittens on post-natal day 42, at the end of the first week of the 2-week period of MD, the same age when IRSD was started in the earlier study. LGN interlaminar cell-size disparity increased in the PGO-wave-suppressed animals as it had in behaviorally REM sleep-deprived animals. Smaller A1/A-interlaminar ratios reflect the increased disparity effect in both the REM sleep- and PGO-suppressed groups compared to animals subjected to MD-alone. With IRSD, the effect was achieved because the occluded eye-related, LGN A1-lamina cells tended to be smaller relative to their size after MD-alone, whereas after PGO-suppressing lesions, the A1-lamina cells retained their size and the non-occluded eye-related, A-lamina cells tended to be larger than after MD-alone. Despite this difference, for which several possible explanations are offered, these A1/A-interlaminar ratio data indicate that in conjunction either with suppression of the whole of the REMS state or selective removal of REM sleep phasic activity at the LGN, altered visual input evokes more LGN cell plasticity during the developmental period than it would otherwise. These data further support involvement of the REM sleep state in reducing susceptibility to plasticity changes and undesirable variability in the course of normative CNS growth and maturation. Copyright 1999 Elsevier Science B.V.

Isobolographic analysis of the opioid-opioid interactions in a tonic and a phasic mouse model of induced nociceptive pain.

PubMed

Miranda, Hugo F; Noriega, Viviana; Zanetta, Pilar; Prieto, Juan Carlos; Prieto-Rayo, Juan Carlos; Aranda, Nicolás; Sierralta, Fernando

2014-07-15

Opioids have been used for the management of pain and coadministration of two opioids may induce synergism. In a model of tonic pain, the acetic acid writhing test and in a phasic model, the hot plate, the antinociceptive interaction between fentanyl, methadone, morphine, and tramadol was evaluated. The potency of opioids in the writhing test compared to the hot plate assay was from 2.5 (fentanyl) to 15.5 (morphine) times, respectively. The ED50 was used in a fixed ratio for each of the six pairs of opioid combinations, which, resulted in a synergistic antinociception except for methadone/tramadol and fentanyl/tramadol which were additive, in the hot plate. The opioid antagonists naltrexone, naltrindole and nor-binaltorphimine, suggests that the synergism of morphine combinations are due to the activation of MOR subtypes with partially contribution of DOR and KOR, however fentanyl and methadone combinations are partially due to the activation of MOR and DOR subtypes and KOR lack of participation. The antinociceptive effects of tramadol combinations, are partially due to the activation of MOR, DOR and KOR opioid subtypes. These results suggets that effectiveness and magnitude of the interactions between opioids are dependent on pain stimulus intensity.

Isobolographic analysis of the opioid-opioid interactions in a tonic and a phasic mouse model of induced nociceptive pain

PubMed Central

2014-01-01

Background Opioids have been used for the management of pain and coadministration of two opioids may induce synergism. In a model of tonic pain, the acetic acid writhing test and in a phasic model, the hot plate, the antinociceptive interaction between fentanyl, methadone, morphine, and tramadol was evaluated. Results The potency of opioids in the writhing test compared to the hot plate assay was from 2.5 (fentanyl) to 15.5 (morphine) times, respectively. The ED50 was used in a fixed ratio for each of the six pairs of opioid combinations, which, resulted in a synergistic antinociception except for methadone/tramadol and fentanyl/tramadol which were additive, in the hot plate. The opioid antagonists naltrexone, naltrindole and nor-binaltorphimine, suggests that the synergism of morphine combinations are due to the activation of MOR subtypes with partially contribution of DOR and KOR, however fentanyl and methadone combinations are partially due to the activation of MOR and DOR subtypes and KOR lack of participation. The antinociceptive effects of tramadol combinations, are partially due to the activation of MOR, DOR and KOR opioid subtypes. Conclusion These results suggets that effectiveness and magnitude of the interactions between opioids are dependent on pain stimulus intensity. PMID:25017386

Stimulus change detection in phasic auditory units in the frog midbrain: frequency and ear specific adaptation.

PubMed

Ponnath, Abhilash; Hoke, Kim L; Farris, Hamilton E

2013-04-01

Neural adaptation, a reduction in the response to a maintained stimulus, is an important mechanism for detecting stimulus change. Contributing to change detection is the fact that adaptation is often stimulus specific: adaptation to a particular stimulus reduces excitability to a specific subset of stimuli, while the ability to respond to other stimuli is unaffected. Phasic cells (e.g., cells responding to stimulus onset) are good candidates for detecting the most rapid changes in natural auditory scenes, as they exhibit fast and complete adaptation to an initial stimulus presentation. We made recordings of single phasic auditory units in the frog midbrain to determine if adaptation was specific to stimulus frequency and ear of input. In response to an instantaneous frequency step in a tone, 28% of phasic cells exhibited frequency specific adaptation based on a relative frequency change (delta-f=±16%). Frequency specific adaptation was not limited to frequency steps, however, as adaptation was also overcome during continuous frequency modulated stimuli and in response to spectral transients interrupting tones. The results suggest that adaptation is separated for peripheral (e.g., frequency) channels. This was tested directly using dichotic stimuli. In 45% of binaural phasic units, adaptation was ear specific: adaptation to stimulation of one ear did not affect responses to stimulation of the other ear. Thus, adaptation exhibited specificity for stimulus frequency and lateralization at the level of the midbrain. This mechanism could be employed to detect rapid stimulus change within and between sound sources in complex acoustic environments.

Orbitofrontal participation in sign- and goal-tracking conditioned responses: Effects of nicotine.

PubMed

Stringfield, Sierra J; Palmatier, Matthew I; Boettiger, Charlotte A; Robinson, Donita L

2017-04-01

Pavlovian conditioned stimuli can acquire incentive motivational properties, and this phenomenon can be measured in animals using Pavlovian conditioned approach behavior. Drugs of abuse can influence the expression of this behavior, and nicotine in particular exhibits incentive amplifying effects. Both conditioned approach behavior and drug abuse rely on overlapping corticolimbic circuitry. We hypothesize that the orbitofrontal cortex (OFC) regulates conditioned approach, and that one site of nicotine action is in the OFC where it reduces cortical output. To test this, we repeatedly exposed rats to 0.4 mg/kg nicotine (s.c.) during training and then pharmacologically inactivated the lateral OFC or performed in vivo electrophysiological recordings of lateral OFC neurons in the presence or absence of nicotine. In Experiment 1, animals were trained in a Pavlovian conditioning paradigm and behavior was evaluated after inactivation of the OFC by microinfusion of the GABA agonists baclofen and muscimol. In Experiment 2, we monitored phasic firing of OFC neurons during Pavlovian conditioning sessions. Nicotine reliably enhanced conditioned responding to the conditioned cue, and inactivation of the OFC reduced conditioned responding, especially the sign-tracking response. OFC neurons exhibited phasic excitations to cue presentation and during goal tracking, and nicotine acutely blunted this phasic neuronal firing. When nicotine was withheld, both conditioned responding and phasic firing in the OFC returned to the level of controls. These results suggest that the OFC is recruited for the expression of conditioned responses, and that nicotine acutely influences this behavior by reducing phasic firing in the OFC. Copyright © 2016 Elsevier Ltd. All rights reserved.

Stimulus change detection in phasic auditory units in the frog midbrain: frequency and ear specific adaptation

PubMed Central

Ponnath, Abhilash; Hoke, Kim L.

2013-01-01

Neural adaptation, a reduction in the response to a maintained stimulus, is an important mechanism for detecting stimulus change. Contributing to change detection is the fact that adaptation is often stimulus specific: adaptation to a particular stimulus reduces excitability to a specific subset of stimuli, while the ability to respond to other stimuli is unaffected. Phasic cells (e.g., cells responding to stimulus onset) are good candidates for detecting the most rapid changes in natural auditory scenes, as they exhibit fast and complete adaptation to an initial stimulus presentation. We made recordings of single phasic auditory units in the frog midbrain to determine if adaptation was specific to stimulus frequency and ear of input. In response to an instantaneous frequency step in a tone, 28 % of phasic cells exhibited frequency specific adaptation based on a relative frequency change (delta-f = ±16 %). Frequency specific adaptation was not limited to frequency steps, however, as adaptation was also overcome during continuous frequency modulated stimuli and in response to spectral transients interrupting tones. The results suggest that adaptation is separated for peripheral (e.g., frequency) channels. This was tested directly using dichotic stimuli. In 45 % of binaural phasic units, adaptation was ear specific: adaptation to stimulation of one ear did not affect responses to stimulation of the other ear. Thus, adaptation exhibited specificity for stimulus frequency and lateralization at the level of the midbrain. This mechanism could be employed to detect rapid stimulus change within and between sound sources in complex acoustic environments. PMID:23344947

Autonomic responses to correct outcomes and interaction errors during single-switch scanning among children with severe spastic quadriplegic cerebral palsy

PubMed Central

2014-01-01

Background The combination of single-switch access technology and scanning is the most promising means of augmentative and alternative communication for many children with severe physical disabilities. However, the physical impairment of the child and the technology’s limited ability to interpret the child’s intentions often lead to false positives and negatives (corresponding to accidental and missed selections, respectively) occurring at rates that frustrate the user and preclude functional communication. Multiple psychophysiological studies have associated cardiac deceleration and increased phasic electrodermal activity with self-realization of errors among able-bodied individuals. Thus, physiological measurements have potential utility at enhancing single-switch access, provided that such prototypical autonomic responses exist in persons with profound disabilities. Methods The present case series investigated the autonomic responses of three pediatric single-switch users with severe spastic quadriplegic cerebral palsy, in the context of a single-switch letter matching activity. Each participant exhibited distinct autonomic responses to activity engagement. Results Our analysis confirmed the presence of the autonomic response pattern of cardiac deceleration and increased phasic electrodermal activity following true positives, false positives and false negatives errors, but not subsequent to true negative outcomes. Conclusions These findings suggest that there may be merit in complementing single-switch input with autonomic measurements to improve augmentative and alternative communications for pediatric access technology users. PMID:24607065

Potentiation of tonic GABAergic inhibition by activation of postsynaptic kainate receptors.

PubMed

Jiang, L; Kang, D; Kang, J

2015-07-09

Presynaptic kainate-type glutamate ionotropic receptors (KARs) that mediate either the depression or the facilitation of GABA release have been intensively studied. Little attention has been given to the modulation of GABAA receptors (GABAARs) by postsynaptic KARs. Recent studies suggest that two GABAAR populations, synaptic (sGABAAR) and extrasynaptic (eGABAAR) GABAARs, mediate phasic and tonic forms of inhibition, respectively. Tonic inhibition plays an important role in the excitability of neuronal circuits and the occurrence of epileptic seizures. For this study, we are the first to report that the activation of postsynaptic KARs by the KAR agonist, Kainic acid (KA, 5 μM), enhanced tonic inhibition by potentiating eGABAARs. KA enhanced THIP-induced eGABAAR currents and prolonged the rise and decay time of muscimol-induced sGABAAR/eGABAAR currents, but also depressed the amplitude of evoked inhibitory postsynaptic currents (IPSCs), unitary IPSCs (uIPSCs), and muscimol-induced sGABAAR/eGABAAR currents. The PKC inhibitor, staurosporine (1 μM), in the patch pipette solution fully blocked the KA-induced potentiation of tonic inhibition, suggesting the involvement of an intracellular PKC pathway. Our study suggests that the activation of postsynaptic KARs potentiates eGABAARs but depresses sGABAARs. By activating postsynaptic KARs, synaptically released glutamate depresses phasic inhibition to facilitate neuronal plasticity, but potentiates tonic inhibition to protect neurons from over-excitation. Copyright © 2015 IBRO. Published by Elsevier Ltd. All rights reserved.

Autonomic responses to correct outcomes and interaction errors during single-switch scanning among children with severe spastic quadriplegic cerebral palsy.

PubMed

Leung, Brian; Chau, Tom

2014-03-08

The combination of single-switch access technology and scanning is the most promising means of augmentative and alternative communication for many children with severe physical disabilities. However, the physical impairment of the child and the technology's limited ability to interpret the child's intentions often lead to false positives and negatives (corresponding to accidental and missed selections, respectively) occurring at rates that frustrate the user and preclude functional communication. Multiple psychophysiological studies have associated cardiac deceleration and increased phasic electrodermal activity with self-realization of errors among able-bodied individuals. Thus, physiological measurements have potential utility at enhancing single-switch access, provided that such prototypical autonomic responses exist in persons with profound disabilities. The present case series investigated the autonomic responses of three pediatric single-switch users with severe spastic quadriplegic cerebral palsy, in the context of a single-switch letter matching activity. Each participant exhibited distinct autonomic responses to activity engagement. Our analysis confirmed the presence of the autonomic response pattern of cardiac deceleration and increased phasic electrodermal activity following true positives, false positives and false negatives errors, but not subsequent to true negative outcomes. These findings suggest that there may be merit in complementing single-switch input with autonomic measurements to improve augmentative and alternative communications for pediatric access technology users.

The human respiratory gate

NASA Technical Reports Server (NTRS)

Eckberg, Dwain L.

2003-01-01

Respiratory activity phasically alters membrane potentials of preganglionic vagal and sympathetic motoneurones and continuously modulates their responsiveness to stimulatory inputs. The most obvious manifestation of this 'respiratory gating' is respiratory sinus arrhythmia, the rhythmic fluctuations of electrocardiographic R-R intervals observed in healthy resting humans. Phasic autonomic motoneurone firing, reflecting the throughput of the system, depends importantly on the intensity of stimulatory inputs, such that when levels of stimulation are low (as with high arterial pressure and sympathetic activity, or low arterial pressure and vagal activity), respiratory fluctuations of sympathetic or vagal firing are also low. The respiratory gate has a finite capacity, and high levels of stimulation override the ability of respiration to gate autonomic responsiveness. Autonomic throughput also depends importantly on other factors, including especially, the frequency of breathing, the rate at which the gate opens and closes. Respiratory sinus arrhythmia is small at rapid, and large at slow breathing rates. The strong correlation between systolic pressure and R-R intervals at respiratory frequencies reflects the influence of respiration on these two measures, rather than arterial baroreflex physiology. A wide range of evidence suggests that respiratory activity gates the timing of autonomic motoneurone firing, but does not influence its tonic level. I propose that the most enduring significance of respiratory gating is its use as a precisely controlled experimental tool to tease out and better understand otherwise inaccessible human autonomic neurophysiological mechanisms.

Evidence for repetitive load in the trapezius muscle during a tapping task.

PubMed

Tomatis, L; Müller, C; Nakaseko, M; Läubli, T

2012-08-01

Many studies describe the trapezius muscle activation pattern during repetitive key-tapping focusing on continuous activation. The objectives of this study were to determine whether the upper trapezius is phasically active during supported key tapping, whether this activity is cross-correlated with forearm muscle activity, and whether trapezius activity depends on key characteristic. Thirteen subjects (29.7 ± 11.4 years) were tested. Surface EMG of the finger's extensor and flexor and of the trapezius muscles, as well as the key on-off signal was recorded while the subject performed a 2-min session of key tapping at 4 Hz. The linear envelopes obtained were cut into single tapping cycles extending from one onset to the next onset signal and subsequently time-normalized. Effect size between mean range and maximal standard deviation was calculated to determine as to whether a burst of trapezius muscle activation was present. Cross-correlation was used to determine the time-lag of the activity bursts between forearm and trapezius muscles. For each person the mean and standard deviation of the cross-correlations coefficient between forearm muscles and trapezius were determined. Results showed a burst of activation in the trapezius muscle during most of the tapping cycles. The calculated effect size was ≥0.5 in 67% of the cases. Cross-correlation factors between forearm and trapezius muscle activity were between 0.75 and 0.98 for both extensor and flexor muscles. The cross-correlated phasic trapezius activity did not depend on key characteristics. Trapezius muscle was dynamically active during key tapping; its activity was clearly correlated with forearm muscles' activity.

Affect Intensity and Phasic REM Sleep in Depressed Men before and after Treatment with Cognitive-Behavioral Therapy.

ERIC Educational Resources Information Center

Nofzinger, Eric A.; And Others

1994-01-01

Explored relationship between daytime affect and REM (rapid eye movement) sleep in 45 depressed men before and after treatment with cognitive-behavioral therapy and in control group of 43 healthy subjects. For depressed subjects only, intensity of daytime affect correlated significantly and positively with phasic REM sleep measures at pre- and…

Endogenous Cortisol Exposure and Declarative Verbal Memory: A Longitudinal Study of Healthy Older Adults.

PubMed

Segerstrom, Suzanne C; Geiger, Paul J; Boggero, Ian A; Schmitt, Fredrick A; Sephton, Sandra E

2016-01-01

Exposure to endogenous cortisol is associated with hippocampal degeneration and may contribute to problems with declarative memory, but effects of persistent versus phasic cortisol elevations have not been established. The present longitudinal investigation examined persistent individual differences and phasic changes in cortisol as they related to verbal memory, executive functions, and subjective cognitive function. Older adults (n = 132, aged 60-93 years) were followed up for up to 5 years. They were assessed annually for verbal memory and every 6 months for executive functions, subjective cognitive function, and cortisol area under the curve (averaged over 3 days). In multilevel models, persistently but not phasically higher cortisol was associated with worse verbal memory in both learning (t(181) = 2.99, p = .003) and recall (t(280) = 3.10, p = .002). This effect withstood adjustment for stress, depression, metabolic health, and age. There was evidence for attenuated primacy in learning with higher persistent cortisol. Phasic increases in cortisol were not associated with changes in memory, and cortisol was not related to executive functions or subjective cognitive function. Higher secretion of cortisol may, over time, contribute to memory dysfunction in older adults.

Attentional control of associative learning--a possible role of the central cholinergic system.

PubMed

Pauli, Wolfgang M; O'Reilly, Randall C

2008-04-02

How does attention interact with learning? Kruschke [Kruschke, J.K. (2001). Toward a unified Model of Attention in Associative Learning. J. Math. Psychol. 45, 812-863.] proposed a model (EXIT) that captures Mackintosh's [Mackintosh, N.J. (1975). A theory of attention: Variations in the associability of stimuli with reinforcement. Psychological Review, 82(4), 276-298.] framework for attentional modulation of associative learning. We developed a computational model that showed analogous interactions between selective attention and associative learning, but is significantly simplified and, in contrast to EXIT, is motivated by neurophysiological findings. Competition among input representations in the internal representation layer, which increases the contrast between stimuli, is critical for simulating these interactions in human behavior. Furthermore, this competition is modulated in a way that might be consistent with the phasic activation of the central cholinergic system, which modulates activity in sensory cortices. Specifically, phasic increases in acetylcholine can cause increased excitability of both pyramidal excitatory neurons in cortical layers II/III and cortical GABAergic inhibitory interneurons targeting the same pyramidal neurons. These effects result in increased attentional contrast in our model. This model thus represents an initial attempt to link human attentional learning data with underlying neural substrates.

Attentional control of associative learning—A possible role of the central cholinergic system

PubMed Central

Pauli, Wolfgang M.; O'Reilly, Randall C.

2010-01-01

How does attention interact with learning? Kruschke [Kruschke, J.K. (2001). Toward a unified Model of Attention in Associative Learning. J. Math. Psychol. 45, 812–863.] proposed a model (EXIT) that captures Mackintosh's [Mackintosh, N.J. (1975). A theory of attention: Variations in the associability of stimuli with reinforcement. Psychological Review, 82(4), 276–298.] framework for attentional modulation of associative learning. We developed a computational model that showed analogous interactions between selective attention and associative learning, but is significantly simplified and, in contrast to EXIT, is motivated by neurophysiological findings. Competition among input representations in the internal representation layer, which increases the contrast between stimuli, is critical for simulating these interactions in human behavior. Furthermore, this competition is modulated in a way that might be consistent with the phasic activation of the central cholinergic system, which modulates activity in sensory cortices. Specifically, phasic increases in acetylcholine can cause increased excitability of both pyramidal excitatory neurons in cortical layers II/III and cortical GABAergic inhibitory interneurons targeting the same pyramidal neurons. These effects result in increased attentional contrast in our model. This model thus represents an initial attempt to link human attentional learning data with underlying neural substrates. PMID:17870060

Candida albicans yeast and hyphae are discriminated by MAPK signaling in vaginal epithelial cells.

PubMed

Moyes, David L; Murciano, Celia; Runglall, Manohursingh; Islam, Ayesha; Thavaraj, Selvam; Naglik, Julian R

2011-01-01

We previously reported that a bi-phasic innate immune MAPK response, constituting activation of the mitogen-activated protein kinase (MAPK) phosphatase MKP1 and c-Fos transcription factor, discriminates between the yeast and hyphal forms of Candida albicans in oral epithelial cells (ECs). Since the vast majority of mucosal Candida infections are vaginal, we sought to determine whether a similar bi-phasic MAPK-based immune response was activated by C. albicans in vaginal ECs. Here, we demonstrate that vaginal ECs orchestrate an innate response to C. albicans via NF-κB and MAPK signaling pathways. However, unlike in oral ECs, the first MAPK response, defined by c-Jun transcription factor activation, is delayed until 2 h in vaginal ECs but is still independent of hypha formation. The 'second' or 'late' MAPK response, constituting MKP1 and c-Fos transcription factor activation, is identical to oral ECs and is dependent upon both hypha formation and fungal burdens. NF-κB activation is immediate but independent of morphology. Furthermore, the proinflammatory response in vaginal ECs is different to oral ECs, with an absence of G-CSF and CCL20 and low level IL-6 production. Therefore, differences exist in how C. albicans activates signaling mechanisms in oral and vaginal ECs; however, the activation of MAPK-based pathways that discriminate between yeast and hyphal forms is retained between these mucosal sites. We conclude that this MAPK-based signaling pathway is a common mechanism enabling different human epithelial tissues to orchestrate innate immune responses specifically against C. albicans hyphae.

[Myocardial contractility and hemodynamics in hypothyroidism].

PubMed

Selivonenko, V G

1977-01-01

The author determined the phasic structure of the systole of the left ventricle by the method of polycardiography and hemodynamics in 20 patients suffering from hypothyrodism. Blood plasma and erythrocyte electrolytes were examined at the same time. Patients with hypothyroidism displayed a phasic syndrome of hypodynamia and a marked correlation between the phase of the synchronous contraction, the period of ejection, the strength of contraction of the left ventricle and the electrolyte content. Sodium and magnesium produced the greatest influence on the phasic structure of the systole; potassium and calcium had a lesser effect. The heart stroke volume diminished; as to the cardiac index, expenditure of the energy of cardiac contractions directed to the maintenance of movement of 1 litre of the minute blood volume; the external work, and the peripheral vascular resistance displayed no significant change.

A mechanized gait trainer for restoration of gait.

PubMed

Hesse, S; Uhlenbrock, D

2000-01-01

The newly developed gait trainer allows wheel-chair-bound subjects the repetitive practice of a gait-like movement without overstressing therapists. The device simulates the phases of gait, supports the subjects according to their abilities, and controls the center of mass (CoM) in the vertical and horizontal directions. The patterns of sagittal lower limb joint kinematics and of muscle activation for a normal subject were similar when using the mechanized trainer and when walking on a treadmill. A non-ambulatory hemiparetic subject required little help from one therapist on the gait trainer, while two therapists were required to support treadmill walking. Gait movements on the trainer were highly symmetrical, impact free, and less spastic. The vertical displacement of the CoM was bi-phasic instead of mono-phasic during each gait cycle on the new device. Two cases of non-ambulatory patients, who regained their walking ability after 4 weeks of daily training on the gait trainer, are reported.

Clustering of Ca2+ transients in interstitial cells of Cajal defines slow wave duration

PubMed Central

Drumm, Bernard T.; Hennig, Grant W.; Battersby, Matthew J.; Sung, Tae Sik

2017-01-01

Interstitial cells of Cajal (ICC) in the myenteric plexus region (ICC-MY) of the small intestine are pacemakers that generate rhythmic depolarizations known as slow waves. Slow waves depend on activation of Ca2+-activated Cl− channels (ANO1) in ICC, propagate actively within networks of ICC-MY, and conduct to smooth muscle cells where they generate action potentials and phasic contractions. Thus, mechanisms of Ca2+ regulation in ICC are fundamental to the motor patterns of the bowel. Here, we characterize the nature of Ca2+ transients in ICC-MY within intact muscles, using mice expressing a genetically encoded Ca2+ sensor, GCaMP3, in ICC. Ca2+ transients in ICC-MY display a complex firing pattern caused by localized Ca2+ release events arising from multiple sites in cell somata and processes. Ca2+ transients are clustered within the time course of slow waves but fire asynchronously during these clusters. The durations of Ca2+ transient clusters (CTCs) correspond to slow wave durations (plateau phase). Simultaneous imaging and intracellular electrical recordings revealed that the upstroke depolarization of slow waves precedes clusters of Ca2+ transients. Summation of CTCs results in relatively uniform Ca2+ responses from one slow wave to another. These Ca2+ transients are caused by Ca2+ release from intracellular stores and depend on ryanodine receptors as well as amplification from IP3 receptors. Reduced extracellular Ca2+ concentrations and T-type Ca2+ channel blockers decreased the number of firing sites and firing probability of Ca2+ transients. In summary, the fundamental electrical events of small intestinal muscles generated by ICC-MY depend on asynchronous firing of Ca2+ transients from multiple intracellular release sites. These events are organized into clusters by Ca2+ influx through T-type Ca2+ channels to sustain activation of ANO1 channels and generate the plateau phase of slow waves. PMID:28592421

An intracellular characterization of neurones and neural connexions within the left coeliac ganglion of cats.

PubMed Central

Decktor, D L; Weems, W A

1983-01-01

Intracellular recordings were made in vitro from neurones located within the left coeliac ganglion of the cat solar plexus. Thirty percent of the neurones within left coeliac ganglia were identified as efferent neurones. Within this neuronal population, splenic-efferent and renal-efferent neurones were identified specifically. Neurones within left coeliac ganglia were characterized as either phasic (fast adapting) neurones or tonic (slowly adapting) neurones depending upon their prolonged firing behaviour. Electrophysiological properties of neurones varied considerably. The wide range of values obtained for both input resistance and input capacitance suggest that sizeable differences in either specific membrane resistance or cell geometry exist within the over-all neurone population. Frequency distributions of input resistance, time constant, input capacitance and current threshold for tonic and phasic neurones were found to be significantly different. Compound excitatory post-synaptic potentials were produced by stimulation of the ipsilateral splanchnic nerves in 69% of the neurones tested and in 3% of the neurones tested upon stimulation of the contralateral splanchnic nerves. Electrical stimulation of nerve fibres located in the coeliac plexus, the superior mesenteric plexus or the left renal nerves generated excitatory synaptic potentials in neurones located within left coeliac ganglia. It is concluded that neurones within the left coeliac ganglion are innervated by splanchnic nerve fibres primarily contained within the left splanchnic nerves, receive excitatory synaptic input from splenic, renal and other peripheral preganglionic fibres and have extremely varied electrophysiological properties. PMID:6620179

Phasic valence and arousal do not influence post-conflict adjustments in the Simon task.

PubMed

Dignath, David; Janczyk, Markus; Eder, Andreas B

2017-03-01

According to theoretical accounts of cognitive control, conflict between competing responses is monitored and triggers post conflict behavioural adjustments. Some models proposed that conflict is detected as an affective signal. While the conflict monitoring theory assumed that conflict is registered as a negative valence signal, the adaptation by binding model hypothesized that conflict provides a high arousal signal. The present research induced phasic affect in a Simon task with presentations of pleasant and unpleasant pictures that were high or low in arousal. If conflict is registered as an affective signal, the presentation of a corresponding affective signal should potentiate post conflict adjustments. Results did not support the hypothesis, and Bayesian analyses corroborated the conclusion that phasic affects do not influence post conflict behavioural adjustments in the Simon task. Copyright © 2017 Elsevier B.V. All rights reserved.

Tonic vibration reflex in spasticity, Parkinson's disease, and normal subjects

PubMed Central

Burke, David; Andrews, Colin J.; Lance, James W.

1972-01-01

The tonic vibration reflex (TVR) has been studied in the quadriceps and triceps surae muscles of 34 spastic, 15 Parkinsonism, and 10 normal subjects. The TVR of spasticity develops rapidly, reaching a plateau level within 2-4 sec of the onset of vibration. The tonic contraction was often preceded by a phasic spike which appeared to be a vibration-induced equivalent of the tendon jerk. The initial phasic spike was usually followed by a silent period, and induced clonus in some patients. No correlation was found between the shape of the TVR and the site of the lesion in the central nervous system. The TVR of normal subjects and patients with Parkinsonism developed slowly, starting some seconds after the onset of vibration, and reaching a plateau level in 20-60 sec. A phasic spike was recorded occasionally in these subjects, but the subsequent tonic contraction followed the usual time course. Muscle stretch increased the quadriceps TVR of all subjects, including those with spasticity in whom the quadriceps stretch reflex decreased with increasing stretch. It is suggested that this difference between the tonic vibration reflex and the tonic stretch reflex arises from the selective activation of spindle primary endings by vibration, while both the primary and the secondary endings are responsive to muscle stretch. The TVR could be potentiated by reinforcement in some subjects. Potentiation outlasted the reinforcing manoeuvre, and was most apparent at short muscle lengths. As muscle stretch increased, thus producing a larger TVR, the degree of potentiation decreased. It is therefore suggested that the effects of reinforcement result at least partially from the activation of the fusimotor system. Since reinforcement potentiated the TVR of patients with spinal spasticity in whom a prominent clasp-knife phenomenon could be demonstrated, it is suggested that the effects of reinforcement are mediated by a descending pathway that traverses the anterior quadrant of the spinal cord. PMID:4261955

Reducing prefrontal gamma-aminobutyric acid activity induces cognitive, behavioral, and dopaminergic abnormalities that resemble schizophrenia.

PubMed

Enomoto, Takeshi; Tse, Maric T; Floresco, Stan B

2011-03-01

Perturbations in gamma-aminobutyric acid (GABA)-related markers have been reported in the prefrontal cortex of schizophrenic patients. However, a preclinical assessment of how suppression of prefrontal cortex GABA activity may reflect behavioral and cognitive pathologies observed in schizophrenia is forthcoming. We assessed the effects of pharmacologic blockade of prefrontal cortex GABA(A) receptors in rats on executive functions and other behaviors related to schizophrenia, as well as neural activity of midbrain dopamine neurons. Blockade of prefrontal cortex GABA(A) receptors with bicuculline (12.5-50 ng) did not affect working memory accuracy but did increase response latencies, resembling speed of processing deficits observed in schizophrenia. Prefrontal cortex GABA(A) blockade did not impede simple discrimination or reversal learning but did impair set-shifting in a manner dependent on when these treatments were given. Reducing GABA activity before the set-shift impaired the ability to acquire a novel strategy, whereas treatment before the initial discrimination increased perseveration during the shift. Latent inhibition was unaffected by bicuculline infusions before the preexposure/conditioning phases, suggesting that reduced prefrontal cortex GABA activity does not impair "learned irrelevance." GABA(A) blockade increased locomotor activity and showed synergic effects with a subthreshold dose of amphetamine. Furthermore, reducing medial prefrontal cortex GABA activity selectively increased phasic burst firing of ventral tegmental area dopamine neurons, without altering the their overall population activity. These results suggest that prefrontal cortex GABA hypofunction may be a key contributing factor to deficits in speed of processing, cognitive flexibility, and enhanced phasic dopamine activity observed in schizophrenia. Copyright © 2011 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.

EEG during pedaling: Evidence for cortical control of locomotor tasks

PubMed Central

Jain, Sanket; Gourab, Krishnaj; Schindler-Ivens, Sheila; Schmit, Brian D.

2014-01-01

Objective This study characterized the brain electrical activity during pedaling, a locomotor-like task, in humans. We postulated that phasic brain activity would be associated with active pedaling, consistent with a cortical role in locomotor tasks. Methods Sixty four channels of electroencephalogram (EEG) and 10 channels of electromyogram (EMG) data were recorded from 10 neurologically-intact volunteers while they performed active and passive (no effort) pedaling on a custom-designed stationary bicycle. Ensemble averaged waveforms, 2 dimensional topographic maps and amplitude of the β (13–35 Hz) frequency band were analyzed and compared between active and passive trials. Results The peak-to-peak amplitude (peak positive–peak negative) of the EEG waveform recorded at the Cz electrode was higher in the passive than the active trials (p < 0.01). β-band oscillations in electrodes overlying the leg representation area of the cortex were significantly desynchronized during active compared to the passive pedaling (p < 0.01). A significant negative correlation was observed between the average EEG waveform for active trials and the composite EMG (summated EMG from both limbs for each muscle) of the rectus femoris (r = −0.77, p < 0.01) the medial hamstrings (r = −0.85, p < 0.01) and the tibialis anterior (r = −0.70, p < 0.01) muscles. Conclusions These results demonstrated that substantial sensorimotor processing occurs in the brain during pedaling in humans. Further, cortical activity seemed to be greatest during recruitment of the muscles critical for transitioning the legs from flexion to extension and vice versa. Significance This is the first study demonstrating the feasibility of EEG recording during pedaling, and owing to similarities between pedaling and bipedal walking, may provide valuable insight into brain activity during locomotion in humans. PMID:23036179

Discharge patterns of human tensor palatini motor units during sleep onset.

PubMed

Nicholas, Christian L; Jordan, Amy S; Heckel, Leila; Worsnop, Christopher; Bei, Bei; Saboisky, Julian P; Eckert, Danny J; White, David P; Malhotra, Atul; Trinder, John

2012-05-01

Upper airway muscles such as genioglossus (GG) and tensor palatini (TP) reduce activity at sleep onset. In GG reduced muscle activity is primarily due to inspiratory modulated motor units becoming silent, suggesting reduced respiratory pattern generator (RPG) output. However, unlike GG, TP shows minimal respiratory modulation and presumably has few inspiratory modulated motor units and minimal input from the RPG. Thus, we investigated the mechanism by which TP reduces activity at sleep onset. The activity of TP motor units were studied during relaxed wakefulness and over the transition from wakefulness to sleep. Sleep laboratory. Nine young (21.4 ± 3.4 years) males were studied on a total of 11 nights. Sleep onset. Two TP EMGs (thin, hooked wire electrodes), and sleep and respiratory measures were recorded. One hundred twenty-one sleep onsets were identified (13.4 ± 7.2/subject), resulting in 128 motor units (14.3 ± 13.0/subject); 29% of units were tonic, 43% inspiratory modulated (inspiratory phasic 18%, inspiratory tonic 25%), and 28% expiratory modulated (expiratory phasic 21%, expiratory tonic 7%). There was a reduction in both expiratory and inspiratory modulated units, but not tonic units, at sleep onset. Reduced TP activity was almost entirely due to de-recruitment. TP showed a similar distribution of motor units as other airway muscles. However, a greater proportion of expiratory modulated motor units were active in TP and these expiratory units, along with inspiratory units, tended to become silent over sleep onset. The data suggest that both expiratory and inspiratory drive components from the RPG are reduced at sleep onset in TP.

Optogenetically-induced tonic dopamine release from VTA-nucleus accumbens projections inhibits reward consummatory behaviors

PubMed Central

Mikhailova, Maria A.; Bass, Caroline E.; Grinevich, Valentina P.; Chappell, Ann M.; Deal, Alex L.; Bonin, Keith D.; Weiner, Jeff L.; Gainetdinov, Raul R.; Budygin, Evgeny A.

2016-01-01

Recent optogenetic studies demonstrated that phasic dopamine release in the nucleus accumbens may play a causal role in multiple aspects of natural and drug reward-related behaviors. The role of tonic dopamine release in reward consummatory behavior remains unclear. The current study used a combinatorial viral-mediated gene delivery approach to express ChR2 on mesolimbic dopamine neurons in rats. We used optical activation of this dopamine circuit to mimic tonic dopamine release in the nucleus accumbens and to explore the causal relationship between this form of dopamine signaling within the ventral tegmental area (VTA)-nucleus accumbens projection and consumption of a natural reward. Using a two bottle choice paradigm (sucrose vs. water), the experiments revealed that tonic optogenetic stimulation of mesolimbic dopamine transmission significantly decreased reward consummatory behaviors. Specifically, there was a significant decrease in the number of bouts, licks and amount of sucrose obtained during the drinking session. Notably, activation of VTA dopamine cell bodies or dopamine terminals in the nucleus accumbens resulted in identical behavioral consequences. No changes in the water intake were evident under the same experimental conditions. Collectively, these data demonstrate that tonic optogenetic stimulation of VTA-nucleus accumbens dopamine release is sufficient to inhibit reward consummatory behavior, possibly by preventing this circuit from engaging in phasic activity that is thought to be essential for reward-based behaviors. PMID:27421228

Histochemistry profile of the biceps brachii muscle fibres of capuchin monkeys (Cebus apella, Linnaeus, 1758).

PubMed

Bortoluci, C H F; Simionato, L H; Rosa Junior, G M; Oliveira, J A; Lauris, J R P; Moraes, L H R; Rodrigues, A C; Andreo, J C

2014-08-01

A general analysis of the behaviour of "Cebus" shows that when this primate moves position to feed or perform another activity, it presents different ways of locomotion. This information shows that the brachial biceps muscle of this animal is frequently used in their locomotion activities, but it should also be remembered that this muscle is also used for other development activities like hiding, searching for objects, searching out in the woods, and digging in the soil. Considering the above, it was decided to research the histoenzimologic characteristics of the brachial biceps muscle to observe whether it is better adpted to postural or phasic function. To that end, samples were taken from the superficial and deep regions, the inserts proximal (medial and lateral) and distal brachial biceps six capuchin monkeys male and adult, which were subjected to the reactions of m-ATPase, NADH-Tr. Based on the results of these reactions fibres were classified as in Fast Twitch Glycolitic (FG), Fast Twitch Oxidative Glycolitic (FOG) and Slow Twitc (SO). In general, the results, considering the muscle as a whole, show a trend of frequency FOG> FG> SO. The data on the frequency were studied on three superficial regions FOG=FG>SO; the deep regions of the inserts proximal FOG=FG=SO and inserting the distal FOG>FG=SO. In conclusion, the biceps brachii of the capuchin monkey is well adapted for both postural and phasic activities.

Phasic dopamine release in the rat nucleus accumbens predicts approach and avoidance performance

PubMed Central

Gentry, Ronny N.; Lee, Brian; Roesch, Matthew R.

2016-01-01

Dopamine (DA) is critical for reward processing, but significantly less is known about its role in punishment avoidance. Using a combined approach-avoidance task, we measured phasic DA release in the nucleus accumbens (NAc) of rats during presentation of cues that predicted reward, punishment or neutral outcomes and investigated individual differences based on avoidance performance. Here we show that DA release within a single microenvironment is higher for reward and avoidance cues compared with neutral cues and positively correlated with poor avoidance behaviour. We found that DA release delineates trial-type during sessions with good avoidance but is non-selective during poor avoidance, with high release correlating with poor performance. These data demonstrate that phasic DA is released during cued approach and avoidance within the same microenvironment and abnormal processing of value signals is correlated with poor performance. PMID:27786172

Certain aspects of normal and abnormal motility of sphincter of Oddi.

PubMed

Coelho, J C; Moody, F G

1987-01-01

Applications of electromyographic and endoscopic manometric techniques in experimental and clinical studies have enhanced our knowledge of the normal physiology and motility disturbances of the sphincter of Oddi. The sphincter of Oddi has an active role in coordinating the time and rate of secretion of biliopancreatic juice into the duodenum. In the opossum, the sphincter of Oddi exhibits spontaneous contractions that migrate distally along the sphincter and expels its contents into the duodenum. Although the motor activity of the sphincter of Oddi is independent from that of the duodenum, there is a correlation between the frequency of bursts of spike potentials in the sphincter of Oddi and the migrating motor complex phases in the duodenum. Abnormal motility of the sphincter of Oddi has been reported during endoscopic manometric evaluation of patients with choledocholithiasis and sphincter of Oddi dyskinesia. Patients with common bile duct stones have an increase in the frequency of retrograde propagation of phasic waves. Elevation of basal pressure as well as an increase in the frequency and amplitude of sphincter of Oddi phasic waves and the common bile duct-duodenum gradient pressure may occur in patients with sphincter of Oddi dyskinesia. Endoscopic manometric studies of the sphincter of Oddi may become an important method to diagnose sphincter of Oddi dyskinesia.

Expectancy modulates pupil size during endogenous orienting of spatial attention.

PubMed

Dragone, Alessio; Lasaponara, Stefano; Pinto, Mario; Rotondaro, Francesca; De Luca, Maria; Doricchi, Fabrizio

2018-05-01

fMRI investigations in healthy humans have documented phasic changes in the level of activation of the right temporal-parietal junction (TPJ) during cued voluntary orienting of spatial attention. Cues that correctly predict the position of upcoming targets in the majority of trials, i.e., predictive cues, produce higher deactivation of the right TPJ as compared with non-predictive cues. Since the right TPJ is the recipient of noradrenergic (NE) innervation, it has been hypothesised that changes in the level of TPJ activity are matched with changes in the level of NE activity. Based on aforementioned fMRI findings, this might imply that orienting with predictive cues is matched with different levels of NE activity as compared with non-predictive cues. To test this hypothesis, we measured changes in pupil dilation, an indirect index of NE activity, during voluntary orienting of attention with highly predictive (80% validity) or non-predictive (50% validity) cues. In agreement with current interpretations of the tonic/phasic activity of the Locus Coeruleus-Norepinephrinic system (LC-NE), we found that the steady level of cue predictiveness that characterised both the predictive and non-predictive conditions caused, across consecutive blocks of trials, a progressive decrement in pupil dilation during the baseline-fixation period that anticipated the cue period. With predictive cues we observed increased pupil dilation as compared with non-predictive cues. In addition, the relative reduction in pupil size observed with non-predictive cues increased as a function of cue-duration. These results show that changes in the predictiveness of cues that guide voluntary orienting of spatial attention are matched with changes in pupil dilation and, putatively, with corresponding changes in LC-NE activity. Copyright © 2017 Elsevier Ltd. All rights reserved.

The rate of change of vergence-accommodation conflict affects visual discomfort.

PubMed

Kim, Joohwan; Kane, David; Banks, Martin S

2014-12-01

Stereoscopic (S3D) displays create conflicts between the distance to which the eyes must converge and the distance to which the eyes must accommodate. Such conflicts require the viewer to overcome the normal coupling between vergence and accommodation, and this effort appears to cause viewer discomfort. Vergence-accommodation coupling is driven by the phasic components of the underlying control systems, and those components respond to relatively fast changes in vergence and accommodative stimuli. Given the relationship between phasic changes and vergence-accommodation coupling, we examined how the rate of change in the vergence-accommodation conflict affects viewer discomfort. We used a stereoscopic display that allows independent manipulation of the stimuli to vergence and accommodation. We presented stimuli that simulate natural viewing (i.e., vergence and accommodative stimuli changed together) and stimuli that simulate S3D viewing (i.e., vergence stimulus changes but accommodative stimulus remains fixed). The changes occurred at 0.01, 0.05, or 0.25 Hz. The lowest rate is too slow to stimulate the phasic components while the highest rate is well within the phasic range. The results were consistent with our expectation: somewhat greater discomfort was experienced when stimulus distance changed rapidly, particularly in S3D viewing when the vergence stimulus changed but the accommodative stimulus did not. These results may help in the generation of guidelines for the creation and viewing of stereo content with acceptable viewer comfort.

Distinct state anxiety after predictable and unpredictable fear training in mice.

PubMed

Seidenbecher, Thomas; Remmes, Jasmin; Daldrup, Thiemo; Lesting, Jörg; Pape, Hans-Christian

2016-05-01

Sustained fear paradigms in rodents have been developed to monitor states of anxious apprehension and to model situations in patients suffering from long-lasting anxiety disorders. A recent report describes a fear conditioning paradigm, allowing distinction between phasic and sustained states of conditioned fear in non-restrained mice. However, so far no prospective studies have yet been conducted to elucidate whether induction of phasic or sustained fear can affect states of anxiety. Here, we used CS (conditioned stimulus) and US (unconditioned stimulus) pairing with predictable and unpredictable timing to induce phasic and sustained fear in mice. State anxiety during various fear response components was assessed using the elevated plus-maze test. Training with unpredictable CS-US timing resulted in CS-evoked sustained components of fear (freezing), while predictable CS-US timing resulted in rapid decline. Data suggested the influence of training procedure on state anxiety which is dependent on progression of conditioned fear during fear memory retrieval. Animals trained with unpredictable CS-US timing showed an unchanged high anxiety state throughout behavioral observation. In contrast, mice trained with predictable CS-US timing showed anxiolytic-like behavior 3 min after CS onset, which was accompanied by a fast decline of the fear conditioned response (freezing). Further systematic studies are needed to validate the phasic/sustained fear model in rodents as translational model for anxiety disorders in humans. Copyright © 2016 Elsevier B.V. All rights reserved.

Analysis of the Angle of Maximal Stability and Flow Regime Transitions in Different Proportions of Bi-phasic Granular Matter Mixtures

NASA Astrophysics Data System (ADS)

Maquiling, Joel Tiu; Visaga, Shane Marie

This study investigates the dependence of the critical angle θc of stability on different mass ratios γ of layered bi-phasic granular matter mixtures and on the critical angle of its mono-disperse individual components. It also aims to investigate and explain regime transitions of granular matter flowing down a tilted rough inclined plane. Critical angles and flow regimes for a bi-phasic mixture of sago spheres and bi-phasic pepper mixture of fine powder and rough spheres were observed and measured using video analysis. The critical angles θc MD of mono-disperse granular matter and θc BP of biphasic granular matter mixtures were observed and compared. All types of flow regimes and a supramaximal critical angle of stability exist at mass ratio γ = 0.5 for all biphasic granular matter mixtures. The θc BP of sago spheres was higher than the θc MD of sago spheres. Moreover, the θc BP of the pepper mixture was in between the θc MD of fine pepper and θc MD of rough pepper spheres. Comparison of different granular material shows that θc MD is not simply a function of particle diameter but of particle roughness as well. Results point to a superposition mechanism of the critical angles of biphasic sphere mixtures.

Contractile activity of the bladder urothelium/lamina propria and its regulation by nitric oxide.

PubMed

Moro, Christian; Leeds, Charlotte; Chess-Williams, Russ

2012-01-15

In the bladder, nitric oxide (NO) is released from neuronal and non-neuronal sources, but its actions are unclear. Strips of urothelium plus lamina propria contract in response to agonists and develop spontaneous phasic contractions, and the aim of this study was to investigate the influence of NO on this activity. Isolated strips of urothelium/lamina propria from porcine bladder developed spontaneous contractions (3.5 ± 0.3 cycles/min) and contracted in response to carbachol and electrical field stimulation (EFS). The NO synthase inhibitor N(ω)-nitro-l-arginine (L-NNA, 100 μM) had no effects on the tissues, but the NO donors diethylamine NONOate (DEANO, 100 μM) and nitroprusside (10 μM) caused relaxation, slowed the spontaneous rate of contractions and inhibited responses to carbachol. Maximum tonic contractions to carbachol were reduced by 17 ± 4% (P<0.001) and 35 ± 5% (P<0.001) by DEANO and nitroprusside respectively and the potency of carbachol was also reduced. Carbachol also increased the spontaneous frequency of contraction and these rate responses were again inhibited by DEANO and nitroprusside, but unaffected by L-NNA. Similarly, responses to EFS were significantly depressed (52-70%) by DEANO (P<0.05), but were unaffected by L-NNA. These data demonstrate spontaneous contractile activity and also nerve and agonist-induced tonic contractile activity within the urothelium and lamina propria. This activity is sensitive to depression by NO, but NO does not appear to be spontaneously released to influence this activity, nor does it appear to be released by muscarinic receptor stimulation. However the results suggest that in situations where NO production is increased, NO can influence the contractile activity of this tissue. Copyright © 2011 Elsevier B.V. All rights reserved.

Phasic alertness cues modulate visual processing speed in healthy aging.

PubMed

Haupt, Marleen; Sorg, Christian; Napiórkowski, Natan; Finke, Kathrin

2018-05-31

Warning signals temporarily increase the rate of visual information in younger participants and thus optimize perception in critical situations. It is unclear whether such important preparatory processes are preserved in healthy aging. We parametrically assessed the effects of auditory alertness cues on visual processing speed and their time course using a whole report paradigm based on the computational Theory of Visual Attention. We replicated prior findings of significant alerting benefits in younger adults. In conditions with short cue-target onset asynchronies, this effect was baseline-dependent. As younger participants with high baseline speed did not show a profit, an inverted U-shaped function of phasic alerting and visual processing speed was implied. Older adults also showed a significant cue-induced benefit. Bayesian analyses indicated that the cueing benefit on visual processing speed was comparably strong across age groups. Our results indicate that in aging individuals, comparable to younger ones, perception is active and increased expectancy of the appearance of a relevant stimulus can increase the rate of visual information uptake. Copyright © 2018 Elsevier Inc. All rights reserved.

Muscarinic Long-Term Enhancement of Tonic and Phasic GABAA Inhibition in Rat CA1 Pyramidal Neurons

PubMed Central

Domínguez, Soledad; Fernández de Sevilla, David; Buño, Washington

2016-01-01

Acetylcholine (ACh) regulates network operation in the hippocampus by controlling excitation and inhibition in rat CA1 pyramidal neurons (PCs), the latter through gamma-aminobutyric acid type-A receptors (GABAARs). Although, the enhancing effects of ACh on GABAARs have been reported (Dominguez et al., 2014, 2015), its role in regulating tonic GABAA inhibition has not been explored in depth. Therefore, we aimed at determining the effects of the activation of ACh receptors on responses mediated by synaptic and extrasynaptic GABAARs. Here, we show that under blockade of ionotropic glutamate receptors ACh, acting through muscarinic type 1 receptors, paired with post-synaptic depolarization induced a long-term enhancement of tonic GABAA currents (tGABAA) and puff-evoked GABAA currents (pGABAA). ACh combined with depolarization also potentiated IPSCs (i.e., phasic inhibition) in the same PCs, without signs of interactions of synaptic responses with pGABAA and tGABAA, suggesting the contribution of two different GABAA receptor pools. The long-term enhancement of GABAA currents and IPSCs reduced the excitability of PCs, possibly regulating plasticity and learning in behaving animals. PMID:27833531

Intraduodenal and intrajejunal administration of the herbal medicine, dai-kenchu-tou, stimulates small intestinal motility via cholinergic receptors in conscious dogs.

PubMed

Jin, X L; Shibata, C; Naito, H; Ueno, T; Funayama, Y; Fukushima, K; Matsuno, S; Sasaki, I

2001-06-01

The aim of the present study was to study the effect and mechanism of action of intraduodenal and intrajejunal dai-kenchu-to, an herbal medicine clinically effective for uncomplicated postoperative adhesive intestinal obstruction, on upper gastrointestinal motility. Five mongrel dogs were equipped with four strain-gauge force transducers on the antrum, duodenum, and proximal and distal jejunum to measure contractile activity. Dai-kenchu-to (0.5, 1.5, and 3.0 g) was administered into the duodenal or proximal jejunal lumen. The effect of atropine, hexamethonium, phentolamine, propranolol, and ondansetron on intraduodenal and intrajejunal dai-kenchu-to-induced contractions was studied. Plasma motilin was measured by specific radioimmunoassay. Intraduodenal and intrajejunal dai-kenchu-to induced phasic contractions in the duodenum and proximal jejunum, respectively, and those contractions migrated distally. Phasic contractions induced by intraduodenal and intrajejunal dai-kenchu-to were inhibited by atropine and hexamethonium at all sites. Plasma motilin was not affected by dai-kenchu-to. Intraduodenal and intrajejunal dai-kenchu-to stimulates upper gastrointestinal motility at and distal to the administration sites through cholinergic receptors.

Differential representation of Pavlovian-instrumental transfer by prefrontal cortex subregions and striatum.

PubMed

Homayoun, Houman; Moghaddam, Bita

2009-04-01

Environmental cues that once predicted reward can restore extinguished behavior directed toward that reward. This process may be modeled by the Pavlovian-instrumental transfer (PIT) paradigm where a previously learned Pavlovian conditioned stimulus (CS) elicits a representation of the reward associated with that CS, prompts motivation toward the absent reward, and triggers an instrumental action. We recorded in the medial and orbital prefrontal cortex (mPFC and OFC) and dorsal striatum (DS) of freely moving rats during PIT and found that a Pavlovian CS, as compared with neutral or no stimuli, amplified the phasic neuronal responses to instrumental nosepokes ('transfer' event). In mPFC and OFC, but not the DS, representation of the transfer event correlated with the strength of PIT behavior. Neurons in all three regions showed CS-selective amplification of Pavlovian approaches toward the reward delivery site. Whereas striatal neurons represented transfer and approach behavior through mostly segregated neuronal subsets, overlapping subsets represented these events in the mPFC and OFC. These findings suggest that parallel phasic activation of mPFC and OFC neuronal subsets participates in the transfer from Pavlovian incentives to instrumental actions.

Gender influences sphincter of Oddi response to cholecystokinin in the prairie dog.

PubMed

Tierney, S; Qian, Z; Yung, B; Lipsett, P A; Pitt, H A; Sostre, S; Lillemoe, K D

1995-10-01

Although gallstones and disorders of biliary tract motility are both more common in women than men, sphincter of Oddi motility has not previously been compared between the sexes. In this study, cholescintigraphy (under ketamine and diazepam anesthesia) was used to determine gallbladder emptying rate and ejection fraction in response to cholecystokinin (CCK) in eight male and six female prairie dogs fed a nonlithogenic diet. Ten days later, under alpha-chloralose anesthesia, sphincter of Oddi phasic wave activity was monitored for 10-min intervals before (control), during 20 min of CCK infusion, and for 20 min after infusion. Gallbladder emptying rate and ejection fraction and baseline sphincter of Oddi frequency, amplitude, and motility index (= frequency x amplitude) did not differ significantly between the sexes. Sphincter of Oddi phasic wave frequency was increased during CCK infusion in both males and females, but the change in amplitude was significantly greater in females, than males. We conclude that the increased incidence of biliary tract disease in women may be due to altered sphincter of Oddi hormonal response.

Vagally mediated effects of brain stem dopamine on gastric tone and phasic contractions of the rat.

PubMed

Anselmi, L; Toti, L; Bove, C; Travagli, R A

2017-11-01

Dopamine (DA)-containing fibers and neurons are embedded within the brain stem dorsal vagal complex (DVC); we have shown previously that DA modulates the membrane properties of neurons of the dorsal motor nucleus of the vagus (DMV) via DA1 and DA2 receptors. The vagally dependent modulation of gastric tone and phasic contractions, i.e., motility, by DA, however, has not been characterized. With the use of microinjections of DA in the DVC while recording gastric tone and motility, the aims of the present study were 1 ) assess the gastric effects of brain stem DA application, 2 ) identify the DA receptor subtype, and, 3 ) identify the postganglionic pathway(s) activated. Dopamine microinjection in the DVC decreased gastric tone and motility in both corpus and antrum in 29 of 34 rats, and the effects were abolished by ipsilateral vagotomy and fourth ventricular treatment with the selective DA2 receptor antagonist L741,626 but not by application of the selective DA1 receptor antagonist SCH 23390. Systemic administration of the cholinergic antagonist atropine attenuated the inhibition of corpus and antrum tone in response to DA microinjection in the DVC. Conversely, systemic administration of the nitric oxide synthase inhibitor nitro-l-arginine methyl ester did not alter the DA-induced decrease in gastric tone and motility. Our data provide evidence of a dopaminergic modulation of a brain stem vagal neurocircuit that controls gastric tone and motility. NEW & NOTEWORTHY Dopamine administration in the brain stem decreases gastric tone and phasic contractions. The gastric effects of dopamine are mediated via dopamine 2 receptors on neurons of the dorsal motor nucleus of the vagus. The inhibitory effects of dopamine are mediated via inhibition of the postganglionic cholinergic pathway. Copyright © 2017 the American Physiological Society.

Evolution of a new sense for wind in flying phasmids? Afferents and interneurons

NASA Astrophysics Data System (ADS)

Hustert, Reinhold; Klug, Rebecca

2009-12-01

The evolution of winged stick insects (phasmids) from secondarily wingless ancestors was proposed in recent studies. We explored the cuticle of flying phasmids for wind sensors that could be involved in their flight control, comparable to those known for locusts. Surprisingly, wind-sensitive hairs (wsH) occur on the palps of mouthparts and on the antennae of the winged phasmid Sipyloidea sipylus which can fly in tethered position only when air currents blow over the mouthparts. The present study describes the morphology and major functional properties of these “new” wsH with soft and bulging hair bases which are different from the beaker-like hair bases of the wsH on the cerci of phasmids and the wsH described in other insects. The most sensitive wsH of antennae and palps respond with phasic-tonic afferents to air currents exceeding 0.2 ms-1. The fields of wsH on one side of the animal respond mainly to ventral, lateral, and frontal wind on the ipsilateral side of the head. Afferent inputs from the wsH converge but also diverge to a group of specific interneurons at their branches in the suboesophageal ganglion and can send their integrated input from wsH fields of the palps and antennae to the thoracic central nervous system. Response types of individual wsH-interneurons are either phasic or phasic-tonic to air puffs or constant air currents and also, the receptive fields of individual interneurons differ. We conclude that the “new” wsH system and its interneurons mainly serve to maintain flight activity in airborne phasmids and also, the “new” wsH must have emerged together with the integrating interneurons during the evolution from wingless to the recent winged forms of phasmids.

Motor unit recruitment in human genioglossus muscle in response to hypercapnia.

PubMed

Nicholas, Christian L; Bei, Bei; Worsnop, Christopher; Malhotra, Atul; Jordan, Amy S; Saboisky, Julian P; Chan, Julia K M; Duckworth, Ella; White, David P; Trinder, John

2010-11-01

single motor unit recordings of the genioglossus (GG) muscle indicate that GG motor units have a variety of discharge patterns, including units that have higher discharge rates during inspiration (inspiratory phasic and inspiratory tonic), or expiration (expiratory phasic and expiratory tonic), or do not modify their rate with respiration (tonic). Previous studies have shown that an increase in GG muscle activity is a consequence of increased activity in inspiratory units. However, there are differences between studies as to whether this increase is primarily due to recruitment of new motor units (motor unit recruitment) or to increased discharge rate of already active units (rate coding). Sleep-wake state studies in humans have suggested the former, while hypercapnia experiments in rats have suggested the latter. In this study, we investigated the effect of hypercapnia on GG motor unit activity in humans during wakefulness. sleep research laboratory. sixteen healthy men. each participant was administered at least 6 trials with P(et)CO(2) being elevated 8.4 (SD = 1.96) mm Hg over 2 min following a 30-s baseline. Subjects were instrumented for GG EMG and respiratory measurements with 4 fine wire electrodes inserted subcutaneously into the muscle. One hundred forty-one motor units were identified during the baseline: 47% were inspiratory modulated, 29% expiratory modulated, and 24% showed no respiratory related modulation. Sixty-two new units were recruited during hypercapnia. The distribution of recruited units was significantly different from the baseline distribution, with 84% being inspiratory modulated (P < 0.001). Neither units active during baseline, nor new units recruited during hypercapnia, increased their discharge rate as P(et)CO(2) increased (P > 0.05 for all comparisons). increased GG muscle activity in humans occurs because of recruitment of previously inactive inspiratory modulated units.

Numbness in clinical and experimental pain--a cross-sectional study exploring the mechanisms of reduced tactile function.

PubMed

Geber, Christian; Magerl, Walter; Fondel, Ricarda; Fechir, Marcel; Rolke, Roman; Vogt, Thomas; Treede, Rolf-Detlef; Birklein, Frank

2008-09-30

Pain patients often report distinct numbness of the painful skin although no structural peripheral or central nerve lesion is obvious. In this cross-sectional study we assessed the reduction of tactile function and studied underlying mechanisms in patients with chronic pain and in healthy participants exposed to phasic and tonic experimental nociceptive stimulation. Mechanical detection (MDT) and pain thresholds (MPT) were assessed in the painful area and the non-painful contralateral side in 10 patients with unilateral musculoskeletal pain. Additionally, 10 healthy participants were exposed to nociceptive stimulation applied to the volar forearms (capsaicin; electrical stimulation, twice each). Areas of tactile hypaesthesia and mechanical hyperalgesia were assessed. MDT and MPT were quantified adjacent to the stimulation site. Tactile hypaesthesia in pain patients and in experimental pain (MDT-z-scores: -0.66+/-0.30 and -0.42+/-0.15, respectively, both p<0.01) was paralleled by mechanical hyperalgesia (MPT-z-scores: +0.51+/-0.27, p<0.05; and +0.48+/-0.10, p<0.001). However, hypaesthesia and hyperalgesia were not correlated. Although 9 patients reported numbness, only 3 of them were able to delineate circumscript areas of tactile hypaesthesia. In experimental pain, the area of tactile hypaesthesia could be mapped in 31/40 experiments (78%). Irrespective of the mode of nociceptive stimulation (phasic vs. tonic) tactile hypaesthesia and hyperalgesia developed with a similar time course and disappeared within approximately 1 day. Hypaesthesia (numbness) often encountered in clinical pain can be reproduced by experimental nociceptive stimulation. The time course of effects suggests a mechanism involving central plasticity.

Force-related neuronal activity in two regions of the primate ventral premotor cortex.

PubMed

Hepp-Reymond, M C; Hüsler, E J; Maier, M A; Ql, H X

1994-05-01

Neuronal activity was recorded in the ventral premotor cortex of one monkey (Macaca fascicularis) trained to exert finely graded forces with thumb and index finger on a force sensor in a visuomotor step-tracking paradigm. Trials with two or three consecutive ramp-and-hold force steps were presented randomly. Most neurons displayed similar discharge patterns in the two- and three-step trials and were assigned to one of the following classes: phasic, phasic-tonic, tonic, decreasing, and mixed. For more than 50% of the neurons with tonic activity, positive or negative correlations between firing rate and force were statistically significant. The indices of force sensitivity were on average higher for the two-step than for the three-step trials, indicating that the correlations yielded linearity over only a limited force range. The force-related cells were located in two regions of the ventral premotor cortex. One group was ying rostrally within the inferior limb of the arcuate sulcus, from which microstimulation elicited movements of fingers and hand. In the other more caudal region, adjacent to the finger region of primary motor cortex, microstimulation was rarely effective, but all neurons had clear peripheral receptive fields on finger and hand. The data indicate that two populations of neurons, located in the ventral premotor cortex, are related to movement execution. Effective microstimulation also suggests that one of the populations has fairly direct access to the spinal motor apparatus.

A connectionist modeling study of the neural mechanisms underlying pain's ability to reorient attention.

PubMed

Dowman, Robert; Ritz, Benjamin; Fowler, Kathleen

2016-08-01

Connectionist modeling was used to investigate the brain mechanisms responsible for pain's ability to shift attention away from another stimulus modality and toward itself. Different connectionist model architectures were used to simulate the different possible brain mechanisms underlying this attentional bias, where nodes in the model simulated the brain areas thought to mediate the attentional bias, and the connections between the nodes simulated the interactions between the brain areas. Mathematical optimization techniques were used to find the model parameters, such as connection strengths, that produced the best quantitative fits of reaction time and event-related potential data obtained in our previous work. Of the several architectures tested, two produced excellent quantitative fits of the experimental data. One involved an unexpected pain stimulus activating somatic threat detectors in the dorsal posterior insula. This threat detector activity was monitored by the medial prefrontal cortex, which in turn evoked a phasic response in the locus coeruleus. The locus coeruleus phasic response resulted in a facilitation of the cortical areas involved in decision and response processes time-locked to the painful stimulus. The second architecture involved the presence of pain causing an increase in general arousal. The increase in arousal was mediated by locus coeruleus tonic activity, which facilitated responses in the cortical areas mediating the sensory, decision, and response processes involved in the task. These two neural network architectures generated competing predictions that can be tested in future studies.

Fear Extinction Memory Consolidation Requires Potentiation of Pontine-Wave Activity during REM Sleep

PubMed Central

Datta, Subimal; O'Malley, Matthew W .

2013-01-01

Sleep plays an important role in memory consolidation within multiple memory systems including contextual fear extinction memory, but little is known about the mechanisms that underlie this process. Here, we show that fear extinction training in rats, which extinguished conditioned fear, increased both slow-wave sleep and rapid-eye movement (REM) sleep. Surprisingly, 24 h later, during memory testing, only 57% of the fear-extinguished animals retained fear extinction memory. We found that these animals exhibited an increase in phasic pontine-wave (P-wave) activity during post-training REM sleep, which was absent in the 43% of animals that failed to retain fear extinction memory. The results of this study provide evidence that brainstem activation, specifically potentiation of phasic P-wave activity, during post-training REM sleep is critical for consolidation of fear extinction memory. The results of this study also suggest that, contrary to the popular hypothesis of sleep and memory, increased sleep after training alone does not guarantee consolidation and/or retention of fear extinction memory. Rather, the potentiation of specific sleep-dependent physiological events may be a more accurate predictor for successful consolidation of fear extinction memory. Identification of this unique mechanism will significantly improve our present understanding of the cellular and molecular mechanisms that underlie the sleep-dependent regulation of emotional memory. Additionally, this discovery may also initiate development of a new, more targeted treatment method for clinical disorders of fear and anxiety in humans that is more efficacious than existing methods such as exposure therapy that incorporate only fear extinction. PMID:23467372

Nucleus accumbens neurons encode Pavlovian approach behaviors: evidence from an autoshaping paradigm.

PubMed

Day, Jeremy J; Wheeler, Robert A; Roitman, Mitchell F; Carelli, Regina M

2006-03-01

Environmental stimuli predictive of appetitive events can elicit Pavlovian approach responses that enhance an organism's ability to track and secure natural rewards, but may also contribute to the compulsive nature of drug addiction. Here, we examined the activity of individual nucleus accumbens (NAc) neurons during an autoshaping paradigm. One conditioned stimulus (CS+, a retractable lever presented for 10 s) was immediately followed by the delivery of a 45-mg sucrose pellet to a food receptacle, while another stimulus (CS-, a separate retractable lever presented for 10 s) was never followed by sucrose. Approach responses directed at the CS+ and CS- were recorded as lever presses and had no experimental consequence. Rats (n = 9) selectively approached the CS+ on more than 80% of trials and were surgically prepared for electrophysiological recording. Of 76 NAc neurons, 57 cells (75%) exhibited increases and/or decreases in firing rate (i.e. termed 'phasically active') during the CS+ presentation and corresponding approach response. Forty-seven percent of phasically active cells (27 out of 57) were characterized by time-locked but transient increases in cell firing, while 53% (30 out of 57) showed a significant reduction in firing for the duration of the CS+. In contrast, the same excitatory subpopulation exhibited smaller increases in activity relative to CS- onset, while the inhibitory subpopulation showed no change in firing during the CS- period. The magnitude and prevalence of cue-related neural responses reported here indicates that the NAc encodes biologically significant, repetitive approach responses that may model the compulsive nature of drug addiction in humans.

Anatase/rutile bi-phasic titanium dioxide nanoparticles for photocatalytic applications enhanced by nitrogen doping and platinum nano-islands.

PubMed

Bear, Joseph C; Gomez, Virginia; Kefallinos, Nikolaos S; McGettrick, James D; Barron, Andrew R; Dunnill, Charles W

2015-12-15

Titanium dioxide (TiO2) bi-phasic powders with individual particles containing an anatase and rutile hetero-junction have been prepared using a sequential layer sol-gel deposition technique to soluble substrates. Sequential thin films of rutile and subsequently anatase TiO2 were deposited onto sodium chloride substrates yielding extremely fragile composite layered discs that fractured into "Janus-like" like powders on substrate dissolution. Nitrogen doped and platinum sputtered analogues were also prepared, and analysed for photocatalytic potential using the photodegradation of Rhodamine B, a model organic pollutant under UV and visible light irradiation. The materials were characterised using X-ray diffraction, X-ray photoelectron spectroscopy, energy dispersive X-ray spectroscopy, Raman spectroscopy and scanning electron microscopy. This paper sheds light on the relationship between anatase and rutile materials when in direct contact and demonstrates a robust method for the synthesis of bi-phasic nanoparticles, ostensibly of any two materials, for photocatalytic reactions or otherwise. Copyright © 2015 Elsevier Inc. All rights reserved.

Automaticity of phasic alertness: evidence for a three-component model of visual cueing

PubMed Central

Lin, Zhicheng; Lu, Zhong-Lin

2017-01-01

The automaticity of phasic alertness is investigated using the attention network test. Results show that the cueing effect from the alerting cue—double cue—is strongly enhanced by the task relevance of visual cues, as determined by the informativeness of the orienting cue—single cue—that is being mixed (80% vs. 50% valid in predicting where the target will appear). Counterintuitively, the cueing effect from the alerting cue can be negatively affected by its visibility, such that masking the cue from awareness can reveal a cueing effect that is otherwise absent when the cue is visible. Evidently, top-down influences—in the form of contextual relevance and cue awareness—can have opposite influences on the cueing effect by the alerting cue. These findings lead us to the view that a visual cue can engage three components of attention—orienting, alerting, and inhibition—to determine the behavioral cueing effect. We propose that phasic alertness, particularly in the form of specific response readiness, is regulated by both internal, top-down expectation and external, bottom-up stimulus properties. In contrast to some existing views, we advance the perspective that phasic alertness is strongly tied to temporal orienting, attentional capture, and spatial orienting. Finally, we discuss how translating attention research to clinical applications would benefit from an improved ability to measure attention. To this end, controlling the degree of intraindividual variability in the attentional components and improving the precision of the measurement tools may prove vital. PMID:27173487

Automaticity of phasic alertness: Evidence for a three-component model of visual cueing.

PubMed

Lin, Zhicheng; Lu, Zhong-Lin

2016-10-01

The automaticity of phasic alertness is investigated using the attention network test. Results show that the cueing effect from the alerting cue-double cue-is strongly enhanced by the task relevance of visual cues, as determined by the informativeness of the orienting cue-single cue-that is being mixed (80 % vs. 50 % valid in predicting where the target will appear). Counterintuitively, the cueing effect from the alerting cue can be negatively affected by its visibility, such that masking the cue from awareness can reveal a cueing effect that is otherwise absent when the cue is visible. Evidently, then, top-down influences-in the form of contextual relevance and cue awareness-can have opposite influences on the cueing effect from the alerting cue. These findings lead us to the view that a visual cue can engage three components of attention-orienting, alerting, and inhibition-to determine the behavioral cueing effect. We propose that phasic alertness, particularly in the form of specific response readiness, is regulated by both internal, top-down expectation and external, bottom-up stimulus properties. In contrast to some existing views, we advance the perspective that phasic alertness is strongly tied to temporal orienting, attentional capture, and spatial orienting. Finally, we discuss how translating attention research to clinical applications would benefit from an improved ability to measure attention. To this end, controlling the degree of intraindividual variability in the attentional components and improving the precision of the measurement tools may prove vital.

Temporal kinetics of prefrontal modulation of the extrastriate cortex during visual attention.

PubMed

Yago, Elena; Duarte, Audrey; Wong, Ting; Barceló, Francisco; Knight, Robert T

2004-12-01

Single-unit, event-related potential (ERP), and neuroimaging studies have implicated the prefrontal cortex (PFC) in top-down control of attention and working memory. We conducted an experiment in patients with unilateral PFC damage (n = 8) to assess the temporal kinetics of PFC-extrastriate interactions during visual attention. Subjects alternated attention between the left and the right hemifields in successive runs while they detected target stimuli embedded in streams of repetitive task-irrelevant stimuli (standards). The design enabled us to examine tonic (spatial selection) and phasic (feature selection) PFC-extrastriate interactions. PFC damage impaired performance in the visual field contralateral to lesions, as manifested by both larger reaction times and error rates. Assessment of the extrastriate P1 ERP revealed that the PFC exerts a tonic (spatial selection) excitatory input to the ipsilateral extrastriate cortex as early as 100 msec post stimulus delivery. The PFC exerts a second phasic (feature selection) excitatory extrastriate modulation from 180 to 300 msec, as evidenced by reductions in selection negativity after damage. Finally, reductions of the N2 ERP to target stimuli supports the notion that the PFC exerts a third phasic (target selection) signal necessary for successful template matching during postselection analysis of target features. The results provide electrophysiological evidence of three distinct tonic and phasic PFC inputs to the extrastriate cortex in the initial few hundred milliseconds of stimulus processing. Damage to this network appears to underlie the pervasive deficits in attention observed in patients with prefrontal lesions.

The Rate of Change of Vergence-Accommodation Conflict Affects Visual Discomfort

PubMed Central

Kane, David; Banks, Martin S.

2014-01-01

Stereoscopic (S3D) displays create conflicts between the distance to which the eyes must converge and the distance to which the eyes must accommodate. Such conflicts require the viewer to overcome the normal coupling between vergence and accommodation, and this effort appears to cause viewer discomfort. Vergence-accommodation coupling is driven by the phasic components of the underlying control systems, and those components respond to relatively fast changes in vergence and accommodative stimuli. Given the relationship between phasic changes and vergence-accommodation coupling, we examined how the rate of change in the vergence-accommodation conflict affects viewer discomfort. We used a stereoscopic display that allows independent manipulation of the stimuli to vergence and accommodation. We presented stimuli that simulate natural viewing (i.e., vergence and accommodative stimuli changed together) and stimuli that simulate S3D viewing (i.e., vergence stimulus changes but accommodative stimulus remains fixed). The changes occurred at 0.01, 0.05, or 0.25Hz. The lowest rate is too slow to stimulate the phasic components while the highest rate is well within the phasic range. The results were consistent with our expectation: somewhat greater discomfort was experienced when stimulus distance changed rapidly, particularly in S3D viewing when the vergence stimulus changed but the accommodative stimulus did not. These results may help in the generation of guidelines for the creation and viewing of stereo content with acceptable viewer comfort. PMID:25448713

Effects of substance P on spontaneous contraction in the flexure region of the guinea pig colon.

PubMed

Chowdhury, J U; Nahar, N S

2007-01-01

Effects of Substance P on spontaneous contractions of the circular muscle of the flexure region of guinea pig colon were studied by mechanical tension recording. Substance P (3 nM-10 nM) produced tonic contraction associated with phasic activities but the contraction was found stronger at higher concentration. Verapamil (3 microM), a voltage dependent L-type Ca(2+) channel blocker completely blocked the spontaneous activities and also Substance P induced contraction. These results suggest that Substance P produce contraction by Ca(2+) influx and the Ca(2+) influx occurs by activating verapamil sensitive Ca(2+) channel.

Arousal amplifies biased competition between high and low priority memories more in women than in men: the role of elevated noradrenergic activity

PubMed Central

Clewett, David; Sakaki, Michiko; Huang, Ringo; Nielsen, Shawn E.; Mather, Mara

2017-01-01

Recent findings indicate that emotional arousal can enhance memory consolidation of goal-relevant stimuli while impairing it for irrelevant stimuli. According to one recent model, these goal-dependent memory tradeoffs are driven by arousal-induced release of norepinephrine (NE), which amplifies neural gain in target sensory and memory processing brain regions. Past work also shows that ovarian hormones modulate activity in the same regions thought to support NE’s effects on memory, such as the amygdala, suggesting that men and women may be differentially susceptible to arousal’s dual effects on episodic memory. Here, we aimed to determine the neurohormonal mechanisms that mediate arousal-biased competition processes in memory. In a competitive visuo-attention task, participants viewed images of a transparent object overlaid on a background scene and explicitly memorized one of these stimuli while ignoring the other. Participants then heard emotional or neutral audio-clips and provided a subjective arousal rating. Hierarchical generalized linear modeling (HGLM) analyses revealed that greater pre-to-post task increases in salivary alpha-amylase (sAA), a biomarker of noradrenergic activity, was associated with significantly greater arousal-enhanced memory tradeoffs in women than in men. These sex-dependent effects appeared to result from phasic and background noradrenergic activity interacting to suppress task-irrelevant representations in women but enhancing them in men. Additionally, in naturally cycling women, low ovarian hormone levels interacted with increased noradrenergic activity to amplify memory selectivity independently of emotion-induced arousal. Together these findings suggest that increased noradrenergic transmission enhances preferential consolidation of goal-relevant memory traces according to phasic arousal and ovarian hormone levels in women. PMID:28324703

Human thoracic duct in vitro: diameter-tension properties, spontaneous and evoked contractile activity.

PubMed

Telinius, Niklas; Drewsen, Nanna; Pilegaard, Hans; Kold-Petersen, Henrik; de Leval, Marc; Aalkjaer, Christian; Hjortdal, Vibeke; Boedtkjer, Donna Briggs

2010-09-01

The current study characterizes the mechanical properties of the human thoracic duct and demonstrates a role for adrenoceptors, thromboxane, and endothelin receptors in human lymph vessel function. With ethical permission and informed consent, portions of the thoracic duct (2-5 cm) were resected and retrieved at T(7)-T(9) during esophageal and cardia cancer surgery. Ring segments (2 mm long) were mounted in a myograph for isometric tension (N/m) measurement. The diameter-tension relationship was established using ducts from 10 individuals. Peak active tension of 6.24 +/- 0.75 N/m was observed with a corresponding passive tension of 3.11 +/- 0.67 N/m and average internal diameter of 2.21 mm. The equivalent active and passive transmural pressures by LaPlace's law were 47.3 +/- 4.7 and 20.6 +/- 3.2 mmHg, respectively. Subsequently, pharmacology was performed on rings from 15 ducts that were normalized by stretching them until an equivalent pressure of 21 mmHg was calculable from the wall tension. At low concentrations, norepinephrine, endothelin-1, and the thromboxane-A(2) analog U-46619 evoked phasic contractions (analogous to lymphatic pumping), whereas at higher contractions they induced tonic activity (maximum tension values of 4.46 +/- 0.63, 5.90 +/- 1.4, and 6.78 +/- 1.4 N/m, respectively). Spontaneous activity was observed in 44% of ducts while 51% of all the segments produced phasic contractions after agonist application. Acetylcholine and bradykinin relaxed norepinephrine preconstrictions by approximately 20% and approximately 40%, respectively. These results demonstrate that the human thoracic duct can develop wall tensions that permit contractility to be maintained across a wide range of transmural pressures and that isolated ducts contract in response to important vasoactive agents.

Arousal amplifies biased competition between high and low priority memories more in women than in men: The role of elevated noradrenergic activity.

PubMed

Clewett, David; Sakaki, Michiko; Huang, Ringo; Nielsen, Shawn E; Mather, Mara

2017-06-01

Recent findings indicate that emotional arousal can enhance memory consolidation of goal-relevant stimuli while impairing it for irrelevant stimuli. According to one recent model, these goal-dependent memory tradeoffs are driven by arousal-induced release of norepinephrine (NE), which amplifies neural gain in target sensory and memory processing brain regions. Past work also shows that ovarian hormones modulate activity in the same regions thought to support NE's effects on memory, such as the amygdala, suggesting that men and women may be differentially susceptible to arousal's dual effects on episodic memory. Here, we aimed to determine the neurohormonal mechanisms that mediate arousal-biased competition processes in memory. In a competitive visuo-attention task, participants viewed images of a transparent object overlaid on a background scene and explicitly memorized one of these stimuli while ignoring the other. Participants then heard emotional or neutral audio-clips and provided a subjective arousal rating. Hierarchical generalized linear modeling (HGLM) analyses revealed that greater pre-to-post task increases in salivary alpha-amylase (sAA), a biomarker of noradrenergic activity, was associated with significantly greater arousal-enhanced memory tradeoffs in women than in men. These sex-dependent effects appeared to result from phasic and background noradrenergic activity interacting to suppress task-irrelevant representations in women but enhancing them in men. Additionally, in naturally cycling women, low ovarian hormone levels interacted with increased noradrenergic activity to amplify memory selectivity independently of emotion-induced arousal. Together these findings suggest that increased noradrenergic transmission enhances preferential consolidation of goal-relevant memory traces according to phasic arousal and ovarian hormone levels in women. Copyright © 2017 Elsevier Ltd. All rights reserved.

The NADPH oxidase inhibitor diphenyleneiodonium is also a potent inhibitor of cholinesterases and the internal Ca2+ pump

PubMed Central

Tazzeo, T; Worek, F; Janssen, LJ

2009-01-01

Background and purpose: Diphenyleneiodonium (DPI) is often used as an NADPH oxidase inhibitor, but is increasingly being found to have unrelated side effects. We investigated its effects on smooth muscle contractions and the related mechanisms. Experimental approach: We studied isometric contractions in smooth muscle strips from bovine trachea. Cholinesterase activity was measured using a spectrophotometric assay; internal Ca2+ pump activity was assessed by Ca2+ uptake into smooth muscle microsomes. Key results: Contractions to acetylcholine were markedly enhanced by DPI (10−4 M), whereas those to carbachol (CCh) were not, suggesting a possible inhibition of cholinesterase. DPI markedly suppressed contractions evoked by CCh, KCl and 5-HT, and also unmasked phasic activity in otherwise sustained responses. Direct biochemical assays confirmed that DPI was a potent inhibitor of acetylcholinesterase and butyrylcholinesterase (IC50∼8 × 10−6 M and 6 × 10−7 M, respectively), following a readily reversible, mixed non-competitive type of inhibition. The inhibitory effects of DPI on CCh contractions were not mimicked by another NADPH oxidase inhibitor (apocynin), nor the Src inhibitors PP1 or PP2, ruling out an action through the NADPH oxidase signalling pathway. Several features of the DPI-mediated suppression of agonist-evoked responses (i.e. suppression of peak magnitudes and unmasking of phasic activity) are similar to those of cyclopiazonic acid, an inhibitor of the internal Ca2+ pump. Direct measurement of microsomal Ca2+ uptake revealed that DPI modestly inhibits the internal Ca2+ pump. Conclusions and implications: DPI inhibits cholinesterase activity and the internal Ca2+ pump in tracheal smooth muscle. PMID:19788497

[Flexibility of cognitive activity depends on its context].

PubMed

Kostandov, É A

2010-01-01

The main purpose of this survey is to explain the importance of set-shifting for a flexible cognitive activity. Working memory overload may result in set-shifting slowdown, i.e., in a more rigid set and in a less flexible cognitive activity. This effect displays itself in an increase of erroneous perceptions of external stimuli. Set rigidity level also depends on the cognitive activity context (i.e., on the type of external stimuli the person has to deal with). We analyzed EEG-coherence function and induced synchronization/desynchronization responses in theta (4-7 Hz) and low alpha (8-10 Hz) bands. Basing on these data, we discuss the role of tonic and phasic forms of cortico-hippocampal and fronto-thalamic systems' activation in cognitive activity flexibility.

Episodic Social Stress-Escalated Cocaine Self-Administration: Role of Phasic and Tonic Corticotropin Releasing Factor in the Anterior and Posterior Ventral Tegmental Area.

PubMed

Holly, Elizabeth N; Boyson, Christopher O; Montagud-Romero, Sandra; Stein, Dirson J; Gobrogge, Kyle L; DeBold, Joseph F; Miczek, Klaus A

2016-04-06

Intermittent social defeat stress escalates later cocaine self-administration. Reward and stress both activate ventral tegmental area (VTA) dopamine neurons, increasing downstream extracellular dopamine concentration in the medial prefrontal cortex and nucleus accumbens. The stress neuropeptide corticotropin releasing factor (CRF) and its receptors (CRF-R1, CRF-R2) are located in the VTA and influence dopaminergic activity. These experiments explore how CRF release and the activation of its receptors within the VTA both during and after stress influence later cocaine self-administration in rats.In vivo microdialysis of CRF in the VTA demonstrated that CRF is phasically released in the posterior VTA (pVTA) during acute defeat, but, with repeated defeat, CRF is recruited into the anterior VTA (aVTA) and CRF tone is increased in both subregions. Intra-VTA antagonism of CRF-R1 in the pVTA and CRF-R2 in the aVTA during each social defeat prevented escalated cocaine self-administration in a 24 h "binge." VTA CRF continues to influence cocaine seeking in stressed animals long after social defeat exposure. Unlike nonstressed controls, previously stressed rats show significant cocaine seeking after 15 d of forced abstinence. Previously stressed rats continue to express elevated CRF tone within the VTA and antagonism of pVTA CRF-R1 or aVTA CRF-R2 reverses cocaine seeking. In conclusion, these experiments demonstrate neuroadaptive changes in tonic and phasic CRF with repeated stress, that CRF release during stress may contribute to later escalated cocaine taking, and that persistently elevated CRF tone in the VTA may drive later cocaine seeking through increased activation of pVTA CRF-R1 and aVTA CRF-R2. Corticotropin releasing factor (CRF) within the ventral tegmental area (VTA) has emerged as a likely candidate molecule underlying the fundamental link between stress history and escalated drug self-administration. However, the nature of CRF release in the VTA during acute and repeated stress, as well as its role in enduring neuroadaptations driving later drug taking and seeking, are poorly understood. These experiments explore how CRF is released and interacts with its receptors in specific regions of the VTA both during and after stress to fuel later escalated cocaine taking and seeking behavior. Understanding these acute and persistent changes to the VTA CRF system may lead to better therapeutic interventions for addiction. Copyright © 2016 the authors 0270-6474/16/364094-13$15.00/0.

Episodic Social Stress-Escalated Cocaine Self-Administration: Role of Phasic and Tonic Corticotropin Releasing Factor in the Anterior and Posterior Ventral Tegmental Area

PubMed Central

Boyson, Christopher O.; Montagud-Romero, Sandra; Stein, Dirson J.; Gobrogge, Kyle L.; DeBold, Joseph F.; Miczek, Klaus A.

2016-01-01

Intermittent social defeat stress escalates later cocaine self-administration. Reward and stress both activate ventral tegmental area (VTA) dopamine neurons, increasing downstream extracellular dopamine concentration in the medial prefrontal cortex and nucleus accumbens. The stress neuropeptide corticotropin releasing factor (CRF) and its receptors (CRF-R1, CRF-R2) are located in the VTA and influence dopaminergic activity. These experiments explore how CRF release and the activation of its receptors within the VTA both during and after stress influence later cocaine self-administration in rats. In vivo microdialysis of CRF in the VTA demonstrated that CRF is phasically released in the posterior VTA (pVTA) during acute defeat, but, with repeated defeat, CRF is recruited into the anterior VTA (aVTA) and CRF tone is increased in both subregions. Intra-VTA antagonism of CRF-R1 in the pVTA and CRF-R2 in the aVTA during each social defeat prevented escalated cocaine self-administration in a 24 h “binge.” VTA CRF continues to influence cocaine seeking in stressed animals long after social defeat exposure. Unlike nonstressed controls, previously stressed rats show significant cocaine seeking after 15 d of forced abstinence. Previously stressed rats continue to express elevated CRF tone within the VTA and antagonism of pVTA CRF-R1 or aVTA CRF-R2 reverses cocaine seeking. In conclusion, these experiments demonstrate neuroadaptive changes in tonic and phasic CRF with repeated stress, that CRF release during stress may contribute to later escalated cocaine taking, and that persistently elevated CRF tone in the VTA may drive later cocaine seeking through increased activation of pVTA CRF-R1 and aVTA CRF-R2. SIGNIFICANCE STATEMENT Corticotropin releasing factor (CRF) within the ventral tegmental area (VTA) has emerged as a likely candidate molecule underlying the fundamental link between stress history and escalated drug self-administration. However, the nature of CRF release in the VTA during acute and repeated stress, as well as its role in enduring neuroadaptations driving later drug taking and seeking, are poorly understood. These experiments explore how CRF is released and interacts with its receptors in specific regions of the VTA both during and after stress to fuel later escalated cocaine taking and seeking behavior. Understanding these acute and persistent changes to the VTA CRF system may lead to better therapeutic interventions for addiction. PMID:27053215

Coexistence of gamma and high-frequency oscillations in rat medial entorhinal cortex in vitro

PubMed Central

Cunningham, M O; Halliday, David M; Davies, Ceri H; Traub, Roger D; Buhl, Eberhard H; Whittington, Miles A

2004-01-01

High frequency oscillations (> 80–90 Hz) occur in neocortex and hippocampus in vivo where they are associated with specific behavioural states and more classical EEG frequency bands. In the hippocampus in vitro these oscillations can occur in the absence of pyramidal neuronal somatodendritic compartments and are temporally correlated with on-going, persistent gamma frequency oscillations. Their occurrence in the hippocampus is dependent on gap-junctional communication and it has been suggested that these high frequency oscillations originate as collective behaviour in populations of electrically coupled principal cell axonal compartments. Here we demonstrate that the superficial layers of medial entorhinal cortex can also generate high frequency oscillations associated with gamma rhythms. During persistent gamma frequency oscillations high frequency oscillations occur with a high bispectral coherence with the field gamma activity. Bursts of high frequency oscillations are temporally correlated with both the onset of compound excitatory postsynaptic potentials in fast-spiking interneurones and spikelet potentials in both pyramidal and stellate principal neurones. Both the gamma frequency and high frequency oscillations were attenuated by the gap junction blocker carbenoxolone. These data suggest that high frequency oscillations may represent the substrate for phasic drive to interneurones during persistent gamma oscillations in the medial entorhinal cortex. PMID:15254156

Dependence of intramyocardial pressure and coronary flow on ventricular loading and contractility: a model study.

PubMed

Bovendeerd, Peter H M; Borsje, Petra; Arts, Theo; van De Vosse, Frans N

2006-12-01

The phasic coronary arterial inflow during the normal cardiac cycle has been explained with simple (waterfall, intramyocardial pump) models, emphasizing the role of ventricular pressure. To explain changes in isovolumic and low afterload beats, these models were extended with the effect of three-dimensional wall stress, nonlinear characteristics of the coronary bed, and extravascular fluid exchange. With the associated increase in the number of model parameters, a detailed parameter sensitivity analysis has become difficult. Therefore we investigated the primary relations between ventricular pressure and volume, wall stress, intramyocardial pressure and coronary blood flow, with a mathematical model with a limited number of parameters. The model replicates several experimental observations: the phasic character of coronary inflow is virtually independent of maximum ventricular pressure, the amplitude of the coronary flow signal varies about proportionally with cardiac contractility, and intramyocardial pressure in the ventricular wall may exceed ventricular pressure. A parameter sensitivity analysis shows that the normalized amplitude of coronary inflow is mainly determined by contractility, reflected in ventricular pressure and, at low ventricular volumes, radial wall stress. Normalized flow amplitude is less sensitive to myocardial coronary compliance and resistance, and to the relation between active fiber stress, time, and sarcomere shortening velocity.

Acute phenylalanine/tyrosine depletion of phasic dopamine in the rat brain.

PubMed

Shnitko, Tatiana A; Taylor, Sarah C; Stringfield, Sierra J; Zandy, Shannon L; Cofresí, Roberto U; Doherty, James M; Lynch, William B; Boettiger, Charlotte A; Gonzales, Rueben A; Robinson, Donita L

2016-06-01

Dopamine plays a critical role in striatal and cortical function, and depletion of the dopamine precursors phenylalanine and tyrosine is used in humans to temporarily reduce dopamine and probe the role of dopamine in behavior. This method has been shown to alter addiction-related behaviors and cognitive functioning presumably by reducing dopamine transmission, but it is unclear what specific aspects of dopamine transmission are altered. We performed this study to confirm that administration of an amino acid mixture omitting phenylalanine and tyrosine (Phe/Tyr[-]) reduces tyrosine tissue content in the prefrontal cortex (PFC) and nucleus accumbens (NAc), and to test the hypothesis that Phe/Tyr[-] administration reduces phasic dopamine release in the NAc. Rats were injected with a Phe/Tyr[-] amino acid mixture, a control amino acid mixture, or saline. High-performance liquid chromatography was used to determine the concentration of tyrosine, dopamine, or norepinephrine in tissue punches from the PFC and ventral striatum. In a separate group of rats, phasic dopamine release was measured with fast-scan cyclic voltammetry in the NAc core after injection with either the Phe/Tyr[-] mixture or the control amino acid solution. Phe/Tyr[-] reduced tyrosine content in the PFC and NAc, but dopamine and norepinephrine tissue content were not reduced. Moreover, Phe/Tyr[-] decreased the frequency of dopamine transients, but not their amplitude, in freely moving rats. These results indicate that depletion of tyrosine via Phe/Tyr[-] decreases phasic dopamine transmission, providing insight into the mechanism by which this method modifies dopamine-dependent behaviors in human imaging studies.

Dopamine reward prediction-error signalling: a two-component response

PubMed Central

Schultz, Wolfram

2017-01-01

Environmental stimuli and objects, including rewards, are often processed sequentially in the brain. Recent work suggests that the phasic dopamine reward prediction-error response follows a similar sequential pattern. An initial brief, unselective and highly sensitive increase in activity unspecifically detects a wide range of environmental stimuli, then quickly evolves into the main response component, which reflects subjective reward value and utility. This temporal evolution allows the dopamine reward prediction-error signal to optimally combine speed and accuracy. PMID:26865020

Behavior-associated and post-consumption glucose entry into the nucleus accumbens extracellular space during glucose free-drinking in trained rats

PubMed Central

Wakabayashi, Ken T.; Kiyatkin, Eugene A.

2015-01-01

Glucose is the primary energetic substrate for the metabolic activity of brain cells and its proper delivery from the arterial blood is essential for neural activity and normal brain functions. Glucose is also a unique natural reinforcer, supporting glucose-drinking behavior without food or water deprivation. While it is known that glucose enters brain tissue via gradient-dependent facilitated diffusion, it remains unclear how glucose levels are changed during natural behavior and whether the direct central action of ingested glucose can be involved in regulating glucose-drinking behavior. Here, we used glucose biosensors with high-speed amperometry to examine the pattern of phasic and tonic changes in extracellular glucose in the nucleus accumbens (NAc) during unrestricted glucose-drinking in well-trained rats. We found that the drinking behavior is highly cyclic and is associated with relatively large and prolonged increases in extracellular glucose levels. These increases had two distinct components: a highly phasic but relatively small behavior-related rise and a larger tonic elevation that results from the arrival of consumed glucose into the brain’s extracellular space. The large post-ingestion increases in NAc glucose began minutes after the cessation of drinking and were consistently associated with periods of non-drinking, suggesting that the central action of ingested glucose could inhibit drinking behavior by inducing a pause in activity between repeated drinking bouts. Finally, the difference in NAc glucose responses found between active, behavior-mediated and passive glucose delivery via an intra-gastric catheter confirms that motivated behavior is also associated with metabolic glucose use by brain cells. PMID:26190984

Rapid signalling in distinct dopaminergic axons during locomotion and reward.

PubMed

Howe, M W; Dombeck, D A

2016-07-28

Dopaminergic projection axons from the midbrain to the striatum are crucial for motor control, as their degeneration in Parkinson disease results in profound movement deficits. Paradoxically, most recording methods report rapid phasic dopamine signalling (~100-ms bursts) in response to unpredicted rewards, with little evidence for movement-related signalling. The leading model posits that phasic signalling in striatum-targeting dopamine neurons drives reward-based learning, whereas slow variations in firing (tens of seconds to minutes) in these same neurons bias animals towards or away from movement. However, current methods have provided little evidence to support or refute this model. Here, using new optical recording methods, we report the discovery of rapid phasic signalling in striatum-targeting dopaminergic axons that is associated with, and capable of triggering, locomotion in mice. Axons expressing these signals were largely distinct from those that responded to unexpected rewards. These results suggest that dopaminergic neuromodulation can differentially impact motor control and reward learning with sub-second precision, and indicate that both precise signal timing and neuronal subtype are important parameters to consider in the treatment of dopamine-related disorders.

Rapid signaling in distinct dopaminergic axons during locomotion and reward

PubMed Central

Howe, MW; Dombeck, DA

2016-01-01

Summary Dopaminergic projections from the midbrain to striatum are critical for motor control, as their degeneration in Parkinson’s disease results in profound movement deficits. Paradoxically, most recording methods report rapid phasic dopamine signaling (~100ms bursts) to unpredicted rewards, with little evidence for movement-related signaling. The leading model posits that phasic signaling in striatum targeting dopamine neurons drive reward-based learning, while slow variations in firing (tens of seconds to minutes) in these same neurons bias animals towards or away from movement. However, despite widespread acceptance of this model, current methods have provided little evidence to support or refute it. Here, using new optical recording methods, we report the discovery of rapid phasic signaling in striatum-targeting dopaminergic axons that was associated with, and capable of triggering, locomotion in mice. Axons expressing these signals were largely distinct from those signaling during unexpected rewards. These results suggest that dopaminergic neuromodulation can differentially impact motor control and reward learning with sub-second precision and suggest that both precise signal timing and neuronal subtype are important parameters to consider in the treatment of dopamine-related disorders. PMID:27398617

Dynamic Interaction of Spindles and Gamma Activity during Cortical Slow Oscillations and Its Modulation by Subcortical Afferents

PubMed Central

Valencia, Miguel; Artieda, Julio; Bolam, J. Paul; Mena-Segovia, Juan

2013-01-01

Slow oscillations are a hallmark of slow wave sleep. They provide a temporal framework for a variety of phasic events to occur and interact during sleep, including the expression of high-frequency oscillations and the discharge of neurons across the entire brain. Evidence shows that the emergence of distinct high-frequency oscillations during slow oscillations facilitates the communication among brain regions whose activity was correlated during the preceding waking period. While the frequencies of oscillations involved in such interactions have been identified, their dynamics and the correlations between them require further investigation. Here we analyzed the structure and dynamics of these signals in anesthetized rats. We show that spindles and gamma oscillations coexist but have distinct temporal dynamics across the slow oscillation cycle. Furthermore, we observed that spindles and gamma are functionally coupled to the slow oscillations and between each other. Following the activation of ascending pathways from the brainstem by means of a carbachol injection in the pedunculopontine nucleus, we were able to modify the gain in the gamma oscillations that are independent of the spindles while the spindle amplitude was reduced. Furthermore, carbachol produced a decoupling of the gamma oscillations that are dependent on the spindles but with no effect on their amplitude. None of the changes in the high-frequency oscillations affected the onset or shape of the slow oscillations, suggesting that slow oscillations occur independently of the phasic events that coexist with them. Our results provide novel insights into the regulation, dynamics and homeostasis of cortical slow oscillations. PMID:23844020

The Generation of Antiphase Oscillations and Synchrony by a Rebound-Based Vertebrate Central Pattern Generator

PubMed Central

Merrison-Hort, Robert; Zhang, Hong-Yan; Borisyuk, Roman

2014-01-01

Many neural circuits are capable of generating multiple stereotyped outputs after different sensory inputs or neuromodulation. We have previously identified the central pattern generator (CPG) for Xenopus tadpole swimming that involves antiphase oscillations of activity between the left and right sides. Here we analyze the cellular basis for spontaneous left–right motor synchrony characterized by simultaneous bursting on both sides at twice the swimming frequency. Spontaneous synchrony bouts are rare in most tadpoles, and they instantly emerge from and switch back to swimming, most frequently within the first second after skin stimulation. Analyses show that only neurons that are active during swimming fire action potentials in synchrony, suggesting both output patterns derive from the same neural circuit. The firing of excitatory descending interneurons (dINs) leads that of other types of neurons in synchrony as it does in swimming. During synchrony, the time window between phasic excitation and inhibition is 7.9 ± 1 ms, shorter than that in swimming (41 ± 2.3 ms). The occasional, extra midcycle firing of dINs during swimming may initiate synchrony, and mismatches of timing in the left and right activity can switch synchrony back to swimming. Computer modeling supports these findings by showing that the same neural network, in which reciprocal inhibition mediates rebound firing, can generate both swimming and synchrony without circuit reconfiguration. Modeling also shows that lengthening the time window between phasic excitation and inhibition by increasing dIN synaptic/conduction delay can improve the stability of synchrony. PMID:24760866

Shades of grey; Assessing the contribution of the magno- and parvocellular systems to neural processing of the retinal input in the human visual system from the influence of neural population size and its discharge activity on the VEP.

PubMed

Marcar, Valentine L; Baselgia, Silvana; Lüthi-Eisenegger, Barbara; Jäncke, Lutz

2018-03-01

Retinal input processing in the human visual system involves a phasic and tonic neural response. We investigated the role of the magno- and parvocellular systems by comparing the influence of the active neural population size and its discharge activity on the amplitude and latency of four VEP components. We recorded the scalp electric potential of 20 human volunteers viewing a series of dartboard images presented as a pattern reversing and pattern on-/offset stimulus. These patterns were designed to vary both neural population size coding the temporal- and spatial luminance contrast property and the discharge activity of the population involved in a systematic manner. When the VEP amplitude reflected the size of the neural population coding the temporal luminance contrast property of the image, the influence of luminance contrast followed the contrast response function of the parvocellular system. When the VEP amplitude reflected the size of the neural population responding to the spatial luminance contrast property the image, the influence of luminance contrast followed the contrast response function of the magnocellular system. The latencies of the VEP components examined exhibited the same behavior across our stimulus series. This investigation demonstrates the complex interplay of the magno- and parvocellular systems on the neural response as captured by the VEP. It also demonstrates a linear relationship between stimulus property, neural response, and the VEP and reveals the importance of feedback projections in modulating the ongoing neural response. In doing so, it corroborates the conclusions of our previous study.

Modulation of the masseteric reflex by gastric vagal afferents.

PubMed

Pettorossi, V E

1983-04-01

Several investigations have shown that the vagal nerve can affect the reflex responses of the masticatory muscles acting at level either of trigeminal motoneurons or of the mesencephalic trigeminal nucleus (MTN). The present experiments have been devoted to establish the origin of the vagal afferent fibres involved in modulating the masseteric reflex. In particular, the gastric vagal afferents were taken into consideration and selective stimulations of such fibres were performed in rabbit. Conditioning electrical stimulation of truncus vagalis ventralis (TVV) reduced the excitability of the MTN cells as shown by a decrease of the antidromic response recorded from the semilunar ganglion and elicited by MTN single-shock electrical stimulation. Sympathetic and cardiovascular influences were not involved in these responses. Mechanical stimulation of gastric receptors, by means of gastric distension, clearly diminished the amplitude of twitch tension of masseteric reflex and inhibited the discharge frequency of proprioceptive MTN units. The effect was phasic and depended upon the velocity of distension. Thus the sensory volleys originating from rapid adapting receptors reach the brain stem through vagal afferents and by means of a polysynaptic connection inhibits the masseteric reflex at level of MTN cells.

Tri-phasic fever in dengue fever.

PubMed

D, Pradeepa H; Rao, Sathish B; B, Ganaraj; Bhat, Gopalakrishna; M, Chakrapani

2018-04-01

Dengue fever is an acute febrile illness with a duration of 2-12 days. Our observational study observed the 24-h continuous tympanic temperature pattern of 15 patients with dengue fever and compared this with 26 others with fever due to a non-dengue aetiology. A tri-phasic fever pattern was seen among two-thirds of dengue fever patients, but in only one with an inflammatory disease. One-third of dengue fever patients exhibited a single peak temperature. Continuous temperature monitoring and temperature pattern analysis in clinical settings can aid in the early differentiation of dengue fever from non-dengue aetiology.

Three-dimensional real-time imaging of bi-phasic flow through porous media

NASA Astrophysics Data System (ADS)

Sharma, Prerna; Aswathi, P.; Sane, Anit; Ghosh, Shankar; Bhattacharya, S.

2011-11-01

We present a scanning laser-sheet video imaging technique to image bi-phasic flow in three-dimensional porous media in real time with pore-scale spatial resolution, i.e., 35 μm and 500 μm for directions parallel and perpendicular to the flow, respectively. The technique is illustrated for the case of viscous fingering. Using suitable image processing protocols, both the morphology and the movement of the two-fluid interface, were quantitatively estimated. Furthermore, a macroscopic parameter such as the displacement efficiency obtained from a microscopic (pore-scale) analysis demonstrates the versatility and usefulness of the method.

Extrasynaptic Glycine Receptors of Rodent Dorsal Raphe Serotonergic Neurons: A Sensitive Target for Ethanol

PubMed Central

Maguire, Edward P; Mitchell, Elizabeth A; Greig, Scott J; Corteen, Nicole; Balfour, David J K; Swinny, Jerome D; Lambert, Jeremy J; Belelli, Delia

2014-01-01

Alcohol abuse is a significant medical and social problem. Several neurotransmitter systems are implicated in ethanol's actions, with certain receptors and ion channels emerging as putative targets. The dorsal raphe (DR) nucleus is associated with the behavioral actions of alcohol, but ethanol actions on these neurons are not well understood. Here, using immunohistochemistry and electrophysiology we characterize DR inhibitory transmission and its sensitivity to ethanol. DR neurons exhibit inhibitory ‘phasic' post-synaptic currents mediated primarily by synaptic GABAA receptors (GABAAR) and, to a lesser extent, by synaptic glycine receptors (GlyR). In addition to such phasic transmission mediated by the vesicular release of neurotransmitter, the activity of certain neurons may be governed by a ‘tonic' conductance resulting from ambient GABA activating extrasynaptic GABAARs. However, for DR neurons extrasynaptic GABAARs exert only a limited influence. By contrast, we report that unusually the GlyR antagonist strychnine reveals a large tonic conductance mediated by extrasynaptic GlyRs, which dominates DR inhibition. In agreement, for DR neurons strychnine increases their input resistance, induces membrane depolarization, and consequently augments their excitability. Importantly, this glycinergic conductance is greatly enhanced in a strychnine-sensitive fashion, by behaviorally relevant ethanol concentrations, by drugs used for the treatment of alcohol withdrawal, and by taurine, an ingredient of certain ‘energy drinks' often imbibed with ethanol. These findings identify extrasynaptic GlyRs as critical regulators of DR excitability and a novel molecular target for ethanol. PMID:24264816

A plastic corticostriatal circuit model of adaptation in perceptual decision making

PubMed Central

Hsiao, Pao-Yueh; Lo, Chung-Chuan

2013-01-01

The ability to optimize decisions and adapt them to changing environments is a crucial brain function that increase survivability. Although much has been learned about the neuronal activity in various brain regions that are associated with decision making, and about how the nervous systems may learn to achieve optimization, the underlying neuronal mechanisms of how the nervous systems optimize decision strategies with preference given to speed or accuracy, and how the systems adapt to changes in the environment, remain unclear. Based on extensive empirical observations, we addressed the question by extending a previously described cortico-basal ganglia circuit model of perceptual decisions with the inclusion of a dynamic dopamine (DA) system that modulates spike-timing dependent plasticity (STDP). We found that, once an optimal model setting that maximized the reward rate was selected, the same setting automatically optimized decisions across different task environments through dynamic balancing between the facilitating and depressing components of the DA dynamics. Interestingly, other model parameters were also optimal if we considered the reward rate that was weighted by the subject's preferences for speed or accuracy. Specifically, the circuit model favored speed if we increased the phasic DA response to the reward prediction error, whereas the model favored accuracy if we reduced the tonic DA activity or the phasic DA responses to the estimated reward probability. The proposed model provides insight into the roles of different components of DA responses in decision adaptation and optimization in a changing environment. PMID:24339814

Methylphenidate attenuates limbic brain inhibition after cocaine-cues exposure in cocaine abusers.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Volkow, N.D.; Wang, G.; Volkow, N.D.

Dopamine (phasic release) is implicated in conditioned responses. Imaging studies in cocaine abusers show decreases in striatal dopamine levels, which we hypothesize may enhance conditioned responses since tonic dopamine levels modulate phasic dopamine release. To test this we assessed the effects of increasing tonic dopamine levels (using oral methylphenidate) on brain activation induced by cocaine-cues in cocaine abusers. Brain metabolism (marker of brain function) was measured with PET and {sup 18}FDG in 24 active cocaine abusers tested four times; twice watching a Neutral video (nature scenes) and twice watching a Cocaine-cues video; each video was preceded once by placebo andmore » once by methylphenidate (20 mg). The Cocaine-cues video increased craving to the same extent with placebo (68%) and with methylphenidate (64%). In contrast, SPM analysis of metabolic images revealed that differences between Neutral versus Cocaine-cues conditions were greater with placebo than methylphenidate; whereas with placebo the Cocaine-cues decreased metabolism (p<0.005) in left limbic regions (insula, orbitofrontal, accumbens) and right parahippocampus, with methylphenidate it only decreased in auditory and visual regions, which also occurred with placebo. Decreases in metabolism in these regions were not associated with craving; in contrast the voxel-wise SPM analysis identified significant correlations with craving in anterior orbitofrontal cortex (p<0.005), amygdala, striatum and middle insula (p<0.05). This suggests that methylphenidate's attenuation of brain reactivity to Cocaine-cues is distinct from that involved in craving. Cocaine-cues decreased metabolism in limbic regions (reflects activity over 30 minutes), which contrasts with activations reported by fMRI studies (reflects activity over 2-5 minutes) that may reflect long-lasting limbic inhibition following activation. Studies to evaluate the clinical significance of methylphenidate's blunting of cue-induced limbic inhibition may help identify potential benefits of this medication in cocaine addiction.« less

Methylphenidate Attenuates Limbic Brain Inhibition after Cocaine-Cues Exposure in Cocaine Abusers

PubMed Central

Volkow, Nora D.; Wang, Gene-Jack; Tomasi, Dardo; Telang, Frank; Fowler, Joanna S.; Pradhan, Kith; Jayne, Millard; Logan, Jean; Goldstein, Rita Z.; Alia-Klein, Nelly; Wong, Christopher

2010-01-01

Dopamine (phasic release) is implicated in conditioned responses. Imaging studies in cocaine abusers show decreases in striatal dopamine levels, which we hypothesize may enhance conditioned responses since tonic dopamine levels modulate phasic dopamine release. To test this we assessed the effects of increasing tonic dopamine levels (using oral methylphenidate) on brain activation induced by cocaine-cues in cocaine abusers. Brain metabolism (marker of brain function) was measured with PET and 18FDG in 24 active cocaine abusers tested four times; twice watching a Neutral video (nature scenes) and twice watching a Cocaine-cues video; each video was preceded once by placebo and once by methylphenidate (20 mg). The Cocaine-cues video increased craving to the same extent with placebo (68%) and with methylphenidate (64%). In contrast, SPM analysis of metabolic images revealed that differences between Neutral versus Cocaine-cues conditions were greater with placebo than methylphenidate; whereas with placebo the Cocaine-cues decreased metabolism (p<0.005) in left limbic regions (insula, orbitofrontal, accumbens) and right parahippocampus, with methylphenidate it only decreased in auditory and visual regions, which also occurred with placebo. Decreases in metabolism in these regions were not associated with craving; in contrast the voxel-wise SPM analysis identified significant correlations with craving in anterior orbitofrontal cortex (p<0.005), amygdala, striatum and middle insula (p<0.05). This suggests that methylphenidate's attenuation of brain reactivity to Cocaine-cues is distinct from that involved in craving. Cocaine-cues decreased metabolism in limbic regions (reflects activity over 30 minutes), which contrasts with activations reported by fMRI studies (reflects activity over 2–5 minutes) that may reflect long-lasting limbic inhibition following activation. Studies to evaluate the clinical significance of methylphenidate's blunting of cue-induced limbic inhibition may help identify potential benefits of this medication in cocaine addiction. PMID:20634975

Afferent control of central pattern generators: experimental analysis of scratching in the decerebrate cat.

PubMed

Baev, K V; Esipenko, V B; Shimansky, Y P

1991-01-01

Systematic quantitative analysis of changes in the spinal scratching generator motor activity evoked by tonic and phasic peripheral afferent signals during "fictitious" scratching was carried out in the cat. Correlations between the kinematics of hindlimb scratching movement, sensory inflow, and primary afferent depolarization were investigated. Reliable correlations between the parameters of generator motor activity during fictitious scratching were revealed: they depended on tonic peripheral afferent inflow. The functional role of these dependencies consists of providing stability for aiming the hindlimb to the itch site. It was shown that scratching generator reaction to a phasic sensory signal depended significantly on afferent input, signal intensity, and its arrival phase in the cycle of motor activity. Phase correction of "scratching" rhythm was performed by inhibition of the current stage of "scratching" cycle, the inhibition magnitude depending on the intensity of a sensory signal run along high threshold afferent fibers. The moments in the scratching cycle, in which the afferent signal caused no rearrangement in scratching generator activity, were discovered for all investigated afferent inputs. These moments corresponded to the transitions from one scratching cycle phase to another. Integral afferent activity was distributed unevenly in the cycle during real scratching. The main part of it was observed just in that scratching cycle part which included the above mentioned no rearrangement phase points. The data obtained allowed us to conclude that the scratching generator should be considered as a working program for the motor optimal control system containing the intrinsic model of the controlled object dynamics (e.g. hindlimb scratching movement dynamics), which produces an inner analog of peripheral flow. This inner flow interacts with peripheral afferent inflow just as one of the latter components. Centrally originated modulation of primary afferent depolarization is a result of affecting the depolarization generating system by this inner "sensory" activity. It is the model, with the aid of which the generator can work after deafferentation. The functional organization of a central pattern generator is considered.

Phasic and tonic fluctuations in brain, muscle, and skin temperatures during motivated drinking behavior in rats: physiological correlates of motivation and reward.

PubMed

Smirnov, Michael S; Kiyatkin, Eugene A

2010-01-15

Since brain metabolism is accompanied by heat production, measurement of brain temperature offers a method for assessing global alterations in metabolic neural activity. This approach, high-resolution (5-s bin) temperature recording from the nucleus accumbens (NAcc), temporal muscle, and facial skin, was used to study motivated drinking behavior in rats. Experienced animals were presented with a cup containing 5-ml of Coca-Cola(R) (Coke) beverage that resulted, within certain latencies, in initiation of a continuous chain of licking until all liquid was fully consumed. While cup presentation induced rapid, gradual NAcc temperature increase peaking at the start of drinking, temperatures slowly decreased during Coke consumption, but phasically increased again in the post-consumption period when rats were hyperactive, showing multiple interactions with an empty cup. Muscle temperatures followed a similar pattern, but the changes were weaker and delayed compared to those in the brain. Skin temperature rapidly dropped after cup presentation, steadily maintained at low levels during consumption, and slowly restored during the post-consumption period. Substitution of the expected Coke with either sugar-free Diet Coke(R) or water resulted in numerous drinking attempts but ultimately no consumption. During these tests, locomotor activation was much greater and more prolonged, brain and muscle temperatures increased monophasically, and their elevation was significantly greater than that with regular Coke tests. Food deprivation decreased drinking latencies, did not change the pattern of temperature fluctuations during Coke consumption, but temperature elevations were greater than in controls. Our data suggest sustained neural activation triggered by appetitive stimuli and associated with activational (seeking) aspects of appetitive motivated behavior. This seeking-related activation is rapidly ceased following consumption, suggesting this change as a neural correlate of reward. In contrast, inability to obtain an expected reward maintains neural activation and seeking behavior, resulting in larger deviations in physiological parameters. Published by Elsevier B.V.

Phasic and tonic fluctuations in brain, muscle and skin temperatures during motivated drinking behavior in rats: physiological correlates of motivation and reward

PubMed Central

Smirnov, Michael S.; Kiyatkin, Eugene A.

2009-01-01

Since brain metabolism is accompanied by heat production, measurement of brain temperature offers a method for assessing global alterations in metabolic neural activity. This approach, high-resolution (5-s bin) temperature recording from the nucleus accumbens (NAcc), temporal muscle, and facial skin, was used to study motivated drinking behavior in rats. Experienced animals were presented with a cup containing 5-ml of Coca-Cola® (Coke) beverage that resulted, within certain latencies, in initiation of a continuous chain of licking until all liquid was fully consumed. While cup presentation induced rapid, gradual NAcc temperature increase peaking at the start of drinking, temperatures slowly decreased during Coke consumption, but phasically increased again in the post-consumption period when rats were hyperactive, showing multiple interactions with an empty cup. Muscle temperatures followed a similar pattern, but the changes were weaker and delayed compared to those in the brain. Skin temperature rapidly dropped after cup presentation, steadily maintained at low levels during consumption, and slowly restored during the post-consumption period. Substitution of the expected Coke with either sugar-free Diet Coke® or water resulted in numerous drinking attempts but ultimately no consumption. During these tests, locomotor activation was much greater and more prolonged, brain and muscle temperatures increased monophasically, and their elevation was significantly greater than that with regular Coke tests. Food deprivation decreased drinking latencies, did not change the pattern of temperature fluctuations during Coke consumption, but temperature elevations were greater than in controls. Our data suggest sustained neural activation triggered by appetitive stimuli and associated with activational (seeking) aspects of appetitive motivated behavior. This seeking-related activation is rapidly ceased following consumption, suggesting this change as a neural correlate of reward. In contrast, inability to obtain an expected reward maintains neural activation and seeking behavior, resulting in larger deviations in physiological parameters. PMID:19932691

Discharge Patterns of Human Tensor Palatini Motor Units During Sleep Onset

PubMed Central

Nicholas, Christian L.; Jordan, Amy S.; Heckel, Leila; Worsnop, Christopher; Bei, Bei; Saboisky, Julian P.; Eckert, Danny J.; White, David P.; Malhotra, Atul; Trinder, John

2012-01-01

Study Objectives: Upper airway muscles such as genioglossus (GG) and tensor palatini (TP) reduce activity at sleep onset. In GG reduced muscle activity is primarily due to inspiratory modulated motor units becoming silent, suggesting reduced respiratory pattern generator (RPG) output. However, unlike GG, TP shows minimal respiratory modulation and presumably has few inspiratory modulated motor units and minimal input from the RPG. Thus, we investigated the mechanism by which TP reduces activity at sleep onset. Design: The activity of TP motor units were studied during relaxed wakefulness and over the transition from wakefulness to sleep. Setting: Sleep laboratory. Participants: Nine young (21.4 ± 3.4 years) males were studied on a total of 11 nights. Intervention: Sleep onset. Measurements and Results: Two TP EMGs (thin, hooked wire electrodes), and sleep and respiratory measures were recorded. One hundred twenty-one sleep onsets were identified (13.4 ± 7.2/subject), resulting in 128 motor units (14.3 ± 13.0/subject); 29% of units were tonic, 43% inspiratory modulated (inspiratory phasic 18%, inspiratory tonic 25%), and 28% expiratory modulated (expiratory phasic 21%, expiratory tonic 7%). There was a reduction in both expiratory and inspiratory modulated units, but not tonic units, at sleep onset. Reduced TP activity was almost entirely due to de-recruitment. Conclusions: TP showed a similar distribution of motor units as other airway muscles. However, a greater proportion of expiratory modulated motor units were active in TP and these expiratory units, along with inspiratory units, tended to become silent over sleep onset. The data suggest that both expiratory and inspiratory drive components from the RPG are reduced at sleep onset in TP. Citation: Nicholas CL; Jordan AS; Heckel L; Worsnop C; Bei B: Saboisky JP; Eckert DJ; White DP; Malhotra A; Trinder J. Discharge patterns of human tensor palatini motor units during sleep onset. SLEEP 2012;35(5):699-707. PMID:22547896

Effects of imatinib mesylate on the spontaneous activity generated by the guinea-pig prostate.

PubMed

Lam, Michelle; Dey, Anupa; Lang, Richard J; Exintaris, Betty

2013-08-01

What's known on the subject? and what does the study add?: Several studies have examined the functional role of tyrosine kinase receptors in the generation of spontaneous activity in various segments of the gastrointestinal and urogenital tracts through the application of its inhibitor, imatinib mesylate (Glivec®), but results are fairly inconsistent. This is the first study detailing the effects of imatinib mesylate on the spontaneous activity in the young and ageing prostate gland. As spontaneous electrical activity underlies the spontaneous rhythmic prostatic contractions that occur at rest, elucidating the mechanisms involved in the regulation of the spontaneous electrical activity and the resultant phasic contractions could conceivably lead to the identification of better targets and the development of more specific therapeutic agents to treat prostate conditions. To investigate the effect of imatinib mesylate, a tyrosine kinase receptor inhibitor, in the generation of spontaneous electrical and contractile activity in the young and ageing guinea-pig prostate. Standard tension and intracellular recording were used to measure spontaneous contractions and slow waves, respectively from the guinea-pig prostate at varying concentrations of imatinib mesylate (1-50 μm). Imatinib mesylate (1-10 μm), did not significantly affect slow waves recorded in the prostate of both age groups but at 50 μm, the amplitude of slow waves from the ageing guinea-pig prostate was significantly reduced (P < 0.05, n = 5). In contrast, the amplitude of contractions across all concentrations in the young guinea-pig prostate was reduced to between 35% and 41% of control, while the frequency was reduced to 15.7% at 1 μm (n = 7), 49.8% at 5 μm (n = 10), 46.2% at 10 μm (n = 7) and 53.1% at 50 μm (n = 5). Similarly, imatinib mesylate attenuated the amplitude and slowed the frequency of contractions in ageing guinea-pigs to 5.15% and 3.3% at 1 μm (n = 6); 21.1% and 20.8% at 5 μm (n = 8); 58.4% and 8.8% at 10 μm (n = 11); 72.7% and 60% at 50 μm (n = 5). A significant reduction in contractions but persistence of slow waves suggests imatinib mesylate may affect the smooth muscle contractile mechanism. Imatinib mesylate also significantly reduced contractions in the prostates of younger guinea pigs more than older ones, which is consistent with the notion that the younger guinea-pig prostate is more reliant on the tyrosine-dependent pacemaker ability of interstitial cells of Cajal-like prostatic interstitial cells. © 2013 The Authors BJU International © 2013 BJU International.

Analysis of electrical and magnetic bio-signals associated with motor performance and fatigue

NASA Astrophysics Data System (ADS)

Yao, Bing

This dissertation reports findings centered principally on comprehensive research related to human bio-signals (EEG, MEG, EMG and fMRI) acquired during repetitive maximal voluntary contractions (MVC) that induced severe fatigue. Fatigue is a common experience that reduces productivity and quality of life and increases chances of injury. Although abundant information has been gained in the last several decades regarding muscular and spinal-level mechanisms of muscle fatigue, very little is known about how cortical centers control and respond to fatigue. The main purpose of this study was to examine the fatigue effects on the central nervous system by analyzing the bio-signals collected in the designed experiments. Healthy human subjects were asked to perform a series of repetitive handgrip MVCs with their dominant hand until exhaustion. Handgrip forces, electrical activity (EMG) from primary and non-primary muscles, and EEG, MEG, or fMRI signals from different locations of the brain were recorded simultaneously. The time series data were segmented into several physiologically meaningful epochs (time phases), from rest to preparation to movement execution/sustaining. A series of studies, including motor-related cortical potential (MRCP) analysis, power spectrum analysis, time-frequency (spectrogram) analysis of EEG, EEG source localization and nonlinear analysis (fractal dimension and largest Lyapunov exponent), and fMRI analysis, was applied to the data. We hypothesized that the fatigue effects would act differently on brain signals of different phases. The MRCP results showed that the negative potential (NP) related to motor task preparation only had minimal changes with fatigue. The power of all EEG frequencies did not alter significantly during the preparation phase but decreased significantly during the sustained phase of the contraction. The fractal dimension and the largest Lyapunov exponent decreased significantly during the sustained phase as fatigue progressed. On the other hand, the fMRI results only exhibited insignificant fatigue-related reductions of brain activation volume and no significant change of dipole strength derived from multi-channel EEG data. These results have been interpreted by a hypothetical neurophysiological model, in which two groups of cortical neurons (phasic and tonic) are preferentially activated in each physiological phase of the voluntary motor action.

Phasic dopamine signals: from subjective reward value to formal economic utility

PubMed Central

Schultz, Wolfram; Carelli, Regina M; Wightman, R Mark

2015-01-01

Although rewards are physical stimuli and objects, their value for survival and reproduction is subjective. The phasic, neurophysiological and voltammetric dopamine reward prediction error response signals subjective reward value. The signal incorporates crucial reward aspects such as amount, probability, type, risk, delay and effort. Differences of dopamine release dynamics with temporal delay and effort in rodents may derive from methodological issues and require further study. Recent designs using concepts and behavioral tools from experimental economics allow to formally characterize the subjective value signal as economic utility and thus to establish a neuronal value function. With these properties, the dopamine response constitutes a utility prediction error signal. PMID:26719853

Trophic Ecology of Benthic Marine Invertebrates with Bi-Phasic Life Cycles: What Are We Still Missing?

PubMed

Calado, Ricardo; Leal, Miguel Costa

2015-01-01

The study of trophic ecology of benthic marine invertebrates with bi-phasic life cycles is critical to understand the mechanisms shaping population dynamics. Moreover, global climate change is impacting the marine environment at an unprecedented level, which promotes trophic mismatches that affect the phenology of these species and, ultimately, act as drivers of ecological and evolutionary change. Assessing the trophic ecology of marine invertebrates is critical to understanding maternal investment, larval survival to metamorphosis, post-metamorphic performance, resource partitioning and trophic cascades. Tools already available to assess the trophic ecology of marine invertebrates, including visual observation, gut content analysis, food concentration, trophic markers, stable isotopes and molecular genetics, are reviewed and their main advantages and disadvantages for qualitative and quantitative approaches are discussed. The challenges to perform the partitioning of ingestion, digestion and assimilation are discussed together with different approaches to address each of these processes for short- and long-term fingerprinting. Future directions for research on the trophic ecology of benthic marine invertebrates with bi-phasic life cycles are discussed with emphasis on five guidelines that will allow for systematic study and comparative meta-analysis to address important unresolved questions. © 2015 Elsevier Ltd. All rights reserved.

Advances in studying phasic dopamine signaling in brain reward mechanisms

PubMed Central

Wickham, Robert J.; Solecki, Wojciech; Rathbun, Liza R.; Neugebauer, Nichole M.; Wightman, R. Mark; Addy, Nii A.

2013-01-01

The last sixty years of research have provided extraordinary advances of our knowledge of the reward system. Since its initial discovery as a neurotransmitter by Carlsson and colleagues (Carlsson et al., 1957), dopamine (DA) has emerged as an important mediator of reward processing. As a result, a number of electrochemical techniques have been developed to directly measure DA levels in the brain using various preparations. Many of these techniques and preparations differ in the types of questions that they can address. Together, these techniques have begun to elucidate the complex roles of tonic and phasic DA signaling in reward processing and in addiction. In this review, we will first provide a guide for the most commonly used electrochemical methods for DA detection and describe their utility in furthering our knowledge about DA's role in reward and addiction. Second, we will review the value of common in vitro and in vivo preparations and describe their ability to address different types of questions. Last, we will review recent data that has provided new insight of the mechanisms of in vivo phasic DA signaling and its role in reward processing and reward-mediated behavior. PMID:23747914

Rat limb unloading - Soleus histochemistry, ultrastructure, and electromyography

NASA Technical Reports Server (NTRS)

Riley, D. A.; Slocum, G. R.; Bain, J. L. W.; Sedlak, F. R.; Sowa, T. E.

1990-01-01

The effects of hindlimb unloading on rat-soleus histochemisty, ultrastructure, and electromyogram (EMG) activity were investigated. It was found that, after 14 days of tail suspension, the area of type I and type IIa muscle fibers decreased by 63 and 47 percent, respectively, mainly due to the degradation of subsarcolemmal mitochondria and myofibrils. After 10 days, 3 percent of type IIa fibers exhibited segmental necrosis. After four days, video monitoring revealed abnormal plantar flexion of the hindfeet, which shortened the soleus working range. The EMG activity shifted from tonic to phasic, and aggregate activity decreased drastically after only seven days. The results indictate that the pathological changes in the soleus resulted from unloaded contractions, reduced use, compromised blood flow, and shortened working length.

Reduced dopamine and glutamate neurotransmission in the nucleus accumbens of quinpirole-sensitized rats hints at inhibitory D2 autoreceptor function.

PubMed

Escobar, Angélica P; Cornejo, Francisca A; Olivares-Costa, Montserrat; González, Marcela; Fuentealba, José A; Gysling, Katia; España, Rodrigo A; Andrés, María E

2015-09-01

Dopamine from the ventral tegmental area and glutamate from several brain nuclei converge in the nucleus accumbens (NAc) to drive motivated behaviors. Repeated activation of D2 receptors with quinpirole (QNP) induces locomotor sensitization and compulsive behaviors, but the mechanisms are unknown. In this study, in vivo microdialysis and fast scan cyclic voltammetry in adult anesthetized rats were used to investigate the effect of repeated QNP on dopamine and glutamate neurotransmission within the NAc. Following eight injections of QNP, a significant decrease in phasic and tonic dopamine release was observed in rats that displayed locomotor sensitization. Either a systemic injection or the infusion of QNP into the NAc decreased dopamine release, and the extent of this effect was similar in QNP-sensitized and control rats, indicating that inhibitory D2 autoreceptor function is maintained despite repeated activation of D2 receptors and decreased dopamine extracellular levels. Basal extracellular levels of glutamate in the NAc were also significantly lower in QNP-treated rats than in controls. Moreover, the increase in NAc glutamate release induced by direct stimulation of medial prefrontal cortex was significantly lower in QNP-sensitized rats. Together, these results indicate that repeated activation of D2 receptors disconnects NAc from medial prefrontal cortex and ventral tegmental area. Repeated administration of the dopamine D2 receptor agonist quinpirole (QNP) induces locomotor sensitization. We found that the NAc of QNP-sensitized rats has reduced glutamate levels coming from prefrontal cortex together with a decreased phasic and tonic dopamine neurotransmission but a conserved presynaptic D2 receptor function. We suggest that locomotor sensitization is because of increased affinity state of D2 post-synaptic receptors. © 2015 International Society for Neurochemistry.

Ponto-medullary nuclei involved in the generation of sequential pharyngeal swallowing and concomitant protective laryngeal adduction in situ

PubMed Central

Bautista, Tara G; Dutschmann, Mathias

2014-01-01

Both swallowing and respiration involve postinspiratory laryngeal adduction. Swallowing-related postinspiratory neurons are likely to be located in the nucleus of the solitary tract (NTS) and those involved in respiration are found in the Kölliker–Fuse nucleus (KF). The function of KF and NTS in the generation of swallowing and its coordination with respiration was investigated in perfused brainstem preparations of juvenile rats (n = 41). Orally injected water evoked sequential pharyngeal swallowing (s-PSW) seen as phasic, spindle-shaped bursting of vagal nerve activity (VNA) against tonic postinspiratory discharge. KF inhibition by microinjecting isoguvacine (GABAA receptor agonist) selectively attenuated tonic postinspiratory VNA (n = 10, P < 0.001) but had no effect on frequency or timing of s-PSW. KF disinhibition after bicuculline (GABAA receptor antagonist) microinjections caused an increase of the tonic VNA (n = 8, P < 0.01) resulting in obscured and delayed phasic s-PSW. Occurrence of spontaneous PSW significantly increased after KF inhibition (P < 0.0001) but not after KF disinhibition (P = 0.14). NTS isoguvacine microinjections attenuated the occurrence of all PSW (n = 5, P < 0.01). NTS bicuculline microinjections (n = 6) resulted in spontaneous activation of a disordered PSW pattern and long-lasting suppression of respiratory activity. Pharmacological manipulation of either KF or NTS also triggered profound changes in respiratory postinspiratory VNA. Our results indicate that the s-PSW comprises two functionally distinct components. While the primary s-PSW is generated within the NTS, a KF-mediated laryngeal adductor reflex safeguards the lower airways from aspiration. Synaptic interaction between KF and NTS is required for s-PSW coordination with respiration as well as for proper gating and timing of s-PSW. PMID:24639482

GABAA-current rundown of temporal lobe epilepsy is associated with repetitive activation of GABAA “phasic” receptors

PubMed Central

Palma, Eleonora; Roseti, Cristina; Maiolino, Francesca; Fucile, Sergio; Martinello, Katiuscia; Mazzuferi, Manuela; Aronica, Eleonora; Manfredi, Mario; Esposito, Vincenzo; Cantore, Gianpaolo; Miledi, Ricardo; Simonato, Michele; Eusebi, Fabrizio

2007-01-01

A study was made of the “rundown” of GABAA receptors, microtransplanted to Xenopus oocytes from surgically resected brain tissues of patients afflicted with drug-resistant human mesial temporal lobe epilepsy (mTLE). Cell membranes, isolated from mTLE neocortex specimens, were injected into frog oocytes that rapidly incorporated functional GABAA receptors. Upon repetitive activation with GABA (1 mM), “epileptic” GABAA receptors exhibited a GABAA-current (IGABA) rundown that was significantly enhanced by Zn2+ (≤250 μM), and practically abolished by the high-affinity GABAA receptor inverse agonist SR95531 (gabazine; 2.5–25 μM). Conversely, IGABA generated by “control” GABAA receptors microtransplanted from nonepileptic temporal lobe, lesional TLE, or authoptic disease-free tissues remained stable during repetitive stimulation, even in oocytes treated with Zn2+. We conclude that rundown of mTLE epileptic receptors depends on the presence of “phasic GABAA receptors” that have low sensitivity to antagonism by Zn2+. Additionally, we found that GABAA receptors, microtransplanted from the cerebral cortex of adult rats exhibiting recurrent seizures, caused by pilocarpine-induced status epilepticus, showed greater rundown than control tissue, an event also occurring in patch-clamped rat pyramidal neurons. Rundown of epileptic rat receptors resembled that of human mTLE receptors, being enhanced by Zn2+ (40 μM) and sensitive to the antiepileptic agent levetiracetam, the neurotrophin brain-derived neurotrophic factor, and the phosphatase blocker okadaic acid. Our findings point to the rundown of GABAA receptors as a hallmark of TLE and suggest that modulating tonic and phasic mTLE GABAA receptor activity may represent a useful therapeutic approach to the disease. PMID:18083839

Diversity within a Birdsong

NASA Astrophysics Data System (ADS)

Laje, Rodrigo; Mindlin, Gabriel B.

2002-12-01

We present a model for the activities of neural circuits in a nucleus found in the brains of songbirds: the robust nucleus of the archistriatum (RA). This is a fore brain song control nucleus responsible for the phasic and precise neural signals driving vocal and respiratory motor neurons during singing. Driving a physical model of the avian vocal organ with the signals generated by the neural model, we produce synthetic songs. This allows us to show that certain connectivity architectures in the RA give rise to a wide range of different vocalizations under simple excitatory instructions.

Reciprocal links between metabolic and ionic events in islet cells. Their relevance to the rhythmics of insulin release.

PubMed

Malaisse, W J

1998-02-01

The notion of reciprocal links between metabolic and ionic events in islet cells and the rhythmics of insulin release is based on (i) the rhythmic pattern of hormonal release from isolated perfused rat pancreas, which supports the concept of an intrapancreatic pacemaker; (ii) the assumption that this phasic pattern is due to the integration of secretory activity in distinct functional units, e.g. distinct islets; and (iii) the fact that reciprocal coupling between metabolic and ionic events is operative in the secretory sequence.

Dependence of Intramyocardial Pressure and Coronary Flow on Ventricular Loading and Contractility: A Model Study

PubMed Central

Borsje, Petra; Arts, Theo; van De Vosse, Frans N.

2006-01-01

The phasic coronary arterial inflow during the normal cardiac cycle has been explained with simple (waterfall, intramyocardial pump) models, emphasizing the role of ventricular pressure. To explain changes in isovolumic and low afterload beats, these models were extended with the effect of three-dimensional wall stress, nonlinear characteristics of the coronary bed, and extravascular fluid exchange. With the associated increase in the number of model parameters, a detailed parameter sensitivity analysis has become difficult. Therefore we investigated the primary relations between ventricular pressure and volume, wall stress, intramyocardial pressure and coronary blood flow, with a mathematical model with a limited number of parameters. The model replicates several experimental observations: the phasic character of coronary inflow is virtually independent of maximum ventricular pressure, the amplitude of the coronary flow signal varies about proportionally with cardiac contractility, and intramyocardial pressure in the ventricular wall may exceed ventricular pressure. A parameter sensitivity analysis shows that the normalized amplitude of coronary inflow is mainly determined by contractility, reflected in ventricular pressure and, at low ventricular volumes, radial wall stress. Normalized flow amplitude is less sensitive to myocardial coronary compliance and resistance, and to the relation between active fiber stress, time, and sarcomere shortening velocity. PMID:17048105

Contributions of the Central Extended Amygdala to Fear and Anxiety.

PubMed

Shackman, Alexander J; Fox, Andrew S

2016-08-03

It is widely thought that phasic and sustained responses to threat reflect dissociable circuits centered on the central nucleus of the amygdala (Ce) and the bed nucleus of the stria terminalis (BST), the two major subdivisions of the central extended amygdala. Early versions of this hypothesis remain highly influential and have been incorporated into the National Institute of Mental Health Research Research Domain Criteria framework. However, new observations encourage a different perspective. Anatomical studies show that the Ce and BST form a tightly interconnected unit, where different kinds of threat-relevant information can be integrated and used to assemble states of fear and anxiety. Imaging studies in humans and monkeys show that the Ce and BST exhibit similar functional profiles. Both regions are sensitive to a range of aversive challenges, including uncertain or temporally remote threat; both covary with concurrent signs and symptoms of fear and anxiety; both show phasic responses to short-lived threat; and both show heightened activity during sustained exposure to diffusely threatening contexts. Mechanistic studies demonstrate that both regions can control the expression of fear and anxiety during sustained exposure to diffuse threat. These observations compel a reconsideration of the central extended amygdala's contributions to fear and anxiety and its role in neuropsychiatric disease. Copyright © 2016 the authors 0270-6474/16/368050-14$15.00/0.

Contributions of the Central Extended Amygdala to Fear and Anxiety

PubMed Central

2016-01-01

It is widely thought that phasic and sustained responses to threat reflect dissociable circuits centered on the central nucleus of the amygdala (Ce) and the bed nucleus of the stria terminalis (BST), the two major subdivisions of the central extended amygdala. Early versions of this hypothesis remain highly influential and have been incorporated into the National Institute of Mental Health Research Research Domain Criteria framework. However, new observations encourage a different perspective. Anatomical studies show that the Ce and BST form a tightly interconnected unit, where different kinds of threat-relevant information can be integrated and used to assemble states of fear and anxiety. Imaging studies in humans and monkeys show that the Ce and BST exhibit similar functional profiles. Both regions are sensitive to a range of aversive challenges, including uncertain or temporally remote threat; both covary with concurrent signs and symptoms of fear and anxiety; both show phasic responses to short-lived threat; and both show heightened activity during sustained exposure to diffusely threatening contexts. Mechanistic studies demonstrate that both regions can control the expression of fear and anxiety during sustained exposure to diffuse threat. These observations compel a reconsideration of the central extended amygdala's contributions to fear and anxiety and its role in neuropsychiatric disease. PMID:27488625

Maintenance of long-term adaptation of synaptic transmission requires axonal transport following induction in an identified crayfish motoneuron.

PubMed

Nguyen, P V; Atwood, H L

1992-03-01

Motoneurons can adapt to altered levels of electrical activity by effecting semi-permanent changes in their neuromuscular synaptic physiology. In the present study, we tested the hypothesis that maintenance of activity-dependent long-term adaptation of synaptic transmission in a crayfish abdominal extensor motoneuron (phasic axon 3) required axonal transport following induction. Intact crayfish were chronically wired for periodic in vivo stimulation of axon 3. Periodic unilateral stimulation for 3-5 consecutive days (2 h/day) induced long-term adaptation (LTA) of neuromuscular synaptic transmission in axon 3. Initial EPSP amplitudes (measured at 0.1 Hz) were significantly reduced to approximately 40% of contralateral control amplitudes over a 7-day poststimulation period. Additionally, synaptic depression during 5 Hz test stimulation of axon 3 was significantly less in chronically stimulated neurons: excitatory postsynaptic potential (EPSP) amplitudes measured after 20 min of 5 Hz test stimulation (final EPSPs) were significantly larger in conditioned neurons than in unstimulated controls. The depression of initial EPSP amplitudes persisted for 7 days postinduction, while the increased synaptic stamina persisted for 4 days but was absent at 7 days postinduction. Axotomy of axon 3 following induction of LTA had no effect on long-term maintenance of the activity-induced reduction in initial EPSP amplitudes. Initial EPSP amplitudes in conditioned, axotomized neurons were still reduced to 42% of control amplitudes over the 7-day postinduction period. In contrast, postinduction axotomy of axon 3 elicited an accelerated decay of the enhanced synaptic stamina. Following axotomy, final EPSP amplitudes were significantly larger in conditioned neurons for only 1 day poststimulation.(ABSTRACT TRUNCATED AT 250 WORDS)

Computer-assisted three-dimensional reconstructions of ( sup 14 C)-2-deoxy-D-glucose metabolism in cat lumbosacral spinal cord following cutaneous stimulation of the hindfoot

DOE Office of Scientific and Technical Information (OSTI.GOV)

Crockett, D.P.; Smith, W.K.; Proshansky, E.

1989-10-08

We report on computer-assisted three-dimensional reconstruction of spinal cord activity associated with stimulation of the plantar cushion (PC) as revealed by (14C)-2-deoxy-D-glucose (2-DG) serial autoradiographs. Moderate PC stimulation in cats elicits a reflex phasic plantar flexion of the toes. Four cats were chronically spinalized at about T6 under barbiturate anesthesia. Four to 11 days later, the cats were injected (i.v.) with 2-DG (100 microCi/kg) and the PC was electrically stimulated with needle electrodes at 2-5 times threshold for eliciting a reflex. Following stimulation, the spinal cord was processed for autoradiography. Subsequently, autoradiographs, representing approximately 8-18 mm from spinal segments L6-S1,more » were digitized for computer analysis and 3-D reconstruction. Several strategies of analysis were employed: (1) Three-dimensional volume images were color-coded to represent different levels of functional activity. (2) On the reconstructed volumes, virtual sections were made in the horizontal, sagittal, and transverse planes to view regions of 2-DG activity. (3) In addition, we were able to sample different regions within the grey and white matter semi-quantitatively (i.e., pixel intensity) from section to section to reveal differences between ipsi- and contralateral activity, as well as possible variation between sections. These analyses revealed 2-DG activity associated with moderate PC stimulation, not only in the ipsilateral dorsal horn as we had previously demonstrated, but also in both the ipsilateral and contralateral ventral horns, as well as in the intermediate grey matter. The use of novel computer analysis techniques--combined with an unanesthetized preparation--enabled us to demonstrate that the increased metabolic activity in the lumbosacral spinal cord associated with PC stimulation was much more extensive than had heretofore been observed.« less

Microprocessor controlled movement of solid colonic content using sequential neural electrical stimulation

PubMed Central

Amaris, M A; Rashev, P Z; Mintchev, M P; Bowes, K L

2002-01-01

Background and aims: Invoked peristaltic contractions and movement of solid content have not been attempted in normal canine colon. The purpose of this study was to determine if movement of solid content through the colon could be produced by microprocessor controlled sequential stimulation. Methods: The study was performed on six anaesthetised dogs. At laparotomy, a 15 cm segment of descending colon was selected, the proximal end closed with a purse string suture, and the distal end opened into a collecting container. Four sets of subserosal stimulating electrodes were implanted at 3 cm intervals. The segment of bowel was filled with a mixture of dog food and 50 plastic pellets before each of 2–5 random sessions of non-stimulated or stimulated emptying. Propagated contractions were generated using microprocessor controlled bipolar trains of 50 Hz rectangular voltage having 20 V (peak to peak) amplitude, 18 second stimulus duration, and a nine second phase lag between stimulation trains in sequential electrode sets. Results: Electrical stimulation using the above mentioned parameters resulted in powerful phasic contractions that closed the lumen. By phase locking the stimulation voltage between adjacent sets of electrodes, propagated contractions could be produced in an aboral or orad direction. The number of evacuated pellets during the stimulation sessions was significantly higher than during the non-stimulated sessions (p<0.01). Conclusions: Microprocessor controlled electrical stimulation accelerated movement of colonic content suggesting the possibility of future implantable colonic stimulators. PMID:11889065

Processing of central and reflex vagal drives by rat cardiac ganglion neurones: an intracellular analysis

PubMed Central

McAllen, Robin M; Salo, Lauren M; Paton, Julian F R; Pickering, Anthony E

2011-01-01

Abstract Cardiac vagal tone is an important indicator of cardiovascular health, and its loss is an independent risk factor for arrhythmias and mortality. Several studies suggest that this loss of vagal tone can occur at the cardiac ganglion but the factors affecting ganglionic transmissionin vivoare poorly understood. We have employed a novel approach allowing intracellular recordings from functionally connected cardiac vagal ganglion cells in the working heart–brainstem preparation. The atria were stabilisedin situpreserving their central neural connections, and ganglion cells (n = 32) were impaled with sharp microelectrodes. Cardiac ganglion cells with vagal synaptic inputs (spontaneous, n = 10; or electrically evoked from the vagus, n = 3) were identified as principal neurones and showed tonic firing responses to current injected to their somata. Cells lacking vagal inputs (n = 19, presumed interneurones) were quiescent but showed phasic firing responses to depolarising current. In principal cells the ongoing action potentials and EPSPs exhibited respiratory modulation, with peak frequency in post-inspiration. Action potentials arose from unitary EPSPs and autocorrelation of those events showed that each ganglion cell received inputs from a single active preganglionic source. Peripheral chemoreceptor, arterial baroreceptor and diving response activation all evoked high frequency synaptic barrages in these cells, always from the same single preganglionic source. EPSP amplitudes showed frequency dependent depression, leading to more spike failures at shorter inter-event intervals. These findings indicate that rather than integrating convergent inputs, cardiac vagal postganglionic neurones gate preganglionic inputs, so regulating the proportion of central parasympathetic tone that is transmitted on to the heart. PMID:22005679

Tonic dopamine induces persistent changes in the transient potassium current through translational regulation

PubMed Central

Rodgers, EW; Krenz, W-D; Baro, DJ

2012-01-01

Neuromodulatory effects can vary with their mode of transmission. Phasic release produces local and transient increases in dopamine (DA) up to micromolar concentrations. Additionally, since DA is released from open synapses and reuptake mechanisms are not nearby, tonic nanomolar DA exists in the extracellular space. Do phasic and tonic transmissions similarly regulate voltage dependent ionic conductances in a given neuron? It was previously shown that DA could immediately alter the transient potassium current (IA) of identified neurons in the stomatogastric ganglion (STG) of the spiny lobster, Panulirus interruptus. Here we show that DA can also persistently alter IA, and that DA’s immediate and persistent effects oppose one another. The lateral pyloric neuron (LP) exclusively expresses type 1 DA receptors (D1Rs). Micromolar DA produces immediate depolarizing shifts in the voltage dependence of LP IA, whereas tonic nanomolar DA produces a persistent increase in LP IA maximal conductance (Gmax) through a translation dependent mechanism involving target of rapamycin (TOR). The pyloric dilator neuron (PD) exclusively expresses type 2 DA receptors (D2Rs). Micromolar DA produces an immediate hyperpolarizing shift in PD IA voltage dependence of activation, whereas tonic DA persistently decreases PD IA Gmax through a translation dependent mechanism not involving TOR. The persistent effects on IA Gmax do not depend on LP or PD activity. These data suggest a role for tonic modulators in the regulation of voltage gated ion channel number; and furthermore, that dopaminergic systems may be organized to limit the amount of change they can impose on a circuit. PMID:21917788

Immediate effects of endoscopic sphincterotomy on sphincter of Oddi motility.

PubMed

Błaut, U; Marecik, J; Gniady, J; Laskiewicz, J; Thor, P J

2000-01-01

The evidence exists that incomplete sphincterotomy in patients with biliary tract diseases may result in early symptoms reoccurrence or lack of improvement. Sphincter of Oddi manometry (SOM) can be used to verify the completeness of the procedure. The purpose of the study was to investigate the immediate effects of biliary endoscopic sphincterotomy (BES) and common bile duct stones (CBDS) clearance on biliary sphincter of Oddi (SO) motility. Moreover the percentage of incomplete sphincterotomies was estimated. 26 patients (6 male, 20 female, 24-93 years) with confirmed choledocholithiasis were investigated. All underwent BES followed by CBDS extraction, and then SO manometry (SOM) was performed. Moreover 6 patients underwent SOM prior to BES. SOM was performed with a triple lumen 5 Fr catheter attached to the water perfused low compliance system. Immediately after sphincterotomy and extraction of the CBDS common bile duct pressure dropped from a mean of 10.9 mmHg to 2.9 mmHg (p < 0.05). Similarly basal biliary sphincter pressure decreased from 22.7 mmHg to 7.3 mmHg (p < 0.05). 20 patients presented duodeno-choledochal gradient of less than 5 mmHg. However only 10 patients had also basal sphincter pressure lower than 5 mmHg. The phasic sphincter activity was abolished in 16 patients, whereas phasic contractions persisted in 10 patients. Seven patients displayed uncoordinated, low amplitude contractility. BES significantly decreases SO and CBD pressures, but when performed for CBDS extraction, commonly does not abolish SO motor activity nor ablate choledocho-duodenal gradient. Therefore to confirm the completeness of sphincterotomy, SO manometry is recommended.

Effects of arousal on cognitive control: empirical tests of the conflict-modulated Hebbian-learning hypothesis.

PubMed

Brown, Stephen B R E; van Steenbergen, Henk; Kedar, Tomer; Nieuwenhuis, Sander

2014-01-01

An increasing number of empirical phenomena that were previously interpreted as a result of cognitive control, turn out to reflect (in part) simple associative-learning effects. A prime example is the proportion congruency effect, the finding that interference effects (such as the Stroop effect) decrease as the proportion of incongruent stimuli increases. While this was previously regarded as strong evidence for a global conflict monitoring-cognitive control loop, recent evidence has shown that the proportion congruency effect is largely item-specific and hence must be due to associative learning. The goal of our research was to test a recent hypothesis about the mechanism underlying such associative-learning effects, the conflict-modulated Hebbian-learning hypothesis, which proposes that the effect of conflict on associative learning is mediated by phasic arousal responses. In Experiment 1, we examined in detail the relationship between the item-specific proportion congruency effect and an autonomic measure of phasic arousal: task-evoked pupillary responses. In Experiment 2, we used a task-irrelevant phasic arousal manipulation and examined the effect on item-specific learning of incongruent stimulus-response associations. The results provide little evidence for the conflict-modulated Hebbian-learning hypothesis, which requires additional empirical support to remain tenable.

Effects of imidazoline I2 receptor ligands on acute nociception in rats.

PubMed

Sampson, Cristal; Zhang, Yanan; Del Bello, Fabio; Li, Jun-Xu

2012-01-25

This study examined the antinociceptive effects of seven imidazoline I2 receptor ligands in a rat warm water tail withdrawal procedure (46 and 50 °C). Agmatine, 2-BFI, phenyzoline, and diphenyzoline produced a significant antinociceptive activity at 46 °C. BU224, S22687, and idazoxan had no effect at 46 °C up to doses that altered the locomotor activity. None of the drugs showed antinociceptive activity at 50 °C. It is suggested that I2 receptor agonists have antinociceptive activity for acute phasic pain under weak noxious stimulus, and the effects are efficacy-dependent. These data explain the findings that I2 receptor agonists enhance the antinociceptive effects of opioids and support developing higher-efficacy I2 receptor agonists for the treatment of pain. © 2012 Wolters Kluwer Health | Lippincott Williams & Wilkins.

Arousal mechanisms related to posture and locomotion: 1. Descending modulation.

PubMed

Garcia-Rill, Edgar; Homma, Yutaka; Skinner, Robert D

2004-01-01

Much of the controversy surrounding the induction of locomotion following stimulation of mesopontine sites, including the pedunculopontine nucleus (PPN), appears based on procedural differences, including stimulus onset, delay preceding stepping, and frequency of stimuli. The results reviewed in this chapter address these issues and provide novel information suggesting that descending projections from the PPN may exert a frequency-dependent effect. Stimulation at approximately 60 Hz (which induces prolonged tonic firing) may exercise a "push" towards locomotion (activation of pontine interneurons) as well as a "pull" away from decreased muscle tone (inhibiting giant pontine reticulospinal cells). Higher frequencies of stimulation (> 100 Hz, which induces phasic burst-like activity) may "push" towards decreases in muscle tone, including the atonia of rapid eye movement sleep (activating giant pontine reticulospinal cells).

Nicotine-induced Conditional Place Preference is Affected by Head Injury: Correlation with Dopamine Release in the Nucleus Accumbens Shell.

PubMed

Yuan-Hao, Chen; Kuo, Tung-Tai; Huang, Eagle Yi-Kung; Hoffer, Barry J; Kao, Jen-Hsin; Chou, Yu-Ching; Chiang, Yung-Hsiao; Miller, Jonathan

2018-06-14

Traumatic brain injury (TBI) is known to impact dopamine-mediated reward pathways, but the underlying mechanisms have not been fully established. Nicotine-induced conditional place preference (CPP) was used to study rats exposed to a 6-psi fluid percussion injury (FPI) with and without prior exposure to nicotine. Preference was quantified as a score defined as (C1-C2) / (C1+C2), where C1 is time in the nicotine-paired compartment and C2 is time in the saline-paired compartment. Subsequent fast-scan cyclic voltammetry (FSCV) was used to analyze the impact of nicotine infusion on dopamine release in the shell portion of the nucleus accumbens (NAc). To further determine the influence of brain injury on nicotine withdrawal, nicotine infusion was administered to the rats after FPI. The effects of FPI on CPP after prior exposure to nicotine and abstinence or withdrawal from nicotine were also assessed. After TBI, dopamine release was reduced in the NAc shell, and nicotine-induced CPP preference was significantly impaired. Preference scores of control, sham-injured, and FPI groups were 0.1627 ± 0.04204, 0.1515 ± 0.03806, and -0.001300 ± 0.04286, respectively. Nicotine-induced CPP was also seen in animals after nicotine pre-treatment, with a CPP score of 0.07805 ± 0.02838. Nicotine pre-exposure substantially increased tonic dopamine release in sham-injured animals, but it did not change phasic release; nicotine exposure after FPI enhanced phasic release, though not to the same levels seen in sham-injured rats. Conditioned preference was related not only to phasic dopamine release (r= 0.8110) but also to the difference between tonic and phasic dopamine levels (r= 0.9521). TBI suppresses dopamine release from the shell portion of the NAc, which in turn significantly alters reward-seeking behavior. These results have important implications for tobacco and drug use after TBI.

Phasic negative intrathoracic pressures enhance the vascular responses to stimulation of pulmonary arterial baroreceptors in closed-chest anaesthetized dogs

PubMed Central

Moore, Jonathan P; Hainsworth, Roger; Drinkhill, Mark J

2004-01-01

We investigated whether the reflex responses to stimulation of pulmonary arterial baroreceptors were altered by intrathoracic pressure changes similar to those encountered during normal breathing. Dogs were anaesthetized with α-chloralose, a cardiopulmonary bypass was established, and the pulmonary trunk and its main branches as far as the first lobar arteries were vascularly isolated and perfused with venous blood. The chest was closed following connection to the perfusion circuit and pressures distending the aortic arch, carotid sinus and coronary artery baroreceptors were controlled. Changes in the descending aortic (systemic) perfusion pressure (SPP; flow constant) were used to assess changes in systemic vascular resistance. Values of SPP were plotted against mean pulmonary arterial pressure (PAP) and sigmoid functions applied. From these curves we derived the threshold pressures (corresponding to 5% of the overall response of SPP), the maximum slopes (equivalent to peak gain) and the corresponding PAP (equivalent to ‘set point’). Stimulus–response curves were compared between data obtained with intrathoracic pressure at atmospheric and with a phasic intrathoracic pressure ranging from atmospheric to around −10 mmHg (18 cycles min−1). Results were obtained from seven dogs and are given as means ±s.e.m. Compared to the values obtained when intrathoracic pressure was at atmospheric, the phasic intrathoracic pressure decreased the pulmonary arterial threshold pressure in five dogs; average change from 28.4 ± 5.9 to 19.3 ± 5.9 mmHg (P > 0.05). The inflexion pressure was significantly reduced from 37.8 ± 4.8 to 27.4 ± 4.0 mmHg (P < 0.03), but the slopes of the curves were not consistently changed. These results have shown that a phasic intrathoracic pressure, which simulates respiratory oscillations, displaces the stimulus–response curve of the pulmonary arterial baroreceptors to lower pressures so that it lies within a physiological range of pressures. PMID:14724182

Development of in vitro-in vivo correlation of parenteral naltrexone loaded polymeric microspheres.

PubMed

Andhariya, Janki V; Shen, Jie; Choi, Stephanie; Wang, Yan; Zou, Yuan; Burgess, Diane J

2017-06-10

Establishment of in vitro-in vivo correlations (IVIVCs) for parenteral polymeric microspheres has been very challenging, due to their complex multiphase release characteristics (which is affected by the nature of the drug) as well as the lack of compendial in vitro release testing methods. Previously, a Level A correlation has been established and validated for polymeric microspheres containing risperidone (a practically water insoluble small molecule drug). The objectives of the present study were: 1) to investigate whether a Level A IVIVC can be established for polymeric microspheres containing another small molecule drug with different solubility profiles compared to risperidone; and 2) to determine whether release characteristic differences (bi-phasic vs tri-phasic) between microspheres can affect the development and predictability of IVIVCs. Naltrexone was chosen as the model drug. Three compositionally equivalent formulations of naltrexone microspheres with different release characteristics were prepared using different manufacturing processes. The critical physicochemical properties (such as drug loading, particle size, porosity, and morphology) as well as the in vitro release characteristics of the prepared naltrexone microspheres and the reference-listed drug (Vivitrol®) were determined. The pharmacokinetics of the naltrexone microspheres were investigated using a rabbit model. The obtained pharmacokinetic profiles were deconvoluted using the Loo-Riegelman method, and compared with the in vitro release profiles of the naltrexone microspheres obtained using USP apparatus 4. Level A IVIVCs were established and validated for predictability. The results demonstrated that the developed USP 4 method was capable of detecting manufacturing process related performance changes, and most importantly, predicting the in vivo performance of naltrexone microspheres in the investigated animal model. A critical difference between naltrexone and risperidone loaded microspheres is their respective bi-phasic and tri-phasic release profiles with varying burst release and lag phase. These variations in release profiles affect the development of IVIVCs. Nevertheless, IVIVCs have been established and validated for polymeric microspheres with different release characteristics. Copyright © 2017. Published by Elsevier B.V.

Reactive Balance Control in Response to Perturbation in Unilateral Stance: Interaction Effects of Direction, Displacement and Velocity on Compensatory Neuromuscular and Kinematic Responses

PubMed Central

Freyler, Kathrin; Gollhofer, Albert; Colin, Ralf; Brüderlin, Uli; Ritzmann, Ramona

2015-01-01

Unexpected sudden perturbations challenge postural equilibrium and require reactive compensation. This study aimed to assess interaction effects of the direction, displacement and velocity of perturbations on electromyographic (EMG) activity, centre of pressure (COP) displacement and joint kinematics to detect neuromuscular characteristics (phasic and segmental) and kinematic strategies of compensatory reactions in an unilateral balance paradigm. In 20 subjects, COP displacement and velocity, ankle, knee and hip joint excursions and EMG during short (SLR), medium (MLR) and long latency response (LLR) of four shank and five thigh muscles were analysed during random surface translations varying in direction (anterior-posterior (sagittal plane), medial-lateral (frontal plane)), displacement (2 vs. 3cm) and velocity (0.11 vs. 0.18m/s) of perturbation when balancing on one leg on a movable platform. Phases: SLR and MLR were scaled to increased velocity (P<0.05); LLR was scaled to increased displacement (P<0.05). Segments: phasic interrelationships were accompanied by segmental distinctions: distal muscles were used for fast compensation in SLR (P<0.05) and proximal muscles to stabilise in LLR (P<0.05). Kinematics: ankle joints compensated for both increasing displacement and velocity in all directions (P<0.05), whereas knee joint deflections were particularly sensitive to increasing displacement in the sagittal (P<0.05) and hip joint deflections to increasing velocity in the frontal plane (P<0.05). COP measures increased with increasing perturbation velocity and displacement (P<0.05). Interaction effects indicate that compensatory responses are based on complex processes, including different postural strategies characterised by phasic and segmental specifications, precisely adjusted to the type of balance disturbance. To regain balance after surface translation, muscles of the distal segment govern the quick regain of equilibrium; the muscles of the proximal limb serve as delayed stabilisers after a balance disturbance. Further, a kinematic distinction regarding the compensation for balance disturbance indicated different plane- and segment-specific sensitivities with respect to the determinants displacement and velocity. PMID:26678061

Formulation, Implementation and Validation of a Two-Fluid model in a Fuel Cell CFD Code

DOE Office of Scientific and Technical Information (OSTI.GOV)

Jain, Kunal; Cole, J. Vernon; Kumar, Sanjiv

2008-12-01

Water management is one of the main challenges in PEM Fuel Cells. While water is essential for membrane electrical conductivity, excess liquid water leads to flooding of catalyst layers. Despite the fact that accurate prediction of two-phase transport is key for optimal water management, understanding of the two-phase transport in fuel cells is relatively poor. Wang et. al. have studied the two-phase transport in the channel and diffusion layer separately using a multiphase mixture model. The model fails to accurately predict saturation values for high humidity inlet streams. Nguyen et. al. developed a two-dimensional, two-phase, isothermal, isobaric, steady state modelmore » of the catalyst and gas diffusion layers. The model neglects any liquid in the channel. Djilali et. al. developed a three-dimensional two-phase multicomponent model. The model is an improvement over previous models, but neglects drag between the liquid and the gas phases in the channel. In this work, we present a comprehensive two-fluid model relevant to fuel cells. Models for two-phase transport through Channel, Gas Diffusion Layer (GDL) and Channel-GDL interface, are discussed. In the channel, the gas and liquid pressures are assumed to be same. The surface tension effects in the channel are incorporated using the continuum surface force (CSF) model. The force at the surface is expressed as a volumetric body force and added as a source to the momentum equation. In the GDL, the gas and liquid are assumed to be at different pressures. The difference in the pressures (capillary pressure) is calculated using an empirical correlations. At the Channel-GDL interface, the wall adhesion affects need to be taken into account. SIMPLE-type methods recast the continuity equation into a pressure-correction equation, the solution of which then provides corrections for velocities and pressures. However, in the two-fluid model, the presence of two phasic continuity equations gives more freedom and more complications. A general approach would be to form a mixture continuity equation by linearly combining the phasic continuity equations using appropriate weighting factors. Analogous to mixture equation for pressure correction, a difference equation is used for the volume/phase fraction by taking the difference between the phasic continuity equations. The relative advantages of the above mentioned algorithmic variants for computing pressure correction and volume fractions are discussed and quantitatively assessed. Preliminary model validation is done for each component of the fuel cell. The two-phase transport in the channel is validated using empirical correlations. Transport in the GDL is validated against results obtained from LBM and VOF simulation techniques. The Channel-GDL interface transport will be validated against experiment and empirical correlation of droplet detachment at the interface.« less

Motor Events during Healthy Sleep: A Quantitative Polysomnographic Study

PubMed Central

Frauscher, Birgit; Gabelia, David; Mitterling, Thomas; Biermayr, Marlene; Bregler, Deborah; Ehrmann, Laura; Ulmer, Hanno; Högl, Birgit

2014-01-01

Study Objectives: Many sleep disorders are characterized by increased motor activity during sleep. In contrast, studies on motor activity during physiological sleep are largely lacking. We quantitatively investigated a large range of motor phenomena during polysomnography in physiological sleep. Design: Prospective polysomnographic investigation. Setting: Academic referral sleep laboratory. Participants: One hundred healthy sleepers age 19-77 y were strictly selected from a representative population sample by a two-step screening procedure. Interventions: N/A. Measurements and Results: Polysomnography according to American Academy of Sleep Medicine (AASM) standards was performed, and quantitative normative values were established for periodic limb movements in sleep (PLMS), high frequency leg movements (HFLM), fragmentary myoclonus (FM), neck myoclonus (NM), and rapid eye movement (REM)-related electromyographic (EMG) activity. Thirty-six subjects had a PLMS index > 5/h, 18 had a PLMS index > 15/h (90th percentile: 24.8/h). Thirty-three subjects had HFLM (90th percentile: four sequences/night). All subjects had FM (90th percentile 143.7/h sleep). Nine subjects fulfilled AASM criteria for excessive FM. Thirty-five subjects had NM (90th percentile: 8.8/h REM sleep). For REM sleep, different EMG activity measures for the mentalis and flexor digitorum superficialis muscles were calculated: the 90th percentile for phasic mentalis EMG activity for 30-sec epochs according to AASM recommendation was 15.6%, and for tonic mentalis EMG activity 2.6%. Twenty-five subjects exceeded the recently proposed phasic mentalis cutoff of 11%. None of the subjects exceeded the tonic mentalis cutoff of 9.6%. Conclusion: Quantification of motor phenomena is a basic prerequisite to develop normative values, and is a first step toward a more precise description of the various motor phenomena present during sleep. Because rates of motor events were unexpectedly high even in physiological sleep, the future use of normative values for both research and clinical routine is essential. Citation: Frauscher B; Gabelia D; Mitterling T; Biermayr M; Bregler D; Ehrmann L; Ulmer H; Högl B. Motor events during healthy sleep: a quantitative polysomnographic study. SLEEP 2014;37(4):763-773. PMID:24744455

TIDAL WAVES: Network mechanisms in the neuroendocrine control of prolactin release.

PubMed

Lyons, David J; Broberger, Christian

2014-10-01

Neuroendocrine tuberoinfundibular dopamine (TIDA) neurons tonically inhibit pituitary release of the hormone, prolactin. Through the powerful actions of prolactin in promoting lactation and maternal behaviour while suppressing sexual drive and fertility, TIDA neurons play a key role in reproduction. We summarize insights from recent in vitro studies into the membrane properties and network behaviour of TIDA neurons including the observations that TIDA neurons exhibit a robust oscillation that is synchronized between cells and depends on intact gap junction communication. Comparisons are made with phasic firing patterns in other neuronal populations. Modulators involved in the control of lactation - including serotonin, thyrotropin-releasing hormone and prolactin itself - have been shown to change the electrical behaviour of TIDA cells. We propose that TIDA discharge mode may play a central role in tuning the amount of dopamine delivered to the pituitary and hence circulating prolactin concentrations in different reproductive states and pathological conditions. Copyright © 2014 Elsevier Inc. All rights reserved.

Relationships between muscular strength and the level of energy sources in the muscle.

PubMed

Wit, A; Juskiak, R; Wit, B; Zieliński, J R

1978-01-01

Relationships between muscular strength and the level of energy sources in the muscle. Acta Physiol. Pol., 1978, 29 (2): 139--151. An attempt was made to establish a relationship between the post-excercise changes in the level of anaerobic energy sources and changes in the muscular strength. The gastrocnemius muscle of Wistar rats was examined. The muscle strength was measured by the resistance tensometry. In muscle specimens ATP, CP and glycogen contents were determined. It was demonstrated that changes in the post-excersise muscle response to electric stimulus have a phasic character resembling the overcompensation curve. The percent changes in the content of anaerobic energy sources in the muscle after contractions varying in duration suggests also overcompensation the muscle content of these substances. The parallelity between the time of appearance of peak overcompensation phase in the muscle strength and in the post-exercise level of musclar ATP, CP and glycogen contents suggest a casual relationship between these changes.

Glucose rapidly induces different forms of excitatory synaptic plasticity in hypothalamic POMC neurons.

PubMed

Hu, Jun; Jiang, Lin; Low, Malcolm J; Rui, Liangyou

2014-01-01

Hypothalamic POMC neurons are required for glucose and energy homeostasis. POMC neurons have a wide synaptic connection with neurons both within and outside the hypothalamus, and their activity is controlled by a balance between excitatory and inhibitory synaptic inputs. Brain glucose-sensing plays an essential role in the maintenance of normal body weight and metabolism; however, the effect of glucose on synaptic transmission in POMC neurons is largely unknown. Here we identified three types of POMC neurons (EPSC(+), EPSC(-), and EPSC(+/-)) based on their glucose-regulated spontaneous excitatory postsynaptic currents (sEPSCs), using whole-cell patch-clamp recordings. Lowering extracellular glucose decreased the frequency of sEPSCs in EPSC(+) neurons, but increased it in EPSC(-) neurons. Unlike EPSC(+) and EPSC(-) neurons, EPSC(+/-) neurons displayed a bi-phasic sEPSC response to glucoprivation. In the first phase of glucoprivation, both the frequency and the amplitude of sEPSCs decreased, whereas in the second phase, they increased progressively to the levels above the baseline values. Accordingly, lowering glucose exerted a bi-phasic effect on spontaneous action potentials in EPSC(+/-) neurons. Glucoprivation decreased firing rates in the first phase, but increased them in the second phase. These data indicate that glucose induces distinct excitatory synaptic plasticity in different subpopulations of POMC neurons. This synaptic remodeling is likely to regulate the sensitivity of the melanocortin system to neuronal and hormonal signals.

What is the function of hippocampal theta rhythm?--Linking behavioral data to phasic properties of field potential and unit recording data.

PubMed

Hasselmo, Michael E

2005-01-01

The extensive physiological data on hippocampal theta rhythm provide an opportunity to evaluate hypotheses about the role of theta rhythm for hippocampal network function. Computational models based on these hypotheses help to link behavioral data with physiological measurements of different variables during theta rhythm. This paper reviews work on network models in which theta rhythm contributes to the following functions: (1) separating the dynamics of encoding and retrieval, (2) enhancing the context-dependent retrieval of sequences, (3) buffering of novel information in entorhinal cortex (EC) for episodic encoding, and (4) timing interactions between prefrontal cortex and hippocampus for memory-guided action selection. Modeling shows how these functional mechanisms are related to physiological data from the hippocampal formation, including (1) the phase relationships of synaptic currents during theta rhythm measured by current source density analysis of electroencephalographic data from region CA1 and dentate gyrus, (2) the timing of action potentials, including the theta phase precession of single place cells during running on a linear track, the context-dependent changes in theta phase precession across trials on each day, and the context-dependent firing properties of hippocampal neurons in spatial alternation (e.g., "splitter cells"), (3) the cholinergic regulation of sustained activity in entorhinal cortical neurons, and (4) the phasic timing of prefrontal cortical neurons relative to hippocampal theta rhythm. Copyright 2005 Wiley-Liss, Inc.

ILLICIT DOPAMINE TRANSIENTS: RECONCILING ACTIONS OF ABUSED DRUGS

PubMed Central

Covey, Dan P.; Roitman, Mitchell F.; Garris, Paul A.

2014-01-01

Phasic increases in brain dopamine are required for cue-directed reward seeking. While compelling within the framework of appetitive behavior, the view that illicit drugs hijack reward circuits by hyper-activating these dopamine transients is inconsistent with established psychostimulant pharmacology. However, recent work reclassifying amphetamine (AMPH), cocaine, and other addictive dopamine-transporter inhibitors (DAT-Is) supports transient hyper-activation as a unifying hypothesis of abused drugs. We argue here that reclassification also identifies generating burst firing by dopamine neurons as a keystone action. Unlike natural rewards, which are processed by sensory systems, drugs act directly on the brain. Consequently, to mimic natural reward and exploit reward circuits, dopamine transients must be elicited de novo. Of available drug targets, only burst firing achieves this essential outcome. PMID:24656971

Gender-specific automatic valence recognition of affective olfactory stimulation through the analysis of the electrodermal activity.

PubMed

Greco, Alberto; Lanata, Antonio; Valenza, Gaetano; Di Francesco, Fabio; Scilingo, Enzo Pasquale

2016-08-01

This study reports on the development of a gender-specific classification system able to discern between two valence levels of smell, through information gathered from electrodermal activity (EDA) dynamics. Specifically, two odorants were administered to 32 healthy volunteers (16 males) while monitoring EDA. CvxEDA model was used to process the EDA signal and extract features from both tonic and phasic components. The feature set was used as input to a K-NN classifier implementing a leave-one-subject-out procedure. Results show strong differences in the accuracy of valence recognition between men (62.5%) and women (78%). We can conclude that affective olfactory stimulation significantly affect EDA dynamics with a highly specific gender dependency.

The Influence of Buddhist Meditation Traditions on the Autonomic System and Attention

PubMed Central

Amihai, Ido; Kozhevnikov, Maria

2015-01-01

Cognitive and neuroscience research from the past several years has shed new light on the influences that meditative traditions have on the meditation practice. Here we review new evidence that shows that types of meditation that developed out of certain traditions such as Vajrayana and Hindu Tantric lead to heightened sympathetic activation and phasic alertness, while types of meditation from other traditions such as Theravada and Mahayana elicit heightened parasympathetic activity and tonic alertness. Such findings validate Buddhist scriptural descriptions of heightened arousal during Vajrayana practices and a calm and alert state of mind during Theravada and Mahayana types of meditation and demonstrate the importance of the cultural and philosophical context out of which the meditation practices develop. PMID:26146629

Effect of membrane hyperpolarization induced by a K+ channel opener on histamine-induced Ca2+ mobilization in rabbit arterial smooth muscle.

PubMed

Watanabe, Y; Suzuki, A; Suzuki, H; Itoh, T

1996-03-01

1. The role of membrane hyperpolarization on agonist-induced contraction was investigated in intact and alpha-toxin-skinned smooth muscles of rabbit mesenteric artery by use of the ATP-sensitive K+ channel opener, (-)-(3S,4R)-4-(N-acetyl-N-hydroxyamino)-6-cyano-3,4-dihydro-2,2- dimethyl-2H-1-benzopyran-3-ol (Y-26763), and either histamine (Hist) or noradrenaline (NA). 2. Hist (3 microM) and NA (10 microM) both produced a phasic, followed by a tonic increase in intracellular Ca2+ concentration ([Ca2+]i) and force. Y-26763 (10 microM) potently inhibited the NA-induced phasic and tonic increase in [Ca2+]i and force. In contrast, Y-26763 attenuated the Hist-induced phasic increase in [Ca2+]i and force but had almost no effect on the tonic response. However, ryanodine-treatment of muscles in order to inhibit the function of intracellular Ca2+ storage sites altered the action of Y-26763 which now attenuated the Hist-induced tonic increase in [Ca2+]i and force in a concentration-dependent manner (at concentrations > 1 microM). Glibenclamide (10 microM) attenuated the inhibitory action of Y-26763. 3. Hist (3 microM) depolarized the smooth muscle cells to the same extent as NA (10 microM). In the absence of either agonist, Y-26763 (over 30 nM) hyperpolarized the membrane and glibenclamide inhibited this hyperpolarization. Y-26763 (10 microM) almost abolished the NA-induced membrane depolarization, but only slightly attenuated the Hist-induced membrane depolarization in which the delta (delta) value (the difference before and after application of Hist) was not modified by any concentration of Y-26763. In ryanodine-treated smooth muscle cells, Y-26763 hyperpolarized the membrane and potently inhibited the membrane depolarization induced by Hist. 4. In ryanodine-treated muscle, Y-26763 had no measurable effect on the Hist-induced [Ca2+]i-force relationship. Y-26763 also had no apparent effect on the myofilament Ca(2+)-sensitivity in the presence of Hist in alpha-toxin-skinned smooth muscles. 5. It is concluded that the membrane hyperpolarization induced by Y-26763 may not be enough to inhibit the Hist-activated Ca2+ influx. It is also suggested that Hist prevents the membrane hyperpolarization induced by Y-26763, activating an unknown mechanism which is thought to depend on the function of intracellular Ca2+ storage sites.

Transcranial Alternating Current Stimulation (tACS) Mechanisms and Protocols

PubMed Central

Tavakoli, Amir V.; Yun, Kyongsik

2017-01-01

Perception, cognition and consciousness can be modulated as a function of oscillating neural activity, while ongoing neuronal dynamics are influenced by synaptic activity and membrane potential. Consequently, transcranial alternating current stimulation (tACS) may be used for neurological intervention. The advantageous features of tACS include the biphasic and sinusoidal tACS currents, the ability to entrain large neuronal populations, and subtle control over somatic effects. Through neuromodulation of phasic, neural activity, tACS is a powerful tool to investigate the neural correlates of cognition. The rapid development in this area requires clarity about best practices. Here we briefly introduce tACS and review the most compelling findings in the literature to provide a starting point for using tACS. We suggest that tACS protocols be based on functional brain mechanisms and appropriate control experiments, including active sham and condition blinding. PMID:28928634

Evidence for a neural law of effect.

PubMed

Athalye, Vivek R; Santos, Fernando J; Carmena, Jose M; Costa, Rui M

2018-03-02

Thorndike's law of effect states that actions that lead to reinforcements tend to be repeated more often. Accordingly, neural activity patterns leading to reinforcement are also reentered more frequently. Reinforcement relies on dopaminergic activity in the ventral tegmental area (VTA), and animals shape their behavior to receive dopaminergic stimulation. Seeking evidence for a neural law of effect, we found that mice learn to reenter more frequently motor cortical activity patterns that trigger optogenetic VTA self-stimulation. Learning was accompanied by gradual shaping of these patterns, with participating neurons progressively increasing and aligning their covariance to that of the target pattern. Motor cortex patterns that lead to phasic dopaminergic VTA activity are progressively reinforced and shaped, suggesting a mechanism by which animals select and shape actions to reliably achieve reinforcement. Copyright © 2018 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works.

Optogenetic mapping of brain circuitry

NASA Astrophysics Data System (ADS)

Augustine, George J.; Berglund, Ken; Gill, Harin; Hoffmann, Carolin; Katarya, Malvika; Kim, Jinsook; Kudolo, John; Lee, Li M.; Lee, Molly; Lo, Daniel; Nakajima, Ryuichi; Park, Min Yoon; Tan, Gregory; Tang, Yanxia; Teo, Peggy; Tsuda, Sachiko; Wen, Lei; Yoon, Su-In

2012-10-01

Studies of the brain promise to be revolutionized by new experimental strategies that harness the combined power of optical techniques and genetics. We have mapped the circuitry of the mouse brain by using both optogenetic actuators that control neuronal activity and optogenetic sensors that detect neuronal activity. Using the light-activated cation channel, channelrhodopsin-2, to locally photostimulate neurons allows high-speed mapping of local and long-range circuitry. For example, with this approach we have mapped local circuits in the cerebral cortex, cerebellum and many other brain regions. Using the fluorescent sensor for chloride ions, Clomeleon, allows imaging of the spatial and temporal dimensions of inhibitory circuits in the brain. This approach allows imaging of both conventional "phasic" synaptic inhibition as well as unconventional "tonic" inhibition. The combined use of light to both control and monitor neural activity creates unprecedented opportunities to explore brain function, screen pharmaceutical agents, and potentially to use light to ameliorate psychiatric and neurological disorders.

The Biot coefficient for a low permeability heterogeneous limestone

NASA Astrophysics Data System (ADS)

Selvadurai, A. P. S.

2018-04-01

This paper presents the experimental and theoretical developments used to estimate the Biot coefficient for the heterogeneous Cobourg Limestone, which is characterized by its very low permeability. The coefficient forms an important component of the Biot poroelastic model that is used to examine coupled hydro-mechanical and thermo-hydro-mechanical processes in the fluid-saturated Cobourg Limestone. The constraints imposed by both the heterogeneous fabric and its extremely low intact permeability [K \\in (10^{-23},10^{-20}) m2 ] require the development of alternative approaches to estimate the Biot coefficient. Large specimen bench-scale triaxial tests (150 mm diameter and 300 mm long) that account for the scale of the heterogeneous fabric are complemented by results for the volume fraction-based mineralogical composition derived from XRD measurements. The compressibility of the solid phase is based on theoretical developments proposed in the mechanics of multi-phasic elastic materials. An appeal to the theory of multi-phasic elastic solids is the only feasible approach for examining the compressibility of the solid phase. The presence of a number of mineral species necessitates the use of the theories of Voigt, Reuss and Hill along with the theories proposed by Hashin and Shtrikman for developing bounds for the compressibility of the multi-phasic geologic material composing the skeletal fabric. The analytical estimates for the Biot coefficient for the Cobourg Limestone are compared with results for similar low permeability rocks reported in the literature.

Cardiac Concomitants of Feedback and Prediction Error Processing in Reinforcement Learning.

PubMed

Kastner, Lucas; Kube, Jana; Villringer, Arno; Neumann, Jane

2017-01-01

Successful learning hinges on the evaluation of positive and negative feedback. We assessed differential learning from reward and punishment in a monetary reinforcement learning paradigm, together with cardiac concomitants of positive and negative feedback processing. On the behavioral level, learning from reward resulted in more advantageous behavior than learning from punishment, suggesting a differential impact of reward and punishment on successful feedback-based learning. On the autonomic level, learning and feedback processing were closely mirrored by phasic cardiac responses on a trial-by-trial basis: (1) Negative feedback was accompanied by faster and prolonged heart rate deceleration compared to positive feedback. (2) Cardiac responses shifted from feedback presentation at the beginning of learning to stimulus presentation later on. (3) Most importantly, the strength of phasic cardiac responses to the presentation of feedback correlated with the strength of prediction error signals that alert the learner to the necessity for behavioral adaptation. Considering participants' weight status and gender revealed obesity-related deficits in learning to avoid negative consequences and less consistent behavioral adaptation in women compared to men. In sum, our results provide strong new evidence for the notion that during learning phasic cardiac responses reflect an internal value and feedback monitoring system that is sensitive to the violation of performance-based expectations. Moreover, inter-individual differences in weight status and gender may affect both behavioral and autonomic responses in reinforcement-based learning.

Design and hydraulic characteristics of a field-scale bi-phasic bioretention rain garden system for storm water management.

PubMed

Yang, H; Florence, D C; McCoy, E L; Dick, W A; Grewal, P S

2009-01-01

A field-scale bioretention rain garden system was constructed using a novel bi-phasic (i.e. sequence of anaerobic to aerobic) concept for improving retention and removal of storm water runoff pollutants. Hydraulic tests with bromide tracer and simulated runoff pollutants (nitrate-N, phosphate-P, Cu, Pb, and Zn) were performed in the system under a simulated continuous rainfall. The objectives of the tests were (1) to determine hydraulic characteristics of the system, and (2) to evaluate the movement of runoff pollutants through the system. For the 180 mm/24 h rainfall, the bi-phasic bioretention system effectively reduced both peak flow (approximately 70%) and runoff volume (approximately 42%). The breakthrough curves (BTCs) of bromide tracer suggest that the transport pattern of the system is similar to dispersed plug flow under this large runoff event. The BTCs of bromide showed mean 10% and 90% breakthrough times of 5.7 h and 12.5 h, respectively. Under the continuous rainfall, a significantly different transport pattern was found between each runoff pollutant. Nitrate-N was easily transported through the system with potential leaching risk from the initial soil medium, whereas phosphate-P and metals were significantly retained indicating sorption-mediated transport. These findings support the importance of hydraulics, in combination with the soil medium, when creating bioretention systems for bioremediation that are effective for various rainfall sizes and intervals.

Cardiac Concomitants of Feedback and Prediction Error Processing in Reinforcement Learning

PubMed Central

Kastner, Lucas; Kube, Jana; Villringer, Arno; Neumann, Jane

2017-01-01

Successful learning hinges on the evaluation of positive and negative feedback. We assessed differential learning from reward and punishment in a monetary reinforcement learning paradigm, together with cardiac concomitants of positive and negative feedback processing. On the behavioral level, learning from reward resulted in more advantageous behavior than learning from punishment, suggesting a differential impact of reward and punishment on successful feedback-based learning. On the autonomic level, learning and feedback processing were closely mirrored by phasic cardiac responses on a trial-by-trial basis: (1) Negative feedback was accompanied by faster and prolonged heart rate deceleration compared to positive feedback. (2) Cardiac responses shifted from feedback presentation at the beginning of learning to stimulus presentation later on. (3) Most importantly, the strength of phasic cardiac responses to the presentation of feedback correlated with the strength of prediction error signals that alert the learner to the necessity for behavioral adaptation. Considering participants' weight status and gender revealed obesity-related deficits in learning to avoid negative consequences and less consistent behavioral adaptation in women compared to men. In sum, our results provide strong new evidence for the notion that during learning phasic cardiac responses reflect an internal value and feedback monitoring system that is sensitive to the violation of performance-based expectations. Moreover, inter-individual differences in weight status and gender may affect both behavioral and autonomic responses in reinforcement-based learning. PMID:29163004

Arousal and consumer in-store behavior.

PubMed

Groeppel-Klein, Andrea

2005-11-15

From a psychophysiological point of view, arousal is a fundamental feature of behavior. As reported in different empirical studies based on insights from theories of consumer behavior, store atmosphere should evoke phasic arousal reactions to attract consumers. Most of these empirical investigations used verbal scales to measure consumers' perceived phasic arousal at the point-of-sale (POS). However, the validity of verbal arousal measurement is questioned; self-reporting methods only allow a time-lagged measurement. Furthermore, the selection of inappropriate items to represent perceived arousal is criticized, and verbal reports require some form of cognitive evaluation of perceived arousal by the individual, who might (in a non-measurement condition) not even be aware of the arousal. By contrast, phasic electrodermal reaction (EDR) has proven to be the most appropriate and valid indicator for measuring arousal [W. Boucsein, Physiologische Grundlagen und Messmethoden der dermalen Aktivität. In: F. Rösler (Ed.), Enzyklopädie der Psychologie, Bereich Psychophysiologie, Band 1: Grundlagen and Methoden der Psychophysiologie, Kapitel, Vol. 7, Hogrefe, Göttingen, 2001, pp. 551-623] that could be relevant to behavior. EDR can be recorded simultaneously to the perception of stimuli. Furthermore, telemetric online device can be used, which enables physiological arousal measurement while participants can move freely through the store and perform the assigned task in the experiments. The present paper delivers insights on arousal theory and results from empirical studies using EDR to measure arousal at the POS.

Time-dependent expression of hypertonic effects on bullfrog taste nerve responses to salts and bitter substances.

PubMed

Mashiyama, Kazunori; Nozawa, Yuhei; Ohtubo, Yoshitaka; Kumazawa, Takashi; Yoshii, Kiyonori

2014-03-27

We previously showed that the hypertonicity of taste stimulating solutions modified tonic responses, the quasi-steady state component following the transient (phasic) component of each integrated taste nerve response. Here we show that the hypertonicity opens tight junctions surrounding taste receptor cells in a time-dependent manner and modifies whole taste nerve responses in bullfrogs. We increased the tonicity of stimulating solutions with non-taste substances such as urea or ethylene glycol. The hypertonicity enhanced phasic responses to NaCl>0.2M, and suppressed those to NaCl<0.1M, 1mM CaCl2, and 1mM bitter substances (quinine, denatonium and strychnine). The hypertonicity also enhanced the phasic responses to a variety of 0.5M salts such as LiCl and KCl. The enhancing effect was increased by increasing the difference between the ionic mobilities of the cations and anions in the salt. A preincubation time >20s in the presence of 1M non-taste substances was needed to elicit both the enhancing and suppressing effects. Lucifer Yellow CH, a paracellular marker dye, diffused into bullfrog taste receptor organs in 30s in the presence of hypertonicity. These results agreed with our proposed mechanism of hypertonic effects that considered the diffusion potential across open tight junctions. Copyright © 2014 Elsevier B.V. All rights reserved.

Tyrosine Phosphorylation of GABAA Receptor γ2-Subunit Regulates Tonic and Phasic Inhibition in the Thalamus

PubMed Central

Nani, Francesca; Bright, Damian P.; Revilla-Sanchez, Raquel; Tretter, Verena; Moss, Stephen J.

2013-01-01

GABA-mediated tonic and phasic inhibition of thalamic relay neurons of the dorsal lateral geniculate nucleus (dLGN) was studied after ablating tyrosine (Y) phosphorylation of receptor γ2-subunits. As phosphorylation of γ2 Y365 and Y367 reduces receptor internalization, to understand their importance for inhibition we created a knock-in mouse in which these residues are replaced by phenylalanines. On comparing wild-type (WT) and γ2Y365/367F+/− (HT) animals (homozygotes are not viable in utero), the expression levels of GABAA receptor α4-subunits were increased in the thalamus of female, but not male mice. Raised δ-subunit expression levels were also observed in female γ2Y365/367F +/− thalamus. Electrophysiological analyses revealed no difference in the level of inhibition in male WT and HT dLGN, while both the spontaneous inhibitory postsynaptic activity and the tonic current were significantly augmented in female HT relay cells. The sensitivity of tonic currents to the δ-subunit superagonist THIP, and the blocker Zn2+, were higher in female HT relay cells. This is consistent with upregulation of extrasynaptic GABAA receptors containing α4- and δ-subunits to enhance tonic inhibition. In contrast, the sensitivity of GABAA receptors mediating inhibition in the female γ2Y356/367F +/− to neurosteroids was markedly reduced compared with WT. We conclude that disrupting tyrosine phosphorylation of the γ2-subunit activates a sex-specific increase in tonic inhibition, and this most likely reflects a genomic-based compensation mechanism for the reduced neurosteroid sensitivity of inhibition measured in female HT relay neurons. PMID:23904608

Quantitative analysis of neuronal response properties in primary and higher-order auditory cortical fields of awake house mice (Mus musculus)

PubMed Central

Joachimsthaler, Bettina; Uhlmann, Michaela; Miller, Frank; Ehret, Günter; Kurt, Simone

2014-01-01

Because of its great genetic potential, the mouse (Mus musculus) has become a popular model species for studies on hearing and sound processing along the auditory pathways. Here, we present the first comparative study on the representation of neuronal response parameters to tones in primary and higher-order auditory cortical fields of awake mice. We quantified 12 neuronal properties of tone processing in order to estimate similarities and differences of function between the fields, and to discuss how far auditory cortex (AC) function in the mouse is comparable to that in awake monkeys and cats. Extracellular recordings were made from 1400 small clusters of neurons from cortical layers III/IV in the primary fields AI (primary auditory field) and AAF (anterior auditory field), and the higher-order fields AII (second auditory field) and DP (dorsoposterior field). Field specificity was shown with regard to spontaneous activity, correlation between spontaneous and evoked activity, tone response latency, sharpness of frequency tuning, temporal response patterns (occurrence of phasic responses, phasic-tonic responses, tonic responses, and off-responses), and degree of variation between the characteristic frequency (CF) and the best frequency (BF) (CF–BF relationship). Field similarities were noted as significant correlations between CFs and BFs, V-shaped frequency tuning curves, similar minimum response thresholds and non-monotonic rate-level functions in approximately two-thirds of the neurons. Comparative and quantitative analyses showed that the measured response characteristics were, to various degrees, susceptible to influences of anesthetics. Therefore, studies of neuronal responses in the awake AC are important in order to establish adequate relationships between neuronal data and auditory perception and acoustic response behavior. PMID:24506843

An Imperfect Dopaminergic Error Signal Can Drive Temporal-Difference Learning

PubMed Central

Potjans, Wiebke; Diesmann, Markus; Morrison, Abigail

2011-01-01

An open problem in the field of computational neuroscience is how to link synaptic plasticity to system-level learning. A promising framework in this context is temporal-difference (TD) learning. Experimental evidence that supports the hypothesis that the mammalian brain performs temporal-difference learning includes the resemblance of the phasic activity of the midbrain dopaminergic neurons to the TD error and the discovery that cortico-striatal synaptic plasticity is modulated by dopamine. However, as the phasic dopaminergic signal does not reproduce all the properties of the theoretical TD error, it is unclear whether it is capable of driving behavior adaptation in complex tasks. Here, we present a spiking temporal-difference learning model based on the actor-critic architecture. The model dynamically generates a dopaminergic signal with realistic firing rates and exploits this signal to modulate the plasticity of synapses as a third factor. The predictions of our proposed plasticity dynamics are in good agreement with experimental results with respect to dopamine, pre- and post-synaptic activity. An analytical mapping from the parameters of our proposed plasticity dynamics to those of the classical discrete-time TD algorithm reveals that the biological constraints of the dopaminergic signal entail a modified TD algorithm with self-adapting learning parameters and an adapting offset. We show that the neuronal network is able to learn a task with sparse positive rewards as fast as the corresponding classical discrete-time TD algorithm. However, the performance of the neuronal network is impaired with respect to the traditional algorithm on a task with both positive and negative rewards and breaks down entirely on a task with purely negative rewards. Our model demonstrates that the asymmetry of a realistic dopaminergic signal enables TD learning when learning is driven by positive rewards but not when driven by negative rewards. PMID:21589888

Amphetamine elevates nucleus accumbens dopamine via an action potential-dependent mechanism that is modulated by endocannabinoids

PubMed Central

Covey, Dan P.; Bunner, Kendra D.; Schuweiler, Douglas R.; Cheer, Joseph F.; Garris, Paul A.

2018-01-01

The reinforcing effects of abused drugs are mediated by their ability to elevate nucleus accumbens dopamine. Amphetamine (AMPH) was historically thought to increase dopamine by an action potential-independent, non-exocytotic type of release called efflux, involving reversal of dopamine transporter function and driven by vesicular dopamine depletion. Growing evidence suggests that AMPH also acts by an action potential-dependent mechanism. Indeed, fast-scan cyclic voltammetry demonstrates that AMPH activates dopamine transients, reward-related phasic signals generated by burst firing of dopamine neurons and dependent on intact vesicular dopamine. Not established for AMPH but indicating a shared mechanism, endocannabinoids facilitate this activation of dopamine transients by broad classes of abused drugs. Here, using fast-scan cyclic voltammetry coupled to pharmacological manipulations in awake rats, we investigated the action potential and endocannabinoid dependence of AMPH-induced elevations in nucleus accumbens dopamine. AMPH increased the frequency, amplitude and duration of transients, which were observed riding on top of slower dopamine increases. Surprisingly, silencing dopamine neuron firing abolished all AMPH-induced dopamine elevations, identifying an action potential-dependent origin. Blocking cannabinoid type 1 receptors prevented AMPH from increasing transient frequency, similar to reported effects on other abused drugs, but not from increasing transient duration and inhibiting dopamine uptake. Thus, AMPH elevates nucleus accumbens dopamine by eliciting transients via cannabinoid type 1 receptors and promoting the summation of temporally coincident transients, made more numerous, larger and wider by AMPH. Collectively, these findings are inconsistent with AMPH eliciting action potential-independent dopamine efflux and vesicular dopamine depletion, and support endocannabinoids facilitating phasic dopamine signalling as a common action in drug reinforcement. PMID:27038339

Amphetamine elevates nucleus accumbens dopamine via an action potential-dependent mechanism that is modulated by endocannabinoids.

PubMed

Covey, Dan P; Bunner, Kendra D; Schuweiler, Douglas R; Cheer, Joseph F; Garris, Paul A

2016-06-01

The reinforcing effects of abused drugs are mediated by their ability to elevate nucleus accumbens dopamine. Amphetamine (AMPH) was historically thought to increase dopamine by an action potential-independent, non-exocytotic type of release called efflux, involving reversal of dopamine transporter function and driven by vesicular dopamine depletion. Growing evidence suggests that AMPH also acts by an action potential-dependent mechanism. Indeed, fast-scan cyclic voltammetry demonstrates that AMPH activates dopamine transients, reward-related phasic signals generated by burst firing of dopamine neurons and dependent on intact vesicular dopamine. Not established for AMPH but indicating a shared mechanism, endocannabinoids facilitate this activation of dopamine transients by broad classes of abused drugs. Here, using fast-scan cyclic voltammetry coupled to pharmacological manipulations in awake rats, we investigated the action potential and endocannabinoid dependence of AMPH-induced elevations in nucleus accumbens dopamine. AMPH increased the frequency, amplitude and duration of transients, which were observed riding on top of slower dopamine increases. Surprisingly, silencing dopamine neuron firing abolished all AMPH-induced dopamine elevations, identifying an action potential-dependent origin. Blocking cannabinoid type 1 receptors prevented AMPH from increasing transient frequency, similar to reported effects on other abused drugs, but not from increasing transient duration and inhibiting dopamine uptake. Thus, AMPH elevates nucleus accumbens dopamine by eliciting transients via cannabinoid type 1 receptors and promoting the summation of temporally coincident transients, made more numerous, larger and wider by AMPH. Collectively, these findings are inconsistent with AMPH eliciting action potential-independent dopamine efflux and vesicular dopamine depletion, and support endocannabinoids facilitating phasic dopamine signalling as a common action in drug reinforcement. © 2016 Federation of European Neuroscience Societies and John Wiley & Sons Ltd.

Professional musicians listen differently to music.

PubMed

Mikutta, C A; Maissen, G; Altorfer, A; Strik, W; Koenig, T

2014-05-30

Experience-based adaptation of emotional responses is an important faculty for cognitive and emotional functioning. Professional musicians represent an ideal model in which to elicit experience-driven changes in the emotional processing domain. The changes of the central representation of emotional arousal due to musical expertise are still largely unknown. The aim of the present study was to investigate the electroencephalogram (EEG) correlates of experience-driven changes in the domain of emotional arousal. Therefore, the differences in perceived (subjective arousal via ratings) and physiologically measured (EEG) arousal between amateur and professional musicians were examined. A total of 15 professional and 19 amateur musicians listened to the first movement of Ludwig van Beethoven's 5th symphony (duration=∼7.4min), during which a continuous 76-channel EEG was recorded. In a second session, the participants evaluated their emotional arousal during listening. In a tonic analysis, we examined the average EEG data over the time course of the music piece. For a phasic analysis, a fast Fourier transform was performed and covariance maps of spectral power were computed in association with the subjective arousal ratings. The subjective arousal ratings of the professional musicians were more consistent than those of the amateur musicians. In the tonic EEG analysis, a mid-frontal theta activity was observed in the professionals. In the phasic EEG, the professionals exhibited an increase of posterior alpha, central delta, and beta rhythm during high arousal. Professionals exhibited different and/or more intense patterns of emotional activation when they listened to the music. The results of the present study underscore the impact of music experience on emotional reactions. Copyright © 2014 IBRO. Published by Elsevier Ltd. All rights reserved.

Brain Serotonin Receptors and Transporters: Initiation vs. Termination of Escalated Aggression

PubMed Central

Takahashi, Aki; Quadros, Isabel M.; de Almeida, Rosa M. M.; Miczek, Klaus A.

2013-01-01

Rationale Recent findings have shown a complexly regulated 5-HT system as it is linked to different kinds of aggression. Objective We focus on (1) phasic and tonic changes of 5-HT and (2) state and trait of aggression, and emphasize the different receptor subtypes, their role in specific brain regions, feed-back regulation and modulation by other amines, acids and peptides. Results New pharmacological tools differentiate the first three 5-HT receptor families and their modulation by GABA, glutamate and CRF. Activation of 5-HT1A, 5-HT1B and 5-HT2A/2C receptors in mesocorticolimbic areas, reduce species-typical and other aggressive behaviors. In contrast, agonists at 5-HT1A and 5-HT1B receptors in the medial prefrontal cortex or septal area can increase aggressive behavior under specific conditions. Activation of serotonin transporters reduce mainly pathological aggression. Genetic analyses of aggressive individuals have identified several molecules that affect the 5-HT system directly (e.g., Tph2, 5-HT1B, 5-HT transporter, Pet1, MAOA) or indirectly (e.g., Neuropeptide Y, αCaMKII, NOS, BDNF). Dysfunction in genes for MAOA escalates pathological aggression in rodents and humans, particularly in interaction with specific experiences. Conclusions Feedback to autoreceptors of the 5-HT1 family and modulation via heteroreceptors are important in the expression of aggressive behavior. Tonic increase of the 5-HT2 family expression may cause escalated aggression, whereas the phasic increase of 5-HT2 receptors inhibits aggressive behaviors. Polymorphisms in the genes of 5-HT transporters or rate-limiting synthetic and metabolic enzymes of 5-HT modulate aggression, often requiring interaction with the rearing environment. PMID:20938650

Towards a Reconceptualization of Striatal Interactions Between Glutamatergic and Dopaminergic Neurotransmission and Their Contribution to the Production of Movements

PubMed Central

David, Hélène N

2009-01-01

According to the current model of the basal ganglia organization, simultaneous activation of the striato-nigral direct pathway by glutamatergic and dopaminergic neurotransmission should lead to a synergistic facilitatory action on locomotor activity, while in contrast activation of the indirect pathway by these two neurotransmittions should lead to antagonistic effects on locomotor activity. Based on published data, as a break with the current thinking, we propose a reconceptualization of functional interactions between dopaminergic and glutamatergic neurotransmission. In this model, dopaminergic neurotransmission is seen as a motor pacemaker responsible for the basal and primary activation of striatal output neurons and glutamate as a driver providing a multiple combination of tonic, phasic, facilitatory and inhibitory influxes resulting from the processing of environmental, emotional and mnesic stimuli. Thus, in the model, glutamate-coded inputs would allow tuning the intrinsic motor-activating properties of dopamine to adjust the production of locomotor activity into goal-oriented movements. PMID:19949572

Effects of weightlessness on the muscle system. new results of simulation's studies

NASA Astrophysics Data System (ADS)

Kozlovskaya, I. B.; Shenkman, B. S.; Grigoriev, A. I.

Results of studies of phenomenology and nature of the hypogravitational motor syndrome, provided at the Institute of Biomedical Problems of RAS, have shown that a decline of gravitational load is followed consistently by deep disturbances in all parts and structures of the motor system. An important role in their development plays the withdrawal of the support and, accordingly the decrease of the intensity of the support afferentation activities that provokes a decline of tonic motor units' activities and correspondingly a decline of the muscle tone in the first phase and the development of atrophic processes in slow fibers of antigravitational muscles in the second one (Kozlovskaya et.al., 1987). This hypothesis was tested in experiments with 7-hours and 7-days "dry immersion" (DI), in which effects of pure supportless environment and pure supportless environment coupled with mechanical stimulation of the support zones of the soles were compared. Stimulation with the pressure of 0,2 kg/sm^2 value to forefoot and heel support zones for 20 minutes every hour during 6 hours was applied daily in the regimen of slow and fast locomotion (pacing with the rate of 60 and 120 steps/min). The subjects exposed to the pure DI environment revealed after exposition a significant decline of the transverse stiffness and of the maximal isokinetic force of the leg postural muscles, a decrease of the postural muscles participation in the locomotions along with the increase of the phasic muscles' part, a significant decrease of the absolute force of m.soleus single skinned fibers evoked by Ca++, and an obvious decline of their transverse cross sectional areas as well as prominent disturbances of the activities of spinal and supraspinal motor control systems. Mechanical stimulation of the soles support zones eliminated all the above effects, minimizing the changes of the muscle stiffness and the maximal isokinetic force, taking away the signs of the isolated muscle fibers force decline and of the atrophic changes, preserving close to control relations of the activities of postural (m.soleus) and phasic (m.gastrocnemius) muscles in locomotor movements and normal characteristics of activities of motor control mechanisms.

Nicotine Withdrawal Induces Neural Deficits in Reward Processing.

PubMed

Oliver, Jason A; Evans, David E; Addicott, Merideth A; Potts, Geoffrey F; Brandon, Thomas H; Drobes, David J

2017-06-01

Nicotine withdrawal reduces neurobiological responses to nonsmoking rewards. Insight into these reward deficits could inform the development of targeted interventions. This study examined the effect of withdrawal on neural and behavioral responses during a reward prediction task. Smokers (N = 48) attended two laboratory sessions following overnight abstinence. Withdrawal was manipulated by having participants smoke three regular nicotine (0.6 mg yield; satiation) or very low nicotine (0.05 mg yield; withdrawal) cigarettes. Electrophysiological recordings of neural activity were obtained while participants completed a reward prediction task that involved viewing four combinations of predictive and reward-determining stimuli: (1) Unexpected Reward; (2) Predicted Reward; (3) Predicted Punishment; (4) Unexpected Punishment. The task evokes a medial frontal negativity that mimics the phasic pattern of dopaminergic firing in ventral tegmental regions associated with reward prediction errors. Nicotine withdrawal decreased the amplitude of the medial frontal negativity equally across all trial types (p < .001). Exploratory analyses indicated withdrawal increased time to initiate the next trial following unexpected punishment trials (p < .001) and response time on reward trials during withdrawal was positively related to nicotine dependence (p < .001). Nicotine withdrawal had equivocal impact across trial types, suggesting reward processing deficits are unlikely to stem from changes in phasic dopaminergic activity during prediction errors. Effects on tonic activity may be more pronounced. Pharmacological interventions directly targeting the dopamine system and behavioral interventions designed to increase reward motivation and responsiveness (eg, behavioral activation) may aid in mitigating withdrawal symptoms and potentially improving smoking cessation outcomes. Findings from this study indicate nicotine withdrawal impacts reward processing signals that are observable in smokers' neural activity. This may play a role in the subjective aversive experience of nicotine withdrawal and potentially contribute to smoking relapse. Interventions that address abnormal responding to both pleasant and unpleasant stimuli may be particularly effective for alleviating nicotine withdrawal. © The Author 2017. Published by Oxford University Press on behalf of the Society for Research on Nicotine and Tobacco. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Study of the initial stages of drug release from a degradable matrix of poly(d,l-lactide-co-glycolide).

PubMed

Frank, Alexis; Kumar Rath, Santosh; Boey, Freddy; Venkatraman, Subbu

2004-02-01

The initial stages of the in vitro degradation of and the drug release from a matrix made of poly(d,l-lactide-co-glycolide) was carried out in a phosphate buffer saline (pH 7.0) medium. It has been observed that substantial matrix degradation occurs at the end of 2 weeks of immersion. The drug release using films of the polymer shows a tri-phasic pattern, unlike the bi-phasic patterns usually seen. Mechanisms are proposed for each phase of release, based on results from weight loss, amount of water absorption and scanning electron microscopy. The details of the structural changes and their effects on drug release may have implications for delivering potent drugs over a 2-week period.

Effect of inactivity and passive stretch on protein turnover in phasic and postural rat muscles

NASA Technical Reports Server (NTRS)

Loughna, P.; Goldspink, G.; Goldspink, D. F.

1986-01-01

Muscle atrophy in humans can occur during prolonged bed rest, plaster cast immobilization, and space flight. In the present study, the suspension model used by Musacchia et al. (1983) is employed to investigate changes in protein synthesis and degradation in fast-twitch phasic (extensor digitorum longus) and slow-twitch postural (soleus) muscles in the rat, following hypokinesia and hypodynamia. In addition, the use of passive stretch was examined as a means of preventing atrophy. The obtained results suggest that the mechanisms controlling the processes of protein synthesis and protein breakdown during muscle disuse atrophy may be independent of each other. It appears, however, that the muscle atrophy due to hypokinesia and hypodynamia can be temporarily prevented by passively stretching a muscle.

Mechanisms of Kappa Opioid Receptor Potentiation of Dopamine D2 Receptor Function in Quinpirole-Induced Locomotor Sensitization in Rats.

PubMed

Escobar, Angélica P; González, Marcela P; Meza, Rodrigo C; Noches, Verónica; Henny, Pablo; Gysling, Katia; España, Rodrigo A; Fuentealba, José A; Andrés, María E

2017-08-01

Increased locomotor activity in response to the same stimulus is an index of behavioral sensitization observed in preclinical models of drug addiction and compulsive behaviors. Repeated administration of quinpirole, a D2/D3 dopamine agonist, induces locomotor sensitization. This effect is potentiated and accelerated by co-administration of U69593, a kappa opioid receptor agonist. The mechanism underlying kappa opioid receptor potentiation of quinpirole-induced locomotor sensitization remains to be elucidated. Immunofluorescence anatomical studies were undertaken in mice brain slices and rat presynaptic synaptosomes to reveal kappa opioid receptor and D2R pre- and postsynaptic colocalization in the nucleus accumbens. Tonic and phasic dopamine release in the nucleus accumbens of rats repeatedly treated with U69593 and quinpirole was assessed by microdialysis and fast scan cyclic voltammetry. Anatomical data show that kappa opioid receptor and D2R colocalize postsynaptically in medium spiny neurons of the nucleus accumbens and the highest presynaptic colocalization occurs on the same dopamine terminals. Significantly reduced dopamine levels were observed in quinpirole, and U69593-quinpirole treated rats, explaining sensitization of D2R. Presynaptic inhibition induced by kappa opioid receptor and D2R of electrically evoked dopamine release was faster in U69593-quinpirole compared with quinpirole-repeatedly treated rats. Pre- and postsynaptic colocalization of kappa opioid receptor and D2R supports a role for kappa opioid receptor potentiating both the D2R inhibitory autoreceptor function and the inhibitory action of D2R on efferent medium spiny neurons. Kappa opioid receptor co-activation accelerates D2R sensitization by contributing to decrease dopamine release in the nucleus accumbens. © The Author 2017. Published by Oxford University Press on behalf of CINP.

TRPM4 channel: a new player in urinary bladder smooth muscle function in rats

PubMed Central

Smith, Amy C.; Parajuli, Shankar P.; Hristov, Kiril L.; Cheng, Qiuping; Soder, Rupal P.; Afeli, Serge A. Y.; Earley, Scott; Xin, Wenkuan; Malysz, John

2013-01-01

The TRPM4 channel is a Ca2+-activated, monovalent cation-selective channel of the melastatin transient receptor potential (TRPM) family. The TRPM4 channel is implicated in the regulation of many cellular processes including the immune response, insulin secretion, and pressure-induced vasoconstriction of cerebral arteries. However, the expression and function of the TRPM4 channels in detrusor smooth muscle (DSM) have not yet been explored. Here, we provide the first molecular, electrophysiological, and functional evidence for the presence of TRPM4 channels in rat DSM. We detected the expression of TRPM4 channels at mRNA and protein levels in freshly isolated DSM single cells and DSM tissue using RT-PCR, Western blotting, immunohistochemistry, and immunocytochemistry. 9-Hydroxyphenanthrene (9-phenanthrol), a novel selective inhibitor of TRPM4 channels, was used to examine their role in DSM function. In perforated patch-clamp recordings using freshly isolated rat DSM cells, 9-phenanthrol (30 μM) decreased the spontaneous inward current activity at −70 mV. Real-time DSM live-cell Ca2+ imaging showed that selective inhibition of TRPM4 channels with 9-phenanthrol (30 μM) significantly reduced the intracellular Ca2+ levels. Isometric DSM tension recordings revealed that 9-phenanthrol (0.1–30 μM) significantly inhibited the amplitude, muscle force integral, and frequency of the spontaneous phasic and pharmacologically induced contractions of rat DSM isolated strips. 9-Phenanthrol also decreased the amplitude and muscle force integral of electrical field stimulation-induced contractions. In conclusion, this is the first study to examine the expression and provide evidence for TRPM4 channels as critical regulators of rat DSM excitability and contractility. PMID:23283997

Differential effects of respiratory and electrical stimulation-induced dilator muscle contraction on mechanical properties of the pharynx in the pig.

PubMed

Brodsky, A; Dotan, Y; Samri, M; Schwartz, A R; Oliven, A

2016-09-01

Respiratory stimulation (RS) during sleep often fails to discontinue flow limitation, whereas electrical stimulation (ES) of the hypoglossus (HG) nerve frequently prevents obstruction. The present work compares the effects of RS and HG-ES on pharyngeal mechanics and the relative contribution of tongue muscles and thoracic forces to pharyngeal patency. We determined the pressure-area relationship of the collapsible segment of the pharynx in anesthetized pigs under the following three conditions: baseline (BL), RS induced by partial obstruction of the tracheostomy tube, and HG-ES. Parameters were obtained also after transection of the neck muscles and the trachea (NMT) and after additional bilateral HG transection (HGT). In addition, we measured the force produced by in situ isolated geniohyoid (GH) during RS and HG-ES. Intense RS was recognized by large negative intrathoracic pressures and triggered high phasic genioglossus and GH EMG activity. GH contraction produced during maximal RS less than a quarter of the force obtained during HG-ES. The major finding of the study was that RS and ES differed in the mechanism by which they stabilized the pharynx: RS lowered the pressure-area slope, i.e., reduced pharyngeal compliance (14.1 ± 2.9 to 9.2 ± 1.9 mm(2)/cmH2O, P < 0.01). HG-ES shifted the slope toward lower pressures, i.e., lowered the calculated extraluminal pressure (17.4 ± 5.8 to 9.2 ± 7.4 cmH2O, P < 0.01). Changes during RS and HG-ES were not affected by NMT, but the effect of RS decreased significantly after HGT. In conclusion, HG-ES and RS affect the pharyngeal site of collapse differently. Tongue muscle contraction contributes to pharyngeal stiffening during RS. Copyright © 2016 the American Physiological Society.

Diagnostic Value of Isolated Mentalis Versus Mentalis Plus Upper Limb Electromyography in Idiopathic REM Sleep Behavior Disorder Patients Eventually Developing a Neurodegenerative Syndrome.

PubMed

Fernández-Arcos, Ana; Iranzo, Alex; Serradell, Mónica; Gaig, Carles; Guaita, Marc; Salamero, Manel; Santamaria, Joan

2017-04-01

To compare two electromyographic (EMG) montages, isolated mentalis muscle versus mentalis in combination with upper limb muscles in the baseline diagnostic video-polysomnography (V-PSG) of patients with idiopathic REM sleep behaviors disorder (IRBD) who eventually were diagnosed with a clinically defined neurodegenerative syndrome. Forty-nine patients were included. At baseline, diagnosis of RBD was based on a typical history of dream enactment behaviors plus V-PSG showing REM sleep with qualitative increased EMG activity and/or abnormal behaviors. Quantification of EMG activity (tonic, phasic and "any") in the mentalis and upper limb muscles (biceps brachii-BB, n = 36 or flexor digitorum superficialis-FDS, n = 13) was performed manually and compared with published cut-offs. Nine (18.4%) patients had either tonic or phasic EMG below the cut-offs for the isolated mentalis and four of them (11.1 %) also had values below the cut-off for the mentalis combined with BB. All 13 patients recorded with the FDS were above the mentalis combined with FDS cut-off. For the diagnosis of IRBD, sensitivity of isolated mentalis was 81.6% and of the combination of mentalis plus upper limb muscles was 91.8% (p = .03). Audiovisual analysis showed abnormal REM sleep behaviors in all nine patients with values below the cut-offs. Quantification of EMG activity in the upper limbs combined with the mentalis increases the ability to diagnose IRBD when compared with the isolated measurement of the mentalis. Detection of typical abnormal behaviors during REM sleep with audiovisual analysis is essential for the diagnosis of IRBD in patients with EMG values below the published cut-offs. © Sleep Research Society 2017. Published by Oxford University Press on behalf of the Sleep Research Society. All rights reserved. For permissions, please e-mail journals.permissions@oup.com.

Modelling individual differences in the form of Pavlovian conditioned approach responses: a dual learning systems approach with factored representations.

PubMed

Lesaint, Florian; Sigaud, Olivier; Flagel, Shelly B; Robinson, Terry E; Khamassi, Mehdi

2014-02-01

Reinforcement Learning has greatly influenced models of conditioning, providing powerful explanations of acquired behaviour and underlying physiological observations. However, in recent autoshaping experiments in rats, variation in the form of Pavlovian conditioned responses (CRs) and associated dopamine activity, have questioned the classical hypothesis that phasic dopamine activity corresponds to a reward prediction error-like signal arising from a classical Model-Free system, necessary for Pavlovian conditioning. Over the course of Pavlovian conditioning using food as the unconditioned stimulus (US), some rats (sign-trackers) come to approach and engage the conditioned stimulus (CS) itself - a lever - more and more avidly, whereas other rats (goal-trackers) learn to approach the location of food delivery upon CS presentation. Importantly, although both sign-trackers and goal-trackers learn the CS-US association equally well, only in sign-trackers does phasic dopamine activity show classical reward prediction error-like bursts. Furthermore, neither the acquisition nor the expression of a goal-tracking CR is dopamine-dependent. Here we present a computational model that can account for such individual variations. We show that a combination of a Model-Based system and a revised Model-Free system can account for the development of distinct CRs in rats. Moreover, we show that revising a classical Model-Free system to individually process stimuli by using factored representations can explain why classical dopaminergic patterns may be observed for some rats and not for others depending on the CR they develop. In addition, the model can account for other behavioural and pharmacological results obtained using the same, or similar, autoshaping procedures. Finally, the model makes it possible to draw a set of experimental predictions that may be verified in a modified experimental protocol. We suggest that further investigation of factored representations in computational neuroscience studies may be useful.

Modelling Individual Differences in the Form of Pavlovian Conditioned Approach Responses: A Dual Learning Systems Approach with Factored Representations

PubMed Central

Lesaint, Florian; Sigaud, Olivier; Flagel, Shelly B.; Robinson, Terry E.; Khamassi, Mehdi

2014-01-01

Reinforcement Learning has greatly influenced models of conditioning, providing powerful explanations of acquired behaviour and underlying physiological observations. However, in recent autoshaping experiments in rats, variation in the form of Pavlovian conditioned responses (CRs) and associated dopamine activity, have questioned the classical hypothesis that phasic dopamine activity corresponds to a reward prediction error-like signal arising from a classical Model-Free system, necessary for Pavlovian conditioning. Over the course of Pavlovian conditioning using food as the unconditioned stimulus (US), some rats (sign-trackers) come to approach and engage the conditioned stimulus (CS) itself – a lever – more and more avidly, whereas other rats (goal-trackers) learn to approach the location of food delivery upon CS presentation. Importantly, although both sign-trackers and goal-trackers learn the CS-US association equally well, only in sign-trackers does phasic dopamine activity show classical reward prediction error-like bursts. Furthermore, neither the acquisition nor the expression of a goal-tracking CR is dopamine-dependent. Here we present a computational model that can account for such individual variations. We show that a combination of a Model-Based system and a revised Model-Free system can account for the development of distinct CRs in rats. Moreover, we show that revising a classical Model-Free system to individually process stimuli by using factored representations can explain why classical dopaminergic patterns may be observed for some rats and not for others depending on the CR they develop. In addition, the model can account for other behavioural and pharmacological results obtained using the same, or similar, autoshaping procedures. Finally, the model makes it possible to draw a set of experimental predictions that may be verified in a modified experimental protocol. We suggest that further investigation of factored representations in computational neuroscience studies may be useful. PMID:24550719

Deficiency of interstitial cells of Cajal in the small intestine of patients with Crohn's disease.

PubMed

Porcher, Christophe; Baldo, Marjolaine; Henry, Monique; Orsoni, Pierre; Julé, Yvon; Ward, Sean M

2002-01-01

Interstitial cells of Cajal are critical for the generation of electrical slow waves that regulate the phasic contractile activity of the tunica muscularis of the GI tract. Under certain pathophysiological conditions loss of interstitial cells of Cajal may play a role in the generation of certain motility disorders. The aim of the present study was to determine if there is an abnormality in the density or distribution of interstitial cells of Cajal from patients with Crohn's disease. Small intestines from control subjects and patients with Crohn's disease were examined using immunohistochemistry and antibodies against the Kit receptor, which is expressed in interstitial cells of Cajal within the tunica muscularis of the GI tract. The density and distribution of interstitial cells of Cajal were assessed in the longitudinal and circular muscle layers and in the myenteric and deep muscular plexus regions of Crohn's and control tissues. Tissues from Crohn's disease patients showed an almost complete abolition of interstitial cells of Cajal within the longitudinal and circular muscle layers and a significant reduction in numbers at the level of the myenteric and deep muscular plexuses. In tissues from Crohn's disease patients, the density of interstitial cells of Cajal was reduced throughout the tunica muscularis in comparison to control small intestines. The disturbance of intestinal motility that occurs in patients with Crohn's disease may be a consequence of the loss of or defects in specific populations of interstitial cells of Cajal within the tunica muscularis.

Pickpocket1 Is an Ionotropic Molecular Sensory Transducer*

PubMed Central

Boiko, Nina; Kucher, Volodymyr; Stockand, James D.; Eaton, Benjamin A.

2012-01-01

The molecular transformation of an external stimulus into changes in sensory neuron activity is incompletely described. Although a number of molecules have been identified that can respond to stimuli, evidence that these molecules can transduce stimulation into useful neural activity is lacking. Here we demonstrate that pickpocket1 (ppk1), a Drosophila homolog of mammalian Degenerin/epithelial sodium channels, encodes an acid-sensing sodium channel that conducts a transient depolarizing current in multidendritic sensory neurons of Drosophila melanogaster. Stimulation of Ppk1 is sufficient to bring these sensory neurons to threshold, eliciting a burst of action potentials. The transient nature of the neural activity produced by Ppk1 activation is the result of Ppk1 channel gating properties. This model is supported by the observation of enhanced bursting activity in neurons expressing a gain of function ppk1 mutant harboring the degenerin mutation. These findings demonstrate that Ppk1 can function as an ionotropic molecular sensory transducer capable of transforming the perception of a stimulus into phasic neuronal activity in sensory neurons. PMID:23033486

Activity of upper limb muscles during human walking.

PubMed

Kuhtz-Buschbeck, Johann P; Jing, Bo

2012-04-01

The EMG activity of upper limb muscles during human gait has rarely been studied previously. It was examined in 20 normal volunteers in four conditions: walking on a treadmill (1) with unrestrained natural arm swing (Normal), (2) while volitionally holding the arms still (Held), (3) with the arms immobilized (Bound), and (4) with the arms swinging in phase with the ipsilateral legs, i.e. opposite-to-normal phasing (Anti-Normal). Normal arm swing involved weak rhythmical lengthening and shortening contractions of arm and shoulder muscles. Phasic muscle activity was needed to keep the unrestricted arms still during walking (Held), indicating a passive component of arm swing. An active component, possibly programmed centrally, existed as well, because some EMG signals persisted when the arms were immobilized during walking (Bound). Anti-Normal gait involved stronger EMG activity than Normal walking and was uneconomical. The present results indicate that normal arm swing has both passive and active components. Copyright © 2011 Elsevier Ltd. All rights reserved.

Pontine regulation of REM sleep components in cats: integrity of the pedunculopontine tegmentum (PPT) is important for phasic events but unnecessary for atonia during REM sleep.

PubMed

Shouse, M N; Siegel, J M

1992-01-31

Transection, lesion and unit recording studies have localized rapid eye movement (REM) sleep mechanisms to the pons. Recent work has emphasized the role of pontine cholinergic cells, especially those of the pedunculopontine tegmentum (PPT). The present study differentiated REM sleep deficits associated with lesions of the PPT from other pontine regions implicated in REM sleep generation, including those with predominantly cholinergic vs non-cholinergic cells. Twelve hour polygraphic recordings were obtained in 18 cats before and 1-2 weeks after bilateral electrolytic or radio frequency lesions of either: (1) PPT, which contains the dorsolateral pontine cholinergic cell column; (2) laterodorsal tegmental nucleus (LDT), which contains the dorsomedial pontine cholinergic cell column; (3) locus ceruleus (LC), which contains mostly noradrenergic cells; or (4) subceruleus (LC alpha, peri-LC alpha and the lateral tegmental field), which also contains predominantly noncholinergic cells. There were three main findings: (i) Only lesions of PPT and subceruleus significantly affected REM sleep time. These lesions produced comparable reductions in REM sleep time but influenced REM sleep components quite differently: (ii) PPT lesions, estimated to damage 90 +/- 4% of cholinergic cells, reduced the number of REM sleep entrances and phasic events, including ponto-geniculooccipital (PGO) spikes and rapid eye movements (REMs), but did not prevent complete atonia during REM sleep: (iii) Subceruleus lesions eliminated atonia during REM sleep. Mobility appeared to arouse the cat prematurely from REM sleep and may explain the brief duration of REM sleep epochs seen exclusively in this group. Despite the reduced amount of REM sleep, the total number of PGO spikes and REM sleep entrances increased over baseline values. Collectively, the results distinguish pontine loci regulating phasic events vs atonia. PPT lesions reduced phasic events, whereas subceruleus lesions created REM sleep without atonia. Severe REM sleep deficits after large pontine lesions, including PPT and subceruleus, might be explained by simultaneous production of both REM sleep syndromes. However, extensive loss of ACh neurons in the PPT does not disrupt REM sleep atonia.

Two Ca current components of the receptor current in the electroreceptors of the marine catfish Plotosus.

PubMed

Sugawara, Y

1989-02-01

In the isolated sensory epithelium of the Plotosus electroreceptor, the receptor current has been dissected into inward Ca current, ICa, and superimposed outward transient of Ca-gated K current, IK(Ca). In control saline (170 mM/liter Na), with IK(Ca) abolished by K blockers, ICa declined in two successive exponential phases with voltage-dependent time constants. Double-pulse experiments revealed that the test ICa was partially depressed by prepulses, maximally near voltage levels for the control ICa maximum, which suggests current-dependent inactivation. In low Na saline (80 mM/liter), ICa declined in a single phase with time constants similar to those of the slower phase in control saline. The test ICa was then unaffected by prepulses. The implied presence of two Ca current components, the fast and slow ICa's, were further examined. In control saline, the PSP externally recorded from the afferent nerve showed a fast peak and a slow tonic phase. The double-pulse experiments revealed that IK(Ca) and the peak PSP were similarly depressed, i.e., secondarily to inactivation of the peak current. The steady inward current, however, was unaffected by prolonged prepulses that were stepped to 0 mV, the in situ DC level. Therefore, the fast ICa seems to initiate IK(Ca) and phasic release of transmitter, which serves for phasic receptor responses. The slow ICa may provide persistent active current, which has been shown to maintain tonic receptor operation.

Physiology of Normal Esophageal Motility

PubMed Central

Goyal, Raj K; Chaudhury, Arun

2009-01-01

The esophagus consists of two different parts. In humans, the cervical esophagus is composed of striated muscles and the thoracic esophagus is composed of phasic smooth muscles. The striated muscle esophagus is innervated by the lower motor neurons and peristalsis in this segment is due to sequential activation of the motor neurons in the nucleus ambiguus. Both primary and secondary peristaltic contractions are centrally mediated. The smooth muscle of esophagus is phasic in nature and is innervated by intramural inhibitory (nitric oxide releasing) and excitatory (acetylcholine releasing) neurons that receive inputs from separate sets of preganglionic neurons located in the dorsal motor nucleus of vagus. The primary peristalsis in this segment involves both central and peripheral mechanisms. The primary peristalsis consist of inhibition (called deglutitive inhibition) followed by excitation. The secondary peristalsis is entirely due to peripheral mechanisms and also involves inhibition followed by excitation. The lower esophageal sphincter (LES) is characterized by tonic muscle that is different from the muscle of the esophageal body. The LES, like the esophageal body smooth muscle, is also innervated by the inhibitory and excitatory neurons. The LES maintains tonic closure due to its myogenic property. The LES tone is modulated by the inhibitory and the excitatory nerves. Inhibitory nerves mediate LES relaxation and the excitatory nerves mediate reflex contraction or rebound contraction of the LES. Clinical disorders of esophageal motility can be classified on the basis of disorders of the inhibitory and excitatory innervations and the smooth muscles. PMID:18364578

Glucose Rapidly Induces Different Forms of Excitatory Synaptic Plasticity in Hypothalamic POMC Neurons

PubMed Central

Hu, Jun; Jiang, Lin; Low, Malcolm J.; Rui, Liangyou

2014-01-01

Hypothalamic POMC neurons are required for glucose and energy homeostasis. POMC neurons have a wide synaptic connection with neurons both within and outside the hypothalamus, and their activity is controlled by a balance between excitatory and inhibitory synaptic inputs. Brain glucose-sensing plays an essential role in the maintenance of normal body weight and metabolism; however, the effect of glucose on synaptic transmission in POMC neurons is largely unknown. Here we identified three types of POMC neurons (EPSC(+), EPSC(−), and EPSC(+/−)) based on their glucose-regulated spontaneous excitatory postsynaptic currents (sEPSCs), using whole-cell patch-clamp recordings. Lowering extracellular glucose decreased the frequency of sEPSCs in EPSC(+) neurons, but increased it in EPSC(−) neurons. Unlike EPSC(+) and EPSC(−) neurons, EPSC(+/−) neurons displayed a bi-phasic sEPSC response to glucoprivation. In the first phase of glucoprivation, both the frequency and the amplitude of sEPSCs decreased, whereas in the second phase, they increased progressively to the levels above the baseline values. Accordingly, lowering glucose exerted a bi-phasic effect on spontaneous action potentials in EPSC(+/−) neurons. Glucoprivation decreased firing rates in the first phase, but increased them in the second phase. These data indicate that glucose induces distinct excitatory synaptic plasticity in different subpopulations of POMC neurons. This synaptic remodeling is likely to regulate the sensitivity of the melanocortin system to neuronal and hormonal signals. PMID:25127258

Chronic spinal cord stimulation modifies intrinsic cardiac synaptic efficacy in the suppression of atrial fibrillation

PubMed Central

Ardell, Jeffrey L.; Cardinal, René; Beaumont, Eric; Vermeulen, Michel; Smith, Frank M.; Armour, J. Andrew

2014-01-01

We sought to determine whether spinal cord stimulation (SCS) therapy, when applied chronically to canines, imparts long-lasting cardio-protective effects on neurogenic atrial tachyarrhythmia induction and, if so, whether its effects can be attributable to i) changes in intrinsic cardiac (IC) neuronal transmembrane properties vs ii) modification of their interneuronal stochastic interactivity that initiates such pathology. Data derived from canines subjected to long-term SCS [(group 1 studied after 3–4 weeks SCS; n=5) (group 2: studied 5 weeks SCS; n=11)] were compared to data derived from 10 control animals (including 4 sham SCS electrode implantations). During terminal studies conducted under anesthesia, chronotropic and inotropic responses to vagal nerve or stellate ganglion stimulation were similar in all 3 groups. Chronic SCS suppressed atrial tachyarrhythmia induction evoked by mediastinal nerve stimulation. When induced, arrhythmia durations were shortened (controls: median of 27s; SCS 3–4 weeks: median of 16s; SCS 5 weeks: median of 7s). Phasic and accommodating right atrial neuronal somata displayed similar passive and active membrane properties in vitro, whether derived from sham or either chronic SCS groups. Synaptic efficacy was differentially enhanced in accommodating (not phasic) IC neurons by chronic SCS. Taken together these data indicate that chronic SCS therapy modifies IC neuronal stochastic inter-connectivity in atrial fibrillation suppression by altering synaptic function without directly targeting the transmembrane properties of individual IC neuronal somata. PMID:25301713

Irrelevant stimulus processing in ADHD: catecholamine dynamics and attentional networks.

PubMed

Aboitiz, Francisco; Ossandón, Tomás; Zamorano, Francisco; Palma, Bárbara; Carrasco, Ximena

2014-01-01

A cardinal symptom of attention deficit and hyperactivity disorder (ADHD) is a general distractibility where children and adults shift their attentional focus to stimuli that are irrelevant to the ongoing behavior. This has been attributed to a deficit in dopaminergic signaling in cortico-striatal networks that regulate goal-directed behavior. Furthermore, recent imaging evidence points to an impairment of large scale, antagonistic brain networks that normally contribute to attentional engagement and disengagement, such as the task-positive networks and the default mode network (DMN). Related networks are the ventral attentional network (VAN) involved in attentional shifting, and the salience network (SN) related to task expectancy. Here we discuss the tonic-phasic dynamics of catecholaminergic signaling in the brain, and attempt to provide a link between this and the activities of the large-scale cortical networks that regulate behavior. More specifically, we propose that a disbalance of tonic catecholamine levels during task performance produces an emphasis of phasic signaling and increased excitability of the VAN, yielding distractibility symptoms. Likewise, immaturity of the SN may relate to abnormal tonic signaling and an incapacity to build up a proper executive system during task performance. We discuss different lines of evidence including pharmacology, brain imaging and electrophysiology, that are consistent with our proposal. Finally, restoring the pharmacodynamics of catecholaminergic signaling seems crucial to alleviate ADHD symptoms; however, the possibility is open to explore cognitive rehabilitation strategies to top-down modulate network dynamics compensating the pharmacological deficits.

Irrelevant stimulus processing in ADHD: catecholamine dynamics and attentional networks

PubMed Central

Aboitiz, Francisco; Ossandón, Tomás; Zamorano, Francisco; Palma, Bárbara; Carrasco, Ximena

2014-01-01

A cardinal symptom of attention deficit and hyperactivity disorder (ADHD) is a general distractibility where children and adults shift their attentional focus to stimuli that are irrelevant to the ongoing behavior. This has been attributed to a deficit in dopaminergic signaling in cortico-striatal networks that regulate goal-directed behavior. Furthermore, recent imaging evidence points to an impairment of large scale, antagonistic brain networks that normally contribute to attentional engagement and disengagement, such as the task-positive networks and the default mode network (DMN). Related networks are the ventral attentional network (VAN) involved in attentional shifting, and the salience network (SN) related to task expectancy. Here we discuss the tonic–phasic dynamics of catecholaminergic signaling in the brain, and attempt to provide a link between this and the activities of the large-scale cortical networks that regulate behavior. More specifically, we propose that a disbalance of tonic catecholamine levels during task performance produces an emphasis of phasic signaling and increased excitability of the VAN, yielding distractibility symptoms. Likewise, immaturity of the SN may relate to abnormal tonic signaling and an incapacity to build up a proper executive system during task performance. We discuss different lines of evidence including pharmacology, brain imaging and electrophysiology, that are consistent with our proposal. Finally, restoring the pharmacodynamics of catecholaminergic signaling seems crucial to alleviate ADHD symptoms; however, the possibility is open to explore cognitive rehabilitation strategies to top-down modulate network dynamics compensating the pharmacological deficits. PMID:24723897

Potentiation of a functional autoantibody in narcolepsy by a cholinesterase inhibitor.

PubMed

Jackson, Michael W; Spencer, Nicolas J; Reed, Joanne H; Smith, Anthony J F; Gordon, Tom P

2009-12-01

We have recently reported the presence of an immunoglobulin G (IgG) autoantibody (Ab) in patients with narcolepsy with cataplexy that abolishes spontaneous colonic migrating motor complexes (CMMCs) and increases smooth muscle tension and atropine-sensitive phasic contractions in a physiological assay of an isolated colon. In this study, we used the cholinesterase inhibitor, neostigmine, to explore the mechanism of the narcoleptic IgG-mediated disruption of enteric motor function in four patients with narcolepsy with cataplexy and to identify a pharmacological mimic of the Ab. Neostigmine potentiated the narcoleptic IgG-mediated increase in smooth muscle resting tension and phasic smooth muscle contractions by an atropine-sensitive mechanism but exerted no effect on resting tension in the presence of control IgG. Decreased frequency of CMMCs mediated by IgG with anti-M3R activity was reversed by neostigmine. Therefore, a challenge with a cholinesterase inhibitor improves the specificity of the CMMC assay for narcoleptic IgG. Tetrodotoxin (TTX), a neuronal sodium channel blocker, also abolished CMMCs and increased resting tone, and a similar potentiation was observed with neostigmine; thus, TTX is a mimic of the functional effects of the narcoleptic IgG in this bioassay. These findings provide a link to pharmacological studies of canine narcolepsy and are consistent with a functional blockade of both excitatory and inhibitory motor neurons by the narcoleptic Ab, similar to the TTX mimic, presumably by binding to an autoantigenic target expressed in both populations of neurons.

Role of support afferentation in control of the tonic muscle activity

NASA Astrophysics Data System (ADS)

Kozlovskaya, I. B.; Sayenko, I. V.; Sayenko, D. G.; Miller, T. F.; Khusnutdinova, D. R.; Melnik, K. A.

2007-02-01

The paper summarizes the results of experimental studies advocating for the leading role of support afferentation in control of the functional organization of the tonic muscle system. It is shown that transition to supportless conditions is followed by a significant decline of transverse stiffness and maximal voluntary force of postural (extensor) muscles limiting their participation in locomotion and increasing involvement of phasic muscles. Mechanical stimulation of the support zones of the soles under the supportless conditions eliminates all the above-mentioned effects, including changes in transverse stiffness and maximal voluntary forces of postural muscles, and consequent loss of influence of postural muscles in the locomotor activity. It is suggested that support afferentation, facilitating (support is present) or suppressing (support is absent) the tonic motor units (MUs) activities, defines the coordination patterns of postural synergies, and ensures the optimal strategy of corrective postural responses.

Neuromodulated Spike-Timing-Dependent Plasticity, and Theory of Three-Factor Learning Rules.

PubMed

Frémaux, Nicolas; Gerstner, Wulfram

2015-01-01

Classical Hebbian learning puts the emphasis on joint pre- and postsynaptic activity, but neglects the potential role of neuromodulators. Since neuromodulators convey information about novelty or reward, the influence of neuromodulators on synaptic plasticity is useful not just for action learning in classical conditioning, but also to decide "when" to create new memories in response to a flow of sensory stimuli. In this review, we focus on timing requirements for pre- and postsynaptic activity in conjunction with one or several phasic neuromodulatory signals. While the emphasis of the text is on conceptual models and mathematical theories, we also discuss some experimental evidence for neuromodulation of Spike-Timing-Dependent Plasticity. We highlight the importance of synaptic mechanisms in bridging the temporal gap between sensory stimulation and neuromodulatory signals, and develop a framework for a class of neo-Hebbian three-factor learning rules that depend on presynaptic activity, postsynaptic variables as well as the influence of neuromodulators.

Psychophysiology of arterial baroreceptors and the etiology of hypertension.

PubMed

Rau, H; Elbert, T

2001-01-01

Arterial baroreceptors are sensitive to blood pressure dependent blood vessel dilation. They play a key role in the short term regulation of blood pressure. Their impact on psychological and psychophysiological aspects is of increasing interest. The review focuses on experimental techniques for the controlled baroreceptor manipulation. Results from the application of these techniques show that baroreceptor activation influences the cardiovascular system as well as central nervous functioning: Behavioral and electrophysiological measures of arousal, low level reflexes and pain responses are modulated through baroreceptor manipulation. The observation of an overall dampening ('barbiturate like') effect of baroreceptor activity led Dworkin et al. formulate the theory of learned hypertension: Subjects might experience blood pressure dependent baroreceptor activation as stress and pain relieving. High blood pressure periods become negatively reinforced. Phasic high blood pressure might develop as a coping strategy. Data from a longitudinal human study supporting this theory are reported.

Role of SM22 in the differential regulation of phasic vs. tonic smooth muscle

PubMed Central

Ali, Mehboob

2015-01-01

Preliminary proteomics studies between tonic vs. phasic smooth muscles identified three distinct protein spots identified to be those of transgelin (SM22). The latter was found to be distinctly downregulated in the internal anal sphincter (IAS) vs. rectal smooth muscle (RSM) SMC. The major focus of the present studies was to examine the differential molecular control mechanisms by SM22 in the functionality of truly tonic smooth muscle of the IAS vs. the adjoining phasic smooth muscle of the RSM. We monitored SMC lengths before and after incubation with pFLAG-SM22 (for SM22 overexpression), and SM22 small-interfering RNA. pFLAG-SM22 caused concentration-dependent and significantly greater relaxation in the IAS vs. the RSM SMCs. Conversely, temporary silencing of SM22 caused contraction in both types of the SMCs. Further studies revealed a significant reverse relationship between the levels of SM22 phosphorylation and the amount of SM22-actin binding in the IAS and RSM SMC. Data showed higher phospho-SM22 levels and decreased SM22-actin binding in the IAS, and reverse to be the case in the RSM SMCs. Experiments determining the mechanism for SM22 phosphorylation in these smooth muscles revealed that Y-27632 (Rho kinase inhibitor) but not Gö-6850 (protein kinase C inhibitor) caused concentration-dependent decreased phosphorylation of SM22. We speculate that SM22 plays an important role in the regulation of basal tone via Rho kinase-induced phosphorylation of SM22. PMID:25617350

Ultrastructure of identified fast excitatory, slow excitatory and inhibitory neuromuscular junctions in the locust.

PubMed

Titmus, M J

1981-06-01

The specialized jumping muscle of the locust, the metathoracic extensor tibiae (ETi), is innervated by four physiologically different motoneurons, including FETi, a phasic excitor, SETi, a tonic excitor, and CI, a tonic common inhibitor. FETi neuromuscular junctions were examined in three phasic ETi bundles innervated by FETi. FETi terminals were characterized by patchy contacts on to granular sarcoplasm. The ETi accessory extensor, innervated by both SETi and CI, contains two morphologically different types of axon ending. When this muscle was soaked in horseradish peroxidase, stimulation of SETi led to selective uptake in vesicles in terminals similar to those of FETi axons but containing smaller vesicles, while stimulation by CI caused increased uptake into terminals with more extensive contact directly on to fibrillar sarcoplasm. As has been observed in excitatory and inhibitory synapses in some crustacean and vertebrate nervous systems, the synaptic vesicles in the locust excitatory endings are round and electron-lucent while those in the inhibitory endings are more irregular in shape. The tonic neuromuscular junctions, SETi and CI, are more densely packed with vesicles, larger in cross-sectional area and appear to be of more complex shape than the smaller, vesicle-sparse, phasic FETi terminals. Following long duration stimulation at 10 Hz, the tonic neuromuscular junctions showed little morphological change. FETi endings, which fatigue within minutes at the same stimulation frequency, showed a 20% decrease in synaptic vesicle density and an increase in irregularly shaped membrane inclusions.

CRH engagement of the locus coeruleus noradrenergic system mediates stress-induced anxiety

PubMed Central

McCall, Jordan G.; Al-Hasani, Ream; Siuda, Edward R.; Hong, Daniel Y.; Norris, Aaron J.; Ford, Christopher P.; Bruchas, Michael R.

2015-01-01

Summary The locus coeruleus noradrenergic (LC-NE) system is one of the first systems engaged following a stressful event. While numerous groups have demonstrated that LC-NE neurons are activated by many different stressors, the underlying neural circuitry and the role of this activity in generating stress-induced anxiety has not been elucidated. Using a combination of in vivo chemogenetics, optogenetics, and retrograde tracing we determine that increased tonic activity of the LC-NE system is necessary and sufficient for stress-induced anxiety and aversion. Selective inhibition of LC-NE neurons during stress prevents subsequent anxiety-like behavior. Exogenously increasing tonic, but not phasic, activity of LC-NE neurons is alone sufficient for anxiety-like and aversive behavior. Furthermore, endogenous corticotropin releasing hormone+ (CRH+) LC inputs from the amygdala increase tonic LC activity, inducing anxiety-like behaviors. These studies position the LC-NE system as a critical mediator of acute stress-induced anxiety and offer a potential intervention for preventing stress-related affective disorders. PMID:26212712

Acetylcholine Release in Prefrontal Cortex Promotes Gamma Oscillations and Theta–Gamma Coupling during Cue Detection

PubMed Central

Hetrick, Vaughn L.; Berke, Joshua D.

2017-01-01

The capacity for using external cues to guide behavior (“cue detection”) constitutes an essential aspect of attention and goal-directed behavior. The cortical cholinergic input system, via phasic increases in prefrontal acetylcholine release, plays an essential role in attention by mediating such cue detection. However, the relationship between cholinergic signaling during cue detection and neural activity dynamics in prefrontal networks remains unclear. Here we combined subsecond measures of cholinergic signaling, neurophysiological recordings, and cholinergic receptor blockade to delineate the cholinergic contributions to prefrontal oscillations during cue detection in rats. We first confirmed that detected cues evoke phasic acetylcholine release. These cholinergic signals were coincident with increased neuronal synchrony across several frequency bands and the emergence of theta–gamma coupling. Muscarinic and nicotinic cholinergic receptors both contributed specifically to gamma synchrony evoked by detected cues, but the effects of blocking the two receptor subtypes were dissociable. Blocking nicotinic receptors primarily attenuated high-gamma oscillations occurring during the earliest phases of the cue detection process, while muscarinic (M1) receptor activity was preferentially involved in the transition from high to low gamma power that followed and corresponded to the mobilization of networks involved in cue-guided decision making. Detected cues also promoted coupling between gamma and theta oscillations, and both nicotinic and muscarinic receptor activity contributed to this process. These results indicate that acetylcholine release coordinates neural oscillations during the process of cue detection. SIGNIFICANCE STATEMENT The capacity of learned cues to direct attention and guide responding (“cue detection”) is a key component of goal-directed behavior. Rhythmic neural activity and increases in acetylcholine release in the prefrontal cortex contribute to this process; however, the relationship between these neuronal mechanisms is not well understood. Using a combination of in vivo neurochemistry, neurophysiology, and pharmacological methods, we demonstrate that cue-evoked acetylcholine release, through distinct actions at both nicotinic and muscarinic receptors, triggers a procession of neural oscillations that map onto the multiple stages of cue detection. Our data offer new insights into cholinergic function by revealing the temporally orchestrated changes in prefrontal network synchrony modulated by acetylcholine release during cue detection. PMID:28213446

BK Channel-Mediated Relaxation of Urinary Bladder Smooth Muscle: A Novel Paradigm for Phosphodiesterase Type 4 Regulation of Bladder Function

PubMed Central

Xin, Wenkuan; Li, Ning; Cheng, Qiuping

2014-01-01

Elevation of intracellular cAMP and activation of protein kinase A (PKA) lead to activation of large conductance voltage- and Ca2+-activated K+ (BK) channels, thus attenuation of detrusor smooth muscle (DSM) contractility. In this study, we investigated the mechanism by which pharmacological inhibition of cAMP-specific phosphodiesterase 4 (PDE4) with rolipram or Ro-20-1724 (C15H22N2O3) suppresses guinea pig DSM excitability and contractility. We used high-speed line-scanning confocal microscopy, ratiometric fluorescence Ca2+ imaging, and perforated whole-cell patch-clamp techniques on freshly isolated DSM cells, along with isometric tension recordings of DSM isolated strips. Rolipram caused an increase in the frequency of Ca2+ sparks and the spontaneous transient BK currents (TBKCs), hyperpolarized the cell membrane potential (MP), and decreased the intracellular Ca2+ levels. Blocking BK channels with paxilline reversed the hyperpolarizing effect of rolipram and depolarized the MP back to the control levels. In the presence of H-89 [N-[2-[[3-(4-bromophenyl)-2-propenyl]amino]ethyl]-5-isoquinolinesulfonamide dihydrochloride], a PKA inhibitor, rolipram did not cause MP hyperpolarization. Rolipram or Ro-20-1724 reduced DSM spontaneous and carbachol-induced phasic contraction amplitude, muscle force, duration, and frequency, and electrical field stimulation-induced contraction amplitude, muscle force, and tone. Paxilline recovered DSM contractility, which was suppressed by pretreatment with PDE4 inhibitors. Rolipram had reduced inhibitory effects on DSM contractility in DSM strips pretreated with paxilline. This study revealed a novel cellular mechanism whereby pharmacological inhibition of PDE4 leads to suppression of guinea pig DSM contractility by increasing the frequency of Ca2+ sparks and the functionally coupled TBKCs, consequently hyperpolarizing DSM cell MP. Collectively, this decreases the global intracellular Ca2+ levels and DSM contractility in a BK channel-dependent manner. PMID:24459245

The role of spinal cord transmission in the ventilatory response to electrically induced exercise in the anaesthetized dog

PubMed Central

Cross, Brenda A.; Davey, A.; Guz, A.; Katona, P. G.; Maclean, M.; Murphy, K.; Semple, S. J. G.; Stidwill, R.

1982-01-01

1. The ventilatory response to electrically induced `exercise' was studied in six chloralose-anaesthetized dogs. The on-transient and steady-state responses to `exercise' were compared in the same dogs before and after spinal cord transection at T8/9 (dermatome level T6/7) on fifteen occasions. 2. Phasic hind limb `exercise' was induced for periods of 4 min by passing current (2 Hz modulated 50 Hz sine wave) between two needles inserted through the hamstring muscles. The maximum current used was 30 mA. This was below the level previously found to produce an artifactual stimulation of breathing with the cord intact. 3. Cord transection produced no significant change in either the resting values of ventilation (˙VI) and CO2 production (˙VCO2) or the ventilatory equivalent for CO2 during `exercise' (△ ˙VI/ △ ˙VCO2). 4. During the steady state of exercise Pa, CO2 was on average significantly lower than at rest with the cord intact (mean △Pa, CO2, - 2·1 mmHg; range - 5·7 to + 1), and higher, though not significantly, with the cord cut (mean Pa, CO2, + 1·2 mmHg; range - 1·5 to + 4·3). However, even in the absence of spinal cord transmission, the ventilatory response to exercise could not be accounted for on the basis of CO2 sensitivity; the △ ˙VI/ △Pa,CO2 obtained with exercise (apparent sensitivity) was significantly greater than that obtained with CO2 inhalation (true sensitivity) both before and after cord section. 5. ˙VI and ˙VCO2 increased more slowly with the cord cut than with the cord intact. This was thought to be due to a slower increase in venous return in the absence of sympathetic innervation of the lower half of the body following cord transection. 6. Similar experiments were performed during muscle paralysis (following gallamine triethiodide). Ventilation was maintained with a respirator controlled by phrenic nerve activity. These experiments showed an increase in ventilation, independent of muscle contraction, which was only present when the cord was intact and which was confined to the on-transient. Only in the absence of spinal cord transmission could there be certainty that the dynamics of the ventilatory response to electrically induced `exercise' was free of artifact. 7. It was concluded that spinal cord transmission is not necessary for the steady-state ventilatory response to electrically induced exercise of the hind limbs. 8. The dog with spinal cord transection provides a suitable model for the study of the chemical control of breathing during electrically induced exercise. PMID:6292406

Ventral pallidum roles in reward and motivation.

PubMed

Smith, Kyle S; Tindell, Amy J; Aldridge, J Wayne; Berridge, Kent C

2009-01-23

In recent years the ventral pallidum has become a focus of great research interest as a mechanism of reward and incentive motivation. As a major output for limbic signals, the ventral pallidum was once associated primarily with motor functions rather than regarded as a reward structure in its own right. However, ample evidence now suggests that ventral pallidum function is a major mechanism of reward in the brain. We review data indicating that (1) an intact ventral pallidum is necessary for normal reward and motivation, (2) stimulated activation of ventral pallidum is sufficient to cause reward and motivation enhancements, and (3) activation patterns in ventral pallidum neurons specifically encode reward and motivation signals via phasic bursts of excitation to incentive and hedonic stimuli. We conclude that the ventral pallidum may serve as an important 'limbic final common pathway' for mesocorticolimbic processing of many rewards.

The Relationship between Reversed Masked Priming and the Tri-Phasic Pattern of the Lateralised Readiness Potential

PubMed Central

Seiss, Ellen; Klippel, Marie; Hope, Christopher; Boy, Frederic; Sumner, Petroc

2014-01-01

One of the potential explanations for negative compatibility effects (NCE) in subliminal motor priming tasks has been perceptual prime-target interactions. Here, we investigate whether the characteristic tri-phasic LRP pattern associated with the NCE is caused by these prime-target interactions. We found that both the prime-related phase and the critical reversal phase remain present even on trials where the target is omitted, confirming they are elicited by the prime and mask, not by prime-target interactions. We also report that shape and size of the reversal phase are associated with response speed, consistent with a causal role for the reversal for the subsequent response latency. Additionally, we analysed sequential modulation of the NCE by previous conflicting events, even though such conflict is subliminal. In accordance with previous literature, this modulation is small but significant. PMID:24728088

Methodological Gaps in Left Atrial Function Assessment by 2D Speckle Tracking Echocardiography

PubMed Central

Rimbaş, Roxana Cristina; Dulgheru, Raluca Elena; Vinereanu, Dragoş

2015-01-01

The assessment of left atrial (LA) function is used in various cardiovascular diseases. LA plays a complementary role in cardiac performance by modulating left ventricular (LV) function. Transthoracic two-dimensional (2D) phasic volumes and Doppler echocardiography can measure LA function non-invasively. However, evaluation of LA deformation derived from 2D speckle tracking echocardiography (STE) is a new feasible and promising approach for assessment of LA mechanics. These parameters are able to detect subclinical LA dysfunction in different pathological condition. Normal ranges for LA deformation and cut-off values to diagnose LA dysfunction with different diseases have been reported, but data are still conflicting, probably because of some methodological and technical issues. This review highlights the importance of an unique standardized technique to assess the LA phasic functions by STE, and discusses recent studies on the most important clinical applications of this technique. PMID:26761370

The relationship of choline acetyltransferase activity at the neuromuscular junction to changes in muscle mass and function

PubMed Central

Diamond, Ivan; Franklin, Gary M.; Milfay, Dale

1974-01-01

1. The role of muscle mass and function in the regulation of choline acetyltransferase activity at the neuromuscular junction has been investigated in the rat. 2. Choline acetyltransferase (ChAc) is located in presynaptic nerve terminals and is a specific enzymatic marker of cholinergic innervation in muscle. 3. ChAc activity increased co-ordinately with developmental growth of the soleus muscle. However, another form of muscle growth, work hypertrophy, did not produce an increase in ChAc. 4. Growth arrest of muscle by hypophysectomy did not alter the normal development of ChAc activity, and cortisone-induced muscle atrophy did not reduce ChAc activity in the soleus or plantaris. 5. Tenotomy-induced muscle atrophy provoked a significant fall in ChAc in the soleus and plantaris. 6. The tonic soleus had significantly greater ChAc activity than the phasic plantaris. 7. These observations suggest that muscle mass per se does not influence the development and regulation of ChAc in muscle but that the quality of muscle contraction may modulate enzyme activity. PMID:4818500

Additive Effects of Threat-of-Shock and Picture Valence on Startle Reflex Modulation

PubMed Central

Bublatzky, Florian; Guerra, Pedro M.; Pastor, M. Carmen; Schupp, Harald T.; Vila, Jaime

2013-01-01

The present study examined the effects of sustained anticipatory anxiety on the affective modulation of the eyeblink startle reflex. Towards this end, pleasant, neutral and unpleasant pictures were presented as a continuous stream during alternating threat-of-shock and safety periods, which were cued by colored picture frames. Orbicularis-EMG to auditory startle probes and electrodermal activity were recorded. Previous findings regarding affective picture valence and threat-of-shock modulation were replicated. Of main interest, anticipating aversive events and viewing affective pictures additively modulated defensive activation. Specifically, despite overall potentiated startle blink magnitude in threat-of-shock conditions, the startle reflex remained sensitive to hedonic picture valence. Finally, skin conductance level revealed sustained sympathetic activation throughout the entire experiment during threat- compared to safety-periods. Overall, defensive activation by physical threat appears to operate independently from reflex modulation by picture media. The present data confirms the importance of simultaneously manipulating phasic-fear and sustained-anxiety in studying both normal and abnormal anxiety. PMID:23342060

Effect of dietary salt intake on epithelial Na+ channels (ENaC) in vasopressin magnocellular neurosecretory neurons in the rat supraoptic nucleus.

PubMed

Sharma, Kaustubh; Haque, Masudul; Guidry, Richard; Ueta, Yoichi; Teruyama, Ryoichi

2017-09-01

A growing body of evidence suggests that epithelial Na + channels (ENaCs) in the brain play a significant role in the regulation of blood pressure; however, the brain structures that mediate the effect are not well understood. Because vasopressin (VP) neurons play a pivotal role in coordinating neuroendocrine and autonomic responses to maintain cardiovascular homeostasis, a basic understanding of the regulation and activity of ENaC in VP neurons is of great interest. We show that high dietary salt intake caused an increase in the expression and activity of ENaC which resulted in the steady state depolarization of VP neurons. The results help us understand one of the mechanisms underlying how dietary salt intake affects the activity of VP neurons via ENaC activity. All three epithelial Na + channel (ENaC) subunits (α, β and γ) are located in vasopressin (VP) magnocellular neurons in the hypothalamic supraoptic (SON) and paraventricular nuclei. Our previous study demonstrated that ENaC mediates a Na + leak current that affects the steady state membrane potential in VP neurons. In the present study, we evaluated the effect of dietary salt intake on ENaC regulation and activity in VP neurons. High dietary salt intake for 7 days caused an increase in expression of β- and γENaC subunits in the SON and the translocation of αENaC immunoreactivity towards the plasma membrane. Patch clamp experiments on hypothalamic slices showed that the mean amplitude of the putative ENaC currents was significantly greater in VP neurons from animals that were fed a high salt diet compared with controls. The enhanced ENaC current contributed to the more depolarized basal membrane potential observed in VP neurons in the high salt diet group. These findings indicate that high dietary NaCl intake enhances the expression and activity of ENaCs, which augments synaptic drive by depolarizing the basal membrane potential close to the action potential threshold during hormonal demand. However, ENaCs appear to have only a minor role in the regulation of the firing activity of VP neurons in the absence of synaptic inputs as neither the mean intraburst frequency, burst duration, nor interspike interval variability of phasic bursting activity was affected. Moreover, ENaC activity did not affect the initiation, sustention, or termination of the phasic bursting generated in an intrinsic manner without synaptic inputs. © 2017 The Authors. The Journal of Physiology published by John Wiley & Sons Ltd on behalf of The Physiological Society.

Phasic alertness enhances processing of face and non-face stimuli in congenital prosopagnosia.

PubMed

Tanzer, Michal; Weinbach, Noam; Mardo, Elite; Henik, Avishai; Avidan, Galia

2016-08-01

Congenital prosopagnosia (CP) is a severe face processing impairment that occurs in the absence of any obvious brain damage and has often been associated with a more general deficit in deriving holistic relations between facial features or even between non-face shape dimensions. Here we further characterized this deficit and examined a potential way to ameliorate it. To this end we manipulated phasic alertness using alerting cues previously shown to modulate attention and enhance global processing of visual stimuli in normal observers. Specifically, we first examined whether individuals with CP, similarly to controls, would show greater global processing when exposed to an alerting cue in the context of a non-facial task (Navon global/local task). We then explored the effect of an alerting cue on face processing (upright/inverted face discrimination). Confirming previous findings, in the absence of alerting cues, controls showed a typical global bias in the Navon task and an inversion effect indexing holistic processing in the upright/inverted task, while CP failed to show these effects. Critically, when alerting cues preceded the experimental trials, both groups showed enhanced global interference and a larger inversion effect. These results suggest that phasic alertness may modulate visual processing and consequently, affect global/holistic perception. Hence, these findings further reinforce the notion that global/holistic processing may serve as a possible mechanism underlying the face processing deficit in CP. Moreover, they imply a possible route for enhancing face processing in individuals with CP and thus shed new light on potential amelioration of this disorder. Copyright © 2016 Elsevier Ltd. All rights reserved.

Role of prefrontal cortex and the midbrain dopamine system in working memory updating

PubMed Central

D’Ardenne, Kimberlee; Eshel, Neir; Luka, Joseph; Lenartowicz, Agatha; Nystrom, Leigh E.; Cohen, Jonathan D.

2012-01-01

Humans are adept at switching between goal-directed behaviors quickly and effectively. The prefrontal cortex (PFC) is thought to play a critical role by encoding, updating, and maintaining internal representations of task context in working memory. It has also been hypothesized that the encoding of context representations in PFC is regulated by phasic dopamine gating signals. Here we use multimodal methods to test these hypotheses. First we used functional MRI (fMRI) to identify regions of PFC associated with the representation of context in a working memory task. Next we used single-pulse transcranial magnetic stimulation (TMS), guided spatially by our fMRI findings and temporally by previous event-related EEG recordings, to disrupt context encoding while participants performed the same working memory task. We found that TMS pulses to the right dorsolateral PFC (DLPFC) immediately after context presentation, and well in advance of the response, adversely impacted context-dependent relative to context-independent responses. This finding causally implicates right DLPFC function in context encoding. Finally, using the same paradigm, we conducted high-resolution fMRI measurements in brainstem dopaminergic nuclei (ventral tegmental area and substantia nigra) and found phasic responses after presentation of context stimuli relative to other stimuli, consistent with the timing of a gating signal that regulates the encoding of representations in PFC. Furthermore, these responses were positively correlated with behavior, as well as with responses in the same region of right DLPFC targeted in the TMS experiment, lending support to the hypothesis that dopamine phasic signals regulate encoding, and thereby the updating, of context representations in PFC. PMID:23086162

Quantifying excessive mirror overflow in children with attention-deficit/hyperactivity disorder

PubMed Central

MacNeil, L.K.; Xavier, P.; Garvey, M.A.; Gilbert, D.L.; Ranta, M.E.; Denckla, M.B.

2011-01-01

Objectives: Qualitative observations have revealed that children with attention-deficit/hyperactivity disorder (ADHD) show increased overflow movements, a motor sign thought to reflect impaired inhibitory control. The goal of this study was to develop and implement methods for quantifying excessive mirror overflow movements in children with ADHD. Methods: Fifty right-handed children aged 8.2–13.3 years, 25 with ADHD (12 girls) and 25 typically developing (TD) control children (10 girls), performed a sequential finger-tapping task, completing both left-handed (LHFS) and right-handed finger sequencing (RHFS). Phasic overflow of the index and ring fingers was assessed in 34 children with video recording, and total overflow in 48 children was measured by calculating the total angular displacement of the index and ring fingers with electrogoniometer recordings. Results: Phasic overflow and total overflow across both hands were greater in children with ADHD than in TD children, particularly during LHFS. Separate gender analyses revealed that boys, but not girls, with ADHD showed significantly more total phasic overflow and total overflow than did their gender-matched control children. Conclusions: The quantitative overflow measures used in this study support past qualitative findings that motor overflow persists to a greater degree in children with ADHD than in age-matched TD peers. The quantitative findings further suggest that persistence of mirror overflow is more prominent during task execution of the nondominant hand and reveal gender-based differences in developmental neural systems critical to motor control. These quantitative measures will assist future physiologic investigation of the brain basis of motor control in ADHD. PMID:21321336

Conditional Deletion of Bmal1 in Ovarian Theca Cells Disrupts Ovulation in Female Mice.

PubMed

Mereness, Amanda L; Murphy, Zachary C; Forrestel, Andrew C; Butler, Susan; Ko, CheMyong; Richards, JoAnne S; Sellix, Michael T

2016-02-01

Rhythmic events in female reproductive physiology, including ovulation, are tightly controlled by the circadian timing system. The molecular clock, a feedback loop oscillator of clock gene transcription factors, dictates rhythms of gene expression in the hypothalamo-pituitary-ovarian axis. Circadian disruption due to environmental factors (eg, shift work) or genetic manipulation of the clock has negative impacts on fertility. Although the central pacemaker in the suprachiasmatic nucleus classically regulates the timing of ovulation, we have shown that this rhythm also depends on phasic sensitivity to LH. We hypothesized that this rhythm relies on clock function in a specific cellular compartment of the ovarian follicle. To test this hypothesis we generated mice with deletion of the Bmal1 locus in ovarian granulosa cells (GCs) (Granulosa Cell Bmal1 KO; GCKO) or theca cells (TCs) (Theca Cell Bmal1 KO; TCKO). Reproductive cycles, preovulatory LH secretion, ovarian morphology and behavior were not grossly altered in GCKO or TCKO mice. We detected phasic sensitivity to LH in wild-type littermate control (LC) and GCKO mice but not TCKO mice. This decline in sensitivity to LH is coincident with impaired fertility and altered patterns of LH receptor (Lhcgr) mRNA abundance in the ovary of TCKO mice. These data suggest that the TC is a pacemaker that contributes to the timing and amplitude of ovulation by modulating phasic sensitivity to LH. The TC clock may play a critical role in circadian disruption-mediated reproductive pathology and could be a target for chronobiotic management of infertility due to environmental circadian disruption and/or hormone-dependent reprogramming in women.

Aversive Stimuli Differentially Modulate Real-Time Dopamine Transmission Dynamics within the Nucleus Accumbens Core and Shell

PubMed Central

Badrinarayan, Aneesha; Wescott, Seth A.; Vander Weele, Caitlin M.; Saunders, Benjamin T.; Couturier, Brenann E.; Maren, Stephen

2012-01-01

Although fear directs adaptive behavioral responses, how aversive cues recruit motivational neural circuitry is poorly understood. Specifically, while it is known that dopamine (DA) transmission within the nucleus accumbens (NAc) is imperative for mediating appetitive motivated behaviors, its role in aversive behavior is controversial. It has been proposed that divergent phasic DA transmission following aversive events may correspond to segregated mesolimbic dopamine pathways; however, this prediction has never been tested. Here, we used fast-scan cyclic voltammetry to examine real-time DA transmission within NAc core and shell projection systems in response to a fear-evoking cue. In male Sprague Dawley rats, we first demonstrate that a fear cue results in decreased DA transmission within the NAc core, but increased transmission within the NAc shell. We examined whether these changes in DA transmission could be attributed to modulation of phasic transmission evoked by cue presentation. We found that cue presentation decreased the probability of phasic DA release in the core, while the same cue enhanced the amplitude of release events in the NAc shell. We further characterized the relationship between freezing and both changes in DA as well as local pH. Although we found that both analytes were significantly correlated with freezing in the NAc across the session, changes in DA were not strictly associated with freezing while basic pH shifts in the core more consistently followed behavioral expression. Together, these results provide the first real-time neurochemical evidence that aversive cues differentially modulate distinct DA projection systems. PMID:23136417

Rapid infrared heating of a surface

DOEpatents

Sikka, Vinod K.; Blue, Craig A.; Ohriner, Evan Keith

2002-01-01

High energy flux infrared heaters are used to treat an object having a surface section and a base section such that a desired characteristic of the surface section is physically, chemically, or phasically changed while the base section remains unchanged.

Rapid infrared heating of a surface

DOEpatents

Sikka, Vinod K.; Blue, Craig A.; Ohriner, Evan Keith

2001-01-01

High energy flux infrared heaters are used to treat an object having a surface section and a base section such that a desired characteristic of the surface section is physically, chemically, or phasically changed while the base section remains unchanged.

Rapid infrared heating of a surface

DOEpatents

Sikka, Vinod K.; Blue, Craig A.; Ohriner, Evan Keith

2003-12-23

High energy flux infrared heaters are used to treat an object having a surface section and a base section such that a desired characteristic of the surface section is physically, chemically, or phasically changed while the base section remains unchanged.

Stimulus-Elicited Connectivity Influences Resting-State Connectivity Years Later in Human Development: A Prospective Study.

PubMed

Gabard-Durnam, Laurel Joy; Gee, Dylan Grace; Goff, Bonnie; Flannery, Jessica; Telzer, Eva; Humphreys, Kathryn Leigh; Lumian, Daniel Stephen; Fareri, Dominic Stephen; Caldera, Christina; Tottenham, Nim

2016-04-27

Although the functional architecture of the brain is indexed by resting-state connectivity networks, little is currently known about the mechanisms through which these networks assemble into stable mature patterns. The current study posits and tests the long-term phasic molding hypothesis that resting-state networks are gradually shaped by recurring stimulus-elicited connectivity across development by examining how both stimulus-elicited and resting-state functional connections of the human brain emerge over development at the systems level. Using a sequential design following 4- to 18-year-olds over a 2 year period, we examined the predictive associations between stimulus-elicited and resting-state connectivity in amygdala-cortical circuitry as an exemplar case (given this network's protracted development across these ages). Age-related changes in amygdala functional connectivity converged on the same regions of medial prefrontal cortex (mPFC) and inferior frontal gyrus when elicited by emotional stimuli and when measured at rest. Consistent with the long-term phasic molding hypothesis, prospective analyses for both connections showed that the magnitude of an individual's stimulus-elicited connectivity unidirectionally predicted resting-state functional connectivity 2 years later. For the amygdala-mPFC connection, only stimulus-elicited connectivity during childhood and the transition to adolescence shaped future resting-state connectivity, consistent with a sensitive period ending with adolescence for the amygdala-mPFC circuit. Together, these findings suggest that resting-state functional architecture may arise from phasic patterns of functional connectivity elicited by environmental stimuli over the course of development on the order of years. A fundamental issue in understanding the ontogeny of brain function is how resting-state (intrinsic) functional networks emerge and relate to stimulus-elicited functional connectivity. Here, we posit and test the long-term phasic molding hypothesis that resting-state network development is influenced by recurring stimulus-elicited connectivity through prospective examination of the developing human amygdala-cortical functional connections. Our results provide critical insight into how early environmental events sculpt functional network architecture across development and highlight childhood as a potential developmental period of heightened malleability for the amygdala-medial prefrontal cortex circuit. These findings have implications for how both positive and adverse experiences influence the developing brain and motivate future investigations of whether this molding mechanism reflects a general phenomenon of brain development. Copyright © 2016 the authors 0270-6474/16/364772-14$15.00/0.

Stimulus-Elicited Connectivity Influences Resting-State Connectivity Years Later in Human Development: A Prospective Study

PubMed Central

Gee, Dylan Grace; Goff, Bonnie; Flannery, Jessica; Telzer, Eva; Humphreys, Kathryn Leigh; Lumian, Daniel Stephen; Fareri, Dominic Stephen; Caldera, Christina; Tottenham, Nim

2016-01-01

Although the functional architecture of the brain is indexed by resting-state connectivity networks, little is currently known about the mechanisms through which these networks assemble into stable mature patterns. The current study posits and tests the long-term phasic molding hypothesis that resting-state networks are gradually shaped by recurring stimulus-elicited connectivity across development by examining how both stimulus-elicited and resting-state functional connections of the human brain emerge over development at the systems level. Using a sequential design following 4- to 18-year-olds over a 2 year period, we examined the predictive associations between stimulus-elicited and resting-state connectivity in amygdala-cortical circuitry as an exemplar case (given this network's protracted development across these ages). Age-related changes in amygdala functional connectivity converged on the same regions of medial prefrontal cortex (mPFC) and inferior frontal gyrus when elicited by emotional stimuli and when measured at rest. Consistent with the long-term phasic molding hypothesis, prospective analyses for both connections showed that the magnitude of an individual's stimulus-elicited connectivity unidirectionally predicted resting-state functional connectivity 2 years later. For the amygdala-mPFC connection, only stimulus-elicited connectivity during childhood and the transition to adolescence shaped future resting-state connectivity, consistent with a sensitive period ending with adolescence for the amygdala-mPFC circuit. Together, these findings suggest that resting-state functional architecture may arise from phasic patterns of functional connectivity elicited by environmental stimuli over the course of development on the order of years. SIGNIFICANCE STATEMENT A fundamental issue in understanding the ontogeny of brain function is how resting-state (intrinsic) functional networks emerge and relate to stimulus-elicited functional connectivity. Here, we posit and test the long-term phasic molding hypothesis that resting-state network development is influenced by recurring stimulus-elicited connectivity through prospective examination of the developing human amygdala-cortical functional connections. Our results provide critical insight into how early environmental events sculpt functional network architecture across development and highlight childhood as a potential developmental period of heightened malleability for the amygdala-medial prefrontal cortex circuit. These findings have implications for how both positive and adverse experiences influence the developing brain and motivate future investigations of whether this molding mechanism reflects a general phenomenon of brain development. PMID:27122035

Effect of atrial systole on canine and porcine coronary blood flow.

PubMed

Bellamy, R F

1981-09-01

A feature of phasic coronary flow patterns recorded in conscious chronically instrumented dogs is the atrial cove--a transient depression of arterial flow that occurs during atrial systole. The association between the hemodynamic effects of atrial systole and the atrial cove was studied in anesthetized dogs and pigs with complete heart block. Many atrial coves are available for study in these preparations because atrial activity continues unabated during the diastolic ventricular arrest that follows cessation of electrical pacing. The effect of atrial systole is to translate the pressure-flow relation found during diastole to a higher intercept pressure without change in slope. The increase in the intercept pressure equals the increase in intramyocardial pressure measured with microtransducers embedded in the left ventricular wall. The decrement in flow during the atrial cove is a direct function of the change in intramyocardial pressure and an inverse function of coronary vascular resistance. Each atrial systole is associated with a forward flow transient in the coronary veins, the peak of which occurs at the same instant as does the nadir of atrial flow. These data suggest that the coronary vessels are acting as collapsible tubes and that the waterfall model of the coronary circulation is applicable. The following sequence is proposed to account for the atrial cove. Atrial systole ejects a bolus of blood into the left ventricle increasing both ventricular cavity and intramyocardial pressures. The increase in intramyocardial pressure raises the back pressure opposing coronary flow, reducing the arterial perfusion pressure gradient and causing flow to fall.

Spatial organization and coordination of slow waves in the mouse anorectum

PubMed Central

Hall, K A; Ward, S M; Cobine, C A; Keef, K D

2014-01-01

The internal anal sphincter (IAS) develops tone and is important for maintaining a high anal pressure while tone in the rectum is less. The mechanisms responsible for tone generation in the IAS are still uncertain. The present study addressed this question by comparing the electrical properties and morphology of the mouse IAS and distal rectum. The amplitude of tone and the frequency of phasic contractions was greater in the IAS than in rectum while membrane potential (Em) was less negative in the IAS than in rectum. Slow waves (SWs) were of greatest amplitude and frequency at the distal end of the IAS, declining in the oral direction. Dual microelectrode recordings revealed that SWs were coordinated over a much greater distance in the circumferential direction than in the oral direction. The circular muscle layer of the IAS was divided into five to eight ‘minibundles’ separated by connective tissue septa whereas few septa were present in the rectum. The limited coordination of SWs in the oral direction suggests that the activity in adjacent minibundles is not coordinated. Intramuscular interstitial cells of Cajal and platelet-derived growth factor receptor alpha-positive cells were present in each minibundle suggesting a role for one or both of these cells in SW generation. In summary, three important properties distinguish the IAS from the distal rectum: (1) a more depolarized Em; (2) larger and higher frequency SWs; and (3) the multiunit configuration of the muscle. All of these characteristics may contribute to greater tone generation in the IAS than in the distal rectum. PMID:24951622

Metronidazole and 5-aminosalicylic acid enhance the contractile activity of histaminergic agonists on the guinea-pig isolated ileum

DOE Office of Scientific and Technical Information (OSTI.GOV)

Winbery, S.L.; Barker, L.A.

1986-03-01

The effects of metronidazole and 5-aminosalicylic acid (5-ASA) on histamine receptor-effector systems in the small intestine and right atrium of the guinea pig were studied. In an apparently all-or-none manner, both caused a sinistral shift in dose-response curves for the phasic component of the contractile response to histamine at H1 receptors on the ileum. In the presence of either, the EC50 value for histamine was reduced from 0.07 to about 0.03 microM. Similarly, in an apparently all-or-none fashion, both produced an elevation in the dose-response curve for the actions of dimaprit at H2-receptors in the ileum; the response to allmore » doses was increased about 30% with no significant change in the EC50 value. Metronidazole and 5-ASA did not alter dose-response curves for the tonic contractile response to histamine or curves generated by the cumulative addition of histamine. Also, neither altered the positive chronotropic response on isolated right atria or the phasic contractile response on isolated segments of jejunum and duodenum to histamine or dimaprit. Likewise, neither altered dose-response curves for the direct action of carbamylcholine at muscarinic receptors or for the indirect actions of dimethylphenylpiperazinium on the ileum. The effects of 5-ASA or metronidazole on the response to histamine could be prevented as well as reversed by scopolamine or tetrodotoxin. The results suggest that metronidazole and 5-ASA enhance the actions of histamine and dimaprit on the ileum by an action on myenteric plexus neurons.« less

Tectonigral Projections in the Primate: A Pathway for Pre-Attentive Sensory Input to Midbrain Dopaminergic Neurons

PubMed Central

May, Paul J.; McHaffie, John G.; Stanford, Terrence R.; Jiang, Huai; Costello, M. Gabriela; Coizet, Veronique; Hayes, Lauren M.; Haber, Suzanne N.; Redgrave, Peter

2010-01-01

Much of the evidence linking the short-latency phasic signaling of midbrain dopaminergic neurons with reward-prediction errors used in learning and habit formation comes from recording the visual responses of monkey dopaminergic neurons. However, the information encoded by dopaminergic neuron activity is constrained by the qualities of the afferent visual signals made available to these cells. Recent evidence from rats and cats indicates the primary source of this visual input originates subcortically, via a direct tectonigral projection. The present anatomical study sought to establish whether a direct tectonigral projection is a significant feature of the primate brain. Injections of anterograde tracers into the superior colliculus of macaque monkeys labelled terminal arbors throughout the substantia nigra, with the densest terminations in the dorsal tier. Labelled boutons were found in close association (possibly indicative of synaptic contact) with ventral midbrain neurons staining positively for the dopaminergic marker tyrosine hydroxylase. Injections of retrograde tracer confined to the macaque substantia nigra retrogradely labelled small to medium sized neurons in the intermediate and deep layers of the superior colliculus. Together, these data indicate that a direct tectonigral projection is also a feature of the monkey brain, and therefore likely to have been conserved throughout mammalian evolution. Insofar as the superior colliculus is configured to detect unpredicted, biologically salient, sensory events, it may be safer to regard the phasic responses of midbrain dopaminergic neurons as ‘sensory prediction errors’ rather than ‘reward prediction errors’, in which case, dopamine-based theories of reinforcement learning will require revision. PMID:19175405

Mapping anhedonia onto reinforcement learning: a behavioural meta-analysis

PubMed Central

2013-01-01

Background Depression is characterised partly by blunted reactions to reward. However, tasks probing this deficiency have not distinguished insensitivity to reward from insensitivity to the prediction errors for reward that determine learning and are putatively reported by the phasic activity of dopamine neurons. We attempted to disentangle these factors with respect to anhedonia in the context of stress, Major Depressive Disorder (MDD), Bipolar Disorder (BPD) and a dopaminergic challenge. Methods Six behavioural datasets involving 392 experimental sessions were subjected to a model-based, Bayesian meta-analysis. Participants across all six studies performed a probabilistic reward task that used an asymmetric reinforcement schedule to assess reward learning. Healthy controls were tested under baseline conditions, stress or after receiving the dopamine D2 agonist pramipexole. In addition, participants with current or past MDD or BPD were evaluated. Reinforcement learning models isolated the contributions of variation in reward sensitivity and learning rate. Results MDD and anhedonia reduced reward sensitivity more than they affected the learning rate, while a low dose of the dopamine D2 agonist pramipexole showed the opposite pattern. Stress led to a pattern consistent with a mixed effect on reward sensitivity and learning rate. Conclusion Reward-related learning reflected at least two partially separable contributions. The first related to phasic prediction error signalling, and was preferentially modulated by a low dose of the dopamine agonist pramipexole. The second related directly to reward sensitivity, and was preferentially reduced in MDD and anhedonia. Stress altered both components. Collectively, these findings highlight the contribution of model-based reinforcement learning meta-analysis for dissecting anhedonic behavior. PMID:23782813

Nanobubbles Form at Active Hydrophobic Spots on the Luminal Aspect of Blood Vessels: Consequences for Decompression Illness in Diving and Possible Implications for Autoimmune Disease-An Overview.

PubMed

Arieli, Ran

2017-01-01

Decompression illness (DCI) occurs following a reduction in ambient pressure. Decompression bubbles can expand and develop only from pre-existing gas micronuclei. The different hypotheses hitherto proposed regarding the nucleation and stabilization of gas micronuclei have never been validated. It is known that nanobubbles form spontaneously when a smooth hydrophobic surface is submerged in water containing dissolved gas. These nanobubbles may be the long sought-after gas micronuclei underlying decompression bubbles and DCI. We exposed hydrophobic and hydrophilic silicon wafers under water to hyperbaric pressure. After decompression, bubbles appeared on the hydrophobic but not the hydrophilic wafers. In a further series of experiments, we placed large ovine blood vessels in a cooled high pressure chamber at 1,000 kPa for about 20 h. Bubbles evolved at definite spots in all the types of blood vessels. These bubble-producing spots stained positive for lipids, and were henceforth termed "active hydrophobic spots" (AHS). The lung surfactant dipalmitoylphosphatidylcholine (DPPC), was found both in the plasma of the sheep and at the AHS. Bubbles detached from the blood vessel in pulsatile flow after reaching a mean diameter of ~1.0 mm. Bubble expansion was bi-phasic-a slow initiation phase which peaked 45 min after decompression, followed by fast diffusion-controlled growth. Many features of decompression from diving correlate with this finding of AHS on the blood vessels. (1) Variability between bubblers and non-bubblers. (2) An age-related effect and adaptation. (3) The increased risk of DCI on a second dive. (4) Symptoms of neurologic decompression sickness. (5) Preconditioning before a dive. (6) A bi-phasic mechanism of bubble expansion. (7) Increased bubble formation with depth. (8) Endothelial injury. (9) The presence of endothelial microparticles. Finally, constant contact between nanobubbles and plasma may result in distortion of proteins and their transformation into autoantigens.

Neural and psychophysiological correlates of human performance under stress and high mental workload.

PubMed

Mandrick, Kevin; Peysakhovich, Vsevolod; Rémy, Florence; Lepron, Evelyne; Causse, Mickaël

2016-12-01

In our anxiogenic and stressful world, the maintenance of an optimal cognitive performance is a constant challenge. It is particularly true in complex working environments (e.g. flight deck, air traffic control tower), where individuals have sometimes to cope with a high mental workload and stressful situations. Several models (i.e. processing efficiency theory, cognitive-energetical framework) have attempted to provide a conceptual basis on how human performance is modulated by high workload and stress/anxiety. These models predict that stress can reduce human cognitive efficiency, even in the absence of a visible impact on the task performance. Performance may be protected under stress thanks to compensatory effort, but only at the expense of a cognitive cost. Yet, the psychophysiological cost of this regulation remains unclear. We designed two experiments involving pupil diameter, cardiovascular and prefrontal oxygenation measurements. Participants performed the Toulouse N-back Task that intensively engaged both working memory and mental calculation processes under the threat (or not) of unpredictable aversive sounds. The results revealed that higher task difficulty (higher n level) degraded the performance and induced an increased tonic pupil diameter, heart rate and activity in the lateral prefrontal cortex, and a decreased phasic pupil response and heart rate variability. Importantly, the condition of stress did not impact the performance, but at the expense of a psychophysiological cost as demonstrated by lower phasic pupil response, and greater heart rate and prefrontal activity. Prefrontal cortex seems to be a central region for mitigating the influence of stress because it subserves crucial functions (e.g. inhibition, working memory) that can promote the engagement of coping strategies. Overall, findings confirmed the psychophysiological cost of both mental effort and stress. Stress likely triggered increased motivation and the recruitment of additional cognitive resources that minimize its aversive effects on task performance (effectiveness), but these compensatory efforts consumed resources that caused a loss of cognitive efficiency (ratio between performance effectiveness and mental effort). Copyright © 2016 Elsevier B.V. All rights reserved.

Micro-arousals during nocturnal sleep.

PubMed

Halász, P; Kundra, O; Rajna, P; Pál, I; Vargha, M

1979-01-01

In 8 young adult human subjects EEG- and polygraphic characteristics of transient shifts towards arousal (micro-arousal, MA) have been studied during sleep under five different experimental conditions in 40 night sessions. Out of the five applied experimental situations, two (psychostimulant application and sensory stimulation) resulted in a shift of the balance between the systems of sleep and arousal towards an increased activity of the arousal system, while an other condition (rebound following partial sleep deprivation) led to an opposite change to a rise in "sleep pressure". An inverse correlation has been found between the frequency of MA and the depth of sleep, a finding consistently observed in every subject and in every experimental situation. During the process of sleep periodic changes in the dispersity of MA could be seen; the number of MA-s decreased and increased according to the descending and ascending slope of the sleep cycles. During the ascending slope of cycles there was a coupling between the occurence of MA-s and the changes of phases. Increases in the level of activation and in sleep pressure did not influence the occurrence of MA-s. Increasing the tone of the arousal system in chemical way, or by means of enhancing the phasic sensory input resulted in a reduction of the difference between the number of MA on the descending and ascending slopes of cycles. During the phases of sleep, the spontaneous occurrence of MA-s went parallel with the possibility to evoke MA-s by sensory stimuli. These data show that MA is a regular phenomenon of nocturnal sleep; MA manifests itself as a result of phasic functioning of the reticular arousal system and plays a role in the organization of those periods of the sleep cycle, which tend toward arousal. It is suggested that MA-phenomenon is considered a standard measure of sleep and that it could represent an indicator of the function of the arousal system controlled by external or internal mechanisms during sleep.

Adrenoceptor function and expression in bladder urothelium and lamina propria.

PubMed

Moro, Christian; Tajouri, Lotti; Chess-Williams, Russ

2013-01-01

To investigate the role of adrenoceptor subtypes in regulating the spontaneous contractile activity of the inner lining of the urinary bladder (urothelium/lamina propria). The responses of isolated strips of porcine urothelium/lamina propria to noradrenaline, phenylephrine, and isoprenaline were obtained in the absence and presence of receptor subtype-selective antagonists. Quantitative reverse-transcriptase polymerase chain reaction was undertaken to assess the expression of adrenoceptor genes. The tissues expressed all α1- and β-adrenoceptor subtypes, with the α1A-, α1B-, and β2-adrenoceptors the predominant receptors at the messenger RNA level. In the functional experiments, the rate of phasic contractions and the basal tension were increased by the α1-adrenoceptor agonists phenylephrine (100 μM) and A61603 (10 μM). The rate and tension responses to phenylephrine were reduced by low concentrations of tamsulosin (3 nM) and RS100329 (10 nM) but were unaffected by BMY7378 (100 nM), prazosin (10 nM), and RS17053 (1 μM). In contrast, isoprenaline and salbutamol (both 1 μM) induced a relaxation of tissues and slowing of phasic contractions. The rate and tension responses to isoprenaline were inhibited by propranolol (100 nM) or a combination of CGP20712A (30 nM) and ICI118551 (70 nM). The rate responses were also significantly inhibited by ICI118551 alone (70 nM). Although all α1- and β-adrenoceptor subtypes were expressed in the pig urothelium/lamina propria, the α1A/L-adrenoceptor appeared to mediate increases in the contractile rate and tension. The β-adrenoceptor induced inhibition of spontaneous contractile activity appears to be predominately mediated by β2-adrenoceptors, with β1- and β2-adrenoceptors possibly involved in the tension responses. Copyright © 2013 Elsevier Inc. All rights reserved.

Neuromuscular activity during bench press exercise performed with and without the preexhaustion method.

PubMed

Brennecke, Allan; Guimarães, Thiago M; Leone, Ricardo; Cadarci, Mauro; Mochizuki, Luiz; Simão, Roberto; Amadio, Alberto Carlos; Serrão, Júlio C

2009-10-01

The purpose of the present study was to investigate the effects of exercise order on the tonic and phasic characteristics of upper-body muscle activity during bench press exercise in trained subjects. The preexhaustion method involves working a muscle or a muscle group combining a single-joint exercise immediately followed by a multi-joint exercise (e.g., flying exercise followed by bench press exercise). Twelve subjects performed 1 set of bench press exercises with and without the preexhaustion method following 2 protocols (P1-flying before bench press; P2-bench press). Both exercises were performed at a load of 10 repetition maximum (10RM). Electromyography (EMG) sampled at 1 kHz was recorded from the pectoralis major (PM), anterior deltoid (DA), and triceps brachii (TB). Kinematic data (60 Hz) were synchronized to define upward and downward phases of exercise. No significant (p > 0.05) changes were seen in tonic control of PM and DA muscles between P1 and P2. However, TB tonic aspect of neurophysiologic behavior of motor units was significantly higher (p < 0.05) during P1. Moreover, phasic control of PM, DA, and TB muscles were not affected (p > 0.05). The kinematic pattern of movement changed as a result of muscular weakness in P1. Angular velocity of the right shoulder performed during the upward phase of the bench press exercise was significantly slower (p < 0.05) during P1. Our results suggest that the strategies set by the central nervous system to provide the performance required by the exercise are held constant throughout the exercise, but the tonic aspects of the central drive are increased so as to adapt to the progressive occurrence of the neuromuscular fatigue. Changes in tonic control as a result of the muscular weakness and fatigue can cause changes in movement techniques. These changes may be related to limited ability to control mechanical loads and mechanical energy transmission to joints and passive structures.

The Neural Bases of Event Monitoring across Domains: a Simultaneous ERP-fMRI Study

PubMed Central

Tarantino, Vincenza; Mazzonetto, Ilaria; Formica, Silvia; Causin, Francesco; Vallesi, Antonino

2017-01-01

The ability to check and evaluate the environment over time with the aim to detect the occurrence of target stimuli is supported by sustained/tonic as well as transient/phasic control processes, which overall might be referred to as event monitoring. The neural underpinning of sustained attentional control processes involves a fronto-parietal network. However, it has not been well-defined yet whether this cortical circuit acts irrespective of the specific material to be monitored and whether this mediates sustained as well as transient monitoring processes. In the current study, the functional activity of brain during an event monitoring task was investigated and compared between two cognitive domains, whose processing is mediated by differently lateralized areas. Namely, participants were asked to monitor sequences of either faces (supported by right-hemisphere regions) or tools (left-hemisphere). In order to disentangle sustained from transient components of monitoring, a simultaneous EEG-fMRI technique was adopted within a block design. When contrasting monitoring versus control blocks, the conventional fMRI analysis revealed the sustained involvement of bilateral fronto-parietal regions, in both task domains. Event-related potentials (ERPs) showed a more positive amplitude over frontal sites in monitoring compared to control blocks, providing evidence of a transient monitoring component. The joint ERP-fMRI analysis showed that, in the case of face monitoring, this transient component relies on right-lateralized areas, including the inferior parietal lobule and the middle frontal gyrus. In the case of tools, no fronto-parietal areas correlated with the transient ERP activity, suggesting that in this domain phasic monitoring processes were masked by tonic ones. Overall, the present findings highlight the role of bilateral fronto-parietal regions in sustained monitoring, independently of the specific task requirements, and suggest that right-lateralized areas subtend transient monitoring processes, at least in some task contexts. PMID:28785212

Novel mechanism of hydrogen sulfide-induced guinea pig urinary bladder smooth muscle contraction: role of BK channels and cholinergic neurotransmission

PubMed Central

Fernandes, Vítor S.; Xin, Wenkuan

2015-01-01

Hydrogen sulfide (H2S) is a key signaling molecule regulating important physiological processes, including smooth muscle function. However, the mechanisms underlying H2S-induced detrusor smooth muscle (DSM) contractions are not well understood. This study investigates the cellular and tissue mechanisms by which H2S regulates DSM contractility, excitatory neurotransmission, and large-conductance voltage- and Ca2+-activated K+ (BK) channels in freshly isolated guinea pig DSM. We used a multidisciplinary experimental approach including isometric DSM tension recordings, colorimetric ACh measurement, Ca2+ imaging, and patch-clamp electrophysiology. In isolated DSM strips, the novel slow release H2S donor, P-(4-methoxyphenyl)-p-4-morpholinylphosphinodithioic acid morpholine salt (GYY4137), significantly increased the spontaneous phasic and nerve-evoked DSM contractions. The blockade of neuronal voltage-gated Na+ channels or muscarinic ACh receptors with tetrodotoxin or atropine, respectively, reduced the stimulatory effect of GYY4137 on DSM contractility. GYY4137 increased ACh release from bladder nerves, which was inhibited upon blockade of L-type voltage-gated Ca2+ channels with nifedipine. Furthermore, GYY4137 increased the amplitude of the Ca2+ transients and basal Ca2+ levels in isolated DSM strips. GYY4137 reduced the DSM relaxation induced by the BK channel opener, NS11021. In freshly isolated DSM cells, GYY4137 decreased the amplitude and frequency of transient BK currents recorded in a perforated whole cell configuration and reduced the single BK channel open probability measured in excised inside-out patches. GYY4137 inhibited spontaneous transient hyperpolarizations and depolarized the DSM cell membrane potential. Our results reveal the novel findings that H2S increases spontaneous phasic and nerve-evoked DSM contractions by activating ACh release from bladder nerves in combination with a direct inhibition of DSM BK channels. PMID:25948731

Phasic dopamine release in the nucleus accumbens in response to pro-social 50 kHz ultrasonic vocalizations in rats.

PubMed

Willuhn, Ingo; Tose, Amanda; Wanat, Matthew J; Hart, Andrew S; Hollon, Nick G; Phillips, Paul E M; Schwarting, Rainer K W; Wöhr, Markus

2014-08-06

Rats emit ultrasonic vocalizations (USVs) that are thought to serve as situation-dependent affective signals and accomplish important communicative functions. In appetitive situations, rats produce 50 kHz USVs, whereas 22 kHz USVs occur in aversive situations. Reception of 50 kHz USVs induces social approach behavior, while 22 kHz USVs lead to freezing behavior. These opposite behavioral responses are paralleled by distinct brain activation patterns, with 50 kHz USVs, but not 22 kHz USVs, activating neurons in the nucleus accumbens (NAcc). The NAcc mediates appetitive behavior and is critically modulated by dopaminergic afferents that are known to encode the value of reward. Therefore, we hypothesized that 50 kHz USVs, but not 22 kHz USVs, elicit NAcc dopamine release. While recording dopamine signaling with fast-scan cyclic voltammetry, freely moving rats were exposed to playback of four acoustic stimuli via an ultrasonic speaker in random order: (1) 50 kHz USVs, (2) 22 kHz USVs, (3) time- and amplitude-matched white noise, and (4) background noise. Only presentation of 50 kHz USVs induced phasic dopamine release and elicited approach behavior toward the speaker. Both of these effects, neurochemical and behavioral, were most pronounced during initial playback, but then declined rapidly with subsequent presentations, indicating a close temporal relationship between the two measures. Moreover, the magnitudes of these effects during initial playback were significantly correlated. Collectively, our findings show that NAcc dopamine release encodes pro-social 50 kHz USVs, but not alarming 22 kHz USVs. Thus, our results support the hypothesis that these call types are processed in distinct neuroanatomical regions and establish a functional link between pro-social communicative signals and reward-related neurotransmission. Copyright © 2014 the authors 0270-6474/14/3410616-08$15.00/0.

Application of First Principles Ni-Cd and Ni-H2 Battery Models to Spacecraft Operations

NASA Technical Reports Server (NTRS)

Timmerman, Paul; Bugga, Ratnakumar; DiStefano, Salvador

1997-01-01

The conclusions of the application of first principles model to spacecraft operations are: the first principles of Bi-phasic electrode presented model provides an explanation for many behaviors on voltage fading on LEO cycling.

CRH Engagement of the Locus Coeruleus Noradrenergic System Mediates Stress-Induced Anxiety.

PubMed

McCall, Jordan G; Al-Hasani, Ream; Siuda, Edward R; Hong, Daniel Y; Norris, Aaron J; Ford, Christopher P; Bruchas, Michael R

2015-08-05

The locus coeruleus noradrenergic (LC-NE) system is one of the first systems engaged following a stressful event. While numerous groups have demonstrated that LC-NE neurons are activated by many different stressors, the underlying neural circuitry and the role of this activity in generating stress-induced anxiety has not been elucidated. Using a combination of in vivo chemogenetics, optogenetics, and retrograde tracing, we determine that increased tonic activity of the LC-NE system is necessary and sufficient for stress-induced anxiety and aversion. Selective inhibition of LC-NE neurons during stress prevents subsequent anxiety-like behavior. Exogenously increasing tonic, but not phasic, activity of LC-NE neurons is alone sufficient for anxiety-like and aversive behavior. Furthermore, endogenous corticotropin-releasing hormone(+) (CRH(+)) LC inputs from the amygdala increase tonic LC activity, inducing anxiety-like behaviors. These studies position the LC-NE system as a critical mediator of acute stress-induced anxiety and offer a potential intervention for preventing stress-related affective disorders. Copyright © 2015 Elsevier Inc. All rights reserved.

Learning-induced Dependence of Neuronal Activity in Primary Motor Cortex on Motor Task Condition.

PubMed

Cai, X; Shimansky, Y; He, Jiping

2005-01-01

A brain-computer interface (BCI) system such as a cortically controlled robotic arm must have a capacity of adjusting its function to a specific environmental condition. We studied this capacity in non-human primates based on chronic multi-electrode recording from the primary motor cortex of a monkey during the animal's performance of a center-out 3D reaching task and adaptation to external force perturbations. The main condition-related feature of motor cortical activity observed before the onset of force perturbation was a phasic raise of activity immediately before the perturbation onset. This feature was observed during a series of perturbation trials, but were absent under no perturbations. After adaptation has been completed, it usually was taking the subject only one trial to recognize a change in the condition to switch the neuronal activity accordingly. These condition-dependent features of neuronal activity can be used by a BCI for recognizing a change in the environmental condition and making corresponding adjustments, which requires that the BCI-based control system possess such advanced properties of the neural motor control system as capacity to learn and adapt.

Ventral Pallidum Roles in Reward and Motivation

PubMed Central

Smith, Kyle S.; Tindell, Amy J.; Aldridge, J. Wayne; Berridge, Kent C.

2008-01-01

In recent years the ventral pallidum has become a focus of great research interest as a mechanism of reward and incentive motivation. As a major output for limbic signals, the ventral pallidum was once associated primarily with motor functions rather than regarded as a reward structure in its own right. However, ample evidence now suggests that ventral pallidum function is a major mechanism of reward in the brain. We review data indicating that 1) an intact ventral pallidum is necessary for normal reward and motivation, 2) stimulated activation of ventral pallidum is sufficient to cause reward and motivation enhancements, and 3) activation patterns in ventral pallidum neurons specifically encode reward and motivation signals via phasic bursts of excitation to incentive and hedonic stimuli. We conclude that the ventral pallidum may serve as an important ‘limbic final common pathway’ for mesocorticolimbic processing of many rewards. PMID:18955088

Spasmolytic activity of trachylobanes ent-7α-acetoxytrachyloban-18-oic acid and ent-7α-hydroxytrachyloban-18-oic acid isolated from Xylopia langsdorfiana A. St-Hil. & Tul. (Annonaceae).

PubMed

Santos, Rosimeire F; Martins, Italo R R; Monteiro, Fabio de S; Travassos, Rafael de A; Janebro, Daniele I; Tavares, Josean F; Silva, Marcelo S; da Silva, Bagnólia A

2012-01-01

We aimed to investigate the possible spasmolytic activity of ent-7α-acetoxytrachyloban-18-oic acid (1) and ent-7α-hydroxytrachyloban-18-oic acid (2) on smooth muscle models. In male rat aorta and rat uterus, both diterpenes were unable to trigger spasmolytic action. However, 2 relaxed guinea-pig trachea: Compounds 1 and 2 antagonised, significantly and concentration-dependently, carbachol- and histamine-induced phasic contractions in guinea-pig ileum. Moreover, they induced a significant and concentration-dependent relaxation in pre-contracted (KCl, carbachol or histamine) guinea-pig ileum, with 2 being 15 times more potent than 1 in histamine-contracted ileum. These dissimilar results may be due to chemical differences between them. Thus, we demonstrated that 1 and 2 seem to be promising spasmolytic agents, although further studies are required to elucidate the spasmolytic action mechanism.

Dopamine, reward learning, and active inference

PubMed Central

FitzGerald, Thomas H. B.; Dolan, Raymond J.; Friston, Karl

2015-01-01

Temporal difference learning models propose phasic dopamine signaling encodes reward prediction errors that drive learning. This is supported by studies where optogenetic stimulation of dopamine neurons can stand in lieu of actual reward. Nevertheless, a large body of data also shows that dopamine is not necessary for learning, and that dopamine depletion primarily affects task performance. We offer a resolution to this paradox based on an hypothesis that dopamine encodes the precision of beliefs about alternative actions, and thus controls the outcome-sensitivity of behavior. We extend an active inference scheme for solving Markov decision processes to include learning, and show that simulated dopamine dynamics strongly resemble those actually observed during instrumental conditioning. Furthermore, simulated dopamine depletion impairs performance but spares learning, while simulated excitation of dopamine neurons drives reward learning, through aberrant inference about outcome states. Our formal approach provides a novel and parsimonious reconciliation of apparently divergent experimental findings. PMID:26581305

Dopamine, reward learning, and active inference.

PubMed

FitzGerald, Thomas H B; Dolan, Raymond J; Friston, Karl

2015-01-01

Temporal difference learning models propose phasic dopamine signaling encodes reward prediction errors that drive learning. This is supported by studies where optogenetic stimulation of dopamine neurons can stand in lieu of actual reward. Nevertheless, a large body of data also shows that dopamine is not necessary for learning, and that dopamine depletion primarily affects task performance. We offer a resolution to this paradox based on an hypothesis that dopamine encodes the precision of beliefs about alternative actions, and thus controls the outcome-sensitivity of behavior. We extend an active inference scheme for solving Markov decision processes to include learning, and show that simulated dopamine dynamics strongly resemble those actually observed during instrumental conditioning. Furthermore, simulated dopamine depletion impairs performance but spares learning, while simulated excitation of dopamine neurons drives reward learning, through aberrant inference about outcome states. Our formal approach provides a novel and parsimonious reconciliation of apparently divergent experimental findings.

Greater Ethanol Inhibition of Presynaptic Dopamine Release in C57BL/6J than DBA/2J Mice: Role of Nicotinic Acetylcholine Receptors

PubMed Central

Yorgason, Jordan T.; Rose, Jamie H.; McIntosh, J. Michael; Ferris, Mark J.; Jones, Sara R.

2014-01-01

The mesolimbic dopamine system, originating in the ventral tegmental area (VTA) and projecting to the nucleus accumbens (NAc), has been heavily implicated in the reinforcing effects of ethanol. Recent slice voltammetry studies have shown that ethanol inhibits dopamine release selectively during highfrequency activity that elicits phasic dopamine release shown to be important for learning and reinforcement. Presently, we examined ethanol inhibition of electrically evoked NAc dopamine in two mouse strains with divergent dopamine responses to ethanol, C57BL/6 (C57) and DBA/2J (DBA) mice. Previous electrophysiology and microdialysis studies have demonstrated greater ethanol induced VTA dopaminergic firing and NAc dopamine elevations in DBA compared to C57 mice. Additionally, DBA mice have greater ethanol responses in dopamine-related behaviors, including hyperlocomotion and conditioned place preference. Currently, we demonstrate greater sensitivity of ethanol inhibition of NAc dopamine signaling in C57 compared to DBA mice. The reduced sensitivity to ethanol inhibition in DBA mice may contribute to the overall greater ethanol-induced dopamine signaling and related behaviors observed in this strain. NAc cholinergic activity is known to potently modulate terminal dopamine release. Additionally, ethanol is known to interact with multiple aspects of nicotinic acetylcholine receptor activity. Therefore, we examined ethanol-mediated inhibition of dopamine release at two ethanol concentrations (80 and 160mM) during bath application of the non-selective nicotinic receptor antagonist mecamylamine, as well as compounds selective for the β2- (DhβE) and α6- (α-conotoxin MII [H9A; L15A]) subunit-containing receptors. Mecamylamine and DhβE decreased dopamine release and reduced ethanol's inhibitory effects on dopamine in both DBA and C57 mice. Further, α-conotoxin also reduced the dopamine release and the dopamine-inhibiting effects of ethanol at the 80mM, but not 160mM, concentration. These data suggest that ethanol is acting in part through nicotinic acetylcholine receptors, or downstream effectors, to reduce dopamine release during high-frequency activity. PMID:25451295

Dynamic Divisive Normalization Predicts Time-Varying Value Coding in Decision-Related Circuits

PubMed Central

LoFaro, Thomas; Webb, Ryan; Glimcher, Paul W.

2014-01-01

Normalization is a widespread neural computation, mediating divisive gain control in sensory processing and implementing a context-dependent value code in decision-related frontal and parietal cortices. Although decision-making is a dynamic process with complex temporal characteristics, most models of normalization are time-independent and little is known about the dynamic interaction of normalization and choice. Here, we show that a simple differential equation model of normalization explains the characteristic phasic-sustained pattern of cortical decision activity and predicts specific normalization dynamics: value coding during initial transients, time-varying value modulation, and delayed onset of contextual information. Empirically, we observe these predicted dynamics in saccade-related neurons in monkey lateral intraparietal cortex. Furthermore, such models naturally incorporate a time-weighted average of past activity, implementing an intrinsic reference-dependence in value coding. These results suggest that a single network mechanism can explain both transient and sustained decision activity, emphasizing the importance of a dynamic view of normalization in neural coding. PMID:25429145

Hunger and Satiety Signaling: Modeling Two Hypothalamomedullary Pathways for Energy Homeostasis.

PubMed

Nakamura, Kazuhiro; Nakamura, Yoshiko

2018-06-04

The recent discovery of the medullary circuit driving "hunger responses" - reduced thermogenesis and promoted feeding - has greatly expanded our knowledge on the central neural networks for energy homeostasis. However, how hypothalamic hunger and satiety signals generated under fasted and fed conditions, respectively, control the medullary autonomic and somatic motor mechanisms remains unknown. Here, in reviewing this field, we propose two hypothalamomedullary neural pathways for hunger and satiety signaling. To trigger hunger signaling, neuropeptide Y activates a group of neurons in the paraventricular hypothalamic nucleus (PVH), which then stimulate an excitatory pathway to the medullary circuit to drive the hunger responses. In contrast, melanocortin-mediated satiety signaling activates a distinct group of PVH neurons, which then stimulate a putatively inhibitory pathway to the medullary circuit to counteract the hunger signaling. The medullary circuit likely contains inhibitory and excitatory premotor neurons whose alternate phasic activation generates the coordinated masticatory motor rhythms to promote feeding. © 2018 The Authors. BioEssays Published by WILEY Periodicals, Inc.

Cortical membrane potential signature of optimal states for sensory signal detection

PubMed Central

McGinley, Matthew J.; David, Stephen V.; McCormick, David A.

2015-01-01

The neural correlates of optimal states for signal detection task performance are largely unknown. One hypothesis holds that optimal states exhibit tonically depolarized cortical neurons with enhanced spiking activity, such as occur during movement. We recorded membrane potentials of auditory cortical neurons in mice trained on a challenging tone-in-noise detection task while assessing arousal with simultaneous pupillometry and hippocampal recordings. Arousal measures accurately predicted multiple modes of membrane potential activity, including: rhythmic slow oscillations at low arousal, stable hyperpolarization at intermediate arousal, and depolarization during phasic or tonic periods of hyper-arousal. Walking always occurred during hyper-arousal. Optimal signal detection behavior and sound-evoked responses, at both sub-threshold and spiking levels, occurred at intermediate arousal when pre-decision membrane potentials were stably hyperpolarized. These results reveal a cortical physiological signature of the classically-observed inverted-U relationship between task performance and arousal, and that optimal detection exhibits enhanced sensory-evoked responses and reduced background synaptic activity. PMID:26074005

Ventral tegmental area dopamine revisited: effects of acute and repeated stress

PubMed Central

Holly, Elizabeth N.; Miczek, Klaus A.

2015-01-01

Aversive events rapidly and potently excite certain dopamine neurons in the ventral tegmental area (VTA), promoting phasic increases in the medial prefrontal cortex and nucleus accumbens. This is in apparent contradiction to a wealth of literature demonstrating that most VTA dopamine neurons are strongly activated by reward and reward-predictive cues while inhibited by aversive stimuli. How can these divergent processes both be mediated by VTA dopamine neurons? The answer may lie within the functional and anatomical heterogeneity of the VTA. We focus on VTA heterogeneity in anatomy, neurochemistry, electrophysiology, and afferent/efferent connectivity. Second, recent evidence for a critical role of VTA dopamine neurons in response to both acute and repeated stress will be discussed. Understanding which dopamine neurons are activated by stress, the neural mechanisms driving the activation, and where these neurons project will provide valuable insight into how stress can promote psychiatric disorders associated with the dopamine system, such as addiction and depression. PMID:26676983

The role of laryngeal electromyography in vagus nerve stimulation-related vocal fold dysmotility.

PubMed

Saibene, Alberto M; Zambrelli, Elena; Pipolo, Carlotta; Maccari, Alberto; Felisati, Giovanni; Felisati, Elena; Furia, Francesca; Vignoli, Aglaia; Canevini, Maria Paola; Alfonsi, Enrico

2017-03-01

Vagus nerve stimulation (VNS) is a useful tool for drug-resistant epilepsy, but it induces known laryngeal side effects, with a significant role on patients' quality of life. VNS patients may show persistent left vocal fold (LVF) palsy at rest and/or recurrent LVF adduction during stimulation. This study aims at electromyographically evaluating laryngeal muscles abnormalities in VNS patients. We compared endoscopic laryngeal evaluation data in six VNS patients with laryngeal muscle electromyography (LMEMG) carried out on the thyroarytenoid, cricothyroid, posterior cricoarytenoid, and cricopharyngeal muscles. Endoscopy showed LVF palsy at rest in 3/6 patients in whom LMEMG documented a tonic spastic activity with reduced phasic modulation. In four out of six patients with recurrent LVF adduction during VNS activation, LMEMG showed a compound muscle action potential persisting for the whole stimulation. This is the first LMEMG report of VNS-induced motor unit activation via recurrent laryngeal nerve and upper laryngeal nerve stimulation. LMEMG data were could, therefore, be considered consistent with the endoscopic laryngeal examination in all patient.

The Function and Organization of the Motor System Controlling Flight Maneuvers in Flies.

PubMed

Lindsay, Theodore; Sustar, Anne; Dickinson, Michael

2017-02-06

Animals face the daunting task of controlling their limbs using a small set of highly constrained actuators. This problem is particularly demanding for insects such as Drosophila, which must adjust wing motion for both quick voluntary maneuvers and slow compensatory reflexes using only a dozen pairs of muscles. To identify strategies by which animals execute precise actions using sparse motor networks, we imaged the activity of a complete ensemble of wing control muscles in intact, flying flies. Our experiments uncovered a remarkably efficient logic in which each of the four skeletal elements at the base of the wing are equipped with both large phasically active muscles capable of executing large changes and smaller tonically active muscles specialized for continuous fine-scaled adjustments. Based on the responses to a broad panel of visual motion stimuli, we have developed a model by which the motor array regulates aerodynamically functional features of wing motion. VIDEO ABSTRACT. Copyright © 2017 Elsevier Ltd. All rights reserved.

Neuromodulated Spike-Timing-Dependent Plasticity, and Theory of Three-Factor Learning Rules

PubMed Central

Frémaux, Nicolas; Gerstner, Wulfram

2016-01-01

Classical Hebbian learning puts the emphasis on joint pre- and postsynaptic activity, but neglects the potential role of neuromodulators. Since neuromodulators convey information about novelty or reward, the influence of neuromodulators on synaptic plasticity is useful not just for action learning in classical conditioning, but also to decide “when” to create new memories in response to a flow of sensory stimuli. In this review, we focus on timing requirements for pre- and postsynaptic activity in conjunction with one or several phasic neuromodulatory signals. While the emphasis of the text is on conceptual models and mathematical theories, we also discuss some experimental evidence for neuromodulation of Spike-Timing-Dependent Plasticity. We highlight the importance of synaptic mechanisms in bridging the temporal gap between sensory stimulation and neuromodulatory signals, and develop a framework for a class of neo-Hebbian three-factor learning rules that depend on presynaptic activity, postsynaptic variables as well as the influence of neuromodulators. PMID:26834568

Neuron hemilineages provide the functional ground plan for the Drosophila ventral nervous system

PubMed Central

Harris, Robin M; Pfeiffer, Barret D; Rubin, Gerald M; Truman, James W

2015-01-01

Drosophila central neurons arise from neuroblasts that generate neurons in a pair-wise fashion, with the two daughters providing the basis for distinct A and B hemilineage groups. 33 postembryonically-born hemilineages contribute over 90% of the neurons in each thoracic hemisegment. We devised genetic approaches to define the anatomy of most of these hemilineages and to assessed their functional roles using the heat-sensitive channel dTRPA1. The simplest hemilineages contained local interneurons and their activation caused tonic or phasic leg movements lacking interlimb coordination. The next level was hemilineages of similar projection cells that drove intersegmentally coordinated behaviors such as walking. The highest level involved hemilineages whose activation elicited complex behaviors such as takeoff. These activation phenotypes indicate that the hemilineages vary in their behavioral roles with some contributing to local networks for sensorimotor processing and others having higher order functions of coordinating these local networks into complex behavior. DOI: http://dx.doi.org/10.7554/eLife.04493.001 PMID:26193122

The rostromedial tegmental nucleus (RMTg), a major GABAergic afferent to midbrain dopamine neurons, selectively encodes aversive stimuli and promotes behavioral inhibition

PubMed Central

Jhou, Thomas C.; Fields, Howard L.; Baxter, Mark G.; Saper, Clifford B.; Holland, Peter C.

2009-01-01

Summary Separate studies have implicated the lateral habenula (LHb) or amygdala-related regions in processing aversive stimuli, but their relationships to each other and to appetitive motivational systems are poorly understood. We show that neurons in the recently identified GABAergic rostromedial tegmental nucleus (RMTg), which receive a major LHb input, project heavily to midbrain dopamine neurons, and show phasic activations and/or Fos induction after aversive stimuli (footshocks, shock-predictive cues, food deprivation, or reward omission) and inhibitions after rewards or reward-predictive stimuli. RMTg lesions markedly reduce passive fear behaviors (freezing, open-arm avoidance) dependent on the extended amygdala, periaqueductal gray, or septum, all regions that project directly to the RMTg. In contrast, RMTg lesions spare or enhance active fear responses (treading, escape) in these same paradigms. These findings suggest that aversive inputs from widespread brain regions and stimulus modalities converge onto the RMTg, which opposes reward and motor-activating functions of midbrain dopamine neurons PMID:19285474

Which cue to ‘want’? Opioid stimulation of central amygdala makes goal-trackers show stronger goal-tracking, just as sign-trackers show stronger sign-tracking

PubMed Central

DiFeliceantonio, Alexandra G.; Berridge, Kent C.

2012-01-01

Pavlovian cues that have been paired with reward can gain incentive salience. Drug addicts find drug cues motivationally attractive and binge eaters are attracted by food cues. But the level of incentive salience elicited by a cue re-encounter still varies across time and brain states. In an animal model, cues become attractive and ‘wanted’ in an ‘autoshaping’ paradigm, where different targets of incentive salience emerge for different individuals. Some individuals (sign-trackers) find a predictive discrete cue attractive while others find a reward contiguous and goal cue more attractive (location where reward arrives: goal-trackers). Here we assessed whether central amygdala mu opioid receptor stimulation enhances the phasic incentive salience of the goal-cue for goal-trackers during moments of predictive cue presence (expressed in both approach and consummatory behaviors to goal cue), just as it enhances the attractiveness of the predictive cue target for sign-trackers. Using detailed video analysis we measured the approaches, nibbles, sniffs, and bites directed at their preferred target for both sign-trackers and goal-trackers. We report that DAMGO microinjections in central amygdala made goal-trackers, like sign-trackers, show phasic increases in appetitive nibbles and sniffs directed at the goal-cue expressed selectively whenever the predictive cue was present. This indicates enhancement of incentive salience attributed by both goal trackers and sign-trackers, but attributed in different directions: each to their own target cue. For both phenotypes, amygdala opioid stimulation makes the individual’s prepotent cue into a stronger motivational magnet at phasic moments triggered by a CS that predicts the reward UCS. PMID:22391118

Changes of cytosolic calcium and contractility of young rat vas deferens by acute treatment with amphetamine, fluoxetine or sibutramine.

PubMed

Jurkiewicz, Neide Hyppolito; da Silva Júnior, Edilson Dantas; de Souza, Bruno Palmieri; Ferreira Verde, Luciana; Drawanz Pereira, Janaina; Mendes Sobrinho, Cairo; Soubhi Smaili, Soraya; Caricati-Neto, Afonso; Miranda-Ferreira, Regiane; Jurkiewicz, Aron

2012-09-15

Previous studies conducted in our laboratory indicated that administration of amphetamine, fluoxetine or sibutramine affects the sympathetic nervous system of the rat vas deferens. Therefore, our goal was to verify the role of calcium in vasa deferentia from young rats pretreated with a single dose of these drugs. Young 40-day-old male Wistar rats were pretreated with amphetamine 3 mg/kg, fluoxetine 10 mg/kg or sibutramine 6 mg/kg for 4 h before the experiments. CaCl(2) (10 mM) was used to induce contraction through time-effect curves in calcium-free solution to measure phasic and tonic components. We also evaluated the calcium-induced fluorescence of vas deferens cut into thin slices. In rats pretreated with amphetamine, we found an increase of the tonic contraction component which was reduced by verapamil. The phasic and tonic responses were increased in the group treated with fluoxetine, but only the tonic response was more sensitive to the antagonism by verapamil. The group treated with sibutramine showed an increase of phasic response whereas the tonic component was decreased. In this group an increase of the affinity for verapamil antagonism was found. In the calcium fluorescence study it was observed that the group treated with amphetamine, fluoxetine or sibutramine showed higher basal Ca(2+) fluorescence after stimulus with KCl (70 mM), noradrenaline (10(-4)M) or acetylcholine (10(-4)M). In all pretreated groups the calcium fluorescence was diminished by nifedipine 10(-7)M. Therefore, the pretreatment with amphetamine, fluoxetine or sibutramine seems to affect the calcium contractility and homeostasis in young rat vas deferens. Copyright © 2012 Elsevier B.V. All rights reserved.

Menthol enhances phasic and tonic GABAA receptor-mediated currents in midbrain periaqueductal grey neurons

PubMed Central

Lau, Benjamin K; Karim, Shafinaz; Goodchild, Ann K; Vaughan, Christopher W; Drew, Geoffrey M

2014-01-01

Background and Purpose Menthol, a naturally occurring compound in the essential oil of mint leaves, is used for its medicinal, sensory and fragrant properties. Menthol acts via transient receptor potential (TRPM8 and TRPA1) channels and as a positive allosteric modulator of recombinant GABAA receptors. Here, we examined the actions of menthol on GABAA receptor-mediated currents in intact midbrain slices. Experimental Approach Whole-cell voltage-clamp recordings were made from periaqueductal grey (PAG) neurons in midbrain slices from rats to determine the effects of menthol on GABAA receptor-mediated phasic IPSCs and tonic currents. Key Results Menthol (150–750 μM) produced a concentration-dependent prolongation of spontaneous GABAA receptor-mediated IPSCs, but not non-NMDA receptor-mediated EPSCs throughout the PAG. Menthol actions were unaffected by TRPM8 and TRPA1 antagonists, tetrodotoxin and the benzodiazepine antagonist, flumazenil. Menthol also enhanced a tonic current, which was sensitive to the GABAA receptor antagonists, picrotoxin (100 μM), bicuculline (30 μM) and Zn2+ (100 μM), but unaffected by gabazine (10 μM) and a GABAC receptor antagonist, 1,2,5,6-tetrahydropyridin-4-yl)methylphosphinic acid hydrate (TPMPA; 50 μM). In addition, menthol potentiated currents induced by the extrasynaptic GABAA receptor agonist THIP/gaboxadol (10 μM). Conclusions and Implications These results suggest that menthol positively modulates both synaptic and extrasynaptic populations of GABAA receptors in native PAG neurons. The development of agents that potentiate GABAA-mediated tonic currents and phasic IPSCs in a manner similar to menthol could provide a basis for novel GABAA-related pharmacotherapies. PMID:24460753

Electrocatalytic Production of C3-C4 Compounds by Conversion of CO2 on a Chloride-Induced Bi-Phasic Cu2O-Cu Catalyst.

PubMed

Lee, Seunghwa; Kim, Dahee; Lee, Jaeyoung

2015-12-01

Electrocatalytic conversion of carbon dioxide (CO2) has recently received considerable attention as one of the most feasible CO2 utilization techniques. In particular, copper and copper-derived catalysts have exhibited the ability to produce a number of organic molecules from CO2. Herein, we report a chloride (Cl)-induced bi-phasic cuprous oxide (Cu2O) and metallic copper (Cu) electrode (Cu2OCl) as an efficient catalyst for the formation of high-carbon organic molecules by CO2 conversion, and identify the origin of electroselectivity toward the formation of high-carbon organic compounds. The Cu2OCl electrocatalyst results in the preferential formation of multi-carbon fuels, including n-propanol and n-butane C3-C4 compounds. We propose that the remarkable electrocatalytic conversion behavior is due to the favorable affinity between the reaction intermediates and the catalytic surface. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Spontaneous Eye-Blink Rate as an Index of Reward Responsivity: Validation and Links to Bipolar Disorder

PubMed Central

Peckham, Andrew D.; Johnson, Sheri L.

2015-01-01

Extensive research supports the role of striatal dopamine in pursuing and responding to reward, and that eye-blink rate is a valid indicator of striatal dopamine. This study tested whether phasic changes in blink rate could provide an index of reward pursuit. This hypothesis was tested in people with bipolar I disorder (BD; a population with aberrations in reward responsivity), and in those without BD. Thirty-one adults with BD and 28 control participants completed a laboratory task involving effort towards monetary reward. Blink rate was recorded using eye-tracking at baseline, reward anticipation, and post-reward. Those in the BD group completed self-report measures relating to reward and ambition. Results showed that across all participants, blink rates increased from reward anticipation to post-reward. In the BD group, reward-relevant measures were strongly correlated with variation in blink rate. These findings provide validation for phasic changes in blink rate as an index of reward response. PMID:27274949

Phasic Triplet Markov Chains.

PubMed

El Yazid Boudaren, Mohamed; Monfrini, Emmanuel; Pieczynski, Wojciech; Aïssani, Amar

2014-11-01

Hidden Markov chains have been shown to be inadequate for data modeling under some complex conditions. In this work, we address the problem of statistical modeling of phenomena involving two heterogeneous system states. Such phenomena may arise in biology or communications, among other fields. Namely, we consider that a sequence of meaningful words is to be searched within a whole observation that also contains arbitrary one-by-one symbols. Moreover, a word may be interrupted at some site to be carried on later. Applying plain hidden Markov chains to such data, while ignoring their specificity, yields unsatisfactory results. The Phasic triplet Markov chain, proposed in this paper, overcomes this difficulty by means of an auxiliary underlying process in accordance with the triplet Markov chains theory. Related Bayesian restoration techniques and parameters estimation procedures according to the new model are then described. Finally, to assess the performance of the proposed model against the conventional hidden Markov chain model, experiments are conducted on synthetic and real data.

Anthropometry as a predictor of high speed performance.

PubMed

Caruso, J F; Ramey, E; Hastings, L P; Monda, J K; Coday, M A; McLagan, J; Drummond, J

2009-07-01

To assess anthropometry as a predictor of high-speed performance, subjects performed four seated knee- and hip-extension workouts with their left leg on an inertial exercise trainer (Impulse Technologies, Newnan GA). Workouts, done exclusively in either the tonic or phasic contractile mode, entailed two one-minute sets separated by a 90-second rest period and yielded three performance variables: peak force, average force and work. Subjects provided the following anthropometric data: height, weight, body mass index, as well as total, upper and lower left leg lengths. Via multiple regression, anthropometry attempted to predict the variance per performance variable. Anthropometry explained a modest (R2=0.27-0.43) yet significant degree of variance from inertial exercise trainer workouts. Anthropometry was a better predictor of peak force variance from phasic workouts, while it accounted for a significant degree of average force and work variance solely from tonic workouts. Future research should identify variables that account for the unexplained variance from high-speed exercise performance.

Differences in respirogram phase between taekwondo poomsae athletes and nonathletes.

PubMed

Shin, Yong-Sub; Yang, Seung-Min; Kim, Mee-Young; Lee, Lim-Kyu; Park, Byoung-Sun; Lee, Won-Deok; Noh, Ji-Woong; Kim, Ju-Hyun; Lee, Jeong-Uk; Kwak, Taek-Yong; Lee, Tae-Hyun; Park, Jaehong; Kim, Junghwan

2016-09-01

[Purpose] Respiratory physiotherapy is an effective approach to improving lung function in patient, including athletes with respiratory dysfunction caused by sports injury. The purpose of this study was to analyze the differences in the respirograms between taekwondo poomsae athletes and nonathletes according to the respirogram phase. [Subjects and Methods] Respiratory measurements for 13 elite taekwondo poomsae athletes were obtained. Respiratory function was measured using spirometry while the participant was seated. [Results] In respirogram phasic analysis, the inspiratory area of forced vital capacity were significantly increased in the athletes than in the nonathletes. The slopes of the forced vital capacity for athletes at slopes 1, 2, and 3 of the A area were significantly higher than those for the nonathletes. In correlation analysis, chest circumference was significantly correlated with slope 1 of the A area of the forced vital capacity. [Conclusion] Results indicate that differences in respirogram phasic changes between athletes and nonathletes may contribute to better understanding of respiratory function, which is important to sports physiotherapy research.

Diverse modes of synaptic signaling, regulation, and plasticity distinguish two classes of C. elegans glutamatergic neurons.

PubMed

Ventimiglia, Donovan; Bargmann, Cornelia I

2017-11-21

Synaptic vesicle release properties vary between neuronal cell types, but in most cases the molecular basis of this heterogeneity is unknown. Here, we compare in vivo synaptic properties of two neuronal classes in the C. elegans central nervous system, using VGLUT-pHluorin to monitor synaptic vesicle exocytosis and retrieval in intact animals. We show that the glutamatergic sensory neurons AWC ON and ASH have distinct synaptic dynamics associated with tonic and phasic synaptic properties, respectively. Exocytosis in ASH and AWC ON is differentially affected by SNARE-complex regulators that are present in both neurons: phasic ASH release is strongly dependent on UNC-13, whereas tonic AWC ON release relies upon UNC-18 and on the protein kinase C homolog PKC-1. Strong stimuli that elicit high calcium levels increase exocytosis and retrieval rates in AWC ON , generating distinct tonic and evoked synaptic modes. These results highlight the differential deployment of shared presynaptic proteins in neuronal cell type-specific functions.

Diverse modes of synaptic signaling, regulation, and plasticity distinguish two classes of C. elegans glutamatergic neurons

PubMed Central

Ventimiglia, Donovan

2017-01-01

Synaptic vesicle release properties vary between neuronal cell types, but in most cases the molecular basis of this heterogeneity is unknown. Here, we compare in vivo synaptic properties of two neuronal classes in the C. elegans central nervous system, using VGLUT-pHluorin to monitor synaptic vesicle exocytosis and retrieval in intact animals. We show that the glutamatergic sensory neurons AWCON and ASH have distinct synaptic dynamics associated with tonic and phasic synaptic properties, respectively. Exocytosis in ASH and AWCON is differentially affected by SNARE-complex regulators that are present in both neurons: phasic ASH release is strongly dependent on UNC-13, whereas tonic AWCON release relies upon UNC-18 and on the protein kinase C homolog PKC-1. Strong stimuli that elicit high calcium levels increase exocytosis and retrieval rates in AWCON, generating distinct tonic and evoked synaptic modes. These results highlight the differential deployment of shared presynaptic proteins in neuronal cell type-specific functions. PMID:29160768

Dorsomedial Prefrontal Cortex Contribution to Behavioral and Nucleus Accumbens Neuronal Responses to Incentive Cues

PubMed Central

Ishikawa, Akinori; Ambroggi, Frederic; Nicola, Saleem M.; Fields, Howard L.

2008-01-01

Cue-elicited phasic changes in firing of nucleus accumbens (NAc) neurons can facilitate reward-seeking behavior. Here, we test the hypothesis that the medial prefrontal cortex (mPFC), which sends a dense glutamatergic projection to the NAc core, contributes to NAc neuronal firing responses to reward-predictive cues. Rats trained to perform an operant response to a cue for sucrose were implanted with recording electrodes in the core of the NAc and microinjection cannulas in the dorsal mPFC (dmPFC). The cue-evoked firing of NAc neurons was reduced by bilateral injection of GABAA and GABAB agonists into the dmPFC concomitant with loss of behavioral responding to the cue. In addition, unilateral dmPFC inactivation reduced ipsilateral cue excitations and contralateral cue inhibitions. These findings indicate that cue-evoked excitations and inhibitions of NAc core neurons depend on dmPFC projections to the NAc and that these phasic changes contribute to the behavioral response to reward-predictive cues. PMID:18463262

Acetylcholine Release in Prefrontal Cortex Promotes Gamma Oscillations and Theta-Gamma Coupling during Cue Detection.

PubMed

Howe, William M; Gritton, Howard J; Lusk, Nicholas A; Roberts, Erik A; Hetrick, Vaughn L; Berke, Joshua D; Sarter, Martin

2017-03-22

The capacity for using external cues to guide behavior ("cue detection") constitutes an essential aspect of attention and goal-directed behavior. The cortical cholinergic input system, via phasic increases in prefrontal acetylcholine release, plays an essential role in attention by mediating such cue detection. However, the relationship between cholinergic signaling during cue detection and neural activity dynamics in prefrontal networks remains unclear. Here we combined subsecond measures of cholinergic signaling, neurophysiological recordings, and cholinergic receptor blockade to delineate the cholinergic contributions to prefrontal oscillations during cue detection in rats. We first confirmed that detected cues evoke phasic acetylcholine release. These cholinergic signals were coincident with increased neuronal synchrony across several frequency bands and the emergence of theta-gamma coupling. Muscarinic and nicotinic cholinergic receptors both contributed specifically to gamma synchrony evoked by detected cues, but the effects of blocking the two receptor subtypes were dissociable. Blocking nicotinic receptors primarily attenuated high-gamma oscillations occurring during the earliest phases of the cue detection process, while muscarinic (M1) receptor activity was preferentially involved in the transition from high to low gamma power that followed and corresponded to the mobilization of networks involved in cue-guided decision making. Detected cues also promoted coupling between gamma and theta oscillations, and both nicotinic and muscarinic receptor activity contributed to this process. These results indicate that acetylcholine release coordinates neural oscillations during the process of cue detection. SIGNIFICANCE STATEMENT The capacity of learned cues to direct attention and guide responding ("cue detection") is a key component of goal-directed behavior. Rhythmic neural activity and increases in acetylcholine release in the prefrontal cortex contribute to this process; however, the relationship between these neuronal mechanisms is not well understood. Using a combination of in vivo neurochemistry, neurophysiology, and pharmacological methods, we demonstrate that cue-evoked acetylcholine release, through distinct actions at both nicotinic and muscarinic receptors, triggers a procession of neural oscillations that map onto the multiple stages of cue detection. Our data offer new insights into cholinergic function by revealing the temporally orchestrated changes in prefrontal network synchrony modulated by acetylcholine release during cue detection. Copyright © 2017 the authors 0270-6474/17/373215-16$15.00/0.

Temporal Taylor's scaling of facial electromyography and electrodermal activity in the course of emotional stimulation

NASA Astrophysics Data System (ADS)

Chołoniewski, Jan; Chmiel, Anna; Sienkiewicz, Julian; Hołyst, Janusz A.; Küster, Dennis; Kappas, Arvid

2016-09-01

High frequency psychophysiological data create a challenge for quantitative modeling based on Big Data tools since they reflect the complexity of processes taking place in human body and its responses to external events. Here we present studies of fluctuations in facial electromyography (fEMG) and electrodermal activity (EDA) massive time series and changes of such signals in the course of emotional stimulation. Zygomaticus major (ZYG, "smiling" muscle) activity, corrugator supercilii (COR, "frowning"bmuscle) activity, and phasic skin conductance (PHSC, sweating) levels of 65 participants were recorded during experiments that involved exposure to emotional stimuli (i.e., IAPS images, reading and writing messages on an artificial online discussion board). Temporal Taylor's fluctuations scaling were found when signals for various participants and during various types of emotional events were compared. Values of scaling exponents were close to 1, suggesting an external origin of system dynamics and/or strong interactions between system's basic elements (e.g., muscle fibres). Our statistical analysis shows that the scaling exponents enable identification of high valence and arousal levels in ZYG and COR signals.

Intralimb and Interlimb Cutaneous Reflexes during Locomotion in the Intact Cat.

PubMed

Hurteau, Marie-France; Thibaudier, Yann; Dambreville, Charline; Danner, Simon M; Rybak, Ilya A; Frigon, Alain

2018-04-25

When the foot contacts an obstacle during locomotion, cutaneous inputs activate spinal circuits to ensure dynamic balance and forward progression. In quadrupeds, this requires coordinated reflex responses between the four limbs. Here, we investigated the patterns and phasic modulation of cutaneous reflexes in forelimb and hindlimb muscles evoked by inputs from all four limbs. Five female cats were implanted to record muscle activity and to stimulate the superficial peroneal and superficial radial nerves during locomotion. Stimulating these nerves evoked short-, mid-, and longer-latency excitatory and/or inhibitory responses in all four limbs that were phase-dependent. The largest responses were generally observed during the peak activity of the muscle. Cutaneous reflexes during mid-swing were consistent with flexion of the homonymous limb and accompanied by modification of the stance phases of the other three limbs, by coactivating flexors and extensors and/or by delaying push-off. Cutaneous reflexes during mid-stance were consistent with stabilizing the homonymous limb by delaying and then facilitating its push-off and modifying the support phases of the homolateral and diagonal limbs, characterized by coactivating flexors and extensors, reinforcing extensor activity and/or delaying push-off. The shortest latencies of homolateral and diagonal responses were consistent with fast-conducting disynaptic or trisynaptic pathways. Descending homolateral and diagonal pathways from the forelimbs to the hindlimbs had a higher probability of eliciting responses compared with ascending pathways from the hindlimbs to the forelimbs. Thus, in quadrupeds, intralimb and interlimb reflexes activated by cutaneous inputs ensure dynamic coordination of the four limbs, producing a whole-body response. SIGNIFICANCE STATEMENT The skin contains receptors that, when activated, send inputs to spinal circuits, signaling a perturbation. Rapid responses, or reflexes, in muscles of the contacted limb and opposite homologous limb help maintain balance and forward progression. Here, we investigated reflexes during quadrupedal locomotion in the cat by electrically stimulating cutaneous nerves in each of the four limbs. Functionally, responses appear to modify the trajectory or stabilize the movement of the stimulated limb while modifying the support phase of the other limbs. Reflexes between limbs are mediated by fast-conducting pathways that involve excitatory and inhibitory circuits controlling each limb. The comparatively stronger descending pathways from cervical to lumbar circuits controlling the forelimbs and hindlimbs, respectively, could serve a protective function. Copyright © 2018 the authors 0270-6474/18/384104-19$15.00/0.

Stimulus-Dependent Dopamine Release in Attention-Deficit/Hyperactivity Disorder

ERIC Educational Resources Information Center

Sikstrom, Sverker; Soderlund, Goran

2007-01-01

Attention-deficit/hyperactivity disorder (ADHD) is related to an attenuated and dysfunctional dopamine system. Normally, a high extracellular dopamine level yields a tonic dopaminergic input that down-regulates stimuli-evoked phasic dopamine responses through autoreceptors. Abnormally low tonic extracellular dopamine in ADHD up-regulates the…

Respiratory gas exchange as a new aid to monitor acidosis in endotoxemic rats: relationship to metabolic fuel substrates and thermometabolic responses.

PubMed

Steiner, Alexandre A; Flatow, Elizabeth A; Brito, Camila F; Fonseca, Monique T; Komegae, Evilin N

2017-01-01

This study introduces the respiratory exchange ratio (RER; the ratio of whole-body CO 2 production to O 2 consumption) as an aid to monitor metabolic acidosis during the early phase of endotoxic shock in unanesthetized, freely moving rats. Two serotypes of lipopolysaccharide (lipopolysaccharide [LPS] O55:B5 and O127:B8) were tested at shock-inducing doses (0.5-2 mg/kg). Phasic rises in RER were observed consistently across LPS serotypes and doses. The RER rise often exceeded the ceiling of the quotient for oxidative metabolism, and was mirrored by depletion of arterial bicarbonate and decreases in pH It occurred independently of ventilatory adjustments. These data indicate that the rise in RER results from a nonmetabolic CO 2 load produced via an acid-induced equilibrium shift in the bicarbonate buffer. Having validated this new experimental aid, we asked whether acidosis was interconnected with the metabolic and thermal responses that accompany endotoxic shock in unanesthetized rats. Contrary to this hypothesis, however, acidosis persisted regardless of whether the ambient temperature favored or prevented downregulation of mitochondrial oxidation and regulated hypothermia. We then asked whether the substrate that fuels aerobic metabolism could be a relevant factor in LPS-induced acidosis. Food deprivation was employed to divert metabolism away from glucose oxidation and toward fatty acid oxidation. Interestingly, this intervention attenuated the RER response to LPS by 58%, without suppressing other key aspects of systemic inflammation. We conclude that acid production in unanesthetized rats with endotoxic shock results from a phasic activation of glycolysis, which occurs independently of physiological changes in mitochondrial oxidation and body temperature. © 2017 The Authors. Physiological Reports published by Wiley Periodicals, Inc. on behalf of The Physiological Society and the American Physiological Society.

Speed/accuracy trade-off between the habitual and the goal-directed processes.

PubMed

Keramati, Mehdi; Dezfouli, Amir; Piray, Payam

2011-05-01

Instrumental responses are hypothesized to be of two kinds: habitual and goal-directed, mediated by the sensorimotor and the associative cortico-basal ganglia circuits, respectively. The existence of the two heterogeneous associative learning mechanisms can be hypothesized to arise from the comparative advantages that they have at different stages of learning. In this paper, we assume that the goal-directed system is behaviourally flexible, but slow in choice selection. The habitual system, in contrast, is fast in responding, but inflexible in adapting its behavioural strategy to new conditions. Based on these assumptions and using the computational theory of reinforcement learning, we propose a normative model for arbitration between the two processes that makes an approximately optimal balance between search-time and accuracy in decision making. Behaviourally, the model can explain experimental evidence on behavioural sensitivity to outcome at the early stages of learning, but insensitivity at the later stages. It also explains that when two choices with equal incentive values are available concurrently, the behaviour remains outcome-sensitive, even after extensive training. Moreover, the model can explain choice reaction time variations during the course of learning, as well as the experimental observation that as the number of choices increases, the reaction time also increases. Neurobiologically, by assuming that phasic and tonic activities of midbrain dopamine neurons carry the reward prediction error and the average reward signals used by the model, respectively, the model predicts that whereas phasic dopamine indirectly affects behaviour through reinforcing stimulus-response associations, tonic dopamine can directly affect behaviour through manipulating the competition between the habitual and the goal-directed systems and thus, affect reaction time.

Profiling subjective symptoms and autonomic changes associated with cybersickness.

PubMed

Gavgani, Alireza Mazloumi; Nesbitt, Keith V; Blackmore, Karen L; Nalivaiko, Eugene

2017-03-01

Our aim was to expand knowledge of cybersickness - a subtype of motion sickness provoked by immersion into a moving computer-generated virtual reality. Fourteen healthy subjects experienced a 15-min rollercoaster ride presented via a head-mounted display (Oculus Rift), for 3 consecutive days. Heart rate, respiration, finger and forehead skin conductance were measured during the experiment; this was complemented by a subjective nausea rating during the ride and by Motion Sickness Assessment Questionnaire before, immediately after and then 1, 2 and 3h post-ride. Physiological measurements were analysed in three dimensions: ride time, association with subjective nausea rating and experimental day. Forehead, and to a lesser extent finger phasic skin conductance activity showed a correlation with the reported nausea ratings, while alteration in other measured parameters were mostly related to autonomic arousal during the virtual ride onset. A significant habituation was observed in subjective symptom scores and in the duration of tolerated provocation. The latter increased from 7.0±1.3min on the first day to 12.0±2.5min on the third day (p<0.05); this was associated with a reduced slope of nausea rise from 1.3±0.3units/min on the first to 0.7±0.1units/min on the third day (p<0.01). Furthermore, habituation with repetitive exposure was also determined in the total symptom score post-ride: it fell from 1.6±0.1 on the first day to 1.2±0.1 on the third (p<0.001). We conclude that phasic changes of skin conductance on the forehead could be used to objectively quantify nausea; and that repetitive exposure to provocative VR content results in habituation. Copyright © 2016 Elsevier B.V. All rights reserved.

Association of Left Atrial Function and Left Atrial Enhancement in Patients with Atrial Fibrillation: A Cardiac Magnetic Resonance Study

PubMed Central

Habibi, Mohammadali; Lima, Joao A.C.; Khurram, Irfan M.; Zimmerman, Stefan L.; Zipunnikov, Vadim; Fukumoto, Kotaro; Spragg, David; Ashikaga, Hiroshi; Rickard, John; Marine, Joseph E.; Calkins, Hugh; Nazarian, Saman

2015-01-01

Background Atrial fibrillation (AF) is associated with left atrial (LA) structural and functional changes. Cardiac magnetic resonance (CMR) late gadolinium enhancement (LGE) and feature-tracking are capable of noninvasive quantification of LA fibrosis and myocardial motion, respectively. We sought to examine the association of phasic LA function with LA enhancement in patients with AF. Methods and Results LA structure and function was measured in 90 AF patients (age 61 ± 10 years, 76% male) referred for ablation and 14 healthy volunteers. Peak global longitudinal LA strain (PLAS), LA systolic strain rate (SR-s), and early (SR-ed) and late diastolic (SR-ld) strain rates were measured using cine-CMR images acquired during sinus rhythm. The degree of LGE was quantified. Compared to patients with paroxysmal AF (60% of cohort), those with persistent AF had larger maximum LA volume index (LAVImax, 56 ± 17ml/m2 versus 49 ± 13ml/m2 p=0.036), and increased LGE (27.1± 11.7% versus 36.8 ± 14.8% p<0.001). Aside from LA active emptying fraction, all LA parameters (passive emptying fraction, PLAS, SR-s, SR-ed and SR-ld) were lower in patients with persistent AF (p< 0.05 for all). Healthy volunteers had less LGE and higher LA functional parameters compared to AF patients (p<0.05 for all). In multivariable analysis, increased LGE was associated with lower LA passive emptying fraction, PLAS, SR-s, SR-ed, and SR-ld (p<0.05 for all). Conclusions Increased LA enhancement is associated with decreased LA reservoir, conduit, and booster pump functions. Phasic measurement of LA function using feature-tracking CMR may add important information regarding the physiological importance of LA fibrosis. PMID:25652181

Monitoring In Vivo Changes in Tonic Extracellular Dopamine Level by Charge-Balancing Multiple Waveform Fast-Scan Cyclic Voltammetry.

PubMed

Oh, Yoonbae; Park, Cheonho; Kim, Do Hyoung; Shin, Hojin; Kang, Yu Min; DeWaele, Mark; Lee, Jeyeon; Min, Hoon-Ki; Blaha, Charles D; Bennet, Kevin E; Kim, In Young; Lee, Kendall H; Jang, Dong Pyo

2016-11-15

Dopamine (DA) modulates central neuronal activity through both phasic (second to second) and tonic (minutes to hours) terminal release. Conventional fast-scan cyclic voltammetry (FSCV), in combination with carbon fiber microelectrodes, has been used to measure phasic DA release in vivo by adopting a background subtraction procedure to remove background capacitive currents. However, measuring tonic changes in DA concentrations using conventional FSCV has been difficult because background capacitive currents are inherently unstable over long recording periods. To measure tonic changes in DA concentrations over several hours, we applied a novel charge-balancing multiple waveform FSCV (CBM-FSCV), combined with a dual background subtraction technique, to minimize temporal variations in background capacitive currents. Using this method, in vitro, charge variations from a reference time point were nearly zero for 48 h, whereas with conventional background subtraction, charge variations progressively increased. CBM-FSCV also demonstrated a high selectivity against 3,4-dihydroxyphenylacetic acid and ascorbic acid, two major chemical interferents in the brain, yielding a sensitivity of 85.40 ± 14.30 nA/μM and limit of detection of 5.8 ± 0.9 nM for DA while maintaining selectivity. Recorded in vivo by CBM-FSCV, pharmacological inhibition of DA reuptake (nomifensine) resulted in a 235 ± 60 nM increase in tonic extracellular DA concentrations, while inhibition of DA synthesis (α-methyl-dl-tyrosine) resulted in a 72.5 ± 4.8 nM decrease in DA concentrations over a 2 h period. This study showed that CBM-FSCV may serve as a unique voltammetric technique to monitor relatively slow changes in tonic extracellular DA concentrations in vivo over a prolonged time period.

Multidimensional Mixing Behavior of Steam-Water Flow in a Downcomer Annulus During LBLOCA Reflood Phase with a Direct Vessel Injection Mode

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kwon, Tae-Soon; Yun, Byong-Jo; Euh, Dong-Jin

Multidimensional thermal-hydraulic behavior in the downcomer annulus of a pressurized water reactor (PWR) vessel with a direct vessel injection mode is presented based on the experimental observation in the MIDAS (multidimensional investigation in downcomer annulus simulation) steam-water test facility. From the steady-state test results to simulate the late reflood phase of a large-break loss-of-coolant accident (LBLOCA), isothermal lines show the multidimensional phenomena of a phasic interaction between steam and water in the downcomer annulus very well. MIDAS is a steam-water separate effect test facility, which is 1/4.93 linearly scaled down to a 1400-MW(electric) PWR type of a nuclear reactor, focusedmore » on understanding multidimensional thermal-hydraulic phenomena in a downcomer annulus with various types of safety injection during the refill or reflood phase of an LBLOCA. The initial and the boundary conditions are scaled from the pretest analysis based on the preliminary calculation using the TRAC code. The superheated steam with a superheating degree of 80 K at a given downcomer pressure of 180 kPa is injected equally through three intact cold legs into the downcomer.« less

Dense encoding of natural odorants by ensembles of sparsely activated neurons in the olfactory bulb

PubMed Central

Gschwend, Olivier; Beroud, Jonathan; Vincis, Roberto; Rodriguez, Ivan; Carleton, Alan

2016-01-01

Sensory information undergoes substantial transformation along sensory pathways, usually encompassing sparsening of activity. In the olfactory bulb, though natural odorants evoke dense glomerular input maps, mitral and tufted (M/T) cells tuning is considered to be sparse because of highly odor-specific firing rate change. However, experiments used to draw this conclusion were either based on recordings performed in anesthetized preparations or used monomolecular odorants presented at arbitrary concentrations. In this study, we evaluated the lifetime and population sparseness evoked by natural odorants by capturing spike temporal patterning of neuronal assemblies instead of individual M/T tonic activity. Using functional imaging and tetrode recordings in awake mice, we show that natural odorants at their native concentrations are encoded by broad assemblies of M/T cells. While reducing odorant concentrations, we observed a reduced number of activated glomeruli representations and consequently a narrowing of M/T tuning curves. We conclude that natural odorants at their native concentrations recruit M/T cells with phasic rather than tonic activity. When encoding odorants in assemblies, M/T cells carry information about a vast number of odorants (lifetime sparseness). In addition, each natural odorant activates a broad M/T cell assembly (population sparseness). PMID:27824096

METHAMPHETAMINE-INDUCED DOPAMINE TERMINAL DEFICITS IN THE NUCLEUS ACCUMBENS ARE EXACERBATED BY REWARD-ASSOCIATED CUES AND ATTENUATED BY CB1 RECEPTOR ANTAGONISM

PubMed Central

Loewinger, Gabriel C.; Beckert, Michael V.; Tejeda, Hugo A.; Cheer, Joseph F.

2012-01-01

Methamphetamine (METH) exposure is primarily associated with deleterious effects to dopaminergic neurons. While several studies have implicated the endocannabinoid system in METH’s locomotor, rewarding and neurochemical effects, a role for this signaling system in METH’s effects on dopamine terminal dynamics has not been elucidated. Given that CB1 receptor blockade reduces the acute potentiation of phasic extracellular dopamine release from other psychomotor stimulant drugs and that the degree of acute METH-induced increases in extracellular dopamine levels is related to the severity of dopamine depletion, we predicted that pretreatment with the CB1 receptor antagonist rimonabant would reduce METH-induced alterations at dopamine terminals. Furthermore, we hypothesized that administration of METH in environments where reward associated-cues were present would potentiate METH’s acute effects on dopamine release in the nucleus accumbens and exacerbate changes in dopamine terminal activity. Fast-scan cyclic voltammetry was used to measure electrically-evoked dopamine release in the nucleus accumbens and revealed markers of compromised dopamine terminal integrity nine days after a single dose of METH. These were exacerbated in animals that received METH in the presence of reward-associated cues, and attenuated in rimonabant-pretreated animals. While these deficits in dopamine dynamics were associated with reduced operant responding on days following METH administration in animals treated with only METH, rimonabant-pretreated animals exhibited levels of operant responding comparable to control. Moreover, dopamine release correlated significantly with changes in lever pressing behavior that occurred on days following METH administration. Together these data suggest that the endocannabinoid system is involved in the subsecond dopaminergic response to METH. PMID:22306525

A fast BK-type KCa current acts as a postsynaptic modulator of temporal selectivity for communication signals.

PubMed

Kohashi, Tsunehiko; Carlson, Bruce A

2014-01-01

Temporal patterns of spiking often convey behaviorally relevant information. Various synaptic mechanisms and intrinsic membrane properties can influence neuronal selectivity to temporal patterns of input. However, little is known about how synaptic mechanisms and intrinsic properties together determine the temporal selectivity of neuronal output. We tackled this question by recording from midbrain electrosensory neurons in mormyrid fish, in which the processing of temporal intervals between communication signals can be studied in a reduced in vitro preparation. Mormyrids communicate by varying interpulse intervals (IPIs) between electric pulses. Within the midbrain posterior exterolateral nucleus (ELp), the temporal patterns of afferent spike trains are filtered to establish single-neuron IPI tuning. We performed whole-cell recording from ELp neurons in a whole-brain preparation and examined the relationship between intrinsic excitability and IPI tuning. We found that spike frequency adaptation of ELp neurons was highly variable. Postsynaptic potentials (PSPs) of strongly adapting (phasic) neurons were more sharply tuned to IPIs than weakly adapting (tonic) neurons. Further, the synaptic filtering of IPIs by tonic neurons was more faithfully converted into variation in spiking output, particularly at short IPIs. Pharmacological manipulation under current- and voltage-clamp revealed that tonic firing is mediated by a fast, large-conductance Ca(2+)-activated K(+) (KCa) current (BK) that speeds up action potential repolarization. These results suggest that BK currents can shape the temporal filtering of sensory inputs by modifying both synaptic responses and PSP-to-spike conversion. Slow SK-type KCa currents have previously been implicated in temporal processing. Thus, both fast and slow KCa currents can fine-tune temporal selectivity.

How To Help Inattentive Students Find Success in School: Getting the Homework Back from the Dog.

ERIC Educational Resources Information Center

Welton, Evonn N.

1999-01-01

Explores the characteristics of inattention in school children and suggests strategies for teachers. Focuses on the psychological mechanisms of arousal (both tonic and phasic), selective attention, and divided attention. Characteristics of specific attentional problems are listed along with specific suggested teaching strategies. (DB)

Medication Impairs Probabilistic Classification Learning in Parkinson's Disease

ERIC Educational Resources Information Center

Jahanshahi, Marjan; Wilkinson, Leonora; Gahir, Harpreet; Dharminda, Angeline; Lagnado, David A.

2010-01-01

In Parkinson's disease (PD), it is possible that tonic increase of dopamine associated with levodopa medication overshadows phasic release of dopamine, which is essential for learning. Thus while the motor symptoms of PD are improved with levodopa medication, learning would be disrupted. To test this hypothesis, we investigated the effect of…

Testing the Behavioral Interaction and Integration of Attentional Networks

ERIC Educational Resources Information Center

Fan, Jin; Gu, Xiaosi; Guise, Kevin G.; Liu, Xun; Fossella, John; Wang, Hongbin; Posner, Michael I.

2009-01-01

One current conceptualization of attention subdivides it into functions of alerting, orienting, and executive control. Alerting describes the function of tonically maintaining the alert state and phasically responding to a warning signal. Automatic and voluntary orienting are involved in the selection of information among multiple sensory inputs.…

Phasic Affective Modulation of Semantic Priming

ERIC Educational Resources Information Center

Topolinski, Sascha; Deutsch, Roland

2013-01-01

The present research demonstrates that very brief variations in affect, being around 1 s in length and changing from trial to trial independently from semantic relatedness of primes and targets, modulate the amount of semantic priming. Implementing consonant and dissonant chords (Experiments 1 and 5), naturalistic sounds (Experiment 2), and visual…

Effects of backscatter of brief high intensity light on physiological responses of instrument-rated pilots and non-pilots.

DOT National Transportation Integrated Search

1972-03-01

Thirty-nine human subjects were exposed to reptitive backscatter light stimulation (off a white wall or fog) from a Grimes capacitance discharge airplane anticollision light flashing at 1.27 Hertz. Both tonic (light stimulus absent) and phasic (light...

Electromyographic activity of strap and cricothyroid muscles in pitch change.

PubMed

Roubeau, B; Chevrie-Muller, C; Lacau Saint Guily, J

1997-05-01

The EMG activity of the cricothyroid muscle (CT) and the three extrinsic laryngeal muscles (thyohyoid, TH; sternothyroid, ST, and sternohyoid, SH) were recorded throughout the voice range of one female and one male subject, both untrained singers. The voice range was examined using rising and falling glissandos (production of a sustained sound with progressive and continuous variation of fundamental frequency). Muscle activity was observed at various pitches during the glissandos. The strap muscle activity during the production of glissandos appears to be synergistic. At the lowest frequency, the CT is inactive but strap muscles (TH, ST, SH) are active. As frequency increases, strap muscle activity decreases while the CT controls frequency in the middle of the range. At higher frequencies the strap muscles once again become active. This activity might depend on the vocal vibratory mechanism involved. The role of the strap muscles at high pitches is a widely debated point but it seems that in some way they control the phenomena relevant to the rising pitch. The phasic-type strap muscle activity contrasts with the tonic-type activity of the CT. The CT closely controls the frequency, while the straps are not directly linked to the pitch but rather to the evolution of the frequency of voice production (speaking voice, singing voice, held notes, glissandos, trillo, vibrato, etc.).

Real-time monitoring of electrically evoked catecholamine signals in the songbird striatum using in vivo fast-scan cyclic voltammetry.

PubMed

Smith, Amanda R; Garris, Paul A; Casto, Joseph M

2015-01-01

Fast-scan cyclic voltammetry is a powerful technique for monitoring rapid changes in extracellular neurotransmitter levels in the brain. In vivo fast-scan cyclic voltammetry has been used extensively in mammalian models to characterize dopamine signals in both anesthetized and awake preparations, but has yet to be applied to a non-mammalian vertebrate. The goal of this study was to establish in vivo fast-scan cyclic voltammetry in a songbird, the European starling, to facilitate real-time measurements of extracellular catecholamine levels in the avian striatum. In urethane-anesthetized starlings, changes in catecholamine levels were evoked by electrical stimulation of the ventral tegmental area and measured at carbon-fiber microelectrodes positioned in the medial and lateral striata. Catecholamines were elicited by different stimulations, including trains related to phasic dopamine signaling in the rat, and were analyzed to quantify presynaptic mechanisms governing exocytotic release and neuronal uptake. Evoked extracellular catecholamine dynamics, maximal amplitude of the evoked catecholamine signal, and parameters for catecholamine release and uptake did not differ between striatal regions and were similar to those determined for dopamine in the rat dorsomedial striatum under similar conditions. Chemical identification of measured catecholamine by its voltammogram was consistent with the presence of both dopamine and norepinephrine in striatal tissue content. However, the high ratio of dopamine to norepinephrine in tissue content and the greater sensitivity of the carbon-fiber microelectrode to dopamine compared to norepinephrine favored the measurement of dopamine. Thus, converging evidence suggests that dopamine was the predominate analyte of the electrically evoked catecholamine signal measured in the striatum by fast-scan cyclic voltammetry. Overall, comparisons between the characteristics of these evoked signals suggested a similar presynaptic regulation of dopamine in the starling and rat striatum. Fast-scan cyclic voltammetry thus has the potential to be an invaluable tool for investigating the neural underpinnings of behavior in birds. Copyright © 2015 Elsevier B.V. All rights reserved.

Real-time monitoring of electrically evoked catecholamine signals in the songbird striatum using in vivo fast-scan cyclic voltammetry

PubMed Central

Smith, Amanda R.; Garris, Paul A.; Casto, Joseph M.

2015-01-01

Fast-scan cyclic voltammetry is a powerful technique for monitoring rapid changes in extracellular neurotransmitter levels in the brain. In vivo fast-scan cyclic voltammetry has been used extensively in mammalian models to characterize dopamine signals in both anesthetized and awake preparations, but has yet to be applied to a non-mammalian vertebrate. The goal of this study was to establish in vivo fast-scan cyclic voltammetry in a songbird, the European starling, to facilitate real-time measurements of extracellular catecholamine levels in the avian striatum. In urethane-anesthetized starlings, changes in catecholamine levels were evoked by electrical stimulation of the ventral tegmental area and measured at carbon-fiber microelectrodes positioned in the medial and lateral striata. Catecholamines were elicited by different stimulations, including trains related to phasic dopamine signaling in the rat, and were analyzed to quantify presynaptic mechanisms governing exocytotic release and neuronal uptake. Evoked extracellular catecholamine dynamics, maximal amplitude of the evoked catecholamine signal, and parameters for catecholamine release and uptake did not differ between striatal regions and were similar to those determined for dopamine in the rat dorsomedial striatum under similar conditions. Chemical identification of measured catecholamine by its voltammogram was consistent with the presence of both dopamine and norepinephrine in striatal tissue content. However, the high ratio of dopamine to norepinephrine in tissue content and the greater sensitivity of the carbon-fiber microelectrode to dopamine compared to norepinephrine favored the measurement of dopamine. Thus, converging evidence suggests that dopamine was the predominate analyte of the electrically evoked catecholamine signal measured in the striatum by fast-scan cyclic voltammetry. Overall, comparisons between the characteristics of these evoked signals suggested a similar presynaptic regulation of dopamine in the starling and rat striatum. Fast-scan cyclic voltammetry thus has the potential to be an invaluable tool for investigating the neural underpinnings of behavior in birds. PMID:25900708

Separation of active laccases from Pleurotus sapidus culture supernatant using aqueous two-phase systems in centrifugal partition chromatography.

PubMed

Schwienheer, C; Prinz, A; Zeiner, T; Merz, J

2015-10-01

For the production of bio active compounds, e.g., active enzymes or antibodies, a conserved purification process with a minimum loss of active compounds is necessary. In centrifugal partition chromatography (CPC), the separation effect is based on the different distribution of the components to be separated between two immiscible liquid phases. Thereby, one liquid phase is kept stationary in chambers by a centrifugal field and the mobile phase is pumped through via connecting ducts. Aqueous two phase systems (ATPS) are known to provide benign conditions for biochemical products and seem to be promising when used in CPC for purification tasks. However, it is not known if active biochemical compounds can "survive" the conditions in a CPC where strong shear forces can occur due to the two-phasic flow under centrifugal forces. Therefore, this aspect has been faced within this study by the separation of active laccases from a fermentation broth of Pleurotus sapidus. After selecting a suitable ATPS and operating conditions, the activity yield was calculated and the preservation of the active enzymes could be observed. Therefore, CPC could be shown as potentially suitable for the purification of bio-active compounds. Copyright © 2015 Elsevier B.V. All rights reserved.

Aspects of the homeostaic plasticity of GABAA receptor-mediated inhibition

PubMed Central

Mody, Istvan

2005-01-01

Plasticity of ligand-gated ion channels plays a critical role in nervous system development, circuit formation and refinement, and pathological processes. Recent advances have mainly focused on the plasticity of channels gated by excitatory amino acids, including their acclaimed role in learning and memory. These receptors, together with voltage-gated ion channels, have also been known to be subjected to a homeostatic form of plasticity that prevents destabilization of the neurone's function and that of the network during various physiological processes. To date, the plasticity of GABAA receptors has been examined mainly from a developmental and a pathological point of view. Little is known about homeostatic mechanisms governing their plasticity. This review summarizes some of the findings on the homeostatic plasticity of tonic and phasic inhibitory activity. PMID:15528237

Understanding dopamine and reinforcement learning: the dopamine reward prediction error hypothesis.

PubMed

Glimcher, Paul W

2011-09-13

A number of recent advances have been achieved in the study of midbrain dopaminergic neurons. Understanding these advances and how they relate to one another requires a deep understanding of the computational models that serve as an explanatory framework and guide ongoing experimental inquiry. This intertwining of theory and experiment now suggests very clearly that the phasic activity of the midbrain dopamine neurons provides a global mechanism for synaptic modification. These synaptic modifications, in turn, provide the mechanistic underpinning for a specific class of reinforcement learning mechanisms that now seem to underlie much of human and animal behavior. This review describes both the critical empirical findings that are at the root of this conclusion and the fantastic theoretical advances from which this conclusion is drawn.

Understanding dopamine and reinforcement learning: The dopamine reward prediction error hypothesis

PubMed Central

Glimcher, Paul W.

2011-01-01

A number of recent advances have been achieved in the study of midbrain dopaminergic neurons. Understanding these advances and how they relate to one another requires a deep understanding of the computational models that serve as an explanatory framework and guide ongoing experimental inquiry. This intertwining of theory and experiment now suggests very clearly that the phasic activity of the midbrain dopamine neurons provides a global mechanism for synaptic modification. These synaptic modifications, in turn, provide the mechanistic underpinning for a specific class of reinforcement learning mechanisms that now seem to underlie much of human and animal behavior. This review describes both the critical empirical findings that are at the root of this conclusion and the fantastic theoretical advances from which this conclusion is drawn. PMID:21389268

Neuropharmacology of cognition and memory: a unifying theory of neuromodulator imbalance in psychiatry and amnesia.

PubMed

Vakalopoulos, Costa

2006-01-01

The case of HM, a man with intractable epilepsy who became amnesic following bilateral medial temporal lobe surgery nearly half a century ago has instigated ongoing research and theoretical speculation on the nature of memory and the role of the hippocampus. Neuropsychological testing showed that although HM had extensive anterograde memory loss he could still acquire motor and cognitive skills implicitly, but could not remember the context of this learning. This has lead to declarative and procedural descriptions of the memory process. Cholinergic and monoaminergic neurotransmitter systems have also been implicated in the memory process and anticholinergic drugs traditionally have been associated with impairment of declarative memory. The cholinergic hypothesis of Alzheimer's disease is a classic example of an application of these neuropharmacological findings. In schizophrenia, preattentive deficits have been amply demonstrated by unconscious priming studies. Memory processes are also impaired in these patients. Dopamine, glutamate and even cholinergic dysfunction has been implicated in the clinical picture of schizophrenia. The present paper will attempt to bring together both the anatomical and pharmacological data from these disparate fields of research under a cohesive theory of cognition and memory. A hypothesis is presented for an inverse relationship between monoaminergic and cholinergic systems in the modulation of implicit (unconscious) and explicit (conscious) cognitive processes. It is postulated that muscarinic cholinergic receptors and monoaminergic systems facilitate unconscious and conscious processes, respectively, and they disfacilitate conscious and unconscious processes, respectively (the purported inverse relationship). In fact, the muscarinic and monoaminergic modulations of a neural network are proposed to be finely balanced such that, if, the activity of one receptor system is modified then this by necessity has effects on the other system. It takes into account receptor subtypes and their effects mediated through excitatory and inhibitory G-protein complexes. For example, m1/D2 and D1/m4 paired receptor subtypes, colocalized on separate neurons would have opposing functional effects. A theory is then presented that the critical underlying pathophysiology of schizophrenia involves a hypofunctional muscarinic cholinergic system, which induces abnormal facilitation of monoaminergic subsystems such as dopamine (e.g., a decrease in m1R function would potentiate D2R function). This extends the idea of an inverted U function for optimal monoaminergic concentrations. Not only would this impair unconscious preattentive processes, but according to the hypothesis, explicit cognition as well including memory deficits and would underlie the mechanism of psychosis. Contrary to current thinking a different view is also presented for the role of the hippocampus in the memory process. It is postulated that long-term explicit memory traces in the neocortex are laid down by phasic coactivation of forebrain projecting monoaminergic systems above some basal firing rate, such as the rostral serotonergic raphe, which projects diffusely to the cortex and according to a modified Hebbian principle. This is the proposed principal function of the hippocampal theta rhythm. The phasic activation of the cholinergic basal forebrain is mediated by projections from a separate cortical structure, possibly the lateral prefrontal cortex. Phasic muscarinic receptor activation is proposed to strengthen implicit memory traces (at a synaptic level) in the neocortex. Thus, the latter are spared by medial temporal surgery explaining the dissociation of explicit from implicit memory.

GABA regulates synaptic integration of newly generated neurons in the adult brain

NASA Astrophysics Data System (ADS)

Ge, Shaoyu; Goh, Eyleen L. K.; Sailor, Kurt A.; Kitabatake, Yasuji; Ming, Guo-Li; Song, Hongjun

2006-02-01

Adult neurogenesis, the birth and integration of new neurons from adult neural stem cells, is a striking form of structural plasticity and highlights the regenerative capacity of the adult mammalian brain. Accumulating evidence suggests that neuronal activity regulates adult neurogenesis and that new neurons contribute to specific brain functions. The mechanism that regulates the integration of newly generated neurons into the pre-existing functional circuitry in the adult brain is unknown. Here we show that newborn granule cells in the dentate gyrus of the adult hippocampus are tonically activated by ambient GABA (γ-aminobutyric acid) before being sequentially innervated by GABA- and glutamate-mediated synaptic inputs. GABA, the major inhibitory neurotransmitter in the adult brain, initially exerts an excitatory action on newborn neurons owing to their high cytoplasmic chloride ion content. Conversion of GABA-induced depolarization (excitation) into hyperpolarization (inhibition) in newborn neurons leads to marked defects in their synapse formation and dendritic development in vivo. Our study identifies an essential role for GABA in the synaptic integration of newly generated neurons in the adult brain, and suggests an unexpected mechanism for activity-dependent regulation of adult neurogenesis, in which newborn neurons may sense neuronal network activity through tonic and phasic GABA activation.

Probing the Energy Landscape of Activation Gating of the Bacterial Potassium Channel KcsA

PubMed Central

Linder, Tobias; de Groot, Bert L.; Stary-Weinzinger, Anna

2013-01-01

The bacterial potassium channel KcsA, which has been crystallized in several conformations, offers an ideal model to investigate activation gating of ion channels. In this study, essential dynamics simulations are applied to obtain insights into the transition pathways and the energy profile of KcsA pore gating. In agreement with previous hypotheses, our simulations reveal a two phasic activation gating process. In the first phase, local structural rearrangements in TM2 are observed leading to an intermediate channel conformation, followed by large structural rearrangements leading to full opening of KcsA. Conformational changes of a highly conserved phenylalanine, F114, at the bundle crossing region are crucial for the transition from a closed to an intermediate state. 3.9 µs umbrella sampling calculations reveal that there are two well-defined energy barriers dividing closed, intermediate, and open channel states. In agreement with mutational studies, the closed state was found to be energetically more favorable compared to the open state. Further, the simulations provide new insights into the dynamical coupling effects of F103 between the activation gate and the selectivity filter. Investigations on individual subunits support cooperativity of subunits during activation gating. PMID:23658510

Oxygen Level and LFP in Task-Positive and Task-Negative Areas: Bridging BOLD fMRI and Electrophysiology

PubMed Central

Bentley, William J.; Li, Jingfeng M.; Snyder, Abraham Z.; Raichle, Marcus E.; Snyder, Lawrence H.

2016-01-01

The human default mode network (DMN) shows decreased blood oxygen level dependent (BOLD) signals in response to a wide range of attention-demanding tasks. Our understanding of the specifics regarding the neural activity underlying these “task-negative” BOLD responses remains incomplete. We paired oxygen polarography, an electrode-based oxygen measurement technique, with standard electrophysiological recording to assess the relationship of oxygen and neural activity in task-negative posterior cingulate cortex (PCC), a hub of the DMN, and visually responsive task-positive area V3 in the awake macaque. In response to engaging visual stimulation, oxygen, LFP power, and multi-unit activity in PCC showed transient activation followed by sustained suppression. In V3, oxygen, LFP power, and multi-unit activity showed an initial phasic response to the stimulus followed by sustained activation. Oxygen responses were correlated with LFP power in both areas, although the apparent hemodynamic coupling between oxygen level and electrophysiology differed across areas. Our results suggest that oxygen responses reflect changes in LFP power and multi-unit activity and that either the coupling of neural activity to blood flow and metabolism differs between PCC and V3 or computing a linear transformation from a single LFP band to oxygen level does not capture the true physiological process. PMID:25385710

40 CFR 761.1 - Applicability.

Code of Federal Regulations, 2011 CFR

2011-07-01

... concentrations shall be determined on a weight-per-weight basis (e.g., milligrams per kilogram), or for liquids, on a weight-per-volume basis (e.g., milligrams per liter) if the density of the liquid is also... µg/100 cm2. (4) PCBs can be found in liquid, non-liquid and multi-phasic (combinations of liquid and...

Left Atrial Mechanical Functions in Professional Soccer Players: A Pilot Study

ERIC Educational Resources Information Center

Kartal, Alper; Güngör, Hasan; Kartal, Resat; Ergin, Esin

2017-01-01

Long-term regular exercise is associated with physiologic and morphologic alterations in the heart chambers. The aim of this study to evaluate left atrium (LA) phasic functions in professional football players and compare with control subjects. Left atrial volume was calculated at end-systole (Vmax), end-diastole and pre-atrial contraction by…

Neural connectivity in Internet gaming disorder and alcohol use disorder: A resting-state EEG coherence study.

PubMed

Park, Su Mi; Lee, Ji Yoon; Kim, Yeon Jin; Lee, Jun-Young; Jung, Hee Yeon; Sohn, Bo Kyung; Kim, Dai Jin; Choi, Jung-Seok

2017-05-02

The present study compared neural connectivity and the level of phasic synchronization between neural populations in patients with Internet gaming disorder (IGD), patients with alcohol use disorder (AUD), and healthy controls (HCs) using resting-state electroencephalography (EEG) coherence analyses. For this study, 92 adult males were categorized into three groups: IGD (n = 30), AUD (n = 30), and HC (n = 32). The IGD group exhibited increased intrahemispheric gamma (30-40 Hz) coherence compared to the AUD and HC groups regardless of psychological features (e.g., depression, anxiety, and impulsivity) and right fronto-central gamma coherence positively predicted the scores of the Internet addiction test in all groups. In contrast, the AUD group showed marginal tendency of increased intrahemispheric theta (4-8 Hz) coherence relative to the HC group and this was dependent on the psychological features. The present findings indicate that patients with IGD and AUD exhibit different neurophysiological patterns of brain connectivity and that an increase in the fast phasic synchrony of gamma coherence might be a core neurophysiological feature of IGD.

Mechanochemical coupling and bi-phasic force-velocity dependence in the ultra-fast ring ATPase SpoIIIE

DOE Office of Scientific and Technical Information (OSTI.GOV)

Liu, Ninning; Chistol, Gheorghe; Cui, Yuanbo

Multi-subunit ring-shaped ATPases are molecular motors that harness chemical free energy to perform vital mechanical tasks such as polypeptide translocation, DNA unwinding, and chromosome segregation. Previously we reported the intersubunit coordination and stepping behavior of the hexameric ring-shaped ATPase SpoIIIE (Liu et al., 2015). Here we use optical tweezers to characterize the motor’s mechanochemistry. Analysis of the motor response to external force at various nucleotide concentrations identifies phosphate release as the likely force-generating step. Analysis of SpoIIIE pausing indicates that pauses are off-pathway events. Characterization of SpoIIIE slipping behavior reveals that individual motor subunits engage DNA upon ATP binding. Furthermore,more » we find that SpoIIIE’s velocity exhibits an intriguing bi-phasic dependence on force. We hypothesize that this behavior is an adaptation of ultra-fast motors tasked with translocating DNA from which they must also remove DNA-bound protein roadblocks. Based on these results, we formulate a comprehensive mechanochemical model for SpoIIIE.« less

Stress Response and Cognitive Performance Modulation in Classroom versus Natural Environments: A Quasi-Experimental Pilot Study with Children.

PubMed

Mygind, Lærke; Stevenson, Matt P; Liebst, Lasse S; Konvalinka, Ivana; Bentsen, Peter

2018-05-28

Stress during childhood can have mental and somatic health influences that track throughout life. Previous research attributes stress-reducing effects to natural environments, but has mainly focused on adults and often following leisurely relaxation in natural environments. This pilot study explores the impact of natural environments on stress response during rest and mental load and cognitive performance in 47 children aged 10⁻12 years in a school context. Heart rate variability measures indexing tonic, event, and phasic vagal tone and attention scores were compared across classroom and natural environments. Tonic vagal tone was higher in the natural environment than the classrooms, but no differences were found in event or phasic vagal tone or cognitive performance measures. These findings suggest a situational aspect of the conditions under which natural environments may give rise to stress-buffering influences. Further research is warranted to understand the potential benefits in a real-life context, in particular with respect to the underpinning mechanisms and effects of accumulated exposure over time in settings where children spend large proportions of time in natural environments.

The Role of the Right Dorsolateral Prefrontal Cortex in Phasic Alertness: Evidence from a Contingent Negative Variation and Repetitive Transcranial Magnetic Stimulation Study

PubMed Central

Mannarelli, Daniela; Pauletti, Caterina; Grippo, Antonello; Amantini, Aldo; Augugliaro, Vito; Currà, Antonio; Missori, Paolo; Locuratolo, Nicoletta; De Lucia, Maria C.; Rinalduzzi, Steno; Fattapposta, Francesco

2015-01-01

Phasic alertness represents the ability to increase response readiness to a target following an external warning stimulus. Specific networks in the frontal and parietal regions appear to be involved in the alert state. In this study, we examined the role of the right dorsolateral prefrontal cortex (DLPFC) during the attentional processing of a stimulus using a cued double-choice reaction time task. The evaluation of these processes was conducted by means of Event-Related Potentials (ERPs), in particular by using the Contingent Negative Variation (CNV), and repetitive 1-Hz Transcranial Magnetic Stimulation (rTMS). Transient virtual inhibition of the right DLPFC induced by real 1-Hz rTMS stimulation led to a significant decrease in total CNV and W1-CNV areas if compared with the basal and post-sham rTMS conditions. Reaction times (RTs) did not decrease after inhibitory rTMS, but they did improve after sham stimulation. These results suggest that the right DLPFC plays a crucial role in the genesis and maintenance of the alerting state and learning processes. PMID:26090234

Phasic and tonic alerting in mild cognitive impairment: A preliminary study.

PubMed

Martella, Diana; Manzanares, Salvadora; Campoy, Guillermo; Roca, Javier; Antúnez, Carmen; Fuentes, Luis J

2014-01-01

In this preliminary study we assessed the functioning of the different attentional networks in mild cognitive impairment (MCI) patients, taking as theoretical framework the Posner's cognitive neuroscience approach. Two groups of participants were tested in a single short experiment: 20 MCI patients (6 amnestic, 6 non-amnestic and 8 multiple-domain) and 18 healthy matched controls (HC). For attentional assessment we used a version of the Attention Network Test (the ANTI-V) that provided not only a score of the orienting, the executive, and the alerting networks and their interactions, but also an independent measure of vigilance (tonic alerting). The results showed that all subtypes of MCI patients exhibited a selective impairment in the tonic component of alerting, as indexed by a decrease in the d' sensitivity index, and their performance in executive network increased up to the HC group level when phasic alerting was provided by a warning tone. Our findings suggest that a core attentional deficit, especially the endogenous component of alerting, may significantly contribute to the behavioral and cognitive deficits associated with MCI. Copyright © 2013 Elsevier Inc. All rights reserved.

Mechanochemical coupling and bi-phasic force-velocity dependence in the ultra-fast ring ATPase SpoIIIE

DOE PAGES

Liu, Ninning; Chistol, Gheorghe; Cui, Yuanbo; ...

2018-03-05

Multi-subunit ring-shaped ATPases are molecular motors that harness chemical free energy to perform vital mechanical tasks such as polypeptide translocation, DNA unwinding, and chromosome segregation. Previously we reported the intersubunit coordination and stepping behavior of the hexameric ring-shaped ATPase SpoIIIE (Liu et al., 2015). Here we use optical tweezers to characterize the motor’s mechanochemistry. Analysis of the motor response to external force at various nucleotide concentrations identifies phosphate release as the likely force-generating step. Analysis of SpoIIIE pausing indicates that pauses are off-pathway events. Characterization of SpoIIIE slipping behavior reveals that individual motor subunits engage DNA upon ATP binding. Furthermore,more » we find that SpoIIIE’s velocity exhibits an intriguing bi-phasic dependence on force. We hypothesize that this behavior is an adaptation of ultra-fast motors tasked with translocating DNA from which they must also remove DNA-bound protein roadblocks. Based on these results, we formulate a comprehensive mechanochemical model for SpoIIIE.« less

Phasic affective modulation of semantic priming.

PubMed

Topolinski, Sascha; Deutsch, Roland

2013-03-01

The present research demonstrates that very brief variations in affect, being around 1 s in length and changing from trial to trial independently from semantic relatedness of primes and targets, modulate the amount of semantic priming. Implementing consonant and dissonant chords (Experiments 1 and 5), naturalistic sounds (Experiment 2), and visual facial primes (Experiment 3) in an (in)direct semantic priming paradigm, as well as brief facial feedback in a summative priming paradigm (Experiment 4), yielded increased priming effects under brief positive compared to negative affect. Furthermore, this modulation took place on the level of semantic spreading rather than on strategic mechanisms (Experiment 5). Alternative explanations such as distraction, motivation, arousal, and cognitive tuning could be ruled out. This phasic affective modulation constitutes a mechanism overlooked thus far that may contaminate priming effects in all priming paradigms that involve affective stimuli. Furthermore, this mechanism provides a novel explanation for the observation that priming effects are usually larger for positive than for negative stimuli. Finally, it has important implications for linguistic research, by suggesting that association norms may be biased for affective words. (c) 2013 APA, all rights reserved.

Diminished neural responses predict enhanced intrinsic motivation and sensitivity to external incentive.

PubMed

Marsden, Karen E; Ma, Wei Ji; Deci, Edward L; Ryan, Richard M; Chiu, Pearl H

2015-06-01

The duration and quality of human performance depend on both intrinsic motivation and external incentives. However, little is known about the neuroscientific basis of this interplay between internal and external motivators. Here, we used functional magnetic resonance imaging to examine the neural substrates of intrinsic motivation, operationalized as the free-choice time spent on a task when this was not required, and tested the neural and behavioral effects of external reward on intrinsic motivation. We found that increased duration of free-choice time was predicted by generally diminished neural responses in regions associated with cognitive and affective regulation. By comparison, the possibility of additional reward improved task accuracy, and specifically increased neural and behavioral responses following errors. Those individuals with the smallest neural responses associated with intrinsic motivation exhibited the greatest error-related neural enhancement under the external contingency of possible reward. Together, these data suggest that human performance is guided by a "tonic" and "phasic" relationship between the neural substrates of intrinsic motivation (tonic) and the impact of external incentives (phasic).

Cocaine inhibition of nicotinic acetylcholine receptors influences dopamine release

PubMed Central

Acevedo-Rodriguez, Alexandra; Zhang, Lifen; Zhou, Fuwen; Gong, Suzhen; Gu, Howard; De Biasi, Mariella; Zhou, Fu-Ming; Dani, John A.

2014-01-01

Nicotinic acetylcholine receptors (nAChRs) potently regulate dopamine (DA) release in the striatum and alter cocaine's ability to reinforce behaviors. Since cocaine is a weak nAChR inhibitor, we hypothesized that cocaine may alter DA release by inhibiting the nAChRs in DA terminals in the striatum and thus contribute to cocaine's reinforcing properties primarily associated with the inhibition of DA transporters. We found that biologically relevant concentrations of cocaine can mildly inhibit nAChR-mediated currents in midbrain DA neurons and consequently alter DA release in the dorsal and ventral striatum. At very high concentrations, cocaine also inhibits voltage-gated Na channels in DA neurons. Furthermore, our results show that partial inhibition of nAChRs by cocaine reduces evoked DA release. This diminution of DA release via nAChR inhibition more strongly influences release evoked at low or tonic stimulation frequencies than at higher (phasic) stimulation frequencies, particularly in the dorsolateral striatum. This cocaine-induced shift favoring phasic DA release may contribute to the enhanced saliency and motivational value of cocaine-associated memories and behaviors. PMID:25237305

Dynamic divisive normalization predicts time-varying value coding in decision-related circuits.

PubMed

Louie, Kenway; LoFaro, Thomas; Webb, Ryan; Glimcher, Paul W

2014-11-26

Normalization is a widespread neural computation, mediating divisive gain control in sensory processing and implementing a context-dependent value code in decision-related frontal and parietal cortices. Although decision-making is a dynamic process with complex temporal characteristics, most models of normalization are time-independent and little is known about the dynamic interaction of normalization and choice. Here, we show that a simple differential equation model of normalization explains the characteristic phasic-sustained pattern of cortical decision activity and predicts specific normalization dynamics: value coding during initial transients, time-varying value modulation, and delayed onset of contextual information. Empirically, we observe these predicted dynamics in saccade-related neurons in monkey lateral intraparietal cortex. Furthermore, such models naturally incorporate a time-weighted average of past activity, implementing an intrinsic reference-dependence in value coding. These results suggest that a single network mechanism can explain both transient and sustained decision activity, emphasizing the importance of a dynamic view of normalization in neural coding. Copyright © 2014 the authors 0270-6474/14/3416046-12$15.00/0.

Amylin Modulates the Mesolimbic Dopamine System to Control Energy Balance

PubMed Central

Mietlicki-Baase, Elizabeth G; Reiner, David J; Cone, Jackson J; Olivos, Diana R; McGrath, Lauren E; Zimmer, Derek J; Roitman, Mitchell F; Hayes, Matthew R

2015-01-01

Amylin acts in the CNS to reduce feeding and body weight. Recently, the ventral tegmental area (VTA), a mesolimbic nucleus important for food intake and reward, was identified as a site-of-action mediating the anorectic effects of amylin. However, the long-term physiological relevance and mechanisms mediating the intake-suppressive effects of VTA amylin receptor (AmyR) activation are unknown. Data show that the core component of the AmyR, the calcitonin receptor (CTR), is expressed on VTA dopamine (DA) neurons and that activation of VTA AmyRs reduces phasic DA in the nucleus accumbens core (NAcC). Suppression in NAcC DA mediates VTA amylin-induced hypophagia, as combined NAcC D1/D2 receptor agonists block the intake-suppressive effects of VTA AmyR activation. Knockdown of VTA CTR via adeno-associated virus short hairpin RNA resulted in hyperphagia and exacerbated body weight gain in rats maintained on high-fat diet. Collectively, these findings show that VTA AmyR signaling controls energy balance by modulating mesolimbic DA signaling. PMID:25035079

Tonic Inhibitory Control of Dentate Gyrus Granule Cells by α5-Containing GABAA Receptors Reduces Memory Interference.

PubMed

Engin, Elif; Zarnowska, Ewa D; Benke, Dietmar; Tsvetkov, Evgeny; Sigal, Maksim; Keist, Ruth; Bolshakov, Vadim Y; Pearce, Robert A; Rudolph, Uwe

2015-10-07

Interference between similar or overlapping memories formed at different times poses an important challenge on the hippocampal declarative memory system. Difficulties in managing interference are at the core of disabling cognitive deficits in neuropsychiatric disorders. Computational models have suggested that, in the normal brain, the sparse activation of the dentate gyrus granule cells maintained by tonic inhibitory control enables pattern separation, an orthogonalization process that allows distinct representations of memories despite interference. To test this mechanistic hypothesis, we generated mice with significantly reduced expression of the α5-containing GABAA (α5-GABAARs) receptors selectively in the granule cells of the dentate gyrus (α5DGKO mice). α5DGKO mice had reduced tonic inhibition of the granule cells without any change in fast phasic inhibition and showed increased activation in the dentate gyrus when presented with novel stimuli. α5DGKO mice showed impairments in cognitive tasks characterized by high interference, without any deficiencies in low-interference tasks, suggesting specific impairment of pattern separation. Reduction of fast phasic inhibition in the dentate gyrus through granule cell-selective knock-out of α2-GABAARs or the knock-out of the α5-GABAARs in the downstream CA3 area did not detract from pattern separation abilities, which confirms the anatomical and molecular specificity of the findings. In addition to lending empirical support to computational hypotheses, our findings have implications for the treatment of interference-related cognitive symptoms in neuropsychiatric disorders, particularly considering the availability of pharmacological agents selectively targeting α5-GABAARs. Interference between similar memories poses a significant limitation on the hippocampal declarative memory system, and impaired interference management is a cognitive symptom in many disorders. Thus, understanding mechanisms of successful interference management or processes that can lead to interference-related memory problems has high theoretical and translational importance. This study provides empirical evidence that tonic inhibition in the dentate gyrus (DG), which maintains sparseness of neuronal activation in the DG, is essential for management of interference. The specificity of findings to tonic, but not faster, more transient types of neuronal inhibition and to the DG, but not the neighboring brain areas, is presented through control experiments. Thus, the findings link interference management to a specific mechanism, proposed previously by computational models. Copyright © 2015 the authors 0270-6474/15/3513699-15$15.00/0.

Musician's cramp as manifestation of maladaptive brain plasticity: arguments from instrumental differences.

PubMed

Altenmüller, Eckart; Baur, Volker; Hofmann, Aurélie; Lim, Vanessa K; Jabusch, Hans-Christian

2012-04-01

Musician's cramp is a task-specific movement disorder that presents itself as muscular incoordination or loss of voluntary motor control of extensively trained movements while a musician is playing the instrument. It is characterized by task specificity and gender bias, affecting significantly more males than females. The etiology is multifaceted: a combination of a genetic predisposition, termed endophenotype, and behavioral triggering factors being the leading features for the manifestation of the disorder. We present epidemiological data from 591 musician patients from our outpatient clinic demonstrating an influence of fine-motor requirements on the manifestation of dystonia. Brass, guitar, and woodwind players were at greater risk than other instrumentalists. High temporospatial precision of movement patterns, synchronous demands on tonic and phasic muscular activation, in combination with fine-motor burdens of using the dominant hand in daily life activities, constitute as triggering factors for the disorder and may explain why different body parts are affected. © 2012 New York Academy of Sciences.

Four-dimensional maps of the human somatosensory system

PubMed Central

Avanzini, Pietro; Abdollahi, Rouhollah O.; Sartori, Ivana; Caruana, Fausto; Pelliccia, Veronica; Casaceli, Giuseppe; Mai, Roberto; Lo Russo, Giorgio; Rizzolatti, Giacomo; Orban, Guy A.

2016-01-01

A fine-grained description of the spatiotemporal dynamics of human brain activity is a major goal of neuroscientific research. Limitations in spatial and temporal resolution of available noninvasive recording and imaging techniques have hindered so far the acquisition of precise, comprehensive four-dimensional maps of human neural activity. The present study combines anatomical and functional data from intracerebral recordings of nearly 100 patients, to generate highly resolved four-dimensional maps of human cortical processing of nonpainful somatosensory stimuli. These maps indicate that the human somatosensory system devoted to the hand encompasses a widespread network covering more than 10% of the cortical surface of both hemispheres. This network includes phasic components, centered on primary somatosensory cortex and neighboring motor, premotor, and inferior parietal regions, and tonic components, centered on opercular and insular areas, and involving human parietal rostroventral area and ventral medial-superior-temporal area. The technique described opens new avenues for investigating the neural basis of all levels of cortical processing in humans. PMID:26976579

Four-dimensional maps of the human somatosensory system.

PubMed

Avanzini, Pietro; Abdollahi, Rouhollah O; Sartori, Ivana; Caruana, Fausto; Pelliccia, Veronica; Casaceli, Giuseppe; Mai, Roberto; Lo Russo, Giorgio; Rizzolatti, Giacomo; Orban, Guy A

2016-03-29

A fine-grained description of the spatiotemporal dynamics of human brain activity is a major goal of neuroscientific research. Limitations in spatial and temporal resolution of available noninvasive recording and imaging techniques have hindered so far the acquisition of precise, comprehensive four-dimensional maps of human neural activity. The present study combines anatomical and functional data from intracerebral recordings of nearly 100 patients, to generate highly resolved four-dimensional maps of human cortical processing of nonpainful somatosensory stimuli. These maps indicate that the human somatosensory system devoted to the hand encompasses a widespread network covering more than 10% of the cortical surface of both hemispheres. This network includes phasic components, centered on primary somatosensory cortex and neighboring motor, premotor, and inferior parietal regions, and tonic components, centered on opercular and insular areas, and involving human parietal rostroventral area and ventral medial-superior-temporal area. The technique described opens new avenues for investigating the neural basis of all levels of cortical processing in humans.

Essential oil from the leaves of Xylopia langsdorfiana (Annonaceae) as a possible spasmolytic agent.

PubMed

Correia, Ana Carolina de C; Ferreira, Tamyris F; Martins, Italo Rossi R; Macêdo, Cibério L; Monteiro, Fabio de S; Costa, Vicente Carlos O; Tavares, Josean F; Silva, Marcelo S; Paredes-Gamero, Edgar J; Buri, Marcus V; Rigoni, Vera L S; Nouailhetas, Viviane L A; Da Silva, Bagnólia A

2015-01-01

Xylopia langsdorfiana A. St.-Hil. &Tul. (Annonaceae) is popularly known in the northeast of Brazil as 'pimenteira da terra', and an essential oil (XL-OE) was extracted from its leaves. Since Xylopia species are cited in folk medicine and diterpenes from X. langsdorfiana have spasmolytic activity, this study aimed to investigate a possible spasmolytic action of XL-OE on smooth muscle models. XL-OE (243 and 729 μg/mL) showed low pharmacologic efficacy on guinea pig trachea and rat aorta and uterus. However, in guinea pig ileum, XL-OE (27-729 μg/mL) inhibited carbachol or histamine-induced phasic contractions (1 μM) in a significant and concentration-dependent manner. In addition, XL-OE (81 μg/mL) reduced fluorescence intensity in ileal myocytes stimulated by histamine, indicating a decrease in cytosolic calcium concentration, which could explain the spasmolytic activity. Thus, XL-OE proved to be a promising natural product to be used in gastrointestinal diseases acting by modulating the cytosolic calcium concentration.

Fiber type-specific afferent nerve activity induced by transient contractions of rat bladder smooth muscle in pathological states

PubMed Central

Kuga, Nahoko; Tanioka, Asao; Hagihara, Koichiro; Kawai, Tomoyuki

2017-01-01

Bladder smooth muscle shows spontaneous phasic contractions, which undergo a variety of abnormal changes depending on pathological conditions. How abnormal contractions affect the activity of bladder afferent nerves remains to be fully tested. In this study, we examined the relationship between transient increases in bladder pressure, representing transient contraction of bladder smooth muscle, and spiking patterns of bladder afferent fibers of the L6 dorsal root, in rat pathological models. All recordings were performed at a bladder pressure of approximately 10 cmH2O by maintaining the degree of bladder filling. In the cyclophosphamide-induced model, both Aδ and C fibers showed increased sensitivity to transient bladder pressure increases. In the prostaglandin E2-induced model, Aδ fibers, but not C fibers, specifically showed overexcitation that was time-locked with transient bladder pressure increases. These fiber type-specific changes in nerve spike patterns may underlie the symptoms of urinary bladder diseases. PMID:29267380

A Neural Correlate of Predicted and Actual Reward-Value Information in Monkey Pedunculopontine Tegmental and Dorsal Raphe Nucleus during Saccade Tasks

PubMed Central

Okada, Ken-ichi; Nakamura, Kae; Kobayashi, Yasushi

2011-01-01

Dopamine, acetylcholine, and serotonin, the main modulators of the central nervous system, have been proposed to play important roles in the execution of movement, control of several forms of attentional behavior, and reinforcement learning. While the response pattern of midbrain dopaminergic neurons and its specific role in reinforcement learning have been revealed, the role of the other neuromodulators remains rather elusive. Here, we review our recent studies using extracellular recording from neurons in the pedunculopontine tegmental nucleus, where many cholinergic neurons exist, and the dorsal raphe nucleus, where many serotonergic neurons exist, while monkeys performed eye movement tasks to obtain different reward values. The firing patterns of these neurons are often tonic throughout the task period, while dopaminergic neurons exhibited a phasic activity pattern to the task event. The different modulation patterns, together with the activity of dopaminergic neurons, reveal dynamic information processing between these different neuromodulator systems. PMID:22013541

The Novel KV7.2/KV7.3 Channel Opener ICA-069673 Reveals Subtype-Specific Functional Roles in Guinea Pig Detrusor Smooth Muscle Excitability and Contractility

PubMed Central

Provence, Aaron; Malysz, John

2015-01-01

The physiologic roles of voltage-gated KV7 channel subtypes (KV7.1–KV7.5) in detrusor smooth muscle (DSM) are poorly understood. Here, we sought to elucidate the functional roles of KV7.2/KV7.3 channels in guinea pig DSM excitability and contractility using the novel KV7.2/KV7.3 channel activator ICA-069673 [N-(2-chloro-5-pyrimidinyl)-3,4-difluorobenzamide]. We employed a multilevel experimental approach using Western blot analysis, immunocytochemistry, isometric DSM tension recordings, fluorescence Ca2+ imaging, and perforated whole-cell patch-clamp electrophysiology. Western blot experiments revealed the protein expression of KV7.2 and KV7.3 channel subunits in DSM tissue. In isolated DSM cells, immunocytochemistry with confocal microscopy further confirmed protein expression for KV7.2 and KV7.3 channel subunits, where they localize within the vicinity of the cell membrane. ICA-069673 inhibited spontaneous phasic, pharmacologically induced, and nerve-evoked contractions in DSM isolated strips in a concentration-dependent manner. The inhibitory effects of ICA-069673 on DSM spontaneous phasic and tonic contractions were abolished in the presence of the KV7 channel inhibitor XE991 [10,10-bis(4-pyridinylmethyl)-9(10H)-anthracenone dihydrochloride]. Under conditions of elevated extracellular K+ (60 mM), the effects of ICA-069673 on DSM tonic contractions were significantly attenuated. ICA-069673 decreased the global intracellular Ca2+ concentration in DSM cells, an effect blocked by the L-type Ca2+ channel inhibitor nifedipine. ICA-069673 hyperpolarized the membrane potential and inhibited spontaneous action potentials of isolated DSM cells, effects that were blocked in the presence of XE991. In conclusion, using the novel KV7.2/KV7.3 channel activator ICA-069673, this study provides strong evidence for a critical role for the KV7.2- and KV7.3-containing channels in DSM function at both cellular and tissue levels. PMID:26087697

The Novel KV7.2/KV7.3 Channel Opener ICA-069673 Reveals Subtype-Specific Functional Roles in Guinea Pig Detrusor Smooth Muscle Excitability and Contractility.

PubMed

Provence, Aaron; Malysz, John; Petkov, Georgi V

2015-09-01

The physiologic roles of voltage-gated KV7 channel subtypes (KV7.1-KV7.5) in detrusor smooth muscle (DSM) are poorly understood. Here, we sought to elucidate the functional roles of KV7.2/KV7.3 channels in guinea pig DSM excitability and contractility using the novel KV7.2/KV7.3 channel activator ICA-069673 [N-(2-chloro-5-pyrimidinyl)-3,4-difluorobenzamide]. We employed a multilevel experimental approach using Western blot analysis, immunocytochemistry, isometric DSM tension recordings, fluorescence Ca(2+) imaging, and perforated whole-cell patch-clamp electrophysiology. Western blot experiments revealed the protein expression of KV7.2 and KV7.3 channel subunits in DSM tissue. In isolated DSM cells, immunocytochemistry with confocal microscopy further confirmed protein expression for KV7.2 and KV7.3 channel subunits, where they localize within the vicinity of the cell membrane. ICA-069673 inhibited spontaneous phasic, pharmacologically induced, and nerve-evoked contractions in DSM isolated strips in a concentration-dependent manner. The inhibitory effects of ICA-069673 on DSM spontaneous phasic and tonic contractions were abolished in the presence of the KV7 channel inhibitor XE991 [10,10-bis(4-pyridinylmethyl)-9(10H)-anthracenone dihydrochloride]. Under conditions of elevated extracellular K(+) (60 mM), the effects of ICA-069673 on DSM tonic contractions were significantly attenuated. ICA-069673 decreased the global intracellular Ca(2+) concentration in DSM cells, an effect blocked by the L-type Ca(2+) channel inhibitor nifedipine. ICA-069673 hyperpolarized the membrane potential and inhibited spontaneous action potentials of isolated DSM cells, effects that were blocked in the presence of XE991. In conclusion, using the novel KV7.2/KV7.3 channel activator ICA-069673, this study provides strong evidence for a critical role for the KV7.2- and KV7.3-containing channels in DSM function at both cellular and tissue levels. Copyright © 2015 by The American Society for Pharmacology and Experimental Therapeutics.

Running related gluteus medius function in health and injury: A systematic review with meta-analysis.

PubMed

Semciw, Adam; Neate, Racheal; Pizzari, Tania

2016-10-01

Running is a popular sport and recreational physical activity worldwide. Musculoskeletal injuries in runners are common and may be attributed to the inability to control pelvic equilibrium in the coronal plane. This lack of pelvic control in the frontal plane can stem from dysfunction of the gluteus medius. The aim of this systematic review was therefore to: (i) compile evidence of the activity profile of gluteus medius when running; (ii) identify how gluteus medius activity (electromyography) varies with speed, cadence and gender when running; (iii) compare gluteus medius activity in injured runners to matched controls. Seven electronic databases were searched from their earliest date until March 2015. Thirteen studies met our eligibility criteria. The activity profile was mono-phasic with a peak during initial loading (four studies). Gluteus medius amplitude increases with running speed; this is most evident in females. The muscles' activity has been recorded in injured runners with Achilles tendinopathy (two studies) and patellofemoral pain syndrome (three studies). The strongest evidence indicates a moderate and significant reduction in gluteus medius duration of activity when running in people with patellofemoral pain syndrome. This dysfunction can potentially be mediated with running retraining strategies. Crown Copyright © 2016. Published by Elsevier Ltd. All rights reserved.

The effect of oxaloacetic acid on tyrosinase activity and structure: Integration of inhibition kinetics with docking simulation.

PubMed

Gou, Lin; Lee, Jinhyuk; Hao, Hao; Park, Yong-Doo; Zhan, Yi; Lü, Zhi-Rong

2017-08-01

Oxaloacetic acid (OA) is naturally found in organisms and well known as an intermediate of citric acid cycle producing ATP. We evaluated the effects of OA on tyrosinase activity and structure via integrating methods of enzyme kinetics and computational simulations. OA was found to be a reversible inhibitor of tyrosinase and its induced mechanism was the parabolic non-competitive inhibition type (IC 50 =17.5±0.5mM and K i =6.03±1.36mM). Kinetic measurements by real-time interval assay showed that OA induced multi-phasic inactivation process composing with fast (k 1 ) and slow (k 2 ) phases. Spectrofluorimetry studies showed that OA mainly induced regional changes in the active site of tyrosinase accompanying with hydrophobic disruption at high dose. The computational docking simulations further revealed that OA could interact with several residues near the tyrosinase active site pocket such as HIS61, HIS259, HIS263, and VAL283. Our study provides insight into the mechanism by which energy producing intermediate such as OA inhibit tyrosinase and OA is a potential natural anti-pigmentation agent. Copyright © 2017 Elsevier B.V. All rights reserved.

Predicting the threshold of pulse-train electrical stimuli using a stochastic auditory nerve model: the effects of stimulus noise.

PubMed

Xu, Yifang; Collins, Leslie M

2004-04-01

The incorporation of low levels of noise into an electrical stimulus has been shown to improve auditory thresholds in some human subjects (Zeng et al., 2000). In this paper, thresholds for noise-modulated pulse-train stimuli are predicted utilizing a stochastic neural-behavioral model of ensemble fiber responses to bi-phasic stimuli. The neural refractory effect is described using a Markov model for a noise-free pulse-train stimulus and a closed-form solution for the steady-state neural response is provided. For noise-modulated pulse-train stimuli, a recursive method using the conditional probability is utilized to track the neural responses to each successive pulse. A neural spike count rule has been presented for both threshold and intensity discrimination under the assumption that auditory perception occurs via integration over a relatively long time period (Bruce et al., 1999). An alternative approach originates from the hypothesis of the multilook model (Viemeister and Wakefield, 1991), which argues that auditory perception is based on several shorter time integrations and may suggest an NofM model for prediction of pulse-train threshold. This motivates analyzing the neural response to each individual pulse within a pulse train, which is considered to be the brief look. A logarithmic rule is hypothesized for pulse-train threshold. Predictions from the multilook model are shown to match trends in psychophysical data for noise-free stimuli that are not always matched by the long-time integration rule. Theoretical predictions indicate that threshold decreases as noise variance increases. Theoretical models of the neural response to pulse-train stimuli not only reduce calculational overhead but also facilitate utilization of signal detection theory and are easily extended to multichannel psychophysical tasks.

Reflexive contraction of the levator palpebrae superioris muscle to involuntarily sustain the effective eyelid retraction through the transverse trigeminal proprioceptive nerve on the proximal Mueller's muscle: verification with evoked electromyography.

PubMed

Ban, Ryokuya; Matsuo, Kiyoshi; Osada, Yoshiro; Ban, Midori; Yuzuriha, Shunsuke

2010-01-01

We have proposed a hypothetical mechanism to involuntarily sustain the effective eyelid retraction, which consists of not only voluntary but also reflexive contractions of the levator palpebrae superior muscle (LPSM). Voluntary contraction of fast-twitch fibres of the LPSM stretches the mechanoreceptors in Mueller's muscle to evoke trigeminal proprioception, which induces continuous reflexive contraction of slow-twitch fibres of the LPSM through the trigeminal proprioceptive nerve fibres innervating the mechanoreceptors in Mueller's muscle via the oculomotor neurons, as a tonic trigemino-oculomotor reflex. In the common skeletal mixed muscles, electrical stimulation of the proprioceptive nerve, which apparently connects the mechanoreceptors in muscle spindles to the motoneurons, induces the electromyographic response as the Hoffmann reflex. To verify the presence of the trigemino-oculomotor reflex, we confirmed whether intra-operative electrical simulation of the transverse trigeminal proprioceptive nerve on the proximal Mueller's muscle evokes an electromyographic response in the LPSM under general anaesthesia in 12 patients. An ipsilateral, phasic, short-latency response (latency: 2.8+/-0.3 ms) was induced in the ipsilateral LPSM in 10 of 12 subjects. As successful induction of the short-latency response in the ipsilateral LPSM corresponds to the Hoffmann reflex in the common skeletal mixed muscles, the present study is the first electromyographic verification of the presence of the monosynaptic trigemino-oculomotor reflex to induce reflexive contraction of the LPSM. The presence of the trigemino-oculomotor reflex may elucidate the unexplainable blepharoptosis due to surgery, trauma and tumour, all of which may damage the trigeminal proprioceptive nerve fibres to impair the trigemino-oculomotor reflex. Copyright (c) 2008. Published by Elsevier Ltd.

Surface engineering of nanoparticles in suspension for particle based bio-sensing

PubMed Central

Sen, Tapas; Bruce, Ian J.

2012-01-01

Surface activation of nanoparticles in suspension using amino organosilane has been carried out via strict control of a particle surface ad-layer of water using a simple but efficient protocol ‘Tri-phasic Reverse Emulsion’ (TPRE). This approach produced thin and ordered layers of particle surface functional groups which allowed the efficient conjugation of biomolecules. When used in bio-sensing applications, the resultant conjugates were highly efficient in the hybrid capture of complementary oligonucleotides and the detection of food borne microorganism. TPRE overcomes a number of fundamental problems associated with the surface modification of particles in aqueous suspension viz. particle aggregation, density and organization of resultant surface functional groups by controlling surface condensation of the aminosilane. The approach has potential for application in areas as diverse as nanomedicine, to food technology and industrial catalysis. PMID:22872809

Respiratory mechanics and breathing pattern in the neonatal foal.

PubMed

Koterba, A M; Kosch, P C

1987-01-01

Breathing pattern, respiratory muscle activation pattern, lung volumes and volume-pressure characteristics of the respiratory system of normal, term, neonatal foals on Days 2 and 7 of age were determined to test the hypothesis that the foal actively maintains end-expiratory lung volume (EEV) greater than the relaxation volume of the respiratory system (Vrx) because of a highly compliant chest wall. Breathing pattern was measured in the awake, unsedated foal during quiet breathing in lateral and standing positions. The typical neonatal foal breathing pattern was characterized by a monophasic inspiratory and expiratory flow pattern. Both inspiration and expiration were active, with onset of Edi activity preceding onset of inspiratory flow, and phasic abdominal muscle activity detectable throughout most of expiration. No evidence was found to support the hypothesis that the normal, term neonatal foal actively maintains EEV greater than Vrx. In the neonatal foal, normalized lung volume and lung compliance values were similar to those reported for neonates of other species, while normalized chest wall compliance was considerably lower. We conclude that the chest wall of the term neonatal foal is sufficiently rigid to prevent a low Vrx. This characteristic probably prevents the foal from having to use a breathing strategy which maintains an EEV greater than Vrx.

Reading Practices in the Juvenile Correctional Facility Setting: Incarcerated Adolescents Speak Out

ERIC Educational Resources Information Center

Wexler, Jade; Reed, Deborah K.; Sturges, Keith

2015-01-01

This multi-phasic, qualitative study explored the perceptions and provision of research-based reading instruction in the juvenile correctional facility setting. In three settings in two states, we interviewed students (n = 17), teachers (n = 5), and administrators (n = 3); and conducted two focus groups (n = 8), student surveys (n = 49), and seven…

Workshop on Functional and Structural Relationships and Factor Analysis (1983). Summary of Research Interests of Participants.

DTIC Science & Technology

1983-01-01

J. Amer. Statist. Assoc. 75, 687-692. Dahm, P. F., Helton, B. and Fuller, W. A. (1983), Generalized least squares estimation of the genotypic ...with applications to -"insect development times". Austral. J. Statist. 23, 204-213. [2] Angus , J.F., R. Morton and C. Schafer. (1981). "Phasic

Electromyography and vaginal pressure of the pelvic floor muscles in women with recurrent vulvovaginal candidiasis and vulvodynia.

PubMed

Polpeta, Nádia Cristina; Giraldo, Paulo César; Juliato, Cássia Raquel Teatin; Yoshida, Laura Pagotto; do Amaral, Rose Luce Gomes; Eleutério, José

2012-01-01

To evaluate the electrical potentials and pressure exerted by the pelvic floor muscles in women with recurrent vulvovaginal candidiasis (RVVC) or vulvodynia as compared to control women. A cross-sectional study performed in the Female Outpatient Clinic of Genital Infections in the Department of Obstetrics and Gynecology of the Universidade Estadual de Campinas analyzed and compared electromyography (EMG) and vaginal pressure of the pelvic floor muscles in 61 women. Of these 61 women, 19 had vulvodynia, 12 had RVVC and 30 women had no disorder (control group). For data collection, the instrument used was the Miotool Uro device and its software Biotrainer (Miotec Ltd., Porto Alegre, Rio Grande do Sul, Brazil). The EMG evaluation of the pelvic floor muscles showed significantly lower values in the vulvodynia group (tonic contractions) and RVVC group (phasic and tonic contractions) when compared to the control group. No significant differences in basal tone EMG and vaginal pressure values at rest or during pelvic floor muscle contractions were found among groups. The maximum time of sustained contraction in patients with RVVC or vulvodynia was significantly lower (p < 0.0001) than in controls. Women with vulvodynia and RVVC have more frequent pelvic floor muscle dysfunction than controls when observed by EMG evaluation.

Ultrathin MoS2 and WS2 layers on silver nano-tips as electron emitters

NASA Astrophysics Data System (ADS)

Loh, Tamie A. J.; Tanemura, Masaki; Chua, Daniel H. C.

2016-09-01

2-dimensional (2D) inorganic analogues of graphene such as MoS2 and WS2 present interesting opportunities for field emission technology due to their high aspect ratio and good electrical conductivity. However, research on 2D MoS2 and WS2 as potential field emitters remains largely undeveloped compared to graphene. Herein, we present an approach to directly fabricate ultrathin MoS2 and WS2 onto Ag nano-tips using pulsed laser deposition at low temperatures of 450-500 °C. In addition to providing a layer of chemical and mechanical protection for the Ag nano-tips, the growth of ultrathin MoS2 and WS2 layers on Ag led to enhanced emission properties over that of pristine nano-tips due to a reduction of the effective barrier height arising from charge injection from Ag to the overlying MoS2 or WS2. For WS2 on Ag nano-tips, the phasic mixture was also an important factor influencing the field emission performance. The presence of 1T-WS2 at the metal-WS2 interface in a hybrid film of 2H/1T-WS2 leads to improvement in the field emission capabilities as compared to pure 2H-WS2 on Ag nano-tips.

Oxygen Level and LFP in Task-Positive and Task-Negative Areas: Bridging BOLD fMRI and Electrophysiology.

PubMed

Bentley, William J; Li, Jingfeng M; Snyder, Abraham Z; Raichle, Marcus E; Snyder, Lawrence H

2016-01-01

The human default mode network (DMN) shows decreased blood oxygen level dependent (BOLD) signals in response to a wide range of attention-demanding tasks. Our understanding of the specifics regarding the neural activity underlying these "task-negative" BOLD responses remains incomplete. We paired oxygen polarography, an electrode-based oxygen measurement technique, with standard electrophysiological recording to assess the relationship of oxygen and neural activity in task-negative posterior cingulate cortex (PCC), a hub of the DMN, and visually responsive task-positive area V3 in the awake macaque. In response to engaging visual stimulation, oxygen, LFP power, and multi-unit activity in PCC showed transient activation followed by sustained suppression. In V3, oxygen, LFP power, and multi-unit activity showed an initial phasic response to the stimulus followed by sustained activation. Oxygen responses were correlated with LFP power in both areas, although the apparent hemodynamic coupling between oxygen level and electrophysiology differed across areas. Our results suggest that oxygen responses reflect changes in LFP power and multi-unit activity and that either the coupling of neural activity to blood flow and metabolism differs between PCC and V3 or computing a linear transformation from a single LFP band to oxygen level does not capture the true physiological process. © The Author 2014. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

Developmental Change in Feedback Processing as Reflected by Phasic Heart Rate Changes

ERIC Educational Resources Information Center

Crone, Eveline A.; Jennings, J. Richard; Van der Molen, Maurits W.

2004-01-01

Heart rate was recorded from 3 age groups (8-10, 12, and 20-26 years) while they performed a probabilistic learning task. Stimuli had to be sorted by pressing a left versus right key, followed by positive or negative feedback. Adult heart rate slowed following negative feedback when stimuli were consistently mapped onto the left or right key…

Effect of vergence adaptation on convergence-accommodation: model simulations.

PubMed

Sreenivasan, Vidhyapriya; Bobier, William R; Irving, Elizabeth L; Lakshminarayanan, Vasudevan

2009-10-01

Several theoretical control models depict the adaptation effects observed in the accommodation and vergence mechanisms of the human visual system. Two current quantitative models differ in their approach of defining adaptation and in identifying the effect of controller adaptation on their respective cross-links between the vergence and accommodative systems. Here, we compare the simulation results of these adaptation models with empirical data obtained from emmetropic adults when they performed sustained near task through + 2D lens addition. The results of our experimental study showed an initial increase in exophoria (a divergent open-loop vergence position) and convergence-accommodation (CA) when viewing through +2D lenses. Prolonged fixation through the near addition lenses initiated vergence adaptation, which reduced the lens-induced exophoria and resulted in a concurrent reduction of CA. Both models showed good agreement with empirical measures of vergence adaptation. However, only one model predicted the experimental time course of reduction in CA. The pattern of our empirical results seem to be best described by the adaptation model that indicates the total vergence response to be a sum of two controllers, phasic and tonic, with the output of phasic controller providing input to the cross-link interactions.

Phasic changes in bone CO2 fractions, calcium, and phosphorus during chronic hypercapnia.

PubMed

Schaefer, K E; Pasquale, S; Messier, A A; Shea, M

1980-05-01

The bone CO2 buffering system and bone calcium and phosphorus were studied in guinea pigs exposed to 1% CO2 for periods up to 8 wk and killed at weekly intervals together with control animals of the same age. Measurements were made of arterial CO2 tension, pH, standard bicarbonate, and bone Ca and P. Heat-stabile bone CO2 (carbonate) was determined as dry bone CO2 and heat-labile bone CO2 (bicarbonate) as delta wet-dry bone CO2. During the first 3-4 wk of exposure to 1% CO2, a systemic acidosis was found as indicated in a lowered pH, increased arterial CO2 tension, and decreased standard bicarbonate. The acidosis subsided during the last 4 wk of exposure. Phasic changes in bone bicarbonate were observed as shown in immediate rise lasting for 2 wk followed by a 2-wk decline and second rise after 6 and 8 wk. Bone carbonate exhibited the opposite change during the first 4 wk and thereafter remained stable at an elevated level. Bone Ca and P fell in association with increasing bone bicarbonate and rose with increasing bone carbonate.

Temporal selectivity by single neurons in the torus semicircularis of Batrachyla antartandica (Amphibia: Leptodactylidae).

PubMed

Penna, M; Lin, W Y; Feng, A S

2001-12-01

We investigated the response selectivities of single auditory neurons in the torus semicircularis of Batrachyla antartandica (a leptodactylid from southern Chile) to synthetic stimuli having diverse temporal structures. The advertisement call for this species is characterized by a long sequence of brief sound pulses having a dominant frequency of about 2000 Hz. We constructed five different series of synthetic stimuli in which the following acoustic parameters were systematically modified, one at a time: pulse rate, pulse duration, pulse rise time, pulse fall time, and train duration. The carrier frequency of these stimuli was fixed at the characteristic frequency of the units under study (n=44). Response patterns of TS units to these synthetic call variants revealed different degrees of selectivity for each of the temporal variables. A substantial number of neurons showed preference for pulse rates below 2 pulses s(-1), approximating the values found in natural advertisement calls. Tonic neurons generally showed preferences for long pulse durations, long rise and fall times, and long train durations. In contrast, phasic and phasic-burst neurons preferred stimuli with short duration, short rise and fall times and short train durations.

The conduction block produced by oxcarbazepine in the isolated rat sciatic nerve: a comparison with lamotrigine.

PubMed

Guven, Mustafa; Kahraman, Ibrahim; Koc, Filiz; Bozdemir, Hacer; Sarica, Yakup; Gunay, Ismail

2011-01-01

Oxcarbazepine is an antiepileptic drug widely used for the treatment of neuropathic pain. In the present study, the effects of oxcarbazepine and lamotrigine on conduction properties in the rat sciatic nerves were examined. The experiments were conducted with in vitro sucrose-gap technique on the isolated wistar rat sciatic nerves. The compound action potentials were obtained by tonic (single) and phasic (10, 40, and 100 Hz) stimulation. Oxcarbazepine produced a significant concentration- and frequency-dependent reduction in the compound action potential amplitude. When the two drugs were applied at concentrations that produced equal levels of tonic (i.e., non-frequency-dependent) conduction block, oxcarbazepine produced the greatest phasic (i.e., frequency-dependent) conduction block, followed by lamotrigine. Oxcarbazepine and lamotrigine reduced the 4-aminopyridine-induced amplitude of delayed depolarization; however, oxcarbazepine had a significantly greater effect than lamotrigine. These results suggest that oxcarbazepine produces more potent frequency-dependent conduction block than lamotrigine, and suppresses the delayed depolarization which contributes to sensory signaling and may play a role in neuropathic pain. The findings provide insight into the mechanisms of action of oxcarbazepine and lamotrigine and may help in the development of novel therapies for neuropathic pain.

Tracking arousal state and mind wandering with pupillometry.

PubMed

Unsworth, Nash; Robison, Matthew K

2018-04-13

In four experiments, the association between arousal state and different mind-wandering states was examined. Participants performed a sustained attention task while pupil responses were continuously recorded. Periodically during the task, participants were presented with thought probes to determine if they were on task or mind wandering. Across the four experiments, the results suggested that in situations that promoted on-task behaviors and focused external attention, mind wandering was associated with lowered arousal, as seen by smaller tonic pupil diameters and smaller phasic pupillary responses. However, in situations that promoted a more internal focus of attention, there were no differences between on-task states and mind wandering in tonic pupil diameter (although differences emerged for phasic pupillary responses), suggesting similar arousal levels. Furthermore, across the four experiments, mind blanking and mind wandering dissociated in terms of whether the situation promoted focused external attention or focused internal attention. These results are broadly consistent with the notion that mind wandering is a heterogeneous construct, with different forms of mind wandering being associated with different arousal states, and suggest that a combination of behavioral and pupillary measures can be used to track these various states.

Phasic changes in human right coronary blood flow before and after repair of aortic insufficiency.

PubMed

Folts, J D; Rowe, G G; Kahn, D R; Young, W P

1979-02-01

We have shown previously that acute aortic insufficiency in chronically instrumented dogs reverses the normally high ratio of diastolic to systolic coronary blood flow. Phasic blood flow in the dominant right coronary artery was measured directly with an electromagnetic flow meter during surgery in eight patients with severe aortic insufficiency before and after relacement of the aortic valve. Before the insufficiency was eliminated, right coronary flow average 116 +/- 37 ml./minute and the diastolic to systolic flow ratio was 0.88 +/- 17. Mean arterial blood pressure averaged 106 +/- 17 mm. Hg, heart rate 84 +/- 19 beats/minute, and mean diastolic pressure averaged 67 +/- 10 mm. Hg. After the aortic valve was replaced with an average heart rate of 90 +/- 15 and mean blood pressure of 103 +/- 13 mm. Hg, the average right coronary blood flow increased to 180 +/- 40 ml./minute with a D/S ratio of 2.18 +/- 0.8. In all cases the right coronary blood flow increased after the aortic insufficiency was eliminated surgically. Right coronary flow probably increased because of the improved diastolic perfusion pressure and the change from predominantly systolic to diastolic coronary flow.

Detection of Bursts and Pauses in Spike Trains

PubMed Central

Ko, D.; Wilson, C. J.; Lobb, C. J.; Paladini, C. A.

2012-01-01

Midbrain dopaminergic neurons in vivo exhibit a wide range of firing patterns. They normally fire constantly at a low rate, and speed up, firing a phasic burst when reward exceeds prediction, or pause when an expected reward does not occur. Therefore, the detection of bursts and pauses from spike train data is a critical problem when studying the role of phasic dopamine (DA) in reward related learning, and other DA dependent behaviors. However, few statistical methods have been developed that can identify bursts and pauses simultaneously. We propose a new statistical method, the Robust Gaussian Surprise (RGS) method, which performs an exhaustive search of bursts and pauses in spike trains simultaneously. We found that the RGS method is adaptable to various patterns of spike trains recorded in vivo, and is not influenced by baseline firing rate, making it applicable to all in vivo spike trains where baseline firing rates vary over time. We compare the performance of the RGS method to other methods of detecting bursts, such as the Poisson Surprise (PS), Rank Surprise (RS), and Template methods. Analysis of data using the RGS method reveals potential mechanisms underlying how bursts and pauses are controlled in DA neurons. PMID:22939922

Relative evaluation of micronutrients (MN) and its respective nanoparticles (NPs) as additives for the enhanced methane generation.

PubMed

Juntupally, Sudharshan; Begum, Sameena; Allu, Sarat Kumar; Nakkasunchi, Shalini; Madugula, Mrudula; Anupoju, Gangagni Rao

2017-08-01

In the present work, effect of micro nutrients (MN) (NiCl 2 , Fe 2 O 3 , CoCl 2 , (NH 4 ) 6 Mo 7 O 24 ) was compared with nanoparticles (NPs) of respective MN with cattle manure (CM) slurry in single and bi-phasic anaerobic digestion (AD) at a hydraulic residence time (HRT) of 20days at a mesophilic temperature of 37±2°C for the generation of biogas with enhanced methane (70-80%). Experiments were also carried out with CM slurry as control. During single phase AD, highest biogas production of 0.16L/(gVS reduced) and 0.14L/(gVS reduced) was obtained from Fe 3 O 4 NPs and CoCl 2 MN respectively whereas in bi-phasic AD 0.3L/(gVS reduced) and 0.2L/(gVS reduced) was obtained from NiO NPs and NiCl 2 MN correspondingly. The results elucidated that NiCl 2 (either as MN or NPs) yielded highest biogas in comparison with either control or other MN and NPs. Copyright © 2017 Elsevier Ltd. All rights reserved.

Comparison Between Automatic and Visual Scorings of REM Sleep Without Atonia for the Diagnosis of REM Sleep Behavior Disorder in Parkinson Disease.

PubMed

Figorilli, Michela; Ferri, Raffaele; Zibetti, Maurizio; Beudin, Patricia; Puligheddu, Monica; Lopiano, Leonardo; Cicolin, Alessandro; Durif, Frank; Marques, Ana; Fantini, Maria Livia

2017-02-01

To compare three different methods, two visual and one automatic, for the quantification of rapid eye movement (REM) sleep without atonia (RSWA) in the diagnosis of REM sleep behavior disorder (RBD) in Parkinson's disease (PD) patients. Sixty-two consecutive patients with idiopathic PD underwent video-polysomnographic recording and showed more than 5 minutes of REM sleep. The electromyogram during REM sleep was analyzed by means of two visual methods (Montréal and SINBAR) and one automatic analysis (REM Atonia Index or RAI). RBD was diagnosed according to standard criteria and a series of diagnostic accuracy measures were calculated for each method, as well as the agreement between them. RBD was diagnosed in 59.7% of patients. The accuracy (85.5%), receiver operating characteristic (ROC) area (0.833) and Cohen's K coefficient (0.688) obtained with RAI were similar to those of the visual parameters. Visual tonic parameters, alone or in combination with phasic activity, showed high values of accuracy (93.5-95.2%), ROC area (0.92-0.94), and Cohen's K (0.862-0.933). Similarly, the agreement between the two visual methods was very high, and the agreement between each visual methods and RAI was substantial. Visual phasic measures alone performed worse than all the other measures. The diagnostic accuracy of RSWA obtained with both visual and automatic methods was high and there was a general agreement between methods. RAI may be used as the first line method to detect RSWA in the diagnosis of RBD in PD, together with the visual inspection of video-recorded behaviors, while the visual analysis of RSWA might be used in doubtful cases. © Sleep Research Society 2016. Published by Oxford University Press on behalf of the Sleep Research Society. All rights reserved. For permissions, please e-mail journals.permissions@oup.com.

Neuromuscular activation patterns during treadmill walking after space flight

NASA Technical Reports Server (NTRS)

Layne, C. S.; McDonald, P. V.; Bloomberg, J. J.

1997-01-01

Astronauts adopt a variety of neuromuscular control strategies during space flight that are appropriate for locomoting in that unique environment, but are less than optimal upon return to Earth. We report here the first systematic investigation of potential adaptations in neuromuscular activity patterns associated with postflight locomotion. Astronaut-subjects were tasked with walking on a treadmill at 6.4 km/h while fixating a visual target 30 cm away from their eyes after space flights of 8-15 days. Surface electromyography was collected from selected lower limb muscles and normalized with regard to mean amplitude and temporal relation to heel strike. In general, high correlations (more than 0.80) were found between preflight and postflight activation waveforms for each muscle and each subject: however relative activation amplitude around heel strike and toe off was changed as a result of flight. The level of muscle cocontraction and activation variability, and the relationship between the phasic characteristics of the ankle musculature in preparation for toe off also were altered by space flight. Subjects also reported oscillopsia during treadmill walking after flight. These findings indicate that, after space flight, the sensory-motor system can generate neuromuscular-activation strategies that permit treadmill walking, but subtle changes in lower-limb neuromuscular activation are present that may contribute to increased lower limb kinematic variability and oscillopsia also present during postflight walking.

Physiological correlates and emotional specificity of human piloerection

PubMed Central

Benedek, Mathias; Kaernbach, Christian

2011-01-01

Piloerection is known as an indicator of strong emotional experiences. However, little is known about the physiological and emotional specificity of this psychophysiological response. In the presented study, piloerection was elicited by audio stimuli taken from music and film episodes. The physiological response accompanying the incidence of piloerection was recorded with respect to electrodermal, cardiovascular and respiratory measures and compared to a matched control condition. The employment of an optical recording system allowed for a direct and objective assessment of visible piloerection. The occurrence of piloerection was primarily accompanied by an increase of phasic electrodermal activity and increased respiration depth as compared to a matched control condition. This physiological response pattern is discussed in the context of dominant theories of human piloerection. Consideration of all available evidence suggests that emotional piloerection represents a valuable indicator of the state of being moved or touched. PMID:21276827

Basal forebrain neuronal inhibition enables rapid behavioral stopping

PubMed Central

Mayse, Jeffrey D.; Nelson, Geoffrey M.; Avila, Irene; Gallagher, Michela; Lin, Shih-Chieh

2015-01-01

Cognitive inhibitory control, the ability to rapidly suppress responses inappropriate for the context, is essential for flexible and adaptive behavior. While most studies on inhibitory control have focused on the fronto-basal-ganglia circuit, here we explore a novel hypothesis and show that rapid behavioral stopping is enabled by neuronal inhibition in the basal forebrain (BF). In rats performing the stop signal task, putative noncholinergic BF neurons with phasic bursting responses to the go signal were inhibited nearly completely by the stop signal. The onset of BF neuronal inhibition was tightly coupled with and temporally preceded the latency to stop, the stop signal reaction time. Artificial inhibition of BF activity in the absence of the stop signal was sufficient to reproduce rapid behavioral stopping. These results reveal a novel subcortical mechanism of rapid inhibitory control by the BF, which provides bidirectional control over the speed of response generation and inhibition. PMID:26368943

Nonvesicular inhibitory neurotransmission via reversal of the GABA transporter GAT-1

PubMed Central

Wu, Yuanming; Wang, Wengang; Díez-Sampedro, Ana; Richerson, George B.

2007-01-01

SUMMARY GABA transporters play an important but poorly understood role in neuronal inhibition. They can reverse, but this is widely thought to occur only under pathological conditions. Here we use a heterologous expression system to show that the reversal potential of GAT-1 under physiologically relevant conditions is near the normal resting potential of neurons, and that reversal can occur rapidly enough to release GABA during simulated action potentials. We then use paired recordings from cultured hippocampal neurons, and show that GABAergic transmission is not prevented by four methods widely used to block vesicular release. This nonvesicular neurotransmission was potently blocked by GAT-1 antagonists, and was enhanced as predicted by agents that increase cytosolic [GABA] or [Na+]. The results indicate that GAT-1 regulates tonic inhibition by clamping ambient [GABA] at a level high enough to activate high affinity GABAA receptors, and that transporter-mediated GABA release can contribute to phasic inhibition. PMID:18054861

Physiological correlates and emotional specificity of human piloerection.

PubMed

Benedek, Mathias; Kaernbach, Christian

2011-03-01

Piloerection is known as an indicator of strong emotional experiences. However, little is known about the physiological and emotional specificity of this psychophysiological response. In the presented study, piloerection was elicited by audio stimuli taken from music and film episodes. The physiological response accompanying the incidence of piloerection was recorded with respect to electrodermal, cardiovascular and respiratory measures and compared to a matched control condition. The employment of an optical recording system allowed for a direct and objective assessment of visible piloerection. The occurrence of piloerection was primarily accompanied by an increase of phasic electrodermal activity and increased respiration depth as compared to a matched control condition. This physiological response pattern is discussed in the context of dominant theories of human piloerection. Consideration of all available evidence suggests that emotional piloerection represents a valuable indicator of the state of being moved or touched. Copyright © 2011 Elsevier B.V. All rights reserved.

Reward Prediction Errors in Drug Addiction and Parkinson's Disease: from Neurophysiology to Neuroimaging.

PubMed

García-García, Isabel; Zeighami, Yashar; Dagher, Alain

2017-06-01

Surprises are important sources of learning. Cognitive scientists often refer to surprises as "reward prediction errors," a parameter that captures discrepancies between expectations and actual outcomes. Here, we integrate neurophysiological and functional magnetic resonance imaging (fMRI) results addressing the processing of reward prediction errors and how they might be altered in drug addiction and Parkinson's disease. By increasing phasic dopamine responses, drugs might accentuate prediction error signals, causing increases in fMRI activity in mesolimbic areas in response to drugs. Chronic substance dependence, by contrast, has been linked with compromised dopaminergic function, which might be associated with blunted fMRI responses to pleasant non-drug stimuli in mesocorticolimbic areas. In Parkinson's disease, dopamine replacement therapies seem to induce impairments in learning from negative outcomes. The present review provides a holistic overview of reward prediction errors across different pathologies and might inform future clinical strategies targeting impulsive/compulsive disorders.

Influence of sleep deprivation and auditory intensity on reaction time and response force.

PubMed

Włodarczyk, Dariusz; Jaśkowski, Piotr; Nowik, Agnieszka

2002-06-01

Arousal and activation are two variables supposed to underlie change in response force. This study was undertaken to explain these roles, specifically, for strong auditory stimuli and sleep deficit. Loud auditory stimuli can evoke phasic overarousal whereas sleep deficit leads to general underarousal. Moreover, Van der Molen and Keuss (1979, 1981) showed that paradoxically long reaction times occurred with extremely strong auditory stimuli when the task was difficult, e.g., choice reaction or Simon paradigm. It was argued that this paradoxical behavior related to reaction time is due to active disconnecting of the coupling between arousal and activation to prevent false responses. If so, we predicted that for extremely loud stimuli and for difficult tasks, the lengthening of reaction time should be associated with reduction of response force. The effects of loudness and sleep deficit on response time and force were investigated in three different tasks: simple response, choice response, and Simon paradigm. According to our expectation, we found a detrimental effect of sleep deficit on reaction time and on response force. In contrast to Van der Molen and Keuss, we found no increase in reaction time for loud stimuli (up to 110 dB) even on the Simon task.