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Sample records for 3a neuron response

  1. Hypothalamic neuronal responses to cytokines.

    PubMed Central

    Shibata, M.

    1990-01-01

    Fever has been extensively studied in the past few decades. The hypothesis that hypothalamic thermosensitive neurons play a major role in both normal thermoregulation and in fever production and lysis has particularly helped to advance our understanding of the neuronal mechanisms underlying the response to pyrogens. Furthermore, new data in the study of host defense responses induced by pyrogenic cytokines such as interleukin 1, interferon alpha 2, tumor necrosis factor alpha, and interleukin 6 have demonstrated that those factors have multiple, yet coordinated, regulatory activities in the central nervous system, so that our understanding of the role of the brain in the activity of these agents requires a new perspective and dimension. Thus, recent evidence from our laboratory indicates that blood-borne cytokines may be detected in the organum vasculosum laminae terminalis and transduced there into neuronal signals. Such signals may then affect distinct, but partially overlapping, sets of neuronal systems in the preoptic area of the anterior hypothalamus, mediating directly and/or indirectly the array of various host defense responses characteristic of infection that are thought to be induced by blood-borne cytokines. PMID:2205055

  2. Neuronal responses to physiological stress.

    PubMed

    Kagias, Konstantinos; Nehammer, Camilla; Pocock, Roger

    2012-01-01

    Physiological stress can be defined as any external or internal condition that challenges the homeostasis of a cell or an organism. It can be divided into three different aspects: environmental stress, intrinsic developmental stress, and aging. Throughout life all living organisms are challenged by changes in the environment. Fluctuations in oxygen levels, temperature, and redox state for example, trigger molecular events that enable an organism to adapt, survive, and reproduce. In addition to external stressors, organisms experience stress associated with morphogenesis and changes in inner chemistry during normal development. For example, conditions such as intrinsic hypoxia and oxidative stress, due to an increase in tissue mass, have to be confronted by developing embryos in order to complete their development. Finally, organisms face the challenge of stochastic accumulation of molecular damage during aging that results in decline and eventual death. Studies have shown that the nervous system plays a pivotal role in responding to stress. Neurons not only receive and process information from the environment but also actively respond to various stresses to promote survival. These responses include changes in the expression of molecules such as transcription factors and microRNAs that regulate stress resistance and adaptation. Moreover, both intrinsic and extrinsic stresses have a tremendous impact on neuronal development and maintenance with implications in many diseases. Here, we review the responses of neurons to various physiological stressors at the molecular and cellular level. PMID:23112806

  3. Neuronal Responses to Physiological Stress

    PubMed Central

    Kagias, Konstantinos; Nehammer, Camilla; Pocock, Roger

    2012-01-01

    Physiological stress can be defined as any external or internal condition that challenges the homeostasis of a cell or an organism. It can be divided into three different aspects: environmental stress, intrinsic developmental stress, and aging. Throughout life all living organisms are challenged by changes in the environment. Fluctuations in oxygen levels, temperature, and redox state for example, trigger molecular events that enable an organism to adapt, survive, and reproduce. In addition to external stressors, organisms experience stress associated with morphogenesis and changes in inner chemistry during normal development. For example, conditions such as intrinsic hypoxia and oxidative stress, due to an increase in tissue mass, have to be confronted by developing embryos in order to complete their development. Finally, organisms face the challenge of stochastic accumulation of molecular damage during aging that results in decline and eventual death. Studies have shown that the nervous system plays a pivotal role in responding to stress. Neurons not only receive and process information from the environment but also actively respond to various stresses to promote survival. These responses include changes in the expression of molecules such as transcription factors and microRNAs that regulate stress resistance and adaptation. Moreover, both intrinsic and extrinsic stresses have a tremendous impact on neuronal development and maintenance with implications in many diseases. Here, we review the responses of neurons to various physiological stressors at the molecular and cellular level. PMID:23112806

  4. Semaphorin 3A and neurotrophins: a balance between apoptosis and survival signaling in embryonic DRG neurons.

    PubMed

    Ben-Zvi, Ayal; Yagil, Zohar; Hagalili, Yamit; Klein, Hagit; Lerman, Omer; Behar, Oded

    2006-01-01

    Large numbers of neurons are eliminated by apoptosis during nervous system development. For instance, in the mouse dorsal root ganglion (DRG), the highest incidence of cell death occurs between embryonic days 12 and 14 (E12-E14). While the cause of cell death and its biological significance in the nervous system is not entirely understood, it is generally believed that limiting quantities of neurotrophins are responsible for neuronal death. Between E12 and E14, developing DRG neurons pass through tissues expressing high levels of axonal guidance molecules such as Semaphorin 3A (Sema3A) while navigating to their targets. Here, we demonstrate that Sema3A acts as a death-inducing molecule in neurotrophin-3 (NT-3)-, brain-derived neurotrophic factor (BDNF)- and nerve growth factor (NGF)-dependent E12 and E13 cultured DRG neurons. We show that Sema3A most probably induces cell death through activation of the c-Jun N-terminal kinase (JNK)/c-Jun signaling pathway, and that this cell death is blocked by a moderate increase in NGF concentration. Interestingly, increasing concentrations of other neurotrophic factors, such as NT-3 or BDNF, do not elicit similar effects. Our data suggest that the number of DRG neurons is determined by a fine balance between neurotrophins and Semaphorin 3A, and not only by neurotrophin levels. PMID:16336628

  5. Chaotic Response of the Pacemaker Neuron

    NASA Astrophysics Data System (ADS)

    Hayashi, Hatsuo; Ishizuka, Satoru; Hirakawa, Kazuyoshi

    1985-06-01

    Excitable membranes respond irregularly to a periodic stimulation with proper stimulus parameters. Because irregular firing is macroscopic, it seems that irregularity is caused by other factors besides microscopic membrane noise. The responses of the repetitively firing Onchidium pacemaker neuron to a sinusoidal current stimulation were investigated. The irregular responses are classified into three kinds of chaotic oscillation: chaos, intermittency and random alternation. 1/2- and 1/1-harmonic responses bifurcate to chaos via intermittency and random alternation respectively. Harmonic and chaotic responses alternate with each other with increasing frequency of stimulation and with smaller amplitude. Nonlinear factors, threshold and refractory period, are concerned with hyperbolicity of chaotic responses.

  6. Searching for optimal stimuli: ascending a neuron's response function.

    PubMed

    Koelling, Melinda Evrithiki; Nykamp, Duane Q

    2012-12-01

    Many methods used to analyze neuronal response assume that neuronal activity has a fundamentally linear relationship to the stimulus. However, some neurons are strongly sensitive to multiple directions in stimulus space and have a highly nonlinear response. It can be difficult to find optimal stimuli for these neurons. We demonstrate how successive linear approximations of neuronal response can effectively carry out gradient ascent and move through stimulus space towards local maxima of the response. We demonstrate search results for a simple model neuron and two models of a highly selective neuron. PMID:22580579

  7. Anomalous neuronal responses to fluctuated inputs

    NASA Astrophysics Data System (ADS)

    Hosaka, Ryosuke; Sakai, Yutaka

    2015-10-01

    The irregular firing of a cortical neuron is thought to result from a highly fluctuating drive that is generated by the balance of excitatory and inhibitory synaptic inputs. A previous study reported anomalous responses of the Hodgkin-Huxley neuron to the fluctuated inputs where an irregularity of spike trains is inversely proportional to an input irregularity. In the current study, we investigated the origin of these anomalous responses with the Hindmarsh-Rose neuron model, map-based models, and a simple mixture of interspike interval distributions. First, we specified the parameter regions for the bifurcations in the Hindmarsh-Rose model, and we confirmed that the model reproduced the anomalous responses in the dynamics of the saddle-node and subcritical Hopf bifurcations. For both bifurcations, the Hindmarsh-Rose model shows bistability in the resting state and the repetitive firing state, which indicated that the bistability was the origin of the anomalous input-output relationship. Similarly, the map-based model that contained bistability reproduced the anomalous responses, while the model without bistability did not. These results were supported by additional findings that the anomalous responses were reproduced by mimicking the bistable firing with a mixture of two different interspike interval distributions. Decorrelation of spike trains is important for neural information processing. For such spike train decorrelation, irregular firing is key. Our results indicated that irregular firing can emerge from fluctuating drives, even weak ones, under conditions involving bistability. The anomalous responses, therefore, contribute to efficient processing in the brain.

  8. Anomalous neuronal responses to fluctuated inputs.

    PubMed

    Hosaka, Ryosuke; Sakai, Yutaka

    2015-10-01

    The irregular firing of a cortical neuron is thought to result from a highly fluctuating drive that is generated by the balance of excitatory and inhibitory synaptic inputs. A previous study reported anomalous responses of the Hodgkin-Huxley neuron to the fluctuated inputs where an irregularity of spike trains is inversely proportional to an input irregularity. In the current study, we investigated the origin of these anomalous responses with the Hindmarsh-Rose neuron model, map-based models, and a simple mixture of interspike interval distributions. First, we specified the parameter regions for the bifurcations in the Hindmarsh-Rose model, and we confirmed that the model reproduced the anomalous responses in the dynamics of the saddle-node and subcritical Hopf bifurcations. For both bifurcations, the Hindmarsh-Rose model shows bistability in the resting state and the repetitive firing state, which indicated that the bistability was the origin of the anomalous input-output relationship. Similarly, the map-based model that contained bistability reproduced the anomalous responses, while the model without bistability did not. These results were supported by additional findings that the anomalous responses were reproduced by mimicking the bistable firing with a mixture of two different interspike interval distributions. Decorrelation of spike trains is important for neural information processing. For such spike train decorrelation, irregular firing is key. Our results indicated that irregular firing can emerge from fluctuating drives, even weak ones, under conditions involving bistability. The anomalous responses, therefore, contribute to efficient processing in the brain. PMID:26565270

  9. Impaired Neurite Contact Guidance in Ubiquitin Ligase E3a (Ube3a)-Deficient Hippocampal Neurons on Nanostructured Substrates.

    PubMed

    Tonazzini, I; Meucci, S; Van Woerden, G M; Elgersma, Y; Cecchini, M

    2016-04-01

    Recent discoveries indicate that during neuronal development the signaling processes that regulate extracellular sensing (e.g., adhesion, cytoskeletal dynamics) are important targets for ubiquitination-dependent regulation, in particular through E3 ubiquitin ligases. Among these, Ubiquitin E3a ligase (UBE3A) has a key role in brain functioning, but its function and how its deficiency results in the neurodevelopmental disorder Angelman syndrome is still unclear. Here, the role of UBE3A is investigated in neurite contact guidance during neuronal development, in vitro. The microtopography sensing of wild-type and Ube3a-deficient hippocampal neurons is studied by exploiting gratings with different topographical characteristics, with the aim to compare their capabilities to read and follow physical directional stimuli. It is shown that neuronal contact guidance is defective in Ube3a-deficient neurons, and this behavior is linked to an impaired activation of the focal adhesion signaling pathway. Taken together, the results suggest that the neuronal contact sensing machinery might be affected in Angelman syndrome. PMID:26845073

  10. Persistent neuronal Ube3a expression in the suprachiasmatic nucleus of Angelman syndrome model mice.

    PubMed

    Jones, Kelly A; Han, Ji Eun; DeBruyne, Jason P; Philpot, Benjamin D

    2016-01-01

    Mutations or deletions of the maternal allele of the UBE3A gene cause Angelman syndrome (AS), a severe neurodevelopmental disorder. The paternal UBE3A/Ube3a allele becomes epigenetically silenced in most neurons during postnatal development in humans and mice; hence, loss of the maternal allele largely eliminates neuronal expression of UBE3A protein. However, recent studies suggest that paternal Ube3a may escape silencing in certain neuron populations, allowing for persistent expression of paternal UBE3A protein. Here we extend evidence in AS model mice (Ube3a(m-/p+)) of paternal UBE3A expression within the suprachiasmatic nucleus (SCN), the master circadian pacemaker. Paternal UBE3A-positive cells in the SCN show partial colocalization with the neuropeptide arginine vasopressin (AVP) and clock proteins (PER2 and BMAL1), supporting that paternal UBE3A expression in the SCN is often of neuronal origin. Paternal UBE3A also partially colocalizes with a marker of neural progenitors, SOX2, implying that relaxed or incomplete imprinting of paternal Ube3a reflects an overall immature molecular phenotype. Our findings highlight the complexity of Ube3a imprinting in the brain and illuminate a subpopulation of SCN neurons as a focal point for future studies aimed at understanding the mechanisms of Ube3a imprinting. PMID:27306933

  11. Prefrontal Neuronal Responses during Audiovisual Mnemonic Processing

    PubMed Central

    Hwang, Jaewon

    2015-01-01

    During communication we combine auditory and visual information. Neurophysiological research in nonhuman primates has shown that single neurons in ventrolateral prefrontal cortex (VLPFC) exhibit multisensory responses to faces and vocalizations presented simultaneously. However, whether VLPFC is also involved in maintaining those communication stimuli in working memory or combining stored information across different modalities is unknown, although its human homolog, the inferior frontal gyrus, is known to be important in integrating verbal information from auditory and visual working memory. To address this question, we recorded from VLPFC while rhesus macaques (Macaca mulatta) performed an audiovisual working memory task. Unlike traditional match-to-sample/nonmatch-to-sample paradigms, which use unimodal memoranda, our nonmatch-to-sample task used dynamic movies consisting of both facial gestures and the accompanying vocalizations. For the nonmatch conditions, a change in the auditory component (vocalization), the visual component (face), or both components was detected. Our results show that VLPFC neurons are activated by stimulus and task factors: while some neurons simply responded to a particular face or a vocalization regardless of the task period, others exhibited activity patterns typically related to working memory such as sustained delay activity and match enhancement/suppression. In addition, we found neurons that detected the component change during the nonmatch period. Interestingly, some of these neurons were sensitive to the change of both components and therefore combined information from auditory and visual working memory. These results suggest that VLPFC is not only involved in the perceptual processing of faces and vocalizations but also in their mnemonic processing. PMID:25609614

  12. Persistent neuronal Ube3a expression in the suprachiasmatic nucleus of Angelman syndrome model mice

    PubMed Central

    Jones, Kelly A.; Han, Ji Eun; DeBruyne, Jason P.; Philpot, Benjamin D.

    2016-01-01

    Mutations or deletions of the maternal allele of the UBE3A gene cause Angelman syndrome (AS), a severe neurodevelopmental disorder. The paternal UBE3A/Ube3a allele becomes epigenetically silenced in most neurons during postnatal development in humans and mice; hence, loss of the maternal allele largely eliminates neuronal expression of UBE3A protein. However, recent studies suggest that paternal Ube3a may escape silencing in certain neuron populations, allowing for persistent expression of paternal UBE3A protein. Here we extend evidence in AS model mice (Ube3am–/p+) of paternal UBE3A expression within the suprachiasmatic nucleus (SCN), the master circadian pacemaker. Paternal UBE3A-positive cells in the SCN show partial colocalization with the neuropeptide arginine vasopressin (AVP) and clock proteins (PER2 and BMAL1), supporting that paternal UBE3A expression in the SCN is often of neuronal origin. Paternal UBE3A also partially colocalizes with a marker of neural progenitors, SOX2, implying that relaxed or incomplete imprinting of paternal Ube3a reflects an overall immature molecular phenotype. Our findings highlight the complexity of Ube3a imprinting in the brain and illuminate a subpopulation of SCN neurons as a focal point for future studies aimed at understanding the mechanisms of Ube3a imprinting. PMID:27306933

  13. Semaphorin 3A is a retrograde cell death signal in developing sympathetic neurons.

    PubMed

    Wehner, Amanda B; Abdesselem, Houari; Dickendesher, Travis L; Imai, Fumiyasu; Yoshida, Yutaka; Giger, Roman J; Pierchala, Brian A

    2016-05-01

    During development of the peripheral nervous system, excess neurons are generated, most of which will be lost by programmed cell death due to a limited supply of neurotrophic factors from their targets. Other environmental factors, such as 'competition factors' produced by neurons themselves, and axon guidance molecules have also been implicated in developmental cell death. Semaphorin 3A (Sema3A), in addition to its function as a chemorepulsive guidance cue, can also induce death of sensory neurons in vitro The extent to which Sema3A regulates developmental cell death in vivo, however, is debated. We show that in compartmentalized cultures of rat sympathetic neurons, a Sema3A-initiated apoptosis signal is retrogradely transported from axon terminals to cell bodies to induce cell death. Sema3A-mediated apoptosis utilizes the extrinsic pathway and requires both neuropilin 1 and plexin A3. Sema3A is not retrogradely transported in older, survival factor-independent sympathetic neurons, and is much less effective at inducing apoptosis in these neurons. Importantly, deletion of either neuropilin 1 or plexin A3 significantly reduces developmental cell death in the superior cervical ganglia. Taken together, a Sema3A-initiated apoptotic signaling complex regulates the apoptosis of sympathetic neurons during the period of naturally occurring cell death. PMID:27143756

  14. Dopamine neurons share common response function for reward prediction error

    PubMed Central

    Eshel, Neir; Tian, Ju; Bukwich, Michael; Uchida, Naoshige

    2016-01-01

    Dopamine neurons are thought to signal reward prediction error, or the difference between actual and predicted reward. How dopamine neurons jointly encode this information, however, remains unclear. One possibility is that different neurons specialize in different aspects of prediction error; another is that each neuron calculates prediction error in the same way. We recorded from optogenetically-identified dopamine neurons in the lateral ventral tegmental area (VTA) while mice performed classical conditioning tasks. Our tasks allowed us to determine the full prediction error functions of dopamine neurons and compare them to each other. We found striking homogeneity among individual dopamine neurons: their responses to both unexpected and expected rewards followed the same function, just scaled up or down. As a result, we could describe both individual and population responses using just two parameters. Such uniformity ensures robust information coding, allowing each dopamine neuron to contribute fully to the prediction error signal. PMID:26854803

  15. Topoisomerase inhibitors unsilence the dormant allele of Ube3a in neurons

    PubMed Central

    Huang, Hsien-Sung; Allen, John A.; Mabb, Angela M.; King, Ian F.; Miriyala, JayaLakshmi; Taylor-Blake, Bonnie; Sciaky, Noah; Dutton, J. Walter; Lee, Hyeong-Min; Chen, Xin; Jin, Jian; Bridges, Arlene S.; Zylka, Mark J.; Roth, Bryan L.; Philpot, Benjamin D.

    2011-01-01

    Angelman syndrome is a severe neurodevelopmental disorder caused by deletion or mutation of the maternal allele of the ubiquitin protein ligase E3A (Ube3a)1–3. In neurons, the paternal allele of Ube3a is intact but epigenetically silenced4–6, raising the possibility that Angelman syndrome could be treated by activating this silenced allele to restore functional UBE3A protein7,8. Using an unbiased, high-content screen in primary cortical neurons from mice, we identified twelve topoisomerase I inhibitors and four topoisomerase II inhibitors that unsilence the paternal Ube3a allele. These drugs included topotecan, irinotecan, etoposide, and dexrazoxane (ICRF-187). At nanomolar concentrations, topotecan upregulated catalytically active UBE3A in neurons from maternal Ube3a-null mice. Topotecan concomitantly downregulated expression of the Ube3a antisense transcript that overlaps the paternal copy of Ube3a9–11. These results suggest that topotecan unsilences Ube3a in cis by reducing transcription of an imprinted antisense RNA. When administered in vivo, topotecan unsilenced the paternal Ube3a allele in several regions of the nervous system, including neurons in the hippocampus, neocortex, striatum, cerebellum and spinal cord. Paternal expression of Ube3a remained elevated in a subset of spinal cord neurons for at least twelve weeks after cessation of topotecan treatment, suggesting transient topoisomerase inhibition can have enduring effects on gene expression. While potential off-target effects remain to be investigated, our findings suggest a therapeutic strategy for reactivating the functional but dormant allele of Ube3a in patients with Angelman syndrome. PMID:22190039

  16. Taste responses of cortical neurons in freely ingesting rats.

    PubMed

    Yamamoto, T; Matsuo, R; Kiyomitsu, Y; Kitamura, R

    1989-06-01

    1. Activities of 35 taste-responsive neurons in the cortical gustatory area were recorded with chronically implanted fine wires in freely ingesting Wistar rats. Quantitative analyses were performed on responses to distilled water, food solution, and four taste stimuli: sucrose, NaCl, HCl, and quinine hydrochloride. 2. Taste-responsive neurons were classified into type-1 and type-2 groups according to the response patterns to licking of the six taste stimuli. Type-1 neurons (n = 29) responded in excitatory or inhibitory directions to one or more of the taste stimuli. Type-2 neurons (n = 6) showed responses in different directions depending upon palatability of the liquids to rats: neurons showing excitatory (or inhibitory) responses to palatable stimuli exhibited inhibitory (or excitatory) responses to unpalatable stimuli. 3. Correlation coefficients of responses to pairs of stimuli across neurons suggested that palatable stimuli (water, food solution, sucrose, and NaCl) and unpalatable stimuli (HCl and quinine) elicited reciprocal (excitatory vs. inhibitory) responses in type-2 neurons, whereas type-1 neurons showed positively correlated responses to specific combinations of stimuli such as food solution and NaCl, sucrose and HCl, NaCl and quinine, and HCl and quinine. 4. A tendency toward equalization of effectiveness in eliciting responses among the four basic taste stimuli was detected on the cortex. The ratios of mean evoked responses in 29 type-1 neurons in comparison with spontaneous rate (4.4 spikes/s) were 1.7, 1.9, 1.8, and 1.9 for sucrose, NaCl, HCl, and quinine, respectively. 5. The breadth of responsiveness to the four basic taste stimuli was quantified by means of the entropy measure introduced by Smith and Travers (33). The mean entropy value was 0.540 for 29 type-1 neurons, which was similar to 0.588 previously reported for rat chorda tympani fibers, suggesting that breadth of tuning is not more narrowly tuned in a higher level of the gustatory

  17. Unitary response of mouse olfactory receptor neurons

    PubMed Central

    Ben-Chaim, Yair; Cheng, Melody M.; Yau, King-Wai

    2011-01-01

    The sense of smell begins with odorant molecules binding to membrane receptors on the cilia of olfactory receptor neurons (ORNs), thereby activating a G protein, Golf, and the downstream effector enzyme, an adenylyl cyclase (ACIII). Recently, we have found in amphibian ORNs that an odorant-binding event has a low probability of activating sensory transduction at all; even when successful, the resulting unitary response apparently involves a single active Gαolf–ACIII molecular complex. This low amplification is in contrast to rod phototransduction in vision, the best-quantified G-protein signaling pathway, where each photoisomerized rhodopsin molecule is well known to produce substantial amplification by activating many G-protein, and hence effector-enzyme, molecules. We have now carried out similar experiments on mouse ORNs, which offer, additionally, the advantage of genetics. Indeed, we found the same low probability of transduction, based on the unitary olfactory response having a fairly constant amplitude and similar kinetics across different odorants and randomly encountered ORNs. Also, consistent with our picture, the unitary response of Gαolf+/− ORNs was similar to WT in amplitude, although their Gαolf-protein expression was only half of normal. Finally, from the action potential firing, we estimated that ≤19 odorant-binding events successfully triggering transduction in a WT mouse ORN will lead to signaling to the brain. PMID:21187398

  18. Response of Morris-Lecar neurons to various stimuli

    NASA Astrophysics Data System (ADS)

    Wang, Hengtong; Wang, Longfei; Yu, Lianchun; Chen, Yong

    2011-02-01

    We studied the responses of three classes of Morris-Lecar neurons to sinusoidal inputs and synaptic pulselike stimuli with deterministic and random interspike intervals (ISIs). It was found that the responses of the output frequency of class 1 and 2 neurons showed similar evolution properties by varying input amplitudes and frequencies, whereas class 3 neuron exhibited substantially different properties. Specifically, class 1 and 2 neurons display complicated phase locking (p : q, p>q, denoting output action potentials per input spikes) in low-frequency sinusoidal input area when the input amplitude is above their threshold, but a class 3 neuron does not fire action potentials in this area even if the amplitude is much higher. In the case of the deterministic ISI synaptic injection, all the three classes of neurons oscillate spikes with an arbitrary small frequency. When increasing the input frequency (both sinusoidal and deterministic ISI synaptic inputs), all neurons display 1 : 1 phase locking, whereas the response frequency decreases even fall to zero in the high-frequency input area. When the random ISI synaptic pulselike stimuli are injected into the neurons, one can clearly see the low-pass filter behaviors from the return map. The output ISI distribution depends on the mean ISI of input train as well as the ISI variation. Such different responses of three classes of neurons result from their distinct dynamical mechanisms of action potential initiation. It was suggested that the intrinsic dynamical cellular properties are very important to neuron information processing.

  19. Responses of medullary reticular formation neurons to input from the male genitalia.

    PubMed

    Hubscher, C H; Johnson, R D

    1996-10-01

    1. The medullary reticular formation (MRF) is known to be involved in the modulation of certain reproductive behaviors. Ejaculation in the male, disrupted after spinal transection, may depend on a spinal-bulbo-spinal connection. To determine whether single neurons in the MRF receive sensory input from the male genitalia, the present study was undertaken using electrophysiological techniques. 2. The MRF of 14 urethan-anesthetized mature male rats was searched for single neurons responsive to bilateral electrical stimulation of the dorsal nerve of the penis (DNP). In addition, each DNP-responsive neuron was tested for responsiveness to bilateral electrical stimulation of the pelvic nerve (PN) and to mechanical stimulation (gentle touch, pressure, pinch) of the external genitalia, anus, urethra, and skin over most regions of the body. 3. A total of 165 single neurons responsive to bilateral electrical stimulation of the DNP were isolated and characterized throughout the MRF. All neurons responded to both ipsilateral and contralateral DNP stimulation. The majority of responses were excitatory, and most neurons had no background activity. Some neurons required wind-up with bilateral electrical stimulation of the DNP to respond. 4. About half of the neurons were located in the nucleus reticularis gigantocellularis (Gi); the remainder were located in surrounding (dorsal, ventral, lateral) regions of the MRF. Variations in response properties were found among neurons located in different MRF regions. 5. Eighty-eight DNP-responsive neurons were additionally responsive to bilateral electrical stimulation of the PN. None of the responses to bilateral PN were stronger than those for bilateral DNP and many (48%) were weaker. 6. Of the 165 DNP-responsive neurons, all were responsive to pressure/pinching of the penis; 16% responded to gentle stroking of the glans. Most of these neurons were additionally responsive (bilaterally) to pinching more than one (often all) of the

  20. Egr2-neurons control the adult respiratory response to hypercapnia

    PubMed Central

    Ray, Russell S.; Corcoran, Andrea E.; Brust, Rachael D.; Soriano, Laura P.; Nattie, Eugene E.; Dymecki, Susan M.

    2013-01-01

    ‘The early growth response 2 transcription factor, Egr2, establishes a population of brainstem neurons essential for normal breathing at birth. Egr2-null mice die perinatally of respiratory insufficiency characterized by subnormal respiratory rate and severe apneas. Here we bypass this lethality using a noninvasive pharmacogenetic approach to inducibly perturb neuron activity postnatally, and ask if Egr2-neurons control respiration in adult mice. We found that the normal ventilatory increase in response to elevated tissue CO2 was impaired, blunted by 63.1±8.7% after neuron perturbation due to deficits in both respiratory amplitude and frequency. By contrast, room-air breathing was unaffected, suggesting that the drive for baseline breathing may not require those Egr2-neurons manipulated here. Of the multiple brainstem sites proposed to affect ventilation in response to hypercapnia, only the retrotrapezoid nucleus, a portion of the serotonergic raphé, and a portion of the A5 nucleus have a history of Egr2 expression. We recently showed that acute inhibition of serotonergic neurons en masse blunts the CO2 chemoreflex in adults, causing a difference in hypercapnic response of ~50% after neuron perturbation through effects on respiratory amplitude only. The suppressed respiratory frequency upon perturbation of Egr2-neurons thus may stem from non-serotonergic neurons within the Egr2 domain. Perturbation of Egr2-neurons did not affect body temperature, even on exposure to ambient 4 °C. These findings support a model in which Egr2-neurons are a critical component of the respiratory chemoreflex into adulthood. Methodologically, these results highlight how pharmacogenetic approaches allow neuron function to be queried in unanesthetized adult animals, reaching beyond the roadblocks of developmental lethality and compensation as well as the anatomical disturbances associated with invasive methods. PMID:23261662

  1. The effects of cholinergic neuromodulation on neuronal phase-response curves of modeled cortical neurons

    PubMed Central

    Stiefel, Klaus M.; Gutkin, Boris S.; Sejnowski, Terrence J.

    2010-01-01

    The response of an oscillator to perturbations is described by its phase-response curve (PRC), which is related to the type of bifurcation leading from rest to tonic spiking. In a recent experimental study, we have shown that the type of PRC in cortical pyramidal neurons can be switched by cholinergic neuromodulation from type II (biphasic) to type I (monophasic). We explored how intrinsic mechanisms affected by acetylcholine influence the PRC using three different types of neuronal models: a theta neuron, single-compartment neurons and a multi-compartment neuron. In all of these models a decrease in the amount of a spike-frequency adaptation current was a necessary and sufficient condition for the shape of the PRC to change from biphasic (type II) to purely positive (type I). PMID:18784991

  2. A coding-independent function of an alternative Ube3a transcript during neuronal development.

    PubMed

    Valluy, Jeremy; Bicker, Silvia; Aksoy-Aksel, Ayla; Lackinger, Martin; Sumer, Simon; Fiore, Roberto; Wüst, Tatjana; Seffer, Dominik; Metge, Franziska; Dieterich, Christoph; Wöhr, Markus; Schwarting, Rainer; Schratt, Gerhard

    2015-05-01

    The E3 ubiquitin ligase Ube3a is an important regulator of activity-dependent synapse development and plasticity. Ube3a mutations cause Angelman syndrome and have been associated with autism spectrum disorders (ASD). However, the biological significance of alternative Ube3a transcripts generated in mammalian neurons remains unknown. We report here that Ube3a1 RNA, a transcript that encodes a truncated Ube3a protein lacking catalytic activity, prevents exuberant dendrite growth and promotes spine maturation in rat hippocampal neurons. Surprisingly, Ube3a1 RNA function was independent of its coding sequence but instead required a unique 3' untranslated region and an intact microRNA pathway. Ube3a1 RNA knockdown increased activity of the plasticity-regulating miR-134, suggesting that Ube3a1 RNA acts as a dendritic competing endogenous RNA. Accordingly, the dendrite-growth-promoting effect of Ube3a1 RNA knockdown in vivo is abolished in mice lacking miR-134. Taken together, our results define a noncoding function of an alternative Ube3a transcript in dendritic protein synthesis, with potential implications for Angelman syndrome and ASD. PMID:25867122

  3. Angelman syndrome-derived neurons display late onset of paternal UBE3A silencing

    PubMed Central

    Stanurova, Jana; Neureiter, Anika; Hiber, Michaela; de Oliveira Kessler, Hannah; Stolp, Kristin; Goetzke, Roman; Klein, Diana; Bankfalvi, Agnes; Klump, Hannes; Steenpass, Laura

    2016-01-01

    Genomic imprinting is an epigenetic phenomenon resulting in parent-of-origin-specific gene expression that is regulated by a differentially methylated region. Gene mutations or failures in the imprinting process lead to the development of imprinting disorders, such as Angelman syndrome. The symptoms of Angelman syndrome are caused by the absence of functional UBE3A protein in neurons of the brain. To create a human neuronal model for Angelman syndrome, we reprogrammed dermal fibroblasts of a patient carrying a defined three-base pair deletion in UBE3A into induced pluripotent stem cells (iPSCs). In these iPSCs, both parental alleles are present, distinguishable by the mutation, and express UBE3A. Detailed characterization of these iPSCs demonstrated their pluripotency and exceptional stability of the differentially methylated region regulating imprinted UBE3A expression. We observed strong induction of SNHG14 and silencing of paternal UBE3A expression only late during neuronal differentiation, in vitro. This new Angelman syndrome iPSC line allows to study imprinted gene regulation on both parental alleles and to dissect molecular pathways affected by the absence of UBE3A protein. PMID:27484051

  4. Angelman syndrome-derived neurons display late onset of paternal UBE3A silencing.

    PubMed

    Stanurova, Jana; Neureiter, Anika; Hiber, Michaela; de Oliveira Kessler, Hannah; Stolp, Kristin; Goetzke, Roman; Klein, Diana; Bankfalvi, Agnes; Klump, Hannes; Steenpass, Laura

    2016-01-01

    Genomic imprinting is an epigenetic phenomenon resulting in parent-of-origin-specific gene expression that is regulated by a differentially methylated region. Gene mutations or failures in the imprinting process lead to the development of imprinting disorders, such as Angelman syndrome. The symptoms of Angelman syndrome are caused by the absence of functional UBE3A protein in neurons of the brain. To create a human neuronal model for Angelman syndrome, we reprogrammed dermal fibroblasts of a patient carrying a defined three-base pair deletion in UBE3A into induced pluripotent stem cells (iPSCs). In these iPSCs, both parental alleles are present, distinguishable by the mutation, and express UBE3A. Detailed characterization of these iPSCs demonstrated their pluripotency and exceptional stability of the differentially methylated region regulating imprinted UBE3A expression. We observed strong induction of SNHG14 and silencing of paternal UBE3A expression only late during neuronal differentiation, in vitro. This new Angelman syndrome iPSC line allows to study imprinted gene regulation on both parental alleles and to dissect molecular pathways affected by the absence of UBE3A protein. PMID:27484051

  5. Myosin5a Tail Associates Directly with Rab3A-containing Compartments in Neurons*

    PubMed Central

    Wöllert, Torsten; Patel, Anamika; Lee, Ying-Lung; Provance, D. William; Vought, Valarie E.; Cosgrove, Michael S.; Mercer, John A.; Langford, George M.

    2011-01-01

    Myosin-Va (Myo5a) is a motor protein associated with synaptic vesicles (SVs) but the mechanism by which it interacts has not yet been identified. A potential class of binding partners are Rab GTPases and Rab3A is known to associate with SVs and is involved in SV trafficking. We performed experiments to determine whether Rab3A interacts with Myo5a and whether it is required for transport of neuronal vesicles. In vitro motility assays performed with axoplasm from the squid giant axon showed a requirement for a Rab GTPase in Myo5a-dependent vesicle transport. Furthermore, mouse recombinant Myo5a tail revealed that it associated with Rab3A in rat brain synaptosomal preparations in vitro and the association was confirmed by immunofluorescence imaging of primary neurons isolated from the frontal cortex of mouse brains. Synaptosomal Rab3A was retained on recombinant GST-tagged Myo5a tail affinity columns in a GTP-dependent manner. Finally, the direct interaction of Myo5a and Rab3A was determined by sedimentation velocity analytical ultracentrifugation using recombinant mouse Myo5a tail and human Rab3A. When both proteins were incubated in the presence of 1 mm GTPγS, Myo5a tail and Rab3A formed a complex and a direct interaction was observed. Further analysis revealed that GTP-bound Rab3A interacts with both the monomeric and dimeric species of the Myo5a tail. However, the interaction between Myo5a tail and nucleotide-free Rab3A did not occur. Thus, our results show that Myo5a and Rab3A are direct binding partners and interact on SVs and that the Myo5a/Rab3A complex is involved in transport of neuronal vesicles. PMID:21349835

  6. Myosin5a tail associates directly with Rab3A-containing compartments in neurons.

    PubMed

    Wöllert, Torsten; Patel, Anamika; Lee, Ying-Lung; Provance, D William; Vought, Valarie E; Cosgrove, Michael S; Mercer, John A; Langford, George M

    2011-04-22

    Myosin-Va (Myo5a) is a motor protein associated with synaptic vesicles (SVs) but the mechanism by which it interacts has not yet been identified. A potential class of binding partners are Rab GTPases and Rab3A is known to associate with SVs and is involved in SV trafficking. We performed experiments to determine whether Rab3A interacts with Myo5a and whether it is required for transport of neuronal vesicles. In vitro motility assays performed with axoplasm from the squid giant axon showed a requirement for a Rab GTPase in Myo5a-dependent vesicle transport. Furthermore, mouse recombinant Myo5a tail revealed that it associated with Rab3A in rat brain synaptosomal preparations in vitro and the association was confirmed by immunofluorescence imaging of primary neurons isolated from the frontal cortex of mouse brains. Synaptosomal Rab3A was retained on recombinant GST-tagged Myo5a tail affinity columns in a GTP-dependent manner. Finally, the direct interaction of Myo5a and Rab3A was determined by sedimentation velocity analytical ultracentrifugation using recombinant mouse Myo5a tail and human Rab3A. When both proteins were incubated in the presence of 1 mm GTPγS, Myo5a tail and Rab3A formed a complex and a direct interaction was observed. Further analysis revealed that GTP-bound Rab3A interacts with both the monomeric and dimeric species of the Myo5a tail. However, the interaction between Myo5a tail and nucleotide-free Rab3A did not occur. Thus, our results show that Myo5a and Rab3A are direct binding partners and interact on SVs and that the Myo5a/Rab3A complex is involved in transport of neuronal vesicles. PMID:21349835

  7. Predicting olfactory receptor neuron responses from odorant structure

    PubMed Central

    Schmuker, Michael; de Bruyne, Marien; Hähnel, Melanie; Schneider, Gisbert

    2007-01-01

    Background Olfactory receptors work at the interface between the chemical world of volatile molecules and the perception of scent in the brain. Their main purpose is to translate chemical space into information that can be processed by neural circuits. Assuming that these receptors have evolved to cope with this task, the analysis of their coding strategy promises to yield valuable insight in how to encode chemical information in an efficient way. Results We mimicked olfactory coding by modeling responses of primary olfactory neurons to small molecules using a large set of physicochemical molecular descriptors and artificial neural networks. We then tested these models by recording in vivo receptor neuron responses to a new set of odorants and successfully predicted the responses of five out of seven receptor neurons. Correlation coefficients ranged from 0.66 to 0.85, demonstrating the applicability of our approach for the analysis of olfactory receptor activation data. The molecular descriptors that are best-suited for response prediction vary for different receptor neurons, implying that each receptor neuron detects a different aspect of chemical space. Finally, we demonstrate that receptor responses themselves can be used as descriptors in a predictive model of neuron activation. Conclusion The chemical meaning of molecular descriptors helps understand structure-response relationships for olfactory receptors and their "receptive fields". Moreover, it is possible to predict receptor neuron activation from chemical structure using machine-learning techniques, although this is still complicated by a lack of training data. PMID:17880742

  8. The sparseness of neuronal responses in ferret primary visual cortex.

    PubMed

    Tolhurst, David J; Smyth, Darragh; Thompson, Ian D

    2009-02-25

    Various arguments suggest that neuronal coding of natural sensory stimuli should be sparse (i.e., individual neurons should respond rarely but should respond reliably). We examined sparseness of visual cortical neurons in anesthetized ferret to flashed natural scenes. Response behavior differed widely between neurons. The median firing rate of 4.1 impulses per second was slightly higher than predicted from consideration of metabolic load. Thirteen percent of neurons (12 of 89) responded to <5% of the images, but one-half responded to >25% of images. Multivariate analysis of the range of sparseness values showed that 67% of the variance was accounted for by differing response patterns to moving gratings. Repeat presentation of images showed that response variance for natural images exaggerated sparseness measures; variance was scaled with mean response, but with a lower Fano factor than for the responses to moving gratings. This response variability and the "soft" sparse responses (Rehn and Sommer, 2007) raise the question of what constitutes a reliable neuronal response and imply parallel signaling by multiple neurons. We investigated whether the temporal structure of responses might be reliable enough to give additional information about natural scenes. Poststimulus time histogram shape was similar for "strong" and "weak" stimuli, with no systematic change in first-spike latency with stimulus strength. The variance of first-spike latency for repeat presentations of the same image was greater than the latency variance between images. In general, responses to flashed natural scenes do not seem compatible with a sparse encoding in which neurons fire rarely but reliably. PMID:19244512

  9. Temporal Characteristics of Gustatory Responses in Rat Parabrachial Neurons Vary by Stimulus and Chemosensitive Neuron Type

    PubMed Central

    Geran, Laura; Travers, Susan

    2013-01-01

    It has been demonstrated that temporal features of spike trains can increase the amount of information available for gustatory processing. However, the nature of these temporal characteristics and their relationship to different taste qualities and neuron types are not well-defined. The present study analyzed the time course of taste responses from parabrachial (PBN) neurons elicited by multiple applications of “sweet” (sucrose), “salty” (NaCl), “sour” (citric acid), and “bitter” (quinine and cycloheximide) stimuli in an acute preparation. Time course varied significantly by taste stimulus and best-stimulus classification. Across neurons, the ensemble code for the three electrolytes was similar initially but quinine diverged from NaCl and acid during the second 500ms of stimulation and all four qualities became distinct just after 1s. This temporal evolution was reflected in significantly broader tuning during the initial response. Metric space analyses of quality discrimination by individual neurons showed that increases in information (H) afforded by temporal factors was usually explained by differences in rate envelope, which had a greater impact during the initial 2s (22.5% increase in H) compared to the later response (9.5%). Moreover, timing had a differential impact according to cell type, with between-quality discrimination in neurons activated maximally by NaCl or citric acid most affected. Timing was also found to dramatically improve within-quality discrimination (80% increase in H) in neurons that responded optimally to bitter stimuli (B-best). Spikes from B-best neurons were also more likely to occur in bursts. These findings suggest that among PBN taste neurons, time-dependent increases in mutual information can arise from stimulus- and neuron-specific differences in response envelope during the initial dynamic period. A stable rate code predominates in later epochs. PMID:24124597

  10. Asynchronous response of coupled pacemaker neurons

    PubMed Central

    Dodla, Ramana; Wilson, Charles J.

    2009-01-01

    We study a network model of two conductance-based pacemaker neurons of differing natural frequency, coupled with either mutual excitation or inhibition, and receiving shared random inhibitory synaptic input. The networks may phase-lock spike-to-spike for strong mutual coupling. But the shared input can desynchronize the locked spike-pairs by selectively eliminating the lagging spike or modulating its timing with respect to the leading spike depending on their separation time window. Such loss of synchrony is also found in a large network of sparsely coupled heterogeneous spiking neurons receiving shared input. PMID:19257636

  11. Responses of prefrontal multisensory neurons to mismatching faces and vocalizations.

    PubMed

    Diehl, Maria M; Romanski, Lizabeth M

    2014-08-20

    Social communication relies on the integration of auditory and visual information, which are present in faces and vocalizations. Evidence suggests that the integration of information from multiple sources enhances perception compared with the processing of a unimodal stimulus. Our previous studies demonstrated that single neurons in the ventrolateral prefrontal cortex (VLPFC) of the rhesus monkey (Macaca mulatta) respond to and integrate conspecific vocalizations and their accompanying facial gestures. We were therefore interested in how VLPFC neurons respond differentially to matching (congruent) and mismatching (incongruent) faces and vocalizations. We recorded VLPFC neurons during the presentation of movies with congruent or incongruent species-specific facial gestures and vocalizations as well as their unimodal components. Recordings showed that while many VLPFC units are multisensory and respond to faces, vocalizations, or their combination, a subset of neurons showed a significant change in neuronal activity in response to incongruent versus congruent vocalization movies. Among these neurons, we typically observed incongruent suppression during the early stimulus period and incongruent enhancement during the late stimulus period. Incongruent-responsive VLPFC neurons were both bimodal and nonlinear multisensory, fostering their ability to respond to changes in either modality of a face-vocalization stimulus. These results demonstrate that ventral prefrontal neurons respond to changes in either modality of an audiovisual stimulus, which is important in identity processing and for the integration of multisensory communication information. PMID:25143605

  12. Responses to sulfated steroids of female mouse vomeronasal sensory neurons.

    PubMed

    Celsi, Fulvio; D'Errico, Anna; Menini, Anna

    2012-11-01

    The rodent vomeronasal organ plays an important role in many social behaviors. Using the calcium imaging technique with the dye fluo-4 we measured intracellular calcium concentration changes induced by the application of sulfated steroids to neurons isolated from the vomeronasal organ of female mice. We found that a mix of 10 sulfated steroids from the androgen, estrogen, pregnanolone, and glucocorticoid families induced a calcium response in 71% of neurons. Moreover, 31% of the neurons responded to a mix composed of 3 glucocorticoid-derived compounds, and 28% responded to a mix composed of 3 pregnanolone-derived compounds. Immunohistochemistry showed that neurons responding to sulfated steroids expressed phosphodiesterase 4A, a marker specific for apical neurons expressing V1R receptors. None of the neuron that responded to 1 mix responded also to the other, indicating a specificity of the responses. Some neurons responded to more than 1 individual component of the glucocorticoid-derived mix tested at high concentration, suggesting that these neurons are broadly tuned, although they still displayed strong specificity, remaining unresponsive to high concentrations of the ineffective compounds. PMID:22923146

  13. Responses from parabrachial gustatory neurons in behaving rats.

    PubMed

    Nishijo, H; Norgren, R

    1990-04-01

    1. The responses of a total of 70 single neurons were recorded from the parabrachial nuclei (PBN) in awake rats. In 59 neurons, sapid stimuli (0.5 ml) elicited significant taste responses. Of these 59 neurons, 10 also had significant responses to water. The mean spontaneous rate of the taste neurons was 13.4 +/- 6.9 (SD) spikes/s. Of the remaining 11 neurons, 9 responded significantly only to water; 2 had no significant responses to the standard fluid stimuli. 2. Based on the magnitude of their response to our four standard stimuli, the taste neurons were classified as follows: 42 NaCl-best, 14 sucrose-best, 2 citric acid-best, and 1 QHCl-best. Of these, 25 responded only to one of four sapid stimuli; 20 of these specific cells responded only to NaCl. All the remaining 34 neurons responded to two or more of the four sapid stimuli, with NaCl and sucrose responsiveness dominant. For the 59 taste neurons, the mean entropy for the absolute value of the responses was 0.68; for the excitatory activity alone, it was 0.58. 3. The mean responses to NaCl and sucrose concentration series increased monotonically. Except at the lowest concentration, responses to citric acid also increased monotonically, but with a lower slope. Mean responses to QHCl, however, remained stable or even decreased with increasing concentration. Thus the power functions for the NaCl and sucrose intensity-response series were higher than those of citric acid and QHCl. 4. A hierarchical cluster analysis of 59 parabrachial neurons suggested four different categories: NaCl-best, sucrose-best, citric acid-best, and QHCl-best. These categories were less evident in the two-dimensional space produced by multidimensional analysis, because the positions of NaCl- and sucrose-best neurons formed a continuum in which neural response profiles change successively from sucrose-specific to NaCl-specific. 5. The results were consistent with previous anatomic and neurophysiological data suggesting convergence in the

  14. Visual Attention Model Based on Statistical Properties of Neuron Responses

    PubMed Central

    Duan, Haibin; Wang, Xiaohua

    2015-01-01

    Visual attention is a mechanism of the visual system that can select relevant objects from a specific scene. Interactions among neurons in multiple cortical areas are considered to be involved in attentional allocation. However, the characteristics of the encoded features and neuron responses in those attention related cortices are indefinite. Therefore, further investigations carried out in this study aim at demonstrating that unusual regions arousing more attention generally cause particular neuron responses. We suppose that visual saliency is obtained on the basis of neuron responses to contexts in natural scenes. A bottom-up visual attention model is proposed based on the self-information of neuron responses to test and verify the hypothesis. Four different color spaces are adopted and a novel entropy-based combination scheme is designed to make full use of color information. Valuable regions are highlighted while redundant backgrounds are suppressed in the saliency maps obtained by the proposed model. Comparative results reveal that the proposed model outperforms several state-of-the-art models. This study provides insights into the neuron responses based saliency detection and may underlie the neural mechanism of early visual cortices for bottom-up visual attention. PMID:25747859

  15. Neuropilin 1 directly interacts with Fer kinase to mediate semaphorin 3A-induced death of cortical neurons.

    PubMed

    Jiang, Susan X; Whitehead, Shawn; Aylsworth, Amy; Slinn, Jacqueline; Zurakowski, Bogdan; Chan, Kenneth; Li, Jianjun; Hou, Sheng T

    2010-03-26

    Neuropilins (NRPs) are receptors for the major chemorepulsive axonal guidance cue semaphorins (Sema). The interaction of Sema3A/NRP1 during development leads to the collapse of growth cones. Here we show that Sema3A also induces death of cultured cortical neurons through NRP1. A specific NRP1 inhibitory peptide ameliorated Sema3A-evoked cortical axonal retraction and neuronal death. Moreover, Sema3A was also involved in cerebral ischemia-induced neuronal death. Expression levels of Sema3A and NRP1, but not NRP2, were significantly increased early during brain reperfusion following transient focal cerebral ischemia. NRP1 inhibitory peptide delivered to the ischemic brain was potently neuroprotective and prevented the loss of motor functions in mice. The integrity of the injected NRP1 inhibitory peptide into the brain remained unchanged, and the intact peptide permeated the ischemic hemisphere of the brain as determined using MALDI-MS-based imaging. Mechanistically, NRP1-mediated axonal collapse and neuronal death is through direct and selective interaction with the cytoplasmic tyrosine kinase Fer. Fer RNA interference effectively attenuated Sema3A-induced neurite retraction and neuronal death in cortical neurons. More importantly, down-regulation of Fer expression using Fer-specific RNA interference attenuated cerebral ischemia-induced brain damage. Together, these studies revealed a previously unknown function of NRP1 in signaling Sema3A-evoked neuronal death through Fer in cortical neurons. PMID:20133938

  16. Habituation of human limbic neuronal response to sensory stimulation.

    PubMed

    Wilson, C L; Babb, T L; Halgren, E; Wang, M L; Crandall, P H

    1984-04-01

    Hippocampal, parahippocampal gyrus, and amygdalar neuronal responses to visual and acoustic stimuli were analyzed during trains of several hundred stimulus repetitions as part of an investigation of sensory pathways to medial temporal lobe structures in complex-partial epilepsy patients who were being monitored with depth electrodes. Ten percent of more than 500 single and multiple units tested were responsive to simple sensory stimuli. The majority of the responsive units were recorded in the posterior parahippocampal gyrus (HG) during visual stimulation. Although neurons in pes hippocampi (PH; Ammons's horn) were also responsive to photic stimuli, no visually responsive units were found in amygdala. Very few units were responsive to acoustic stimuli, and these were found only in PH and amygdala, and not in HG. Significant trends of increase or decrease in response amplitude during trains of stimuli were found in all acoustically responsive units. Significant trends of visual response amplitude increase or decrease were found in 20% of PH units, and in 44% of HG units. Mean latencies of acoustically responsive units were longer than those of visually responsive units, and latencies of PH sensory units showing decremental response were longer than nondecremental PH units. Rate of response decrement was usually linear for acoustic responses and exponential for visual responses. The response dynamics of medial temporal lobe neurons are compared with those described in the animal limbic system and are related to habituation of human sensory evoked scalp potentials. PMID:6705888

  17. Finding and Not Finding Rat Perirhinal Neuronal Responses to Novelty.

    PubMed

    von Linstow Roloff, Eva; Muller, Robert U; Brown, Malcolm W

    2016-08-01

    There is much evidence that the perirhinal cortex of both rats and monkeys is important for judging the relative familiarity of visual stimuli. In monkeys many studies have found that a proportion of perirhinal neurons respond more to novel than familiar stimuli. There are fewer studies of perirhinal neuronal responses in rats, and those studies based on exploration of objects, have raised into question the encoding of stimulus familiarity by rat perirhinal neurons. For this reason, recordings of single neuronal activity were made from the perirhinal cortex of rats so as to compare responsiveness to novel and familiar stimuli in two different behavioral situations. The first situation was based upon that used in "paired viewing" experiments that have established rat perirhinal differences in immediate early gene expression for novel and familiar visual stimuli displayed on computer monitors. The second situation was similar to that used in the spontaneous object recognition test that has been widely used to establish the involvement of rat perirhinal cortex in familiarity discrimination. In the first condition 30 (25%) of 120 perirhinal neurons were visually responsive; of these responsive neurons 19 (63%) responded significantly differently to novel and familiar stimuli. In the second condition eight (53%) of 15 perirhinal neurons changed activity significantly in the vicinity of objects (had "object fields"); however, for none (0%) of these was there a significant activity change related to the familiarity of an object, an incidence significantly lower than for the first condition. Possible reasons for the difference are discussed. It is argued that the failure to find recognition-related neuronal responses while exploring objects is related to its detectability by the measures used, rather than the absence of all such signals in perirhinal cortex. Indeed, as shown by the results, such signals are found when a different methodology is used. © 2016 The Authors

  18. Finding and Not Finding Rat Perirhinal Neuronal Responses to Novelty

    PubMed Central

    Muller, Robert U.; Brown, Malcolm W.

    2016-01-01

    ABSTRACT There is much evidence that the perirhinal cortex of both rats and monkeys is important for judging the relative familiarity of visual stimuli. In monkeys many studies have found that a proportion of perirhinal neurons respond more to novel than familiar stimuli. There are fewer studies of perirhinal neuronal responses in rats, and those studies based on exploration of objects, have raised into question the encoding of stimulus familiarity by rat perirhinal neurons. For this reason, recordings of single neuronal activity were made from the perirhinal cortex of rats so as to compare responsiveness to novel and familiar stimuli in two different behavioral situations. The first situation was based upon that used in “paired viewing” experiments that have established rat perirhinal differences in immediate early gene expression for novel and familiar visual stimuli displayed on computer monitors. The second situation was similar to that used in the spontaneous object recognition test that has been widely used to establish the involvement of rat perirhinal cortex in familiarity discrimination. In the first condition 30 (25%) of 120 perirhinal neurons were visually responsive; of these responsive neurons 19 (63%) responded significantly differently to novel and familiar stimuli. In the second condition eight (53%) of 15 perirhinal neurons changed activity significantly in the vicinity of objects (had “object fields”); however, for none (0%) of these was there a significant activity change related to the familiarity of an object, an incidence significantly lower than for the first condition. Possible reasons for the difference are discussed. It is argued that the failure to find recognition‐related neuronal responses while exploring objects is related to its detectability by the measures used, rather than the absence of all such signals in perirhinal cortex. Indeed, as shown by the results, such signals are found when a different methodology is used.

  19. Measurement of infinitesimal phase response curves from noisy real neurons

    NASA Astrophysics Data System (ADS)

    Ota, Keisuke; Omori, Toshiaki; Watanabe, Shigeo; Miyakawa, Hiroyoshi; Okada, Masato; Aonishi, Toru

    2011-10-01

    We sought to measure infinitesimal phase response curves (iPRCs) from rat hippocampal CA1 pyramidal neurons. It is difficult to measure iPRCs from noisy neurons because of the dilemma that either the linearity or the signal-to-noise ratio of responses to external perturbations must be sacrificed. To overcome this difficulty, we used an iPRC measurement model formulated as the Langevin phase equation (LPE) to extract iPRCs in the Bayesian scheme. We then simultaneously verified the effectiveness of the measurement model and the reliability of the estimated iPRCs by demonstrating that LPEs with the estimated iPRCs could predict the stochastic behaviors of the same neurons, whose iPRCs had been measured, when they were perturbed by periodic stimulus currents. Our results suggest that the LPE is an effective model for real oscillating neurons and that many theoretical frameworks based on it may be applicable to real nerve systems.

  20. Responses of primate frontal cortex neurons during natural vocal communication

    PubMed Central

    Thomas, A. Wren; Nummela, Samuel U.; de la Mothe, Lisa A.

    2015-01-01

    The role of primate frontal cortex in vocal communication and its significance in language evolution have a controversial history. While evidence indicates that vocalization processing occurs in ventrolateral prefrontal cortex neurons, vocal-motor activity has been conjectured to be primarily subcortical and suggestive of a distinctly different neural architecture from humans. Direct evidence of neural activity during natural vocal communication is limited, as previous studies were performed in chair-restrained animals. Here we recorded the activity of single neurons across multiple regions of prefrontal and premotor cortex while freely moving marmosets engaged in a natural vocal behavior known as antiphonal calling. Our aim was to test whether neurons in marmoset frontal cortex exhibited responses during vocal-signal processing and/or vocal-motor production in the context of active, natural communication. We observed motor-related changes in single neuron activity during vocal production, but relatively weak sensory responses for vocalization processing during this natural behavior. Vocal-motor responses occurred both prior to and during call production and were typically coupled to the timing of each vocalization pulse. Despite the relatively weak sensory responses a population classifier was able to distinguish between neural activity that occurred during presentations of vocalization stimuli that elicited an antiphonal response and those that did not. These findings are suggestive of the role that nonhuman primate frontal cortex neurons play in natural communication and provide an important foundation for more explicit tests of the functional contributions of these neocortical areas during vocal behaviors. PMID:26084912

  1. Dnmt3a in Sim1 Neurons Is Necessary for Normal Energy Homeostasis

    PubMed Central

    Lee, Syann; Harper, Matthew J.; Kim, Ki Woo; Sone, Hideyuki; Sasaki, Tsutomu; Kitamura, Tadahiro; Fan, Guoping

    2014-01-01

    Obesity rates continue to rise throughout the world. Recent evidence has suggested that environmental factors contribute to altered energy balance regulation. However, the role of epigenetic modifications to the central control of energy homeostasis remains unknown. To investigate the role of DNA methylation in the regulation of energy balance, we investigated the role of the de novo DNA methyltransferase, Dnmt3a, in Single-minded 1 (Sim1) cells, including neurons in the paraventricular nucleus of the hypothalamus (PVH). Dnmt3a expression levels were decreased in the PVH of high-fat-fed mice. Mice lacking Dnmt3a specifically in the Sim1 neurons, which are expressed in the forebrain, including PVH, became obese with increased amounts of abdominal and subcutaneous fat. The mice were also found to have hyperphagia, decreased energy expenditure, and glucose intolerance with increased serum insulin and leptin. Furthermore, these mice developed hyper-LDL cholesterolemia when fed a high-fat diet. Gene expression profiling and DNA methylation analysis revealed that the expression of tyrosine hydroxylase and galanin were highly upregulated in the PVH of Sim1-specific Dnmt3a deletion mice. DNA methylation levels of the tyrosine hydroxylase promoter were decreased in the PVH of the deletion mice. These results suggest that Dnmt3a in the PVH is necessary for the normal control of body weight and energy homeostasis and that tyrosine hydroxylase is a putative target of Dnmt3a in the PVH. These results provide evidence for a role for Dnmt3a in the PVH to link environmental conditions to altered energy homeostasis. PMID:25392496

  2. Responses of neurons in the auditory pathway of the barn owl to partially correlated binaural signals.

    PubMed

    Albeck, Y; Konishi, M

    1995-10-01

    1. Extracellular single-unit recording in anesthetized barn owls was used to study neuronal response to dichotic stimuli of variable binaural correlation (BC). Recordings were made in the output fibers of nucleus laminaris (NL), the anterior division of the ventral lateral lemniscal nucleus (VLVa), the core of the central nucleus of the inferior colliculus (ICcC), the lateral shell of the central nucleus of the inferior colliculus (ICcLS), and the external nucleus of the inferior colliculus (ICx). 2. The response of all neurons sensitive to interaural time difference (ITD) varied with BC. The relationship between BC and impulse number fits a linear, a parabolic, or a ramp model. A linear or parabolic model fits most neurons in low-level nuclei. Higher order neurons in ICx did not respond to noise bursts with strong negative binaural correlation, creating a ramp-like response to BC. 3. A neuron's ability to detect ITD varied as a function of BC. Conversely, a neuron's response to BC changed with ITD. Neurons in NL, VLVa, and ICcC show almost periodic ITD response curves. In these neurons peaks and troughs of ITD response curves diminished as BC decreased, creating a flat ITD response when BC = 0. When BC was set to -1, the most favorable ITD became the least favorable one and vice versa. The ITD response curve of ICx neurons usually has a single dominant peak. The response of those neurons to a negatively correlated noise pair (BC = -1) showed two ITD peaks, flanking the position of the primary peak. 4. The parabolic BC response of NL neurons fits the prediction of the cross-correlation model, assuming half-wave rectification of the sound by the cochlea. Linear response is not predicted by the model. However, the parabolic and the linear neurons probably do not belong to two distinct groups as the difference between them is not statistically significant. Thus, the cross-correlation model provides a good description of the binaural response not only in NL but also in

  3. Complement Peptide C3a Promotes Astrocyte Survival in Response to Ischemic Stress.

    PubMed

    Shinjyo, Noriko; de Pablo, Yolanda; Pekny, Milos; Pekna, Marcela

    2016-07-01

    Astrocytes are the most numerous cells in the central nervous system with a range of homeostatic and regulatory functions. Under normal conditions as well as after ischemia, astrocytes promote neuronal survival. We have previously reported that the complement-derived peptide C3a stimulates neuronal differentiation of neural progenitor cells and protects the immature brain tissue against hypoxic-ischemic injury. Here, we studied the effects of C3a on the response of mouse cortical astrocytes to ischemia. We have found that chemical ischemia, induced by combined inhibition of oxidative phosphorylation and glycolysis, upregulates the expression of C3a receptor in cultured primary astrocytes. C3a treatment protected wild-type but not C3a receptor-deficient astrocytes from cell death induced by chemical ischemia or oxygen-glucose deprivation by reducing ERK signaling and caspase-3 activation. C3a attenuated ischemia-induced upregulation of glial fibrillary acidic protein; however, the protective effects of C3a were not dependent on the presence of the astrocyte intermediate filament system. Pre-treatment of astrocytes with C3a during recovery abrogated the ischemia-induced neuroprotective phenotype of astrocytes. Jointly, these results provide the first evidence that the complement peptide C3a modulates the response of astrocytes to ischemia and increases their ability to cope with ischemic stress. PMID:25972241

  4. Phasic activation of ventral tegmental neurons increases response and pattern similarity in prefrontal cortex neurons

    PubMed Central

    Iwashita, Motoko

    2014-01-01

    Dopamine is critical for higher neural processes and modifying the activity of the prefrontal cortex (PFC). However, the mechanism of dopamine contribution to the modification of neural representation is unclear. Using in vivo two-photon population Ca2+ imaging in awake mice, this study investigated how neural representation of visual input to PFC neurons is regulated by dopamine. Phasic stimulation of dopaminergic neurons in the ventral tegmental area (VTA) evoked prolonged Ca2+ transients, lasting ∼30 s in layer 2/3 neurons of the PFC, which are regulated by a dopamine D1 receptor-dependent pathway. Furthermore, only a conditioning protocol with visual sensory input applied 0.5 s before the VTA dopaminergic input could evoke enhanced Ca2+ transients and increased pattern similarity (or establish a neural representation) of PFC neurons to the same sensory input. By increasing both the level of neuronal response and pattern similarity, dopaminergic input may establish robust and reliable cortical representation. DOI: http://dx.doi.org/10.7554/eLife.02726.001 PMID:25269147

  5. Modeling of Auditory Neuron Response Thresholds with Cochlear Implants.

    PubMed

    Venail, Frederic; Mura, Thibault; Akkari, Mohamed; Mathiolon, Caroline; Menjot de Champfleur, Sophie; Piron, Jean Pierre; Sicard, Marielle; Sterkers-Artieres, Françoise; Mondain, Michel; Uziel, Alain

    2015-01-01

    The quality of the prosthetic-neural interface is a critical point for cochlear implant efficiency. It depends not only on technical and anatomical factors such as electrode position into the cochlea (depth and scalar placement), electrode impedance, and distance between the electrode and the stimulated auditory neurons, but also on the number of functional auditory neurons. The efficiency of electrical stimulation can be assessed by the measurement of e-CAP in cochlear implant users. In the present study, we modeled the activation of auditory neurons in cochlear implant recipients (nucleus device). The electrical response, measured using auto-NRT (neural responses telemetry) algorithm, has been analyzed using multivariate regression with cubic splines in order to take into account the variations of insertion depth of electrodes amongst subjects as well as the other technical and anatomical factors listed above. NRT thresholds depend on the electrode squared impedance (β = -0.11 ± 0.02, P < 0.01), the scalar placement of the electrodes (β = -8.50 ± 1.97, P < 0.01), and the depth of insertion calculated as the characteristic frequency of auditory neurons (CNF). Distribution of NRT residues according to CNF could provide a proxy of auditory neurons functioning in implanted cochleas. PMID:26236725

  6. Role of spinal bombesin-responsive neurons in nonhistaminergic itch

    PubMed Central

    Akiyama, Tasuku; Tominaga, Mitsutoshi; Takamori, Kenji; Carstens, E.

    2014-01-01

    Intrathecal administration of the neurotoxin bombesin-saporin reduces or abolishes pruritogen-evoked scratching behavior. We investigated whether spinal neurons that respond to intradermal (ID) injection of pruritogens also respond to spinal superfusion of bombesin and vice versa. Single-unit recordings were made from superficial lumbar spinal dorsal horn neurons in anesthetized mice. We identified neurons with three search strategies: 1) ID injection of the nonhistaminergic itch mediator chloroquine, 2) spinal superfusion of bombesin, and 3) noxious pinch. All units were tested with an array of itch mediators (chloroquine, histamine, SLIGRL, BAM8-22), algogens [capsaicin, allyl isothiocyanate (AITC)], and physical stimuli (brush, pinch, noxious heat, cooling) applied to the hindlimb receptive field. The vast majority of chloroquine-responsive units also responded to bombesin. Of 26 chloroquine-sensitive units tested, most responded to SLIGRL, half responded to histamine and/or BAM8-22, and most responded to capsaicin and/or AITC as well as noxious thermal and mechanical stimuli. Of 29 bombesin-responsive units, a large majority also responded to other itch mediators as well as AITC, capsaicin, and noxious thermal and mechanical stimuli. Responses to successive applications of bombesin exhibited tachyphylaxis. In contrast, of 36 units responsive to noxious pinch, the majority (67%) did not respond to ID chloroquine or spinal bombesin. It is suggested that chloroquine- and bombesin-sensitive spinal neurons signal itch from the skin. PMID:25122701

  7. Neuronal modelling of baroreflex response to orthostatic stress

    NASA Astrophysics Data System (ADS)

    Samin, Azfar

    The accelerations experienced in aerial combat can cause pilot loss of consciousness (GLOC) due to a critical reduction in cerebral blood circulation. The development of smart protective equipment requires understanding of how the brain processes blood pressure (BP) information in response to acceleration. We present a biologically plausible model of the Baroreflex to investigate the neural correlates of short-term BP control under acceleration or orthostatic stress. The neuronal network model, which employs an integrate-and-fire representation of a biological neuron, comprises the sensory, motor, and the central neural processing areas that form the Baroreflex. Our modelling strategy is to test hypotheses relating to the encoding mechanisms of multiple sensory inputs to the nucleus tractus solitarius (NTS), the site of central neural processing. The goal is to run simulations and reproduce model responses that are consistent with the variety of available experimental data. Model construction and connectivity are inspired by the available anatomical and neurophysiological evidence that points to a barotopic organization in the NTS, and the presence of frequency-dependent synaptic depression, which provides a mechanism for generating non-linear local responses in NTS neurons that result in quantifiable dynamic global baroreflex responses. The entire physiological range of BP and rate of change of BP variables is encoded in a palisade of NTS neurons in that the spike responses approximate Gaussian 'tuning' curves. An adapting weighted-average decoding scheme computes the motor responses and a compensatory signal regulates the heart rate (HR). Model simulations suggest that: (1) the NTS neurons can encode the hydrostatic pressure difference between two vertically separated sensory receptor regions at +Gz, and use changes in that difference for the regulation of HR; (2) even though NTS neurons do not fire with a cardiac rhythm seen in the afferents, pulse

  8. Broadband macroscopic cortical oscillations emerge from intrinsic neuronal response failures

    PubMed Central

    Goldental, Amir; Vardi, Roni; Sardi, Shira; Sabo, Pinhas; Kanter, Ido

    2015-01-01

    Broadband spontaneous macroscopic neural oscillations are rhythmic cortical firing which were extensively examined during the last century, however, their possible origination is still controversial. In this work we show how macroscopic oscillations emerge in solely excitatory random networks and without topological constraints. We experimentally and theoretically show that these oscillations stem from the counterintuitive underlying mechanism—the intrinsic stochastic neuronal response failures (NRFs). These NRFs, which are characterized by short-term memory, lead to cooperation among neurons, resulting in sub- or several- Hertz macroscopic oscillations which coexist with high frequency gamma oscillations. A quantitative interplay between the statistical network properties and the emerging oscillations is supported by simulations of large networks based on single-neuron in-vitro experiments and a Langevin equation describing the network dynamics. Results call for the examination of these oscillations in the presence of inhibition and external drives. PMID:26578893

  9. Expression by midbrain dopamine neurons of Sema3A and 3F receptors is associated with chemorepulsion in vitro but a mild in vivo phenotype.

    PubMed

    Torre, Enrique R; Gutekunst, Claire-Anne; Gross, Robert E

    2010-06-01

    Here we explore the role of semaphorin 3A and 3F (Sema3A, Sema3F) in the formation of the mesotelencephalic pathway. We show that Sema3A and 3F are expressed in the ventral mesencephalon (VM) of E13.5 rat embryos; the receptors Neuropilin 1 and Neuropilin 2, and co-receptors L1CAM, NrCAM, and Plexins A1 and A3 but not A4 are expressed by VM dopaminergic neurons; these neurons bind Sema3A and 3F in vitro which induces collapse of their growth cones and elicits, with different potencies, a repulsive response; and this response is absent in axons from Nrp1 and Nrp2 null embryos. Despite these in vitro effects, only very mild anatomical defects were detected in the organization of the mesotelencephalic pathway in embryonic and adult Nrp1 or Nrp2 null mice. However, the dopaminergic meso-habenular pathway and catecholaminergic neurons in the parafascicular and paraventricular nuclei of the thalamus were significantly affected in Nrp2 null mice. These data are consistent with a model whereby Sema3A and 3F, in combination with other guidance molecules, contributes to the navigation of DA axons to their final synaptic targets. PMID:20298787

  10. Finite Post Synaptic Potentials Cause a Fast Neuronal Response

    PubMed Central

    Helias, Moritz; Deger, Moritz; Rotter, Stefan; Diesmann, Markus

    2011-01-01

    A generic property of the communication between neurons is the exchange of pulses at discrete time points, the action potentials. However, the prevalent theory of spiking neuronal networks of integrate-and-fire model neurons relies on two assumptions: the superposition of many afferent synaptic impulses is approximated by Gaussian white noise, equivalent to a vanishing magnitude of the synaptic impulses, and the transfer of time varying signals by neurons is assessable by linearization. Going beyond both approximations, we find that in the presence of synaptic impulses the response to transient inputs differs qualitatively from previous predictions. It is instantaneous rather than exhibiting low-pass characteristics, depends non-linearly on the amplitude of the impulse, is asymmetric for excitation and inhibition and is promoted by a characteristic level of synaptic background noise. These findings resolve contradictions between the earlier theory and experimental observations. Here we review the recent theoretical progress that enabled these insights. We explain why the membrane potential near threshold is sensitive to properties of the afferent noise and show how this shapes the neural response. A further extension of the theory to time evolution in discrete steps quantifies simulation artifacts and yields improved methods to cross check results. PMID:21427776

  11. More sensitivity of cortical GABAergic neurons than glutamatergic neurons in response to acidosis.

    PubMed

    Liu, Hua; Li, Fang; Wang, Chunyan; Su, Zhiqiang

    2016-05-25

    Acidosis impairs brain functions. Neuron-specific mechanisms underlying acidosis-induced brain dysfunction remain elusive. We studied the sensitivity of cortical GABAergic neurons and glutamatergic neurons to acidosis by whole-cell recording in brain slices. The acidification to the neurons was induced by perfusing artificial cerebral spinal fluid with lower pH. This acidification impairs excitability and synaptic transmission in the glutamatergic and GABAergic neurons. Acidosis impairs spiking capacity in the GABAergic neurons more than in the glutamatergic neurons. Acidosis also strengthens glutamatergic synaptic transmission and attenuates GABAergic synaptic transmission on the GABAergic neurons more than the glutamatergic neurons, which results in the functional impairment of these GABAergic neurons. This acidosis-induced dysfunction predominantly in the cortical GABAergic neurons drives the homeostasis of neuronal networks toward overexcitation and exacerbates neuronal impairment. PMID:27116702

  12. 18 CFR 3a.13 - Classification responsibility and procedure.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 18 Conservation of Power and Water Resources 1 2014-04-01 2014-04-01 false Classification responsibility and procedure. 3a.13 Section 3a.13 Conservation of Power and Water Resources FEDERAL ENERGY REGULATORY COMMISSION, DEPARTMENT OF ENERGY GENERAL RULES NATIONAL SECURITY INFORMATION Classification §...

  13. 18 CFR 3a.13 - Classification responsibility and procedure.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 18 Conservation of Power and Water Resources 1 2011-04-01 2011-04-01 false Classification responsibility and procedure. 3a.13 Section 3a.13 Conservation of Power and Water Resources FEDERAL ENERGY REGULATORY COMMISSION, DEPARTMENT OF ENERGY GENERAL RULES NATIONAL SECURITY INFORMATION Classification §...

  14. 18 CFR 3a.13 - Classification responsibility and procedure.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 18 Conservation of Power and Water Resources 1 2013-04-01 2013-04-01 false Classification responsibility and procedure. 3a.13 Section 3a.13 Conservation of Power and Water Resources FEDERAL ENERGY REGULATORY COMMISSION, DEPARTMENT OF ENERGY GENERAL RULES NATIONAL SECURITY INFORMATION Classification §...

  15. 18 CFR 3a.13 - Classification responsibility and procedure.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 18 Conservation of Power and Water Resources 1 2012-04-01 2012-04-01 false Classification responsibility and procedure. 3a.13 Section 3a.13 Conservation of Power and Water Resources FEDERAL ENERGY REGULATORY COMMISSION, DEPARTMENT OF ENERGY GENERAL RULES NATIONAL SECURITY INFORMATION Classification §...

  16. 18 CFR 3a.13 - Classification responsibility and procedure.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 18 Conservation of Power and Water Resources 1 2010-04-01 2010-04-01 false Classification responsibility and procedure. 3a.13 Section 3a.13 Conservation of Power and Water Resources FEDERAL ENERGY REGULATORY COMMISSION, DEPARTMENT OF ENERGY GENERAL RULES NATIONAL SECURITY INFORMATION Classification §...

  17. Whole-mount imaging of responses in mouse vomeronasal neurons.

    PubMed

    Xu, Pei Sabrina; Holy, Timothy E

    2013-01-01

    Imaging permits the visualization of neural activity from the whole-mount vomeronasal sensory epithelium with single-cell resolution. The preparation preserves an intact tissue environment, enabling the robust detection of cellular responses upon chemical stimulation and study of the precise 3D mapping of vomeronasal sensory neuron (VSN) functional types within the epithelium. Using objective-coupled planar illumination (OCPI) microscopy to perform fast volumetric imaging, we routinely record the responses of thousands of VSNs for hours from a single intact vomeronasal organ preparation. Here we document the preparation of the whole-mounted vomeronasal epithelium, multichannel stimulus delivery, and three-dimensional calcium imaging by OCPI microscopy. PMID:24014363

  18. Response characteristics of a low-dimensional model neuron.

    PubMed

    Cartling, B

    1996-11-15

    It is shown that a low-dimensional model neuron with a response time constant smaller than the membrane time constant closely reproduces the activity and excitability behavior of a detailed conductance-based model of Hodgkin-Huxley type. The fast response of the activity variable also makes it possible to reduce the model to a one-dimensional model, in particular for typical conditions. As an example, the reduction to a single-variable model from a multivariable conductance-based model of a neocortical pyramidal cell with somatic input is demonstrated. The conditions for avoiding a spurious damped oscillatory response to a constant input are derived, and it is shown that a limit-cycle response cannot occur. The capability of the low-dimensional model to approximate higher-dimensional models accurately makes it useful for describing complex dynamics of nets of interconnected neurons. The simplicity of the model facilitates analytic studies, elucidations of neurocomputational mechanisms, and applications to large-scale systems. PMID:8888611

  19. Estradiol rapidly modulates odor responses in mouse vomeronasal sensory neurons.

    PubMed

    Cherian, S; Wai Lam, Y; McDaniels, I; Struziak, M; Delay, R J

    2014-06-01

    In rodents, many social behaviors are driven by the sense of smell. The vomeronasal organ (VNO), part of the accessory olfactory system mediates many of these chemically driven behaviors. The VNO is heavily vascularized, and is readily accessible to circulating peptide or steroid hormones. Potentially, this allows circulating hormones to alter behavior through modulating the output of the primary sensory neurons in the VNO, the vomeronasal sensory neurons (VSNs). Based on this, we hypothesized that steroid hormones, in particular 17β-estradiol, would modulate activity of VSNs. In this paper, we show that the estrogen receptors, GPR30 and ERα, were present in VSNs and that estradiol may be synthesized locally in the VNO. Our results also showed that 17β-estradiol decreased responses of isolated VSNs to dilute urine, a potent natural stimulus, with respect to current amplitudes and depolarization. Further, 17β-estradiol increased the latency of the first action potential (AP) and the AP amplitude. Additionally, calcium responses to sulfated steroids (present in the low molecular weight fraction of urine) that act as ligands for apical vomeronasal receptors were decreased by 17β-estradiol. In conclusion, we show that estradiol modulates odorant responses mediated by VSNs and hence paves the way for future studies to better understand the mechanisms by which odorant mediated behavior is altered by endocrine status of the animal. PMID:24680884

  20. Dissociation of neuronal, electrodermal, and evaluative responses in disgust extinction.

    PubMed

    Klucken, Tim; Schweckendiek, Jan; Merz, Christian J; Vaitl, Dieter; Stark, Rudolf

    2013-06-01

    Disgust extinction is an important mechanism relevant for the treatment of psychiatric disorders. However, only a few studies have investigated disgust extinction. Moreover, because disgust sensitivity (DS) is considered as a relevant factor for learning processes, this study also investigated the potential relationship between DS and disgust extinction learning. The aim of this study was to explore the neuronal correlates of disgust extinction, as well as changes in skin conductance responses (SCRs) and evaluative conditioning. Twenty subjects were exposed to a differential extinction paradigm, in which a previous conditioned, and now unreinforced, stimulus (conditioned stimulus, CS+) was compared to a second stimulus (CS-), which was previously not associated with the unconditioned stimulus (UCS). Extinction learning was measured on three different response levels (BOLD responses, SCRs, and evaluative conditioning). Regarding evaluative conditioning, the CS+ was rated as more unpleasant than the CS-. Interestingly, significantly increased amygdala responses and SCRs toward to the CS- were observed. Finally, a (negative) trend was found between DS scores and BOLD responses of the prefrontal cortex. The present findings showed a dissociation of different response levels. The increased CS- responses could be explained by the assumption that the increased amygdala activity may reflect a safety learning signal during the first extinction trials and the subjective focus may therefore shift from the CS+ to the CS-. The correlation finding supports previous studies postulating that DS hampers extinction processes. The present results point toward dissociations between the response levels in context of extinction processes. PMID:23731074

  1. In Vitro Ischemia Triggers a Transcriptional Response to Down-Regulate Synaptic Proteins in Hippocampal Neurons

    PubMed Central

    Fernandes, Joana; Vieira, Marta; Carreto, Laura; Santos, Manuel A. S.; Duarte, Carlos B.; Carvalho, Ana Luísa; Santos, Armanda E.

    2014-01-01

    Transient global cerebral ischemia induces profound changes in the transcriptome of brain cells, which is partially associated with the induction or repression of genes that influence the ischemic response. However, the mechanisms responsible for the selective vulnerability of hippocampal neurons to global ischemia remain to be clarified. To identify molecular changes elicited by ischemic insults, we subjected hippocampal primary cultures to oxygen-glucose deprivation (OGD), an in vitro model for global ischemia that resulted in delayed neuronal death with an excitotoxic component. To investigate changes in the transcriptome of hippocampal neurons submitted to OGD, total RNA was extracted at early (7 h) and delayed (24 h) time points after OGD and used in a whole-genome RNA microarray. We observed that at 7 h after OGD there was a general repression of genes, whereas at 24 h there was a general induction of gene expression. Genes related with functions such as transcription and RNA biosynthesis were highly regulated at both periods of incubation after OGD, confirming that the response to ischemia is a dynamic and coordinated process. Our analysis showed that genes for synaptic proteins, such as those encoding for PICK1, GRIP1, TARPγ3, calsyntenin-2/3, SAPAP2 and SNAP-25, were down-regulated after OGD. Additionally, OGD decreased the mRNA and protein expression levels of the GluA1 AMPA receptor subunit as well as the GluN2A and GluN2B subunits of NMDA receptors, but increased the mRNA expression of the GluN3A subunit, thus altering the composition of ionotropic glutamate receptors in hippocampal neurons. Together, our results present the expression profile elicited by in vitro ischemia in hippocampal neurons, and indicate that OGD activates a transcriptional program leading to down-regulation in the expression of genes coding for synaptic proteins, suggesting that the synaptic proteome may change after ischemia. PMID:24960035

  2. Neuronal response impedance mechanism implementing cooperative networks with low firing rates and μs precision

    PubMed Central

    Vardi, Roni; Goldental, Amir; Marmari, Hagar; Brama, Haya; Stern, Edward A.; Sardi, Shira; Sabo, Pinhas; Kanter, Ido

    2015-01-01

    Realizations of low firing rates in neural networks usually require globally balanced distributions among excitatory and inhibitory links, while feasibility of temporal coding is limited by neuronal millisecond precision. We show that cooperation, governing global network features, emerges through nodal properties, as opposed to link distributions. Using in vitro and in vivo experiments we demonstrate microsecond precision of neuronal response timings under low stimulation frequencies, whereas moderate frequencies result in a chaotic neuronal phase characterized by degraded precision. Above a critical stimulation frequency, which varies among neurons, response failures were found to emerge stochastically such that the neuron functions as a low pass filter, saturating the average inter-spike-interval. This intrinsic neuronal response impedance mechanism leads to cooperation on a network level, such that firing rates are suppressed toward the lowest neuronal critical frequency simultaneously with neuronal microsecond precision. Our findings open up opportunities of controlling global features of network dynamics through few nodes with extreme properties. PMID:26124707

  3. Neuronal response impedance mechanism implementing cooperative networks with low firing rates and μs precision.

    PubMed

    Vardi, Roni; Goldental, Amir; Marmari, Hagar; Brama, Haya; Stern, Edward A; Sardi, Shira; Sabo, Pinhas; Kanter, Ido

    2015-01-01

    Realizations of low firing rates in neural networks usually require globally balanced distributions among excitatory and inhibitory links, while feasibility of temporal coding is limited by neuronal millisecond precision. We show that cooperation, governing global network features, emerges through nodal properties, as opposed to link distributions. Using in vitro and in vivo experiments we demonstrate microsecond precision of neuronal response timings under low stimulation frequencies, whereas moderate frequencies result in a chaotic neuronal phase characterized by degraded precision. Above a critical stimulation frequency, which varies among neurons, response failures were found to emerge stochastically such that the neuron functions as a low pass filter, saturating the average inter-spike-interval. This intrinsic neuronal response impedance mechanism leads to cooperation on a network level, such that firing rates are suppressed toward the lowest neuronal critical frequency simultaneously with neuronal microsecond precision. Our findings open up opportunities of controlling global features of network dynamics through few nodes with extreme properties. PMID:26124707

  4. Responses of rat trigeminal ganglion neurons to longitudinal whisker stimulation.

    PubMed

    Stüttgen, Maik C; Kullmann, Stephanie; Schwarz, Cornelius

    2008-10-01

    Responses of rat trigeminal ganglion neurons to longitudinal whisker stimulation. Rats use their mobile set of whiskers to actively explore their environment. Parameters that play a role to generate movement dynamics of the whisker shaft within the follicle, thus activating primary afferents, are manifold: among them are mechanical properties of the whiskers (curvature, elasticity and taper), active movements (head, body, and whiskers), and finally, object characteristics (surface, geometry, position, and orientation). Hence the whisker system is confronted with forces along all three axes in space. Movements along the two latitudinal axes of the whisker (horizontal and vertical) have been well studied. Here we focus on movement along the whisker's longitudinal axis that has been neglected so far. We employed ramp-and-hold movements that pushed the whisker shaft toward the skin and quantified the resulting activity in trigeminal first-order afferents in anesthetized rats. Virtually all recorded neurons were highly sensitive to longitudinal movement. Neurons could be perfectly segregated into two groups according to their modulation by stimulus amplitude and velocity, respectively. This classification regimen correlated perfectly with the presence or absence of slowly adapting responses in longitudinal stimulation but agreed with classification derived from latitudinal stimulation only if the whisker was engaged in its optimal direction and set point. We conclude that longitudinal stimulation is an extremely effective means to activate the tactile pathway and thus is highly likely to play an important role in tactile coding on the ascending somatosensory pathway. In addition, compared with latitudinal stimulation, it provides a reliable and easy to use method to classify trigeminal first-order afferents. PMID:18684907

  5. ERM proteins regulate growth cone responses to Sema3A

    PubMed Central

    Mintz, C. David; Carcea, Ioana; McNickle, Daniel G.; Dickson, Tracey C.; Ge, Yongchao; Salton, Stephen R.J.; Benson, Deanna L.

    2008-01-01

    Axonal growth cones initiate and sustain directed growth in response to cues in their environment. A variety of events such as receptor internalization, kinase activation, and actin rearrangement can be stimulated by guidance cues and are essential for mediating targeted growth cone behavior. Surprisingly little is known about how such disparate actions are coordinated. Our data suggest that ezrin, radixin, and moesin (ERMs), a family of highly homologous, multifunctional proteins may be able to coordinate growth cone responses to the guidance cue, Sema3A. We show that active ERMs concentrate asymmetrically in neocortical growth cones, are rapidly and transiently inactivated by Sema3A, and are required for Sema3A-mediated growth cone collapse and guidance. The FERM domain of active ERMs regulates internalization of the Sema3A receptor, Npn1 and its co-receptor, L1CAM, while the ERM C-terminal domain binds and caps F-actin. Our data support a model in which ERMs can coordinate membrane and actin dynamics in response to Sema3A. PMID:18651636

  6. Stimulus-induced response patterns of medium-embedded neurons

    NASA Astrophysics Data System (ADS)

    Postnov, D. E.; Chetverikov, A. P.; Postnov, D. D.

    2010-09-01

    Neuronal ensembles in living organisms are often embedded in a media that provides additional interaction pathways and autoregulation. The underlying mechanisms include but are not limited to modulatory activity of some distantly propagated neuromediators like serotonin, variation of extracellular potassium concentration in brain tissue, and calcium waves propagation in networks of astrocytes. Interaction of these diverse processes can lead to formation of complex spatiotemporal patterns, both self-sustained or triggered by external signal. Besides network effects, many dynamical features of such systems originate from reciprocal interaction between single neuron and surrounding medium. In the present paper we study the response of such systems to the application of a single stimulus pulse. We use a minimal mathematical model representing a forced excitable unit that is embedded in a diffusive or (spatially inhomogeneous) excitable medium. We illustrate three different mechanisms for the formation of response patterns: (i) self-sustained depolarization, (ii) propagation of depolarization due to “nearest-neighbor” networks, and (iii) re-entrant waves.

  7. Predicting the response of olfactory sensory neurons to odor mixtures from single odor response

    NASA Astrophysics Data System (ADS)

    Marasco, Addolorata; de Paris, Alessandro; Migliore, Michele

    2016-04-01

    The response of olfactory receptor neurons to odor mixtures is not well understood. Here, using experimental constraints, we investigate the mathematical structure of the odor response space and its consequences. The analysis suggests that the odor response space is 3-dimensional, and predicts that the dose-response curve of an odor receptor can be obtained, in most cases, from three primary components with specific properties. This opens the way to an objective procedure to obtain specific olfactory receptor responses by manipulating mixtures in a mathematically predictable manner. This result is general and applies, independently of the number of odor components, to any olfactory sensory neuron type with a response curve that can be represented as a sigmoidal function of the odor concentration.

  8. Predicting the response of olfactory sensory neurons to odor mixtures from single odor response

    PubMed Central

    Marasco, Addolorata; De Paris, Alessandro; Migliore, Michele

    2016-01-01

    The response of olfactory receptor neurons to odor mixtures is not well understood. Here, using experimental constraints, we investigate the mathematical structure of the odor response space and its consequences. The analysis suggests that the odor response space is 3-dimensional, and predicts that the dose-response curve of an odor receptor can be obtained, in most cases, from three primary components with specific properties. This opens the way to an objective procedure to obtain specific olfactory receptor responses by manipulating mixtures in a mathematically predictable manner. This result is general and applies, independently of the number of odor components, to any olfactory sensory neuron type with a response curve that can be represented as a sigmoidal function of the odor concentration. PMID:27053070

  9. Functional response properties of VIP-expressing inhibitory neurons in mouse visual and auditory cortex

    PubMed Central

    Mesik, Lukas; Ma, Wen-pei; Li, Ling-yun; Ibrahim, Leena A.; Huang, Z. J.; Zhang, Li I.; Tao, Huizhong W.

    2015-01-01

    Despite accounting for about 20% of all the layer 2/3 inhibitory interneurons, the vasoactive intestinal polypeptide (VIP) expressing neurons remain the least thoroughly studied of the major inhibitory subtypes. In recent studies, VIP neurons have been shown to be activated by a variety of cortico-cortical and neuromodulatory inputs, but their basic sensory response properties remain poorly characterized. We set out to explore the functional properties of layer 2/3 VIP neurons in the primary visual (V1) and primary auditory cortex (A1), using two-photon imaging guided patch recordings. We found that in the V1, VIP neurons were generally broadly tuned, with their sensory response properties resembling those of parvalbumin (PV) expressing neurons. With the exception of response latency, they did not exhibit a significant difference from PV neurons across any of the properties tested, including overlap index, response modulation, orientation selectivity, and direction selectivity. In the A1, on the other hand, VIP neurons had a strong tendency to be intensity selective, which is a property associated with a subset of putative pyramidal cells and virtually absent in PV neurons. VIP neurons had a best intensity that was significantly lower than that of PV and putative pyramidal neurons. Finally, sensory evoked spike responses of VIP neurons were delayed relative to pyramidal and PV neurons in both the V1 and A1. Combined, these results demonstrate that the sensory response properties of VIP neurons do not fit a simple model of being either PV-like broadly tuned or pyramidal-like narrowly tuned. Instead, the selectivity pattern varies with sensory area and can even be, as in the case of low sound intensity responsiveness, distinct from both PV and pyramidal neurons. PMID:26106301

  10. Response characteristics of pruriceptive and nociceptive trigeminoparabrachial tract neurons in the rat.

    PubMed

    Jansen, Nico A; Giesler, Glenn J

    2015-01-01

    We tested the possibility that the trigeminoparabrachial tract (VcPbT), a projection thought to be importantly involved in nociception, might also contribute to sensation of itch. In anesthetized rats, 47 antidromically identified VcPbT neurons with receptive fields involving the cheek were characterized for their responses to graded mechanical and thermal stimuli and intradermal injections of pruritogens (serotonin, chloroquine, and β-alanine), partial pruritogens (histamine and capsaicin), and an algogen (mustard oil). All pruriceptive VcPbT neurons were responsive to mechanical stimuli, and more than half were additionally responsive to thermal stimuli. The majority of VcPbT neurons were activated by injections of serotonin, histamine, capsaicin, and/or mustard oil. A subset of neurons were inhibited by injection of chloroquine. The large majority of VcPbT neurons projected to the ipsilateral and/or contralateral external lateral parabrachial and Kölliker-Fuse nuclei, as evidenced by antidromic mapping techniques. Analyses of mean responses and spike-timing dynamics of VcPbT neurons suggested clear differences in firing rates between responses to noxious and pruritic stimuli. Comparisons between the present data and those previously obtained from trigeminothalamic tract (VcTT) neurons demonstrated several differences in responses to some pruritogens. For example, responses of VcPbT neurons to injection of serotonin often endured for nearly an hour and showed a delayed peak in discharge rate. In contrast, responses of VcTT neurons endured for roughly 20 min and no delayed peak of firing was noted. Thus the longer duration responses to 5-HT and the delay in peak firing of VcPbT neurons better matched behavioral responses to stimulation in awake rats than did those of VcTT neurons. The results indicate that VcPbT neurons may have important roles in the signaling of itch as well as pain. PMID:25298386

  11. Encoding of head acceleration in vestibular neurons. I. Spatiotemporal response properties to linear acceleration

    NASA Technical Reports Server (NTRS)

    Bush, G. A.; Perachio, A. A.; Angelaki, D. E.

    1993-01-01

    1. Extracellular recordings were made in and around the medial vestibular nuclei in decerebrated rats. Neurons were functionally identified according to their semicircular canal input on the basis of their responses to angular head rotations around the yaw, pitch, and roll head axes. Those cells responding to angular acceleration were classified as either horizontal semicircular canal-related (HC) or vertical semicircular canal-related (VC) neurons. The HC neurons were further characterized as either type I or type II, depending on the direction of rotation producing excitation. Cells that lacked a response to angular head acceleration, but exhibited sensitivity to a change in head position, were classified as purely otolith organ-related (OTO) neurons. All vestibular neurons were then tested for their response to sinusoidal linear translation in the horizontal head plane. 2. Convergence of macular and canal inputs onto central vestibular nuclei neurons occurred in 73% of the type I HC, 79% of the type II HC, and 86% of the VC neurons. Out of the 223 neurons identified as receiving macular input, 94 neurons were further studied, and their spatiotemporal response properties to sinusoidal stimulation with pure linear acceleration were quantified. Data were obtained from 33 type I HC, 22 type II HC, 22 VC, and 17 OTO neurons. 3. For each neuron the angle of the translational stimulus vector was varied by 15, 30, or 45 degrees increments in the horizontal head plane. In all tested neurons, a direction of maximum sensitivity was identified. An interesting difference among neurons was their response to translation along the direction perpendicular to that that produced the maximum response ("null" direction). For the majority of neurons tested, it was possible to evoke a nonzero response during stimulation along the null direction always had response phases that varied as a function of stimulus direction. 4. These spatiotemporal response properties were quantified in two

  12. Mitochondrial SIRT3 Mediates Adaptive Responses of Neurons to Exercise and Metabolic and Excitatory Challenges.

    PubMed

    Cheng, Aiwu; Yang, Ying; Zhou, Ye; Maharana, Chinmoyee; Lu, Daoyuan; Peng, Wei; Liu, Yong; Wan, Ruiqian; Marosi, Krisztina; Misiak, Magdalena; Bohr, Vilhelm A; Mattson, Mark P

    2016-01-12

    The impact of mitochondrial protein acetylation status on neuronal function and vulnerability to neurological disorders is unknown. Here we show that the mitochondrial protein deacetylase SIRT3 mediates adaptive responses of neurons to bioenergetic, oxidative, and excitatory stress. Cortical neurons lacking SIRT3 exhibit heightened sensitivity to glutamate-induced calcium overload and excitotoxicity and oxidative and mitochondrial stress; AAV-mediated Sirt3 gene delivery restores neuronal stress resistance. In models relevant to Huntington's disease and epilepsy, Sirt3(-/-) mice exhibit increased vulnerability of striatal and hippocampal neurons, respectively. SIRT3 deficiency results in hyperacetylation of several mitochondrial proteins, including superoxide dismutase 2 and cyclophilin D. Running wheel exercise increases the expression of Sirt3 in hippocampal neurons, which is mediated by excitatory glutamatergic neurotransmission and is essential for mitochondrial protein acetylation homeostasis and the neuroprotective effects of running. Our findings suggest that SIRT3 plays pivotal roles in adaptive responses of neurons to physiological challenges and resistance to degeneration. PMID:26698917

  13. Differential susceptibility to chronic social defeat stress relates to the number of Dnmt3a-immunoreactive neurons in the hippocampal dentate gyrus.

    PubMed

    Hammels, Caroline; Prickaerts, Jos; Kenis, Gunter; Vanmierlo, Tim; Fischer, Maximilian; Steinbusch, Harry W M; van Os, Jim; van den Hove, Daniel L A; Rutten, Bart P F

    2015-01-01

    The enzyme DNA methyltransferase 3a (Dnmt3a) is crucially involved in DNA methylation and recent studies have demonstrated that Dnmt3a is functionally involved in mediating and moderating the impact of environmental exposures on gene expression and behavior. Findings in rodents have suggested that DNA methylation is involved in regulating neuronal proliferation and differentiation. So far, it has been shown that chronic social defeat might influence neurogenesis, while susceptibility to social defeat stress is dependent on gene expression changes in the nucleus accumbens and the mesolimbic dopaminergic system. However, the role of Dnmt3a herein has not been fully characterized. Our earlier immunohistochemical work has revealed the existence of two types of Dnmt3a-immunoreactive cells in the mouse hippocampus, of which one represents a distinct type with intense Dnmt3a-immunoreactivity (Dnmt3a type II cells) co-localizing with a marker of recent proliferation. Based on this, we hypothesize that behavioral susceptibility to chronic social defeat stress is linked to (i) Dnmt3a protein levels in the nucleus accumbens and hippocampus, and (ii) to the density of Dnmt3a type II cells in the hippocampal dentate gyrus. While no differences were found in global levels of Dnmt3a protein expression in the nucleus accumbens and hippocampus, our stereological quantifications indicated a significantly increased density of Dnmt3a type II cells in the dentate gyrus of animals resilient to social defeat stress compared to susceptible and control animals. Further characterization of the Dnmt3a type II cells revealed that these cells were mostly doublecortin (25%) or NeuN (60%) immunopositive, thus defining them as immature and mature neurons. Moreover, negative associations between the density of Dnmt3a type II cells and indices of depressive-like behavior in the sucrose intake and forced swim test were found. These correlational data suggest that DNA methylation via Dnmt3a in the

  14. 3K3A-activated protein C stimulates postischemic neuronal repair by human neural stem cells in mice.

    PubMed

    Wang, Yaoming; Zhao, Zhen; Rege, Sanket V; Wang, Min; Si, Gabriel; Zhou, Yi; Wang, Su; Griffin, John H; Goldman, Steven A; Zlokovic, Berislav V

    2016-09-01

    Activated protein C (APC) is a blood protease with anticoagulant activity and cell-signaling activities mediated by the activation of protease-activated receptor 1 (F2R, also known as PAR1) and F2RL1 (also known as PAR3) via noncanonical cleavage. Recombinant variants of APC, such as the 3K3A-APC (Lys191-193Ala) mutant in which three Lys residues (KKK191-193) were replaced with alanine, and/or its other mutants with reduced (>90%) anticoagulant activity, engineered to reduce APC-associated bleeding risk while retaining normal cell-signaling activity, have shown benefits in preclinical models of ischemic stroke, brain trauma, multiple sclerosis, amyotrophic lateral sclerosis, sepsis, ischemic and reperfusion injury of heart, kidney and liver, pulmonary, kidney and gastrointestinal inflammation, diabetes and lethal body radiation. On the basis of proof-of-concept studies and an excellent safety profile in humans, 3K3A-APC has advanced to clinical trials as a neuroprotectant in ischemic stroke. Recently, 3K3A-APC has been shown to stimulate neuronal production by human neural stem and progenitor cells (NSCs) in vitro via a PAR1-PAR3-sphingosine-1-phosphate-receptor 1-Akt pathway, which suggests the potential for APC-based treatment as a strategy for structural repair in the human central nervous (CNS) system. Here we report that late postischemic treatment of mice with 3K3A-APC stimulates neuronal production by transplanted human NSCs, promotes circuit restoration and improves functional recovery. Thus, 3K3A-APC-potentiated neuronal recruitment from engrafted NSCs might offer a new approach to the treatment of stroke and related neurological disorders. PMID:27548576

  15. Responses of cockroach antennal lobe projection neurons to pulsatile olfactory stimuli.

    PubMed

    Lemon, W C; Getz, W M

    1998-11-30

    Behavioral evidence indicates that insects preferentially orient toward pulses of odorants as they occur downwind from a point source. Our recent results have shown that cockroach olfactory receptor neurons are able to reliably resolve 10-Hz pulses of the general "green' odorant 1-hexanol, but it is unknown to what extent the central olfactory pathway is able to resolve temporal aspects of a general odor stimulus. In the present study, temporal response characteristics were measured in antennal lobe projection neurons of female American cockroaches, Periplaneta americana in response to series of short odor pulses (2.5-20 Hz). Odor pulses were delivered to olfactory sensilla in a moving airstream controlled by electromagnetic valves and quantified by replacing the odorant with oil smoke and measuring the concentration of smoke passing through a light beam. The responses of projection neurons were recorded with an intracellular microelectrode placed in the projection neuron cell body. A variety of time courses of responses were recorded. Response patterns were consistent among identical stimuli within a neuron and varied among neurons. Some neurons increased spike frequency with stimulus onset while others decreased spike frequency. The latency to the change in spike frequency and the duration of the response also varied among neurons. Regardless of the temporal characteristics of the responses, nearly all projection neurons were able to resolve pulses of 1-hexanol presented at 5 Hz and some could resolve 10-Hz pulses. Thus, responses of antennal lobe projection neurons can reflect fine structures of non-uniform distributions of general odorants in a turbulent odor plume. In addition, the variety of temporal response characteristics to identical stimuli suggests that odor quality is coded by a temporal code expressed across a population of projection neurons. PMID:10049232

  16. Olfactory receptor neuron responses coding for rapid odour sampling

    PubMed Central

    Ghatpande, Ambarish S; Reisert, Johannes

    2011-01-01

    Abstract Vertebrate olfactory receptor neurons (ORNs) are stimulated in a rhythmic manner in vivo, driven by delivery of odorants to the nasal cavity carried by the inhaled air, making olfaction a sense where animals can control the frequency of stimulus delivery. How ORNs encode repeated stimulation at resting, low breathing frequencies and at increased sniffing frequencies is not known, nor is it known if the olfactory transduction cascade is accurate and fast enough to follow high frequency stimulation. We investigated mouse olfactory responses to stimulus frequencies mimicking odorant exposure during low (2 Hz) and high (5 Hz) frequency sniffing. ORNs reliably follow low frequency stimulations with high fidelity by generating bursts of action potentials at each stimulation at intermediate odorant concentrations, but fail to do so at high odorant concentrations. Higher stimulus frequencies across all odorant concentrations reduced the likelihood of action potential generation, increased the latency of response, and decreased the reliability of encoding the onset of stimulation. Thus an increase in stimulus frequency degrades and at high odorant concentrations entirely prevents action potential generation in individual ORNs, causing reduced signalling to the olfactory bulb. These results demonstrate that ORNs do not simply relay timing and concentration of an odorous stimulus, but also process and modulate the stimulus in a frequency-dependent manner which is controlled by the chosen sniffing rate. PMID:21486768

  17. Astrocyte-to-neuron signaling in response to photostimulation with a femtosecond laser

    NASA Astrophysics Data System (ADS)

    Zhao, Yuan; Liu, Xiuli; Zhou, Wei; Zeng, Shaoqun

    2010-08-01

    Conventional stimulation techniques used in studies of astrocyte-to-neuron signaling are invasive or dependent on additional electrical devices or chemicals. Here, we applied photostimulation with a femtosecond laser to selectively stimulate astrocytes in the hippocampal neural network, and the neuronal responses were examined. The results showed that, after photostimulation, cell-specific astrocyte-to-neuron signaling was triggered; sometimes the neuronal responses were even synchronous. Since photostimulation with a femtosecond laser is noninvasive, agent-free, and highly precise, this method has been proved to be efficient in activating astrocytes for investigations of astrocytic functions in neural networks.

  18. Nerve Growth Factor Inhibits Sympathetic Neurons' Response to an Injury Cytokine

    NASA Astrophysics Data System (ADS)

    Shadiack, Annette M.; Vaccariello, Stacey A.; Sun, Yi; Zigmond, Richard E.

    1998-06-01

    Axonal damage to adult peripheral neurons causes changes in neuronal gene expression. For example, axotomized sympathetic, sensory, and motor neurons begin to express galanin mRNA and protein, and recent evidence suggests that galanin plays a role in peripheral nerve regeneration. Previous studies in sympathetic and sensory neurons have established that galanin expression is triggered by two consequences of nerve transection: the induction of leukemia inhibitory factor (LIF) and the reduction in the availability of the target-derived factor, nerve growth factor. It is shown in the present study that no stimulation of galanin expression occurs following direct application of LIF to intact neurons in the superior cervical sympathetic ganglion. Injection of animals with an antiserum to nerve growth factor concomitant with the application of LIF, on the other hand, does stimulate galanin expression. The data suggest that the response of neurons to an injury factor, LIF, is affected by whether the neurons still receive trophic signals from their targets.

  19. Manipulation of an Innate Escape Response in Drosophila: Photoexcitation of acj6 Neurons Induces the Escape Response

    PubMed Central

    Manoli, Devanand S.; Zhang, Feng; Deisseroth, Karl; Baker, Bruce S.; Scott, Matthew P.

    2009-01-01

    Background The genetic analysis of behavior in Drosophila melanogaster has linked genes controlling neuronal connectivity and physiology to specific neuronal circuits underlying a variety of innate behaviors. We investigated the circuitry underlying the adult startle response, using photoexcitation of neurons that produce the abnormal chemosensory jump 6 (acj6) transcription factor. This transcription factor has previously been shown to play a role in neuronal pathfinding and neurotransmitter modality, but the role of acj6 neurons in the adult startle response was largely unknown. Principal Findings We show that the activity of these neurons is necessary for a wild-type startle response and that excitation is sufficient to generate a synthetic escape response. Further, we show that this synthetic response is still sensitive to the dose of acj6 suggesting that that acj6 mutation alters neuronal activity as well as connectivity and neurotransmitter production. Results/Significance These results extend the understanding of the role of acj6 and of the adult startle response in general. They also demonstrate the usefulness of activity-dependent characterization of neuronal circuits underlying innate behaviors in Drosophila, and the utility of integrating genetic analysis into modern circuit analysis techniques. PMID:19340304

  20. Inflammatory response and neuronal necrosis in rats with cerebral ischemia

    PubMed Central

    Wu, Lingfeng; Zhang, Kunnan; Hu, Guozhu; Yan, Haiyu; Xie, Chen; Wu, Xiaomu

    2014-01-01

    In the middle cerebral artery occlusion model of ischemic injury, inflammation primarily occurs in the infarct and peripheral zones. In the ischemic zone, neurons undergo necrosis and apoptosis, and a large number of reactive microglia are present. In the present study, we investigated the pathological changes in a rat model of middle cerebral artery occlusion. Neuronal necrosis appeared 12 hours after middle cerebral artery occlusion, and the peak of neuronal apoptosis appeared 4 to 6 days after middle cerebral artery occlusion. Inflammatory cytokines and microglia play a role in damage and repair after middle cerebral artery occlusion. Serum intercellular cell adhesion molecule-1 levels were positively correlated with the permeability of the blood-brain barrier. These findings indicate that intercellular cell adhesion molecule-1 may be involved in blood-brain barrier injury, microglial activation, and neuronal apoptosis. Inhibiting blood-brain barrier leakage may alleviate neuronal injury following ischemia. PMID:25422636

  1. Neuron-derived semaphorin 3A is an early inducer of vascular permeability in diabetic retinopathy via neuropilin-1.

    PubMed

    Cerani, Agustin; Tetreault, Nicolas; Menard, Catherine; Lapalme, Eric; Patel, Chintan; Sitaras, Nicholas; Beaudoin, Felix; Leboeuf, Dominique; De Guire, Vincent; Binet, François; Dejda, Agnieszka; Rezende, Flavio A; Miloudi, Khalil; Sapieha, Przemyslaw

    2013-10-01

    The deterioration of the inner blood-retinal barrier and consequent macular edema is a cardinal manifestation of diabetic retinopathy (DR) and the clinical feature most closely associated with loss of sight. We provide evidence from both human and animal studies for the critical role of the classical neuronal guidance cue, semaphorin 3A, in instigating pathological vascular permeability in diabetic retinas via its cognate receptor neuropilin-1. We reveal that semaphorin 3A is induced in early hyperglycemic phases of diabetes within the neuronal retina and precipitates initial breakdown of endothelial barrier function. We demonstrate, by a series of orthogonal approaches, that neutralization of semaphorin 3A efficiently prevents diabetes-induced retinal vascular leakage in a stage of the disease when vascular endothelial growth factor neutralization is inefficient. These observations were corroborated in Tg(Cre-Esr1)/Nrp1(flox/flox) conditional knockout mice. Our findings identify a therapeutic target for macular edema and provide further evidence for neurovascular crosstalk in the pathogenesis of DR. PMID:24093675

  2. Wingless-type family member 3A triggers neuronal polarization via cross-activation of the insulin-like growth factor-1 receptor pathway

    PubMed Central

    Bernis, María E.; Oksdath, Mariana; Dupraz, Sebastián; Nieto Guil, Alvaro; Fernández, Marisa M.; Malchiodi, Emilio L.; Rosso, Silvana B.; Quiroga, Santiago

    2013-01-01

    Initial axonal elongation is essential for neuronal polarization and requires polarized activation of IGF-1 receptors (IGF-1r) and the phosphatidylinositol 3 kinase (PI3k) pathway. Wingless-type family growth factors (Wnts) have also been implied in the regulation of axonal development. It is not known, however, if Wnts have any participation in the regulation of initial axonal outgrowth and the establishment of neuronal polarity. We used cultured hippocampal neurons and growth cone particles (GCPs) isolated from fetal rat brain to show that stimulation with the wingless family factor 3A (Wnt3a) was sufficient to promote neuronal polarization in the absence of IGF-1 or high insulin. We also show that Wnt3a triggered a strong activation of IGF-1r, PI3k, and Akt in developmental Stage 2 neurons and that the presence of activatable IGF-1r and PI3k activation were necessary for Wnt3a polarizing effects. Surface plasmon resonance (SPR) experiments show that Wnt3a did not bind specifically to the IGF-1r. Using crosslinking and immuno-precipitation experiments, we show that stimulation with Wnt3a triggered the formation of a complex including IGF-1r-Wnt3a-Frizzled-7. We conclude that Wnt3a triggers polarization of neurons via cross-activation of the IGF-1r/PI3k pathway upon binding to Fz7. PMID:24298236

  3. Transcriptional regulation of neuronal genes and its effect on neural functions: gene expression in response to static magnetism in cultured rat hippocampal neurons.

    PubMed

    Hirai, Takao; Yoneda, Yukio

    2005-07-01

    We have previously shown a marked but transient increase in DNA binding of the nuclear transcription factor activator protein-1 after brief exposure to static magnetic fields in cultured rat hippocampal neurons, suggesting that exposure to static magnetism would lead to long-term consolidation as well as amplification of different functional alterations through modulation of de novo protein synthesis at the level of gene transcription in the hippocampus. Hippocampal neurons were cultured under sustained exposure to static magnetic fields at 100 mT, followed by extraction of total RNA for differential display (DD) analysis using random primers. The first and the second DD polymerase chain reaction similarly showed the downregulation of particular genes in response to sustained magnetism. Nucleotide sequence analysis followed by BLASTN homology searching revealed high homology of these 2 DD-PCR products to the 3' non-coding regions of the mouse basic helix-loop-helix transcription factor ALF1 and that of histone H3.3A, respectively. On Northern blot analysis using the 2 cloned differentially expressed fragments labeled with [alpha-(32)P]dCTP by the random primer method, a marked decrease was seen in expression of mRNA for ALF1 and histone H3.3A in hippocampal neurons cultured under sustained exposure to static magnetic fields at 100 mT. It thus appears that static magnetism may modulate cellular integrity and functionality through expression of a variety of responsive genes required for gene transcription and translation, proliferation, differentiation, maturation, survival, and so on in cultured rat hippocampal neurons. PMID:16020920

  4. Spinal sensory projection neuron responses to spinal cord stimulation are mediated by circuits beyond gate control

    PubMed Central

    Zhang, Tianhe C.; Janik, John J.; Peters, Ryan V.; Chen, Gang; Ji, Ru-Rong

    2015-01-01

    Spinal cord stimulation (SCS) is a therapy used to treat intractable pain with a putative mechanism of action based on the Gate Control Theory. We hypothesized that sensory projection neuron responses to SCS would follow a single stereotyped response curve as a function of SCS frequency, as predicted by the Gate Control circuit. We recorded the responses of antidromically identified sensory projection neurons in the lumbar spinal cord during 1- to 150-Hz SCS in both healthy rats and neuropathic rats following chronic constriction injury (CCI). The relationship between SCS frequency and projection neuron activity predicted by the Gate Control circuit accounted for a subset of neuronal responses to SCS but could not account for the full range of observed responses. Heterogeneous responses were classifiable into three additional groups and were reproduced using computational models of spinal microcircuits representing other interactions between nociceptive and nonnociceptive sensory inputs. Intrathecal administration of bicuculline, a GABAA receptor antagonist, increased spontaneous and evoked activity in projection neurons, enhanced excitatory responses to SCS, and reduced inhibitory responses to SCS, suggesting that GABAA neurotransmission plays a broad role in regulating projection neuron activity. These in vivo and computational results challenge the Gate Control Theory as the only mechanism underlying SCS and refine our understanding of the effects of SCS on spinal sensory neurons within the framework of contemporary understanding of dorsal horn circuitry. PMID:25972582

  5. Responses of efferent octopaminergic thoracic unpaired median neurons in the locust to visual and mechanosensory signals.

    PubMed

    Field, Laurence H; Duch, Carsten; Pflüger, Hans-Joachim

    2008-01-01

    Insect thoracic ganglia contain efferent octopaminergic unpaired median neurons (UM neurons) located in the midline, projecting bilaterally and modulating neuromuscular transmission, muscle contraction kinetics, sensory sensitivity and muscle metabolism. In locusts, these neurons are located dorsally or ventrally (DUM- or VUM-neurons) and divided into functionally different sub-populations activated during different motor tasks. This study addresses the responsiveness of locust thoracic DUM neurons to various sensory stimuli. Two classes of sense organs, cuticular exteroreceptor mechanosensilla (tactile hairs and campaniform sensilla), and photoreceptors (compound eyes and ocelli) elicited excitatory reflex responses. Chordotonal organ joint receptors caused no responses. The tympanal organ (Müller's organ) elicited weak excitatory responses most likely via generally increased network activity due to increased arousal. Vibratory stimuli to the hind leg subgenual organ never elicited responses. Whereas DUM neurons innervating wing muscles are not very responsive to sensory stimulation, those innervating leg and other muscles are very responsive to stimulation of exteroreceptors and hardly responsive to stimulation of proprioceptors. After cutting both cervical connectives all mechanosensory excitation is lost, even for sensory inputs from the abdomen. This suggests that, in contrast to motor neurons, the sensory inputs to octopaminergic efferent neuromodulatory cells are pre-processed in the suboesophageal ganglion. PMID:18021797

  6. Propensity to Obesity Impacts the Neuronal Response to Energy Imbalance

    PubMed Central

    Cornier, Marc-Andre; McFadden, Kristina L.; Thomas, Elizabeth A.; Bechtell, Jamie L.; Bessesen, Daniel H.; Tregellas, Jason R.

    2015-01-01

    The mechanisms responsible for the propensity to gain weight or remain normal weight are poorly understood. The objective of this study was to study the neuronal response to visual food cues during short-term energy imbalance in healthy adults recruited as obesity-resistant (OR) or obesity-prone (OP) based on self-identification, body mass index, and personal/family weight history. Twenty-five OR and 28 OP subjects were studied in underfed (UF) and overfed (OF) as compared to eucaloric (EU) conditions in a randomized crossover design. Each study phase included a 3-day run-in diet, 1 day of controlled feeding (basal energy needs for EU, 40% above/below basal energy needs for OF/UF), and a test day. On the test day, fMRI was performed in the acute fed stated (30 min after a test meal) while subjects viewed images of foods of high hedonic value and neutral non-food objects. Measures of appetite and hormones were also performed before and every 30 min after the test meal. UF was associated with significantly increased activation of insula, somatosensory cortex, inferior and medial prefrontal cortex (PFC), parahippocampus, precuneus, cingulate, and visual cortex in OR. However, UF had no impact in OP. As a result, UF was associated with significantly greater activation, specifically in the insula, inferior PFC, and somatosensory cortex in OR as compared to OP. While OF was overall associated with reduced activation of inferior visual cortex, no group interaction was observed with OF. In summary, these findings suggest that individuals resistant to weight gain and obesity are more sensitive to short-term energy imbalance, particularly with UF, than those prone to weight gain. The inability to sense or adapt to changes in energy balance may represent an important mechanism contributing to excess energy intake and risk for obesity. PMID:25767441

  7. Propensity to obesity impacts the neuronal response to energy imbalance.

    PubMed

    Cornier, Marc-Andre; McFadden, Kristina L; Thomas, Elizabeth A; Bechtell, Jamie L; Bessesen, Daniel H; Tregellas, Jason R

    2015-01-01

    The mechanisms responsible for the propensity to gain weight or remain normal weight are poorly understood. The objective of this study was to study the neuronal response to visual food cues during short-term energy imbalance in healthy adults recruited as obesity-resistant (OR) or obesity-prone (OP) based on self-identification, body mass index, and personal/family weight history. Twenty-five OR and 28 OP subjects were studied in underfed (UF) and overfed (OF) as compared to eucaloric (EU) conditions in a randomized crossover design. Each study phase included a 3-day run-in diet, 1 day of controlled feeding (basal energy needs for EU, 40% above/below basal energy needs for OF/UF), and a test day. On the test day, fMRI was performed in the acute fed stated (30 min after a test meal) while subjects viewed images of foods of high hedonic value and neutral non-food objects. Measures of appetite and hormones were also performed before and every 30 min after the test meal. UF was associated with significantly increased activation of insula, somatosensory cortex, inferior and medial prefrontal cortex (PFC), parahippocampus, precuneus, cingulate, and visual cortex in OR. However, UF had no impact in OP. As a result, UF was associated with significantly greater activation, specifically in the insula, inferior PFC, and somatosensory cortex in OR as compared to OP. While OF was overall associated with reduced activation of inferior visual cortex, no group interaction was observed with OF. In summary, these findings suggest that individuals resistant to weight gain and obesity are more sensitive to short-term energy imbalance, particularly with UF, than those prone to weight gain. The inability to sense or adapt to changes in energy balance may represent an important mechanism contributing to excess energy intake and risk for obesity. PMID:25767441

  8. Neuron changes in a mollusk in response to proteolytic enzymes.

    PubMed

    Sotnikov, O S; Lukovnikova, M V; Vasyagina, N Yu; Laktionova, A A; Paramonova, N M

    2010-09-01

    The aims of the present work were to investigate the structure of neurons after treatment with proteases and to identify possible recovery of interneuronal syncytial connections. In the first series of experiments, phase-contrast microscopy studies of live dissociated neurons from ganglia of the mollusk Lymnaea stagnalis treated with 0.4% pronase solution demonstrated retraction of nerve processes and biphasic changes in cell body volume. At stage I, at an average of 82.5 min, neuron body volume decreased by 12.1%, after which it increased by a mean of 14.1%. Signs of neuron viability in Ringer's solution were seen for an average of 828 min; survival time in pronase solution was 1.4 times shorter. In the second series of experiments, studies of neuron ultrastructure showed many cases of persistence of mitochondria, the rough and smooth endoplasmic reticulum (ER), Golgi complex, light and granular vesicles, nuclear structure, and neuroplasm optical density. Cells coming close together after centrifugation formed intracellular clefts of uniform width (about 20 nm). There were very rare cases of points at which membranes came into contact. There were no signs of syncytial connections. Lengthening and fusion of smooth ER cisterns separated fragments of neuron bodies from relatively undamaged cells. Some neurons were damaged, with multiple vacuoles formed form swollen mitochondria and ER cisterns. Fragments of nerve processes formed on dissociation were surrounded by a normal outer cell membrane. PMID:20652422

  9. Leptin activates cytosolic calcium responses through protein kinase-C dependent mechanism in immortalized RFamide-related peptide-3 neurons.

    PubMed

    Ozcan, Mete; Saatci, Tugrul; Ayar, Ahmet; Canpolat, Sinan; Kelestimur, Haluk

    2015-03-19

    RFamide-related peptide-3 (RFRP-3), a mammalian ortholog of avian gonadotropin-inhibitory hormone (GnIH), seems to be an important regulator of the hypothalamus-pituitary-gonadal (HPG) reproductive axis. Leptin, a permissive hormonal regulator of fertility, provides energy signal to brain. According to current view, leptin does not act directly on gonadotrophin-releasing hormone (GnRH) neurons. RFRP-3 neurons have been shown to express leptin receptors. The goal of the present study was to examine whether leptin acts through RFRP-3 neurons to modulate activity of the GnRH neurons. For this aim, the effects of leptin on intracellular free Ca(2+) levels ([Ca(2+)]i) in RFRP-3 neurons were investigated by using in vitro calcium imaging system. In the present study, rHypoE-7 cell line was used as a model to explore the effects of leptin on RFRP-3 neurons. rHypoE-7 cells were placed on glass coverslip and loaded with 1 μM Fura-2 AM. [Ca(2+)]i responses were quantified by the changes in 340/380 ratio. Leptin (0.1-10 μM) caused increases in [Ca(2+)]i in a dose-dependent manner. The changes in [Ca(2+)]i were significantly attenuated by pre-treatment with protein kinase C inhibitor. These results demonstrate that leptin activates intracellular calcium signaling in RFRP-3 neurons through PKC-dependent pathway, and thus leptin may exert its effect on GnRH neurons by means of RFRP-3 cells. PMID:25575434

  10. Effects of cooling on the response of the snail bursting neuron to acetylcholine.

    PubMed

    Nedeljković, Miodrag; Kartelija, Gordana; Radenović, Lidija

    2005-06-01

    The Br-type neuron of the snail Helix pomatia, involved in neuronal regulation of various homeostatic and adaptive mechanisms, represents an interesting model for studying effects of temperature change on neuronal activity of poikilotherms. Acetylcholine induces a transient, inward dose-dependent current in the identified Br neuron. In the work presented, we analyzed the effects of cooling on the acetylcholine-induced inward current. The amplitude of acetylcholine-induced inward current was markedly decreased after cooling, and the speed of the decay of acetylcholine response was decreased. PMID:16154950

  11. KIF3C and KIF3A Form a Novel Neuronal Heteromeric Kinesin That Associates with Membrane Vesicles

    PubMed Central

    Muresan, Virgil; Abramson, Tatiana; Lyass, Asya; Winter, Dirk; Porro, Elena; Hong, Filbert; Chamberlin, Nancy L.; Schnapp, Bruce J.

    1998-01-01

    We have cloned from rat brain the cDNA encoding an 89,828-Da kinesin-related polypeptide KIF3C that is enriched in brain, retina, and lung. Immunocytochemistry of hippocampal neurons in culture shows that KIF3C is localized to cell bodies, dendrites, and, in lesser amounts, to axons. In subcellular fractionation experiments, KIF3C cofractionates with a distinct population of membrane vesicles. Native KIF3C binds to microtubules in a kinesin-like, nucleotide-dependent manner. KIF3C is most similar to mouse KIF3B and KIF3A, two closely related kinesins that are normally present as a heteromer. In sucrose density gradients, KIF3C sediments at two distinct densities, suggesting that it may be part of two different multimolecular complexes. Immunoprecipitation experiments show that KIF3C is in part associated with KIF3A, but not with KIF3B. Unlike KIF3B, a significant portion of KIF3C is not associated with KIF3A. Consistent with these biochemical properties, the distribution of KIF3C in the CNS has both similarities and differences compared with KIF3A and KIF3B. These results suggest that KIF3C is a vesicle-associated motor that functions both independently and in association with KIF3A. PMID:9487132

  12. Effects of surround suppression on response adaptation of V1 neurons to visual stimuli

    PubMed Central

    LI, Peng; JIN, Cai-Hong; JIANG, San; LI, Miao-Miao; WANG, Zi-Lu; ZHU, Hui; CHEN, Cui-Yun; HUA, Tian-Miao

    2014-01-01

    The influence of intracortical inhibition on the response adaptation of visual cortical neurons remains in debate. To clarify this issue, in the present study the influence of surround suppression evoked through the local inhibitory interneurons on the adaptation effects of neurons in the primary visual cortex (V1) were observed. Moreover, the adaptations of V1 neurons to both the high-contrast visual stimuli presented in the classical receptive field (CRF) and to the costimulation presented in the CRF and the surrounding nonclassical receptive field (nCRF) were compared. The intensities of surround suppression were modulated with different sized grating stimuli. The results showed that the response adaptation of V1 neurons decreased significantly with the increase of surround suppression and this adaptation decrease was due to the reduction of the initial response of V1 neurons to visual stimuli. However, the plateau response during adaptation showed no significant changes. These findings indicate that the adaptation effects of V1 neurons may not be directly affected by surround suppression, but may be dynamically regulated by a negative feedback network and be finely adjusted by its initial spiking response to stimulus. This adaptive regulation is not only energy efficient for the central nervous system, but also beneficially acts to maintain the homeostasis of neuronal response to long-presenting visual signals. PMID:25297081

  13. Specific responses of human hippocampal neurons are associated with better memory.

    PubMed

    Suthana, Nanthia A; Parikshak, Neelroop N; Ekstrom, Arne D; Ison, Matias J; Knowlton, Barbara J; Bookheimer, Susan Y; Fried, Itzhak

    2015-08-18

    A population of human hippocampal neurons has shown responses to individual concepts (e.g., Jennifer Aniston) that generalize to different instances of the concept. However, recordings from the rodent hippocampus suggest an important function of these neurons is their ability to discriminate overlapping representations, or pattern separate, a process that may facilitate discrimination of similar events for successful memory. In the current study, we explored whether human hippocampal neurons can also demonstrate the ability to discriminate between overlapping representations and whether this selectivity could be directly related to memory performance. We show that among medial temporal lobe (MTL) neurons, certain populations of neurons are selective for a previously studied (target) image in that they show a significant decrease in firing rate to very similar (lure) images. We found that a greater proportion of these neurons can be found in the hippocampus compared with other MTL regions, and that memory for individual items is correlated to the degree of selectivity of hippocampal neurons responsive to those items. Moreover, a greater proportion of hippocampal neurons showed selective firing for target images in good compared with poor performers, with overall memory performance correlated with hippocampal selectivity. In contrast, selectivity in other MTL regions was not associated with memory performance. These findings show that a substantial proportion of human hippocampal neurons encode specific memories that support the discrimination of overlapping representations. These results also provide previously unidentified evidence consistent with a unique role of the human hippocampus in orthogonalization of representations in declarative memory. PMID:26240357

  14. Specific responses of human hippocampal neurons are associated with better memory

    PubMed Central

    Suthana, Nanthia A.; Parikshak, Neelroop N.; Ekstrom, Arne D.; Ison, Matias J.; Knowlton, Barbara J.; Bookheimer, Susan Y.; Fried, Itzhak

    2015-01-01

    A population of human hippocampal neurons has shown responses to individual concepts (e.g., Jennifer Aniston) that generalize to different instances of the concept. However, recordings from the rodent hippocampus suggest an important function of these neurons is their ability to discriminate overlapping representations, or pattern separate, a process that may facilitate discrimination of similar events for successful memory. In the current study, we explored whether human hippocampal neurons can also demonstrate the ability to discriminate between overlapping representations and whether this selectivity could be directly related to memory performance. We show that among medial temporal lobe (MTL) neurons, certain populations of neurons are selective for a previously studied (target) image in that they show a significant decrease in firing rate to very similar (lure) images. We found that a greater proportion of these neurons can be found in the hippocampus compared with other MTL regions, and that memory for individual items is correlated to the degree of selectivity of hippocampal neurons responsive to those items. Moreover, a greater proportion of hippocampal neurons showed selective firing for target images in good compared with poor performers, with overall memory performance correlated with hippocampal selectivity. In contrast, selectivity in other MTL regions was not associated with memory performance. These findings show that a substantial proportion of human hippocampal neurons encode specific memories that support the discrimination of overlapping representations. These results also provide previously unidentified evidence consistent with a unique role of the human hippocampus in orthogonalization of representations in declarative memory. PMID:26240357

  15. Response variability and information transfer in directional neurons of the mammalian horizontal optokinetic system.

    PubMed

    Clifford, C W; Ibbotson, M R

    2000-01-01

    This study is concerned with how information about the direction of visual motion is encoded by motion-sensitive neurons. Motion-sensitive neurons are usually studied using stimuli unchanging in speed and direction over several seconds. Recently, it has been suggested that neuronal responses to more naturalistic stimuli cannot be understood on the basis of experiments with constant-motion stimuli (de Ruyter van Steveninck et al., 1997). We measured the variability and information content of spike trains recorded from directional neurons in the nucleus of the optic tract (NOT) of the wallaby, Macropus eugenii, in response to constant and time-varying motion. While the NOT forms part of the mammalian optokinetic system, we have shown previously that the responses of its directional neurons resemble those of insect H1 in many respects (Ibbotson et al., 1994). We find that directional neurons in the wallaby NOT respond with lower variability and higher rates of information transmission to time-varying stimuli than to constant motion. The difference in response variability is predicted by an inhomogeneous Poisson model of neuronal spiking incorporating an absolute refractory period of 2 ms during which no subsequent spike can be fired. Refractoriness imposes structure on the spike train, reducing variability (de Ruyter van Steveninck & Bialek, 1988; Berry & Meister, 1998). A given refractory period has a greater impact when firing rates are high, as for the responses of NOT neurons to time-varying stimuli. It is in just these cases that variability in experimentally observed spike trains is lowest. Thus, differences in response variability do not necessarily imply that different models are required to predict neuronal responses to constant- and time-varying motion stimuli. PMID:10824675

  16. [Response characteristics of neurons to tone in dorsal nucleus of the lateral lemniscus of the mouse].

    PubMed

    Si, Wen-Juan; Cheng, Yan-Ling; Yang, Dan-Dan; Wang, Xin

    2016-02-25

    The dorsal nucleus of lateral lemniscus (DNLL) is a nucleus in the auditory ascending pathway, and casts inhibitory efferent projections to the inferior colliculus. Studies on the DNLL are less than studies on the auditory brain stem and inferior colliculus. To date, there is no information about response characteristics of neurons in DNLL of albino mouse. Under free field conditions, we used extracellular single unit recording to study the acoustic signal characteristics of DNLL neurons in Kunming mice (Mus musculus). Transient (36%) and ongoing (64%) firing patterns were found in 96 DNLL neurons. Neurons with different firing patterns have significant differences in characteristic frequency and minimal threshold. We recorded frequency tuning curves (FTCs) of 87 DNLL neurons. All of the FTCs exhibit an open "V" shape. There is no significant difference in FTCs between transient and ongoing neurons, but among the ongoing neurons, the FTCs of sustained neurons are sharper than those of onset plus sustained neurons and pauser neurons. Our results showed that the characteristic frequency of DNLL neurons of mice was not correlated with depth, supporting the view that the DNLL of mouse has no frequency topological organization through dorsal-ventral plane, which is different from cats and some other animals. Furthermore, by using rate-intensity function (RIF) analysis the mouse DNLL neurons can be classified as monotonic (60%), saturated (31%) and non-monotonic (8%) types. Each RIF type includes transient and ongoing firing patterns. Dynamic range of the transient firing pattern is smaller than that of ongoing firing ones (P < 0.01), suggesting that the inhibitory inputs may underlie the formation of transient firing pattern. Multiple firing patterns and intensity coding of DNLL neurons may derive from the projections from multiple auditory nuclei, and play different roles in auditory information processing. PMID:26915316

  17. Immature Responses to GABA in Fragile X Neurons Derived from Human Embryonic Stem Cells

    PubMed Central

    Telias, Michael; Segal, Menahem; Ben-Yosef, Dalit

    2016-01-01

    Fragile X Syndrome (FXS) is the most common form of inherited cognitive disability. However, functional deficiencies in FX neurons have been described so far almost exclusively in animal models. In a recent study we found several functional deficits in FX neurons differentiated in-vitro from human embryonic stem cells (hESCs), including their inability to fire repetitive action potentials, and their lack of synaptic activity. Here, we investigated the responses of such neurons to pulse application of the neurotransmitter GABA. We found two distinct types of responses to GABA and sensitivity to the GABA-A receptor antagonist bicuculline; type 1 (mature) characterized by non-desensitized responses to GABA as well as a high sensitivity to bicuculline, and type 2 (immature) which are desensitized to GABA and insensitive to bicuculline. Type 1 responses were age-dependent and dominant in mature WT neurons. In contrast, FX neurons expressed primarily type 2 phenotype. Expression analysis of GABA-A receptor subunits demonstrated that this bias in human FX neurons was associated with a significant alteration in the expression pattern of the GABA-A receptor subunits α2 and β2. Our results indicate that FMRP may play a role in the development of the GABAergic synapse during neurogenesis. This is the first demonstration of the lack of a mature response to GABA in human FX neurons and may explain the inappropriate synaptic functions in FXS. PMID:27242433

  18. Direct effects of endogenous pyrogen on medullary temperature-responsive neurons in rabbits.

    PubMed

    Sakata, Y; Morimoto, A; Takase, Y; Murakami, N

    1981-01-01

    The effect of endogenous pyrogen (E.P.) injected directly into the tissue near the recording site were examined on the activities of the medullary temperature-responsive (TR) neurons in rabbits anesthetized with urethane. Endogenous pyrogen prepared from rabbit's whole blood was administered by a fine glass cannula (100-200 micrometer in diameter) in a fluid volume of 1 to 4 microliter. The cannula was fixed to the manipulator in parallel with a microelectrode and their tips were less than 0.05 mm apart. In rabbits with the intact preoptic/anterior hypothalamic (PO/AH) region, 4 warm-responsive neurons out of 7 were inhibited and 6 cold-responsive neuron out of 7 were excited by the direct administration of the E.P. In rabbits with lesions of the PO/AH, 5 warm-responsive neurons out of 9 were inhibited and 6 cold-responsive neurons out of 8 were facilitated by E.P. Antipyretics administered locally after the E.P. antagonized the pyretic effect, causing a return of the discharge of TR neuron to the control rate within 2.4 +/- 1.2 (mean +/- S.D.) min. The medullary TR neuron itself has the ability to respond to the E.P. and contributes to the development of fever. PMID:7289227

  19. Separate functions for responses to oral temperature in thermo-gustatory and trigeminal neurons.

    PubMed

    Lemon, Christian H; Kang, Yi; Li, Jinrong

    2016-06-01

    Oral temperature is a component and modifier of taste perception. Both trigeminal (V) and taste-sensitive cells, including those in the nucleus of the solitary tract (NTS), can respond to oral temperature. However, functional associations in thermal sensitivity between V and gustatory neurons are poorly understood. To study this we recorded electrophysiological responses to oral stimulation with cool (9, 15, 25, 32, and 34 °C) and warm (40 and 45 °C) temperatures from medullary V (n = 45) and taste-sensitive NTS (n = 27) neurons in anesthetized mice. Results showed temperatures below 34 °C activated the majority of V neurons but only a minority of NTS units. V neurons displayed larger responses to cooling and responded to temperatures that poorly stimulated NTS cells. Multivariate analyses revealed different temperatures induced larger differences in responses across V compared with NTS neurons, indicating V pathways possess greater capacity to signal temperature. Conversely, responses to temperature in NTS units associated with gustatory tuning. Further analyses identified two types of cooling-sensitive V neurons oriented toward innocuous or noxious cooling. Multivariate analyses indicated the combined response of these cells afforded distinction among a broad range of cool temperatures, suggesting multiple types of V neurons work together to represent oral cooling. PMID:26976122

  20. Responses of descending neurons to looming stimuli in the praying mantis Tenodera aridifolia.

    PubMed

    Yamawaki, Yoshifumi; Toh, Yoshihiro

    2009-03-01

    Responses to visual stimuli of some neurons that descend the nerve cord from the brain were recorded extracellularly in the mantis Tenodera aridifolia. Most of the recorded neurons showed their largest responses to looming stimuli that simulated a black circle approaching towards the mantis. The neurons showed a transient excitatory response to a gradually darkening or receding circle. The neurons showed sustained excitation to the linearly expanding stimuli, but the spike frequency decreased rapidly. The responses of the neurons were affected by both the diameter and the speed of looming stimuli. Faster or smaller looming stimuli elicited a higher peak frequency. These responses were observed in both recordings from the connective between suboesophageal and prothoracic ganglia and the connective between prothoracic and mesothoracic ganglia. There was a one-to-one correspondence of spike firing between these two recordings with a fixed delay. The neurons had the receptive field on ipsilateral side to its axon at the cervical connective. These results suggest that there is a looming-sensitive descending neuron, with an axon projecting over prothoracic ganglion, in the mantis nervous system. PMID:19093123

  1. Natural antisense transcripts regulate the neuronal stress response and excitability

    PubMed Central

    Zheng, Xingguo; Valakh, Vera; DiAntonio, Aaron; Ben-Shahar, Yehuda

    2014-01-01

    Neurons regulate ionic fluxes across their plasma membrane to maintain their excitable properties under varying environmental conditions. However, the mechanisms that regulate ion channels abundance remain poorly understood. Here we show that pickpocket 29 (ppk29), a gene that encodes a Drosophila degenerin/epithelial sodium channel (DEG/ENaC), regulates neuronal excitability via a protein-independent mechanism. We demonstrate that the mRNA 3′UTR of ppk29 affects neuronal firing rates and associated heat-induced seizures by acting as a natural antisense transcript (NAT) that regulates the neuronal mRNA levels of seizure (sei), the Drosophila homolog of the human Ether-à-go-go Related Gene (hERG) potassium channel. We find that the regulatory impact of ppk29 mRNA on sei is independent of the sodium channel it encodes. Thus, our studies reveal a novel mRNA dependent mechanism for the regulation of neuronal excitability that is independent of protein-coding capacity. DOI: http://dx.doi.org/10.7554/eLife.01849.001 PMID:24642409

  2. Negative functional MRI response correlates with decreases in neuronal activity in monkey visual area V1.

    PubMed

    Shmuel, Amir; Augath, Mark; Oeltermann, Axel; Logothetis, Nikos K

    2006-04-01

    Most functional brain imaging studies use task-induced hemodynamic responses to infer underlying changes in neuronal activity. In addition to increases in cerebral blood flow and blood oxygenation level-dependent (BOLD) signals, sustained negative responses are pervasive in functional imaging. The origin of negative responses and their relationship to neural activity remain poorly understood. Through simultaneous functional magnetic resonance imaging and electrophysiological recording, we demonstrate a negative BOLD response (NBR) beyond the stimulated regions of visual cortex, associated with local decreases in neuronal activity below spontaneous activity, detected 7.15 +/- 3.14 mm away from the closest positively responding region in V1. Trial-by-trial amplitude fluctuations revealed tight coupling between the NBR and neuronal activity decreases. The NBR was associated with comparable decreases in local field potentials and multiunit activity. Our findings indicate that a significant component of the NBR originates in neuronal activity decreases. PMID:16547508

  3. Cortically evoked responses of superior salivary nucleus neurons in the cat.

    PubMed

    Ishizuka, K; Murakami, T

    1989-01-01

    Salivation can be controlled by the inputs from the cerebral cortex as well as from the sensory nerves. However, there has been no detailed report so far on the inputs to superior salivatory nucleus (SSN) neurons from the cerebral cortex. The responses of SSN neurons to electrical stimulation of orbital and coronal gyri were investigated in ketamine anesthetized cats. A total of 56 SSN neurons were identified by the antidromic spike responses to stimulation of the right chorda tympani nerve. Their responsiveness to stimulation of the orbital and anterior coronal gyri and the lingual nerve at the ipsilateral side was tested. Thirty-five neurons (63%) responded with spikes to stimulation of the orbital and/or coronal gyri. They were also activated by stimulation of the lingual nerve. Other eleven neurons (20%) received the inputs from the lingual nerve only. The remaining 10 neurons (17%) failed to respond to stimulation of either the cerebral cortex or the lingual nerve. The mean latencies of the responses to stimulation of the orbital gyrus, coronal gyrus and lingual nerve were 29.0 ms (n = 28), 22.7 ms (n = 33) and 10.2 ms (n = 46), respectively. In this study, the excitatory inputs converging from the cerebral cortex and the lingual nerve, found in 63% of SSN neurons, could play an important role in submandibular and sublingual salivation. Cortically induced salivation, in particular, may be involved in salivary secretion in the conditioned reflexes as well as in mastication. PMID:2635781

  4. Frequency response properties of primary afferent neurons in the posterior lateral line system of larval zebrafish.

    PubMed

    Levi, Rafael; Akanyeti, Otar; Ballo, Aleksander; Liao, James C

    2015-01-15

    The ability of fishes to detect water flow with the neuromasts of their lateral line system depends on the physiology of afferent neurons as well as the hydrodynamic environment. Using larval zebrafish (Danio rerio), we measured the basic response properties of primary afferent neurons to mechanical deflections of individual superficial neuromasts. We used two types of stimulation protocols. First, we used sine wave stimulation to characterize the response properties of the afferent neurons. The average frequency-response curve was flat across stimulation frequencies between 0 and 100 Hz, matching the filtering properties of a displacement detector. Spike rate increased asymptotically with frequency, and phase locking was maximal between 10 and 60 Hz. Second, we used pulse train stimulation to analyze the maximum spike rate capabilities. We found that afferent neurons could generate up to 80 spikes/s and could follow a pulse train stimulation rate of up to 40 pulses/s in a reliable and precise manner. Both sine wave and pulse stimulation protocols indicate that an afferent neuron can maintain their evoked activity for longer durations at low stimulation frequencies than at high frequencies. We found one type of afferent neuron based on spontaneous activity patterns and discovered a correlation between the level of spontaneous and evoked activity. Overall, our results establish the baseline response properties of lateral line primary afferent neurons in larval zebrafish, which is a crucial step in understanding how vertebrate mechanoreceptive systems sense and subsequently process information from the environment. PMID:25355959

  5. Frequency response properties of primary afferent neurons in the posterior lateral line system of larval zebrafish

    PubMed Central

    Levi, Rafael; Akanyeti, Otar; Ballo, Aleksander

    2014-01-01

    The ability of fishes to detect water flow with the neuromasts of their lateral line system depends on the physiology of afferent neurons as well as the hydrodynamic environment. Using larval zebrafish (Danio rerio), we measured the basic response properties of primary afferent neurons to mechanical deflections of individual superficial neuromasts. We used two types of stimulation protocols. First, we used sine wave stimulation to characterize the response properties of the afferent neurons. The average frequency-response curve was flat across stimulation frequencies between 0 and 100 Hz, matching the filtering properties of a displacement detector. Spike rate increased asymptotically with frequency, and phase locking was maximal between 10 and 60 Hz. Second, we used pulse train stimulation to analyze the maximum spike rate capabilities. We found that afferent neurons could generate up to 80 spikes/s and could follow a pulse train stimulation rate of up to 40 pulses/s in a reliable and precise manner. Both sine wave and pulse stimulation protocols indicate that an afferent neuron can maintain their evoked activity for longer durations at low stimulation frequencies than at high frequencies. We found one type of afferent neuron based on spontaneous activity patterns and discovered a correlation between the level of spontaneous and evoked activity. Overall, our results establish the baseline response properties of lateral line primary afferent neurons in larval zebrafish, which is a crucial step in understanding how vertebrate mechanoreceptive systems sense and subsequently process information from the environment. PMID:25355959

  6. Orthopteran DCMD neuron: a reevaluation of responses to moving objects. I. Selective responses to approaching objects.

    PubMed

    Rind, F C; Simmons, P J

    1992-11-01

    1. The "descending contralateral movement detector" (DCMD) neuron in the locust has been challenged with a variety of moving stimuli, including scenes from a film (Star Wars), moving disks, and images generated by computer. The neuron responds well to any rapid movement. For a dark object moving along a straight path at a uniform velocity, the DCMD gives the strongest response when the object travels directly toward the eye, and the weakest when the object travels away from the eye. Instead of expressing selectivity for movements of small rather than large objects, the DCMD responds preferentially to approaching objects. 2. The neuron shows a clear selectivity for approach over recession for a variety of sizes and velocities of movement both of real objects and in simulated movements. When a disk that subtends > or = 5 degrees at the eye approaches the eye, there are two peaks in spike rate: one immediately after the start of movement; and a second that builds up during the approach. When a disk recedes from the eye, there is a single peak in response as the movement starts. There is a good correlation between spike rate and angular acceleration of the edges of the image over the eye. 3. When an object approaches from a distance sufficient for it to subtend less than one interommatidial angle at the start of its approach, there is a single peak in response. The DCMD tracks the approach, and, if the object moves at 1 m/s or faster, the spike rate increases throughout the duration of object movement. The size of the response depends on the speed of approach. 4. It is unlikely that the DCMD encodes the time to collision accurately, because the response depends on the size as well as the velocity of an approaching object. 5. Wide-field movements suppress the response to an approaching object. The suppression varies with the temporal frequency of the background pattern. 6. Over a wide range of contrasts of object against background, the DCMD gives a stronger response to

  7. Primary motor cortex of the parkinsonian monkey: altered neuronal responses to muscle stretch

    PubMed Central

    Pasquereau, Benjamin; Turner, Robert S.

    2013-01-01

    Exaggeration of the long-latency stretch reflex (LLSR) is a characteristic neurophysiologic feature of Parkinson's disease (PD) that contributes to parkinsonian rigidity. To explore one frequently-hypothesized mechanism, we studied the effects of fast muscle stretches on neuronal activity in the macaque primary motor cortex (M1) before and after the induction of parkinsonism by unilateral administration of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). We compared results from the general population of M1 neurons and two antidromically-identified subpopulations: distant-projecting pyramidal-tract type neurons (PTNs) and intra-telecenphalic-type corticostriatal neurons (CSNs). Rapid rotations of elbow or wrist joints evoked short-latency responses in 62% of arm-related M1 neurons. As in PD, the late electromyographic responses that constitute the LLSR were enhanced following MPTP. This was accompanied by a shortening of M1 neuronal response latencies and a degradation of directional selectivity, but surprisingly, no increase in single unit response magnitudes. The results suggest that parkinsonism alters the timing and specificity of M1 responses to muscle stretch. Observation of an exaggerated LLSR with no change in the magnitude of proprioceptive responses in M1 is consistent with the idea that the increase in LLSR gain that contributes to parkinsonian rigidity is localized to the spinal cord. PMID:24324412

  8. Decreased Response to Acetylcholine during Aging of Aplysia Neuron R15

    PubMed Central

    Kadakkuzha, Beena M.; Carter, Christopher J.; Magoski, Neil S.; Capo, Thomas R.; Puthanveettil, Sathyanarayanan V.

    2013-01-01

    How aging affects the communication between neurons is poorly understood. To address this question, we have studied the electrophysiological properties of identified neuron R15 of the marine mollusk Aplysia californica. R15 is a bursting neuron in the abdominal ganglia of the central nervous system and is implicated in reproduction, water balance, and heart function. Exposure to acetylcholine (ACh) causes an increase in R15 burst firing. Whole-cell recordings of R15 in the intact ganglia dissected from mature and old Aplysia showed specific changes in burst firing and properties of action potentials induced by ACh. We found that while there were no significant changes in resting membrane potential and latency in response to ACh, the burst number and burst duration is altered during aging. The action potential waveform analysis showed that unlike mature neurons, the duration of depolarization and the repolarization amplitude and duration did not change in old neurons in response to ACh. Furthermore, single neuron quantitative analysis of acetylcholine receptors (AChRs) suggested alteration of expression of specific AChRs in R15 neurons during aging. These results suggest a defect in cholinergic transmission during aging of the R15 neuron. PMID:24386417

  9. Measuring Physiological Responses of Drosophila Sensory Neurons to Lipid Pheromones Using Live Calcium Imaging.

    PubMed

    Shankar, Shruti; Calvert, Meredith E K; Yew, Joanne Y

    2016-01-01

    Unlike mammals, insects such as Drosophila have multiple taste organs. The chemosensory neurons on the legs, proboscis, wings and ovipositor of Drosophila express gustatory receptors(1,2), ion channels(3-6), and ionotropic receptors(7) that are involved in the detection of volatile and non-volatile sensory cues. These neurons directly contact tastants such as food, noxious substances and pheromones and therefore influence many complex behaviors such as feeding, egg-laying and mating. Electrode recordings and calcium imaging have been widely used in insects to quantify the neuronal responses evoked by these tastants. However, electrophysiology requires specialized equipment and obtaining measurements from a single taste sensillum can be technically challenging depending on the cell-type, size, and position. In addition, single neuron resolution in Drosophila can be difficult to achieve since taste sensilla house more than one type of chemosensory neuron. The live calcium imaging method described here allows responses of single gustatory neurons in live flies to be measured. This method is especially suitable for imaging neuronal responses to lipid pheromones and other ligand types that have low solubility in water-based solvents. PMID:27168110

  10. Attenuated infrared neuron stimulation response in cochlea of deaf animals may associate with the degeneration of spiral ganglion neurons

    PubMed Central

    Xie, Bingbin; Dai, Chunfu; Li, Huawei

    2015-01-01

    Hypothesis: We hypothesize that degenerated spiral ganglion neurons (SGNs) in guinea pigs reduces auditory brainstem responses evoked by pulsed infrared stimulation. Background: Pulsed infrared laser excitation can directly evoke physiological responses in neuronal and other excitable cells in vivo and in vitro. Laser pulses could benefit patients with cochlear implants to stimulate the auditory system. Methods: Pulsed infrared lasers were used to study evoked optical auditory brainstem responses (oABRs) in normal hearing and deafened animals. Aslo, the morphology and anatomy of SGNs in normal hearing and deafened guinea pigs were compared. Results: By recording oABRs evoked by varying infrared laser pulse durations, it is suggested that degeneration of SGNs in deafened guinea pigs was associated with an elevated oABR threshold and with lower amplitudes. Moreover, oABR threshold decreased while amplitudes increased in both normal hearing and deafened animals as the pulse duration prolonged. Electron microscopy revealed that SGNs in deafened guinea pigs had swollen and vacuolar mitochondria, as well as demyelinated soma and axons. Conclusion: Infrared laser pulses can stimulate SGNs to evoke oABRs in guinea pigs. Deafened guinea pigs have elevated thresholds and smaller amplitude responses, likely a result of degenerated SGNs. Short pulse durations are more suitable to evoke responses in both normal hearing and deafened animals. PMID:26114024

  11. Responses of protocerebral neurons in Manduca sexta to sex-pheromone mixtures

    PubMed Central

    Lei, Hong; Chiu, Hong-Yan; Hildebrand, John G.

    2013-01-01

    Male Manduca sexta moths are attracted to a mixture of two components of the female's sex pheromone at the natural concentration ratio. Deviation from this ratio results in reduced attraction. Projection neurons innervating prominent male-specific glomeruli in the male's antennal lobe produce maximal synchronized spiking activity in response to synthetic mixtures of the two components centering around the natural ratio, suggesting that behaviorally effective mixture ratios are encoded by synchronous neuronal activity. We investigated the physiological activity and morphology of downstream protocerebral neurons that responded to antennal stimulation with single pheromone components and their mixtures at various concentration ratios. Among the tested neurons, only a few gave stronger responses to the mixture at the natural ratio whereas most did not distinguish among the mixtures that were tested. We also found that the population response distinguished among the two pheromone components and their mixtures, prior to the peak population response. This observation is consistent with our previous finding that synchronous firing of antennal-lobe projection neurons reaches its maximum before the firing rate reaches its peak. Moreover, the response patterns of protocerebral neurons are diverse, suggesting that the representation of olfactory stimuli at the level of protocerebrum is complex. PMID:23974854

  12. Responses of spinal dorsal horn neurons to foot movements in rats with a sprained ankle.

    PubMed

    Kim, Jae Hyo; Kim, Hee Young; Chung, Kyungsoon; Chung, Jin Mo

    2011-05-01

    Acute ankle injuries are common problems and often lead to persistent pain. To investigate the underlying mechanism of ankle sprain pain, the response properties of spinal dorsal horn neurons were examined after ankle sprain. Acute ankle sprain was induced manually by overextending the ankle of a rat hindlimb in a direction of plantarflexion and inversion. The weight-bearing ratio (WBR) of the affected foot was used as an indicator of pain. Single unit activities of dorsal horn neurons in response to plantarflexion and inversion of the foot or ankle compression were recorded from the medial part of the deep dorsal horn, laminae IV-VI, in normal and ankle-sprained rats. One day after ankle sprain, rats showed significantly reduced WBRs on the affected foot, and this reduction was partially restored by systemic morphine. The majority of deep dorsal horn neurons responded to a single ankle stimulus modality. After ankle sprain, the mean evoked response rates were significantly increased, and afterdischarges were developed in recorded dorsal horn neurons. The ankle sprain-induced enhanced evoked responses were significantly reduced by morphine, which was reversed by naltrexone. The data indicate that movement-specific dorsal horn neuron responses were enhanced after ankle sprain in a morphine-dependent manner, thus suggesting that hyperactivity of dorsal horn neurons is an underlying mechanism of pain after ankle sprain. PMID:21389306

  13. Learning of anticipatory responses in single neurons of the human medial temporal lobe

    PubMed Central

    Reddy, Leila; Poncet, Marlene; Self, Matthew W.; Peters, Judith C.; Douw, Linda; van Dellen, Edwin; Claus, Steven; Reijneveld, Jaap C.; Baayen, Johannes C.; Roelfsema, Pieter R.

    2015-01-01

    Neuronal processes underlying the formation of new associations in the human brain are not yet well understood. Here human participants, implanted with depth electrodes in the brain, learned arbitrary associations between images presented in an ordered, predictable sequence. During learning we recorded from medial temporal lobe (MTL) neurons that responded to at least one of the pictures in the sequence (the preferred stimulus). We report that as a result of learning, single MTL neurons show asymmetric shifts in activity and start firing earlier in the sequence in anticipation of their preferred stimulus. These effects appear relatively early in learning, after only 11 exposures to the stimulus sequence. The anticipatory neuronal responses emerge while the subjects became faster in reporting the next item in the sequence. These results demonstrate flexible representations that could support learning of new associations between stimuli in a sequence, in single neurons in the human MTL. PMID:26449885

  14. Quantized response times are a signature of a neuronal bottleneck in decision.

    PubMed

    Perona, Pietro

    2014-01-01

    The histograms of response times of optimal YES/NO decisions that are computed from a single sensory Poisson neuron are highly structured. In particular, response times in NO decisions are quantized to a small set of times, while response times in YES decisions have a multimodal structure. Both the times of NO decisions, as well as the modes of the the histogram of YES decisions, are associated to the number of action potentials that were necessary to reach the decision. Their value is a function of the firing rate of the neuron in response to the states of the stimulus. PMID:24782750

  15. Synapsin III Acts Downstream of Semaphorin 3A/CDK5 Signaling to Regulate Radial Migration and Orientation of Pyramidal Neurons In Vivo

    PubMed Central

    Perlini, Laura E.; Szczurkowska, Joanna; Ballif, Bryan A.; Piccini, Alessandra; Sacchetti, Silvio; Giovedì, Silvia; Benfenati, Fabio; Cancedda, Laura

    2015-01-01

    Summary Synapsin III (SynIII) is a phosphoprotein that is highly expressed at early stages of neuronal development. Whereas in vitro evidence suggests a role for SynIII in neuronal differentiation, in vivo evidence is lacking. Here, we demonstrate that in vivo downregulation of SynIII expression affects neuronal migration and orientation. By contrast, SynIII overexpression affects neuronal migration, but not orientation. We identify a cyclin-dependent kinase-5 (CDK5) phosphorylation site on SynIII and use phosphomutant rescue experiments to demonstrate its role in SynIII function. Finally, we show that SynIII phosphorylation at the CDK5 site is induced by activation of the semaphorin-3A (Sema3A) pathway, which is implicated in migration and orientation of cortical pyramidal neurons (PNs) and is known to activate CDK5. Thus, fine-tuning of SynIII expression and phosphorylation by CDK5 activation through Sema3A activity is essential for proper neuronal migration and orientation. PMID:25843720

  16. Odorant Responses and Courtship Behaviors Influenced by at4 Neurons in Drosophila.

    PubMed

    Pitts, Svetlana; Pelser, Elizabeth; Meeks, Julian; Smith, Dean

    2016-01-01

    In insects, pheromones function as triggers to elicit complex behavior programs, such as courtship and mating behavior. In most species, the neurons tuned to pheromones are localized in a specific subset of olfactory sensilla located on the antenna called trichoid sensilla. In Drosophila there are two classes of trichoid sensilla, at1 sensilla that contain the dendrites of a single neuron that is specifically tuned to the male-specific pheromone 11-cis vaccenyl acetate (cVA), and at4 sensilla that contain three neurons with relatively poorly defined chemical specificity and function. Using a combination of odorant receptor mutant analysis, single sensillum electrophysiology and optogenetics, we have examined the chemical tuning and behavioral consequences of the three at4 olfactory neuron classes. Our results indicate that one class, Or65abc neurons, are unresponsive to cVA pheromone, and function to inhibit courtship behaviors in response to an unknown ligand, while the other two neuron classes, Or88a and Or47b neurons, are sensitive to a diverse array of fly and non-fly odors, and activation of these neurons has little direct impact on courtship behaviors. PMID:27617442

  17. Responses of monkey prefrontal neurons during the execution of transverse patterning.

    PubMed

    Nejime, Masafumi; Inoue, Masato; Saruwatari, Masanori; Mikami, Akichika; Nakamura, Katsuki; Miyachi, Shigehiro

    2015-02-01

    Recent functional imaging studies have suggested that the prefrontal cortex (PF) is engaged in the performance of transverse patterning (TP), which consists of 3 conflicting discriminations (A+/B-, B+/C-, C+/A-). However, the roles of PF in TP are still unclear. To address this issue, we examined the neuronal responses in 3 regions [the principal sulcus (PS), dorsal convexity (DC), and medial prefrontal cortex (MPF)] of the macaque PF during the performance of an oculomotor version of TP. A delayed matching-to-sample (DMS) task was used as a control task. The TP task-responsive neurons were most abundant in MPF. We analyzed the dependency of each neuronal response on the task type (TP or DMS), target shape (A, B, or C), and target location (left or right). Immediately after the choice cue presentation, many MPF neurons showed task dependency. Interestingly, some of them already exhibited differential activity between the 2 tasks before the choice cue presentation. Immediately before the saccade, the number of target location-dependent neurons increased in MPF and PS. Among them, many MPF neurons were also influenced by the task type, whereas PS neurons tended to show location dependency without task dependency. These results suggest that MPF and PS are involved in the execution of TP: MPF appears to be more important in the target selection based on the TP rule, whereas PS is apparently more related to the response preparation. In addition, some neurons showed a postsaccadic response, which may be related to the feedback mechanism. PMID:25453739

  18. Human single-neuron responses at the threshold of conscious recognition

    PubMed Central

    Quiroga, R. Quian; Mukamel, R.; Isham, E. A.; Malach, R.; Fried, I.

    2008-01-01

    We studied the responses of single neurons in the human medial temporal lobe while subjects viewed familiar faces, animals, and landmarks. By progressively shortening the duration of stimulus presentation, coupled with backward masking, we show two striking properties of these neurons. (i) Their responses are not statistically different for the 33-ms, 66-ms, and 132-ms stimulus durations, and only for the 264-ms presentations there is a significantly higher firing. (ii) These responses follow conscious perception, as indicated by the subjects' recognition report. Remarkably, when recognized, a single snapshot as brief as 33 ms was sufficient to trigger strong single-unit responses far outlasting stimulus presentation. These results suggest that neurons in the medial temporal lobe can reflect conscious recognition by “all-or-none” responses. PMID:18299568

  19. Neuronal circuitry regulates the response of Caenorhabditis elegans to misfolded proteins.

    PubMed

    Prahlad, Veena; Morimoto, Richard I

    2011-08-23

    The consequence of chronic protein misfolding is the basis of many human diseases. To combat the deleterious effects of accumulated protein damage, all cells possess robust quality-control systems, specifically molecular chaperones and clearance machineries, that sense and respond to protein misfolding. However, for many protein conformational diseases, it is unclear why this quality-control system does not efficiently counter protein aggregation. Previous findings that the heat shock response in Caenorhabditis elegans is regulated by thermosensory neurons led us to consider whether neuronal activity could also be responsible for the inadequate response of an organism to chronic protein misfolding. Here we show, in animals expressing polyglutamine expansion proteins and mutant SOD-1(G93A) in intestinal or muscle cells, that the nervous system does indeed control the cellular response to misfolded proteins. Whereas polyglutamine expansion-expressing animals with WT thermosensory neurons readily express protein aggregates, leading to cellular dysfunction without concomitant up-regulation of molecular chaperones, modulation of the nervous system results in chaperone up-regulation that suppresses aggregation and toxicity. The neuronal signal is transmitted through calcium-activated dense core vesicle neurosecretion. Cell-nonautonomous control of chaperone expression by the thermosensory neurons allows C. elegans to respond differently to acute stress such as heat shock, and chronic stress caused by the expression of misfolded proteins, suggesting that neuronal signaling determines the course of cellular proteotoxicity. PMID:21844355

  20. Plasticity of Fear and Safety Neurons of the Amygdala in Response to Fear Extinction

    PubMed Central

    Sangha, Susan

    2015-01-01

    Fear inhibition learning induces plasticity and remodeling of circuits within the amygdala. Most studies examine these changes in nondiscriminative fear conditioning paradigms. Using a discriminative fear, safety, and reward conditioning task, Sangha et al. (2013) have previously reported several neural microcircuits within the basal amygdala (BA) which discriminate among these cues, including a subpopulation of neurons responding selectively to a safety cue and not a fear cue. Here, the hypothesis that these “safety” neurons isolated during discriminative conditioning are biased to become fear cue responsive as a result of extinction, when fear behavior diminishes, was tested. Although 41% of “safety” neurons became fear cue responsive as a result of extinction, the data revealed that there was no bias for these neurons to become preferentially responsive during fear extinction compared to the other identified subgroups. In addition to the plasticity seen in the “safety” neurons, 44% of neurons unresponsive to either the fear cue or safety cue during discriminative conditioning became fear cue responsive during extinction. Together these emergent responses to the fear cue as a result of extinction support the hypothesis that new learning underlies extinction. In contrast, 47% of neurons responsive to the fear cue during discriminative conditioning became unresponsive to the fear cue during extinction. These findings are consistent with a suppression of neural responding mediated by inhibitory learning, or, potentially, by direct unlearning. Together, the data support extinction as an active process involving both gains and losses of responses to the fear cue and suggests the final output of the integrated BA circuit in influencing fear behavior is a balance of excitation and inhibition, and perhaps reversal of learning-induced changes. PMID:26733838

  1. Turtle Dorsal Cortex Pyramidal Neurons Comprise Two Distinct Cell Types with Indistinguishable Visual Responses

    PubMed Central

    Crockett, Thomas; Wright, Nathaniel; Thornquist, Stephen; Ariel, Michael; Wessel, Ralf

    2015-01-01

    A detailed inventory of the constituent pieces in cerebral cortex is considered essential to understand the principles underlying cortical signal processing. Specifically, the search for pyramidal neuron subtypes is partly motivated by the hypothesis that a subtype-specific division of labor could create a rich substrate for computation. On the other hand, the extreme integration of individual neurons into the collective cortical circuit promotes the hypothesis that cellular individuality represents a smaller computational role within the context of the larger network. These competing hypotheses raise the important question to what extent the computational function of a neuron is determined by its individual type or by its circuit connections. We created electrophysiological profiles from pyramidal neurons within the sole cellular layer of turtle visual cortex by measuring responses to current injection using whole-cell recordings. A blind clustering algorithm applied to these data revealed the presence of two principle types of pyramidal neurons. Brief diffuse light flashes triggered membrane potential fluctuations in those same cortical neurons. The apparently network driven variability of the visual responses concealed the existence of subtypes. In conclusion, our results support the notion that the importance of diverse intrinsic physiological properties is minimized when neurons are embedded in a synaptic recurrent network. PMID:26633877

  2. Neurotoxin-induced selective ubiquitination and regulation of MEF2A isoform in neuronal stress response

    PubMed Central

    She, Hua; Yang, Qian; Mao, Zixu

    2014-01-01

    The myocyte enhancer factor 2A-D (MEF2) proteins are members of the MCM1-agamous-deficiens-serum (MADS) response factor family of transcription factors. Various MEF2 isoform proteins are enriched in neurons and exhibit distinct patterns of expression in different regions of the brain. In neurons, MEF2 functions as a converging factor to regulate many neuronal functions including survival. MEF2 activities are tightly controlled in neurons in response to stress. Whether stress signal may differentially regulate MEF2s remains largely unknown. In this work, we showed that MEF2A but not MEF2C or MEF2D was modified by ubiquitination in dopaminergic neuronal cell line SN4741 cells. MEF2A was ubiquitinated at its N’-terminus, and the ubiquitination of MEF2A was first detectable in the nuclear compartment and later in the cytoplasm. Ubiquitination of MEF2A correlated with reduced DNA-binding activity and transcriptional activity. More importantly, disturbing the degradation of ubiquitinated MEF2A through proteasome pathway by neurotoxins known to induce Parkinson’s disease (PD) features in model animals caused accumulation of ubiquitinated MEF2A, reduced MEF2 activity, and impaired cellular viability. Our work thus provides the first evidence to demonstrate an isoforms specific regulation of MEF2s by ubiquitination-proteasome pathway in dopaminergic neuronal cell by neurotoxins, suggesting that stress signal and cellular context dependent dysregulation of MEF2s may underlie the loss of neuronal viability. PMID:22764880

  3. [Structure of Response and Dynamics of Preferred Orientation in Cat's V1 Neurons].

    PubMed

    Kozhukhov, S A; Saltykov, K A; Lazareva, N A

    2016-01-01

    Preferred orientation of V1 neurons was changed during the respons time course. In order to reveal mechanisms of such changes, spike trains of single neurons to flashed bars of different orientations were studied by means of principal component and frequency-domain analysis of the spike density functions. There was found out that: 1. contribution of each of the components was dependent on the stimulus orientation. 2. the principal components of V1 neurons responses contain different kinds of transient and sustained parts and rhythmic oscillations in the theta/alpha and beta-bands. 3. There was no correlation between transient parts as well as between rhythmic oscillations within the same frequency band in different components. Taken together, the data obtained allow us to suggest that during generation of response there is a shift of dominance of the components with different orientations which determines the dynamics of the preferred orientations of V1 neurons. PMID:27263274

  4. Firing-Rate Response of a Neuron Receiving Excitatory and Inhibitory Synaptic Shot Noise

    NASA Astrophysics Data System (ADS)

    Richardson, Magnus J. E.; Swarbrick, Rupert

    2010-10-01

    The synaptic coupling between neurons in neocortical networks is sufficiently strong so that relatively few synchronous synaptic pulses are required to bring a neuron from rest to the spiking threshold. However, such finite-amplitude effects of fluctuating synaptic drive are missed in the standard diffusion approximation. Here exact solutions for the firing-rate response to modulated presynaptic rates are derived for a neuron receiving additive excitatory and inhibitory synaptic shot noise with exponential amplitude distributions. The shot-noise description of the neuronal response to synaptic dynamics is shown to be richer and qualitatively distinct from that predicted by the diffusion approximation. It is also demonstrated how the framework developed here can be generalized to multiplicative shot noise so as to better capture effects of the inhibitory reversal potential.

  5. SORLA-mediated trafficking of TrkB enhances the response of neurons to BDNF.

    PubMed

    Rohe, Michael; Hartl, Daniela; Fjorback, Anja Nawarecki; Klose, Joachim; Willnow, Thomas E

    2013-01-01

    Stimulation of neurons with brain-derived neurotrophic factor (BDNF) results in robust induction of SORLA, an intracellular sorting receptor of the VPS10P domain receptor gene family. However, the relevance of SORLA for BDNF-induced neuronal responses has not previously been investigated. We now demonstrate that SORLA is a sorting factor for the tropomyosin-related kinase receptor B (TrkB) that facilitates trafficking of this BDNF receptor between synaptic plasma membranes, post-synaptic densities, and cell soma, a step critical for neuronal signal transduction. Loss of SORLA expression results in impaired neuritic transport of TrkB and in blunted response to BDNF in primary neurons; and it aggravates neuromotoric deficits caused by low BDNF activity in a mouse model of Huntington's disease. Thus, our studies revealed a key role for SORLA in mediating BDNF trophic signaling by regulating the intracellular location of TrkB. PMID:23977241

  6. Phase Response Synchronization in Neuronal Population with Time-Varying Coupling Strength

    PubMed Central

    Jiao, Xianfa; Zhao, Wanyu; Cao, Jinde

    2015-01-01

    We present the dynamic model of global coupled neuronal population subject to external stimulus by the use of phase sensitivity function. We investigate the effect of time-varying coupling strength on the synchronized phase response of neural population subjected to external harmonic stimulus. For a time-periodic coupling strength, we found that the stimulus with increasing intensity or frequency can reinforce the phase response synchronization in neuronal population of the weakly coupled neural oscillators, and the neuronal population with stronger coupling strength has good adaptability to stimulus. When we consider the dynamics of coupling strength, we found that a strong stimulus can quickly cause the synchronization in the neuronal population, the degree of synchronization grows with the increasing stimulus intensity, and the period of synchronized oscillation induced by external stimulation is related to stimulus frequency. PMID:26640514

  7. Neurokinins inhibit low threshold inactivating K+ currents in capsaicin responsive DRG neurons

    PubMed Central

    Sculptoreanu, Adrian; Artim, Debra E.; de Groat, William C.

    2009-01-01

    Neurokinins (NK) released from terminals of dorsal root ganglion (DRG) neurons may control firing of these neurons by an autofeedback mechanism. In this study we used patch clamp recording techniques to determine if NKs alter excitability of rat L4-S3 DRG neurons by modulating K+ currents. In capsaicin (CAPS)-responsive phasic neurons substance P (SP) lowered action potential (AP) threshold and increased the number of APs elicited by depolarizing current pulses. SP and a selective NK2 agonist, [βAla8]-neurokinin A (4–10) also inhibited low threshold inactivating K+ currents isolated by blocking non-inactivating currents with a combination of high TEA, (−) verapamil and nifedipine. Currents recorded under these conditions were heteropodatoxin-sensitive (Kv4 blocker) and α-dendrotoxin insensitive (Kv1.1 and Kv1.2 blocker). SP and NKA elicited a >10 mV positive shift of the voltage dependence of activation of the low threshold currents. This effect was absent in CAPS-unresponsive neurons. The effect of SP or NKA on K+ currents in CAPS-responsive phasic neurons was fully reversed by an NK2 receptor antagonist (MEN10376) but only partially reversed by a PKC inhibitor (bisindolylmaleimide). An NK1 selective agonist ([Sar9, Met11]-substance P) or direct activation of PKC with phorbol 12,13-dibutyrate, did not change firing in CAPS-responsive neurons, but did inhibit various types of K+ currents that activated over a wide range of voltages. These data suggest that the excitability of CAPS-responsive phasic afferent neurons is increased by activation of NK2 receptors and that this is due in part to inhibition and a positive voltage shift in the activation of heteropodatoxin-sensitive Kv4 channels. PMID:19631644

  8. Leptin-Responsive GABAergic Neurons Regulate Fertility through Pathways That Result in Reduced Kisspeptinergic Tone

    PubMed Central

    Martin, Cecilia; Navarro, Víctor M.; Simavli, Serap; Vong, Linh; Carroll, Rona S.; Lowell, Bradford B.

    2014-01-01

    The adipocyte-derived hormone leptin plays a critical role in the central transmission of energy balance to modulate reproductive function. However, the neurocircuitry underlying this interaction remains elusive, in part due to incomplete knowledge of first-order leptin-responsive neurons. To address this gap, we explored the contribution of predominantly inhibitory (GABAergic) neurons versus excitatory (glutamatergic) neurons in the female mouse by selective ablation of the leptin receptor in each neuronal population: Vgat-Cre;Leprlox/lox and Vglut2-Cre;Leprlox/lox mice, respectively. Female Vgat-Cre;Leprlox/lox but not Vglut2-Cre;Leprlox/lox mice were obese. Vgat-Cre;Leprlox/lox mice had delayed or absent vaginal opening, persistent diestrus, and atrophic reproductive tracts with absent corpora lutea. In contrast, Vglut2-Cre;Leprlox/lox females exhibited reproductive maturation and function comparable to Leprlox/lox control mice. Intracerebroventricular administration of kisspeptin-10 to Vgat-Cre;Leprlox/lox female mice elicited robust gonadotropin responses, suggesting normal gonadotropin-releasing hormone neuronal and gonadotrope function. However, adult ovariectomized Vgat-Cre;Leprlox/lox mice displayed significantly reduced levels of Kiss1 (but not Tac2) mRNA in the arcuate nucleus, and a reduced compensatory luteinizing hormone increase compared with control animals. Estradiol replacement after ovariectomy inhibited gonadotropin release to a similar extent in both groups. These animals also exhibited a compromised positive feedback response to sex steroids, as shown by significantly lower Kiss1 mRNA levels in the AVPV, compared with Leprlox/lox mice. We conclude that leptin-responsive GABAergic neurons, but not glutamatergic neurons, act as metabolic sensors to regulate fertility, at least in part through modulatory effects on kisspeptin neurons. PMID:24760864

  9. Glial cells, but not neurons, exhibit a controllable response to a localized inflammatory microenvironment in vitro

    PubMed Central

    Sommakia, Salah; Rickus, Jenna L.; Otto, Kevin J.

    2014-01-01

    The ability to design long-lasting intracortical implants hinges on understanding the factors leading to the loss of neuronal density and the formation of the glial scar. In this study, we modify a common in vitro mixed cortical culture model using lipopolysaccharide (LPS) to examine the responses of microglia, astrocytes, and neurons to microwire segments. We also use dip-coated polyethylene glycol (PEG), which we have previously shown can modulate impedance changes to neural microelectrodes, to control the cellular responses. We find that microglia, as expected, exhibit an elevated response to LPS-coated microwire for distances of up to 150 μm, and that this elevated response can be mitigated by co-depositing PEG with LPS. Astrocytes exhibit a more complex, distance-dependent response, whereas neurons do not appear to be affected by the type or magnitude of glial response within this in vitro model. The discrepancy between our in vitro responses and typically observed in vivo responses suggest the importance of using a systems approach to understand the responses of the various brain cell types in a chronic in vivo setting, as well as the necessity of studying the roles of cell types not native to the brain. Our results further indicate that the loss of neuronal density observed in vivo is not a necessary consequence of elevated glial activation. PMID:25452724

  10. Neuron-derived orphan receptor 1 transduces survival signals in neuronal cells in response to hypoxia-induced apoptotic insults.

    PubMed

    Chio, Chung-Ching; Wei, Li; Chen, Tyng Guey; Lin, Chien-Min; Shieh, Ja-Ping; Yeh, Poh-Shiow; Chen, Ruei-Ming

    2016-06-01

    OBJECT Hypoxia can induce cell death or trigger adaptive mechanisms to guarantee cell survival. Neuron-derived orphan receptor 1 (NOR-1) works as an early-response protein in response to a variety of environmental stresses. In this study, the authors evaluated the roles of NOR-1 in hypoxia-induced neuronal insults. METHODS Neuro-2a cells were exposed to oxygen/glucose deprivation (OGD). Cell viability, cell morphology, cas-pase-3 activity, DNA fragmentation, and cell apoptosis were assayed to determine the mechanisms of OGD-induced neuronal insults. RNA and protein analyses were carried out to evaluate the effects of OGD on expressions of NOR-1, cAMP response element-binding (CREB), and cellular inhibitor of apoptosis protein 2 (cIAP2) genes. Translations of these gene expressions were knocked down using RNA interference. Mice subjected to traumatic brain injury (TBI) and NOR-1 was immunodetected. RESULTS Exposure of neuro-2a cells to OGD decreased cell viability in a time-dependent manner. Additionally, OGD led to cell shrinkage, DNA fragmentation, and cell apoptosis. In parallel, treatment of neuro-2a cells with OGD time dependently increased cellular NOR-1 mRNA and protein expressions. Interestingly, administration of TBI also augmented NOR-1 levels in the impacted regions of mice. As to the mechanism, exposure to OGD increased nuclear levels of the transcription factor CREB protein. Downregulating CREB expression using RNA interference simultaneously inhibited OGD-induced NOR-1 mRNA expression. Also, levels of cIAP2 mRNA and protein in neuro-2a cells were augmented by OGD. After reducing cIAP2 translation, OGD-induced cell death was reduced. Sequentially, application of NOR-1 small interfering RNA to neuro-2a cells significantly inhibited OGD-induced cIAP2 mRNA expression and concurrently alleviated hypoxia-induced alterations in cell viability, caspase-3 activation, DNA damage, and cell apoptosis. CONCLUSIONS This study shows that NOR-1 can transduce survival

  11. Sensory neuron response to emission from a CO2 laser

    NASA Astrophysics Data System (ADS)

    Gorobets, V. A.; Petukhov, V. O.; Yachnev, I. L.; Penniyainen, V. A.; Lopatina, E. V.; Podzorova, S. A.; Krylov, B. V.

    2010-07-01

    We have built a wavelength-tunable CO2 laser meeting the requirements for low-intensity laser therapy. At λ = 10.57 μm and 9.24 μm, we observe a physiological effect detectable from the change in the extent of neurite outgrowth from sensory neurons. This makes it possible to study molecular mechanisms for interaction of low-intensity radiation with tissues in a living body. The ATP molecule is considered as the specific molecular target for the action of the radiation.

  12. Responses of vestibular nucleus neurons to inputs from the hindlimb are enhanced following a bilateral labyrinthectomy

    PubMed Central

    Moy, Jennifer D.; Puterbaugh, Sonya R.; DeMayo, William M.; Yates, Bill J.

    2013-01-01

    Vestibular nucleus neurons have been shown to respond to stimulation of afferents innervating the limbs. However, a limitation in the potential translation of these findings is that they were obtained from decerebrate or anesthetized animals. The goal of the present study was to determine whether stimulation of hindlimb nerves similarly affects vestibular nucleus neuronal activity in conscious cats, and whether the responsiveness of neurons to the stimuli is altered following a bilateral labyrinthectomy. In labyrinth-intact animals, the firing rate of 24/59 (41%) of the neurons in the caudal vestibular nucleus complex was affected by hindlimb nerve stimulation. Most responses were excitatory; the median response latency was 20 ms, but some units had response latencies as short as 10 ms. In the first week after a bilateral labyrinthectomy, the proportion of vestibular nucleus neurons that responded to hindlimb nerve stimulation increased slightly (to 24/55 or 44% of units). However, during the subsequent postlabyrinthectomy survival period, the proportion of vestibular nucleus neurons with hindlimb inputs increased significantly (to 30/49 or 61% of units). Stimuli to hindlimb nerves needed to elicit neuronal responses was consistently over three times the threshold for eliciting an afferent volley. These data show that inputs from hindlimb afferents smaller than those innervating muscle spindles and Golgi tendon organs affect the processing of information in the vestibular nuclei, and that these inputs are enhanced following a bilateral labyrinthectomy. These findings have implications for the development of a limb neuroprosthetics device for the management of bilateral vestibular loss. PMID:23305979

  13. Responses of vestibular nucleus neurons to inputs from the hindlimb are enhanced following a bilateral labyrinthectomy.

    PubMed

    McCall, Andrew A; Moy, Jennifer D; Puterbaugh, Sonya R; DeMayo, William M; Yates, Bill J

    2013-03-15

    Vestibular nucleus neurons have been shown to respond to stimulation of afferents innervating the limbs. However, a limitation in the potential translation of these findings is that they were obtained from decerebrate or anesthetized animals. The goal of the present study was to determine whether stimulation of hindlimb nerves similarly affects vestibular nucleus neuronal activity in conscious cats, and whether the responsiveness of neurons to the stimuli is altered following a bilateral labyrinthectomy. In labyrinth-intact animals, the firing rate of 24/59 (41%) of the neurons in the caudal vestibular nucleus complex was affected by hindlimb nerve stimulation. Most responses were excitatory; the median response latency was 20 ms, but some units had response latencies as short as 10 ms. In the first week after a bilateral labyrinthectomy, the proportion of vestibular nucleus neurons that responded to hindlimb nerve stimulation increased slightly (to 24/55 or 44% of units). However, during the subsequent postlabyrinthectomy survival period, the proportion of vestibular nucleus neurons with hindlimb inputs increased significantly (to 30/49 or 61% of units). Stimuli to hindlimb nerves needed to elicit neuronal responses was consistently over three times the threshold for eliciting an afferent volley. These data show that inputs from hindlimb afferents smaller than those innervating muscle spindles and Golgi tendon organs affect the processing of information in the vestibular nuclei, and that these inputs are enhanced following a bilateral labyrinthectomy. These findings have implications for the development of a limb neuroprosthetics device for the management of bilateral vestibular loss. PMID:23305979

  14. Differences in in vitro cerebellar neuronal responses to hypoxia in eider ducks, chicken and rats.

    PubMed

    Ludvigsen, Stian; Folkow, Lars P

    2009-11-01

    Ducks are well-known to be more tolerant to asphyxia than non-diving birds, but it is not known if their defences include enhanced neuronal hypoxia tolerance. To test this, we compared extracellular recordings of spontaneous activity in the Purkinje cell layer of 400 mum thick isolated cerebellar slices from eider ducks, chickens and rats, before, during and after 60 min hypoxia (95%N(2)-5%CO(2)) or chemical anoxia (hypoxia + 2 mM NaCN). Most slices rapidly lost activity in hypoxia, with or without recovery after rinse and return to normoxia (95%O(2)-5%CO(2)), but some maintained spontaneous activity throughout the insult. Proportions of 'surviving' (i.e. recovering or active) duck slices were significantly higher than for chickens in anoxia, and relative activity levels were higher for ducks than for chickens during hypoxia, anoxia and recovery. Survival of rat slices was significantly poorer than for birds under all conditions. Results suggest that (1) duck cerebellar neurons are intrinsically more hypoxia-tolerant than chicken neurons; (2) avian neurons are more hypoxia-tolerant than rat neurons, and (3) the enhanced hypoxic tolerance of duck neurons largely depended on efficient anaerobiosis since it mainly manifested itself in chemical anoxia. Mechanisms underlying the observed differences in neuronal hypoxic responses remain to be elucidated. PMID:19779726

  15. Mitochondrial fission is an acute and adaptive response in injured motor neurons.

    PubMed

    Kiryu-Seo, Sumiko; Tamada, Hiromi; Kato, Yukina; Yasuda, Katsura; Ishihara, Naotada; Nomura, Masatoshi; Mihara, Katsuyoshi; Kiyama, Hiroshi

    2016-01-01

    Successful recovery from neuronal damage requires a huge energy supply, which is provided by mitochondria. However, the physiological relevance of mitochondrial dynamics in damaged neurons in vivo is poorly understood. To address this issue, we established unique bacterial artificial chromosome transgenic (BAC Tg) mice, which develop and function normally, but in which neuronal injury induces labelling of mitochondria with green fluorescent protein (GFP) and expression of cre recombinase. GFP-labelled mitochondria in BAC Tg mice appear shorter in regenerating motor axons soon after nerve injury compared with mitochondria in non-injured axons, suggesting the importance of increased mitochondrial fission during the early phase of nerve regeneration. Crossing the BAC Tg mice with mice carrying a floxed dynamin-related protein 1 gene (Drp1), which is necessary for mitochondrial fission, ablates mitochondrial fission specifically in injured neurons. Injury-induced Drp1-deficient motor neurons show elongated or abnormally gigantic mitochondria, which have impaired membrane potential and axonal transport velocity during the early phase after injury, and eventually promote neuronal death. Our in vivo data suggest that acute and prominent mitochondrial fission during the early stage after nerve injury is an adaptive response and is involved in the maintenance of mitochondrial and neuronal integrity to prevent neurodegeneration. PMID:27319806

  16. Mitochondrial fission is an acute and adaptive response in injured motor neurons

    PubMed Central

    Kiryu-Seo, Sumiko; Tamada, Hiromi; Kato, Yukina; Yasuda, Katsura; Ishihara, Naotada; Nomura, Masatoshi; Mihara, Katsuyoshi; Kiyama, Hiroshi

    2016-01-01

    Successful recovery from neuronal damage requires a huge energy supply, which is provided by mitochondria. However, the physiological relevance of mitochondrial dynamics in damaged neurons in vivo is poorly understood. To address this issue, we established unique bacterial artificial chromosome transgenic (BAC Tg) mice, which develop and function normally, but in which neuronal injury induces labelling of mitochondria with green fluorescent protein (GFP) and expression of cre recombinase. GFP-labelled mitochondria in BAC Tg mice appear shorter in regenerating motor axons soon after nerve injury compared with mitochondria in non-injured axons, suggesting the importance of increased mitochondrial fission during the early phase of nerve regeneration. Crossing the BAC Tg mice with mice carrying a floxed dynamin-related protein 1 gene (Drp1), which is necessary for mitochondrial fission, ablates mitochondrial fission specifically in injured neurons. Injury-induced Drp1-deficient motor neurons show elongated or abnormally gigantic mitochondria, which have impaired membrane potential and axonal transport velocity during the early phase after injury, and eventually promote neuronal death. Our in vivo data suggest that acute and prominent mitochondrial fission during the early stage after nerve injury is an adaptive response and is involved in the maintenance of mitochondrial and neuronal integrity to prevent neurodegeneration. PMID:27319806

  17. Hippocampal adaptive response following extensive neuronal loss in an inducible transgenic mouse model.

    PubMed

    Myczek, Kristoffer; Yeung, Stephen T; Castello, Nicholas; Baglietto-Vargas, David; LaFerla, Frank M

    2014-01-01

    Neuronal loss is a common component of a variety of neurodegenerative disorders (including Alzheimer's, Parkinson's, and Huntington's disease) and brain traumas (stroke, epilepsy, and traumatic brain injury). One brain region that commonly exhibits neuronal loss in several neurodegenerative disorders is the hippocampus, an area of the brain critical for the formation and retrieval of memories. Long-lasting and sometimes unrecoverable deficits caused by neuronal loss present a unique challenge for clinicians and for researchers who attempt to model these traumas in animals. Can these deficits be recovered, and if so, is the brain capable of regeneration following neuronal loss? To address this significant question, we utilized the innovative CaM/Tet-DT(A) mouse model that selectively induces neuronal ablation. We found that we are able to inflict a consistent and significant lesion to the hippocampus, resulting in hippocampally-dependent behavioral deficits and a long-lasting upregulation in neurogenesis, suggesting that this process might be a critical part of hippocampal recovery. In addition, we provide novel evidence of angiogenic and vasculature changes following hippocampal neuronal loss in CaM/Tet-DTA mice. We posit that angiogenesis may be an important factor that promotes neurogenic upregulation following hippocampal neuronal loss, and both factors, angiogenesis and neurogenesis, can contribute to the adaptive response of the brain for behavioral recovery. PMID:25184527

  18. Influenza Virus Induces Inflammatory Response in Mouse Primary Cortical Neurons with Limited Viral Replication.

    PubMed

    Wang, Gefei; Li, Rui; Jiang, Zhiwu; Gu, Liming; Chen, Yanxia; Dai, Jianping; Li, Kangsheng

    2016-01-01

    Unlike stereotypical neurotropic viruses, influenza A viruses have been detected in the brain tissues of human and animal models. To investigate the interaction between neurons and influenza A viruses, mouse cortical neurons were isolated, infected with human H1N1 influenza virus, and then examined for the production of various inflammatory molecules involved in immune response. We found that replication of the influenza virus in neurons was limited, although early viral transcription was not affected. Virus-induced neuron viability decreased at 6 h postinfection (p.i.) but increased at 24 h p.i. depending upon the viral strain. Virus-induced apoptosis and cytopathy in primary cortical neurons were not apparent at 24 h p.i. The mRNA levels of inflammatory cytokines, chemokines, and type I interferons were upregulated at 6 h and 24 h p.i. These results indicate that the influenza virus induces inflammatory response in mouse primary cortical neurons with limited viral replication. The cytokines released in viral infection-induced neuroinflammation might play critical roles in influenza encephalopathy, rather than in viral replication-induced cytopathy. PMID:27525278

  19. Control of dopaminergic neuron survival by the unfolded protein response transcription factor XBP1

    PubMed Central

    Valdés, Pamela; Mercado, Gabriela; Vidal, Rene L.; Molina, Claudia; Parsons, Geoffrey; Court, Felipe A.; Martinez, Alexis; Galleguillos, Danny; Armentano, Donna; Schneider, Bernard L.; Hetz, Claudio

    2014-01-01

    Parkinson disease (PD) is characterized by the selective loss of dopaminergic neurons of the substantia nigra pars compacta (SNpc). Although growing evidence indicates that endoplasmic reticulum (ER) stress is a hallmark of PD, its exact contribution to the disease process is not well understood. Here we report that developmental ablation of X-Box binding protein 1 (XBP1) in the nervous system, a key regulator of the unfolded protein response (UPR), protects dopaminergic neurons against a PD-inducing neurotoxin. This survival effect was associated with a preconditioning condition that resulted from induction of an adaptive ER stress response in dopaminergic neurons of the SNpc, but not in other brain regions. In contrast, silencing XBP1 in adult animals triggered chronic ER stress and dopaminergic neuron degeneration. Supporting this finding, gene therapy to deliver an active form of XBP1 provided neuroprotection and reduced striatal denervation in animals injected with 6-hydroxydopamine. Our results reveal a physiological role of the UPR in the maintenance of protein homeostasis in dopaminergic neurons that may help explain the differential neuronal vulnerability observed in PD. PMID:24753614

  20. Mitogen and stress response kinase-1 (MSK1) mediates excitotoxic induced death of hippocampal neurones.

    PubMed

    Hughes, Jane P; Staton, Penny C; Wilkinson, Marc G; Strijbos, Paul J L M; Skaper, Stephen D; Arthur, J Simon C; Reith, Alastair D

    2003-07-01

    Activation of the mitogen-activated protein kinase (MAPK/ERK) signal transduction pathway may mediate excitotoxic neuronal cell death in vitro and during ischemic brain injury in vivo. However, little is known, of the upstream regulation or downstream consequences of ERK activation under these conditions. Magnesium removal has been described to induce hyperexcitability and degeneration in cultured hippocampal neurones. Here, we show that neurotoxicity evoked by Mg2+ removal in primary hippocampal neurones stimulates ERK, but not p38, phosphorylation. Removal of Mg2+ also resulted in induction of the MAPK/ERK substrate mitogen- and stress-response kinase 1 (MSK1) and induced phosphorylation of the MSK1 substrate, the transcription factor cAMP response element binding protein (CREB). Neuronal death and phosphorylation of components in this cascade were inhibited by the Raf inhibitor SB-386023, by the MEK inhibitor U0126, or by the MSK1 inhibitors H89 and Ro318220. Importantly, this form of cell death was inhibited in hippocampal neurones cultured from MSK1-/- mice and inhibitors of Raf or MEK had no additive neuroprotective effect. Together, these data indicate that MSK1 is a physiological kinase for CREB and that this activity is an essential component of activity-dependent neuronal cell death. PMID:12807421

  1. Influenza Virus Induces Inflammatory Response in Mouse Primary Cortical Neurons with Limited Viral Replication

    PubMed Central

    Jiang, Zhiwu; Gu, Liming; Chen, Yanxia

    2016-01-01

    Unlike stereotypical neurotropic viruses, influenza A viruses have been detected in the brain tissues of human and animal models. To investigate the interaction between neurons and influenza A viruses, mouse cortical neurons were isolated, infected with human H1N1 influenza virus, and then examined for the production of various inflammatory molecules involved in immune response. We found that replication of the influenza virus in neurons was limited, although early viral transcription was not affected. Virus-induced neuron viability decreased at 6 h postinfection (p.i.) but increased at 24 h p.i. depending upon the viral strain. Virus-induced apoptosis and cytopathy in primary cortical neurons were not apparent at 24 h p.i. The mRNA levels of inflammatory cytokines, chemokines, and type I interferons were upregulated at 6 h and 24 h p.i. These results indicate that the influenza virus induces inflammatory response in mouse primary cortical neurons with limited viral replication. The cytokines released in viral infection-induced neuroinflammation might play critical roles in influenza encephalopathy, rather than in viral replication-induced cytopathy. PMID:27525278

  2. Spatiotemporal processing of linear acceleration: primary afferent and central vestibular neuron responses

    NASA Technical Reports Server (NTRS)

    Angelaki, D. E.; Dickman, J. D.

    2000-01-01

    Spatiotemporal convergence and two-dimensional (2-D) neural tuning have been proposed as a major neural mechanism in the signal processing of linear acceleration. To examine this hypothesis, we studied the firing properties of primary otolith afferents and central otolith neurons that respond exclusively to horizontal linear accelerations of the head (0.16-10 Hz) in alert rhesus monkeys. Unlike primary afferents, the majority of central otolith neurons exhibited 2-D spatial tuning to linear acceleration. As a result, central otolith dynamics vary as a function of movement direction. During movement along the maximum sensitivity direction, the dynamics of all central otolith neurons differed significantly from those observed for the primary afferent population. Specifically at low frequencies (neurons peaked in phase with linear velocity, in contrast to primary afferents that peaked in phase with linear acceleration. At least three different groups of central response dynamics were described according to the properties observed for motion along the maximum sensitivity direction. "High-pass" neurons exhibited increasing gains and phase values as a function of frequency. "Flat" neurons were characterized by relatively flat gains and constant phase lags (approximately 20-55 degrees ). A few neurons ("low-pass") were characterized by decreasing gain and phase as a function of frequency. The response dynamics of central otolith neurons suggest that the approximately 90 degrees phase lags observed at low frequencies are not the result of a neural integration but rather the effect of nonminimum phase behavior, which could arise at least partly through spatiotemporal convergence. Neither afferent nor central otolith neurons discriminated between gravitational and inertial components of linear acceleration. Thus response sensitivity was indistinguishable during 0.5-Hz pitch oscillations and fore-aft movements

  3. Neuronal responses to face-like and facial stimuli in the monkey superior colliculus

    PubMed Central

    Nguyen, Minh Nui; Matsumoto, Jumpei; Hori, Etsuro; Maior, Rafael Souto; Tomaz, Carlos; Tran, Anh H.; Ono, Taketoshi; Nishijo, Hisao

    2014-01-01

    The superficial layers of the superior colliculus (sSC) appear to function as a subcortical visual pathway that bypasses the striate cortex for the rapid processing of coarse facial information. We investigated the responses of neurons in the monkey sSC during a delayed non-matching-to-sample (DNMS) task in which monkeys were required to discriminate among five categories of visual stimuli [photos of faces with different gaze directions, line drawings of faces, face-like patterns (three dark blobs on a bright oval), eye-like patterns, and simple geometric patterns]. Of the 605 sSC neurons recorded, 216 neurons responded to the visual stimuli. Among the stimuli, face-like patterns elicited responses with the shortest latencies. Low-pass filtering of the images did not influence the responses. However, scrambling of the images increased the responses in the late phase, and this was consistent with a feedback influence from upstream areas. A multidimensional scaling (MDS) analysis of the population data indicated that the sSC neurons could separately encode face-like patterns during the first 25-ms period after stimulus onset, and stimulus categorization developed in the next three 25-ms periods. The amount of stimulus information conveyed by the sSC neurons and the number of stimulus-differentiating neurons were consistently higher during the 2nd to 4th 25-ms periods than during the first 25-ms period. These results suggested that population activity of the sSC neurons preferentially filtered face-like patterns with short latencies to allow for the rapid processing of coarse facial information and developed categorization of the stimuli in later phases through feedback from upstream areas. PMID:24672448

  4. Activity of Somatosensory-Responsive Neurons in High Subdivisions of SI Cortex during Locomotion

    PubMed Central

    Favorov, Oleg V.; Nilaweera, Wijitha U.; Miasnikov, Alexandre A.

    2015-01-01

    Responses of neurons in the primary somatosensory cortex during movements are poorly understood, even during such simple tasks as walking on a flat surface. In this study, we analyzed spike discharges of neurons in the rostral bank of the ansate sulcus (areas 1–2) in 2 cats while the cats walked on a flat surface or on a horizontal ladder, a complex task requiring accurate stepping. All neurons (n = 82) that had receptive fields (RFs) on the contralateral forelimb exhibited frequency modulation of their activity that was phase locked to the stride cycle during simple locomotion. Neurons with proximal RFs (upper arm/shoulder) and pyramidal tract-projecting neurons (PTNs) with fast-conducting axons tended to fire at peak rates in the middle of the swing phase, whereas neurons with RFs on the distal limb (wrist/paw) and slow-conducting PTNs typically showed peak firing at the transition between swing and stance phases. Eleven of 12 neurons with tactile RFs on the volar forepaw began firing toward the end of swing, with peak activity occurring at the moment of foot contact with floor, thereby preceding the evoked sensory volley from touch receptors. Requirement to step accurately on the ladder affected 91% of the neurons, suggesting their involvement in control of accuracy of stepping. During both tasks, neurons exhibited a wide variety of spike distributions within the stride cycle, suggesting that, during either simple or ladder locomotion, they represent the cycling somatosensory events in their activity both predictively before and reflectively after these events take place. PMID:25995465

  5. Gustatory responses of neurons in the nucleus of the solitary tract of behaving rats.

    PubMed

    Nakamura, K; Norgren, R

    1991-10-01

    1. The activity of 117 single neurons was recorded in the rostral nucleus of the solitary tract (NST) and tested with each of four standard chemical stimuli [sucrose, NaCl, citric acid, and quinine HCl (QHCl)] and distilled water in awake, behaving rats. In 101 of these neurons, at least one sapid stimulus elicited a significant taste response. The mean spontaneous rate of the taste neurons was 4.1 +/- 5.8 (SD) spike/s. The mean response magnitudes were as follows: sucrose, 10.6 +/- 11.7; NaCl, 8.6 +/- 14.6; citric acid, 6.2 +/- 7.8; and QHCl, 2.4 +/- 6.6 spikes/s. 2. On the basis of their largest response, 42 taste neurons were classified as sucrose-best, 25 as NaCl-best, 30 as citric acid-best, and 4 as QHCl-best. The mean spontaneous rates for these categories were 4.9 +/- 6.2 for sucrose-best cells, 5.8 +/- 7.4 for NaCl-best, 1.6 +/- 2.0 for citric acid-best, and 5.8 +/- 6.0 spikes/s for QHCl-best. The spontaneous rate of the citric acid-best neurons was significantly lower than that of the other categories. 3. At the standard concentrations, 45 taste cells (44.6%) responded significantly to only one of the gustatory stimuli. Of the 30 acid-best neurons, 23 (76.7%) responded only to citric acid. For sucrose-best cells, specific sensitivity was less common (18/42, 42.9%), and for NaCl-best neurons, it was relatively uncommon (3/25, 12%). One of the 4 QHCl-best neurons was specific. In a concentration series, more than one-half of the 19 specific neurons tested responded to only one chemical at any strength. 4. The mean entropy for the excitatory responses of all gustatory neurons was 0.60. Citric acid-best cells showed the least breadth of responsiveness (0.49), sucrose-best cells were somewhat broader (0.56), but NaCl-best and QHCl-best cells were considerably less selective (0.77 and 0.79, respectively). Inhibition was observed infrequently and never reached the criterion for significance. 5. In the hierarchical cluster analysis, the four largest clusters

  6. Increased acid responsiveness in vagal sensory neurons in a guinea pig model of eosinophilic esophagitis

    PubMed Central

    Hu, Youtian; Liu, Zhenyu; Yu, Xiaoyun; Pasricha, Pankaj J.; Undem, Bradley J.

    2014-01-01

    Eosinophilic esophagitis (EoE) is characterized with eosinophils and mast cells predominated allergic inflammation in the esophagus and present with esophageal dysfunctions such as dysphagia, food impaction, and heartburn. However, the underlying mechanism of esophageal dysfunctions is unclear. This study aims to determine whether neurons in the vagal sensory ganglia are modulated in a guinea pig model of EoE. Animals were actively sensitized by ovalbumin (OVA) and then challenged with aerosol OVA inhalation for 2 wk. This results in a mild esophagitis with increases in mast cells and eosinophils in the esophageal wall. Vagal nodose and jugular neurons were disassociated, and their responses to acid, capsaicin, and transient receptor potential vanilloid type 1 (TRPV1) antagonist AMG-9810 were studied by calcium imaging and whole cell patch-clamp recording. Compared with naïve animals, antigen challenge significantly increased acid responsiveness in both nodose and jugular neurons. Their responses to capsaicin were also increased after antigen challenge. AMG-9810, at a concentration that blocked capsaicin-evoked calcium influx, abolished the increase in acid-induced activation in both nodose and jugular neurons. Vagotomy strongly attenuated those increased responses of nodose and jugular neurons to both acid and capsaicin induced by antigen challenge. These data for the first time demonstrated that prolonged antigen challenge significantly increases acid responsiveness in vagal nodose and jugular ganglia neurons. This sensitization effect is mediated largely through TRPV1 and initiated at sensory nerve endings in the peripheral tissues. Allergen-induced enhancement of responsiveness to noxious stimulation by acid in sensory nerve may contribute to the development of esophageal dysfunctions such as heartburn in EoE. PMID:24875100

  7. Response characteristics of basolateral and centromedial neurons in the primate amygdala

    PubMed Central

    Mosher, Clayton P.; Zimmerman, Prisca E.; Gothard, Katalin M.

    2010-01-01

    Based on cellular architecture and connectivity, the main nuclei of the primate amygdala are divided in two clusters: basolateral (BL) and centromedial (CM). These anatomical features suggest a functional division of labor among the nuclei. The BL nuclei are thought to be involved primarily in evaluating the emotional significance or context-dependent relevance of all stimuli, including social signals such as facial expressions. The CM nuclei appear to be involved in allocating attention to stimuli of high significance and in initiating situation-appropriate autonomic responses. The goal of this study was to determine how this division of labor manifests in the response properties of neurons recorded from these two nuclear groups. We recorded the activity of 454 single neurons from identified nuclear sites in three monkeys trained to perform an image viewing task. The task required orienting and attending to cues that predicted trial progression and viewing images with broadly varying emotional content. The two populations of neurons showed large overlaps in neurophysiological properties. We found, however, that CM neurons show higher firing and less regular spiking patterns than BL neurons. Furthermore, neurons in the CM nuclei were more likely to respond to task events (fixation, image-on, image-off), while neurons in the BL nuclei were more likely to respond selectively to the content of stimulus images. The overlap in the physiological properties of the CM and BL neurons suggest distributed processing across the nuclear groups. The differences, therefore, appear to be a processing bias rather than a hallmark of mutually exclusive functions. PMID:21123566

  8. Electrosensory Midbrain Neurons Display Feature Invariant Responses to Natural Communication Stimuli

    PubMed Central

    Aumentado-Armstrong, Tristan; Metzen, Michael G.; Sproule, Michael K. J.; Chacron, Maurice J.

    2015-01-01

    Neurons that respond selectively but in an invariant manner to a given feature of natural stimuli have been observed across species and systems. Such responses emerge in higher brain areas, thereby suggesting that they occur by integrating afferent input. However, the mechanisms by which such integration occurs are poorly understood. Here we show that midbrain electrosensory neurons can respond selectively and in an invariant manner to heterogeneity in behaviorally relevant stimulus waveforms. Such invariant responses were not seen in hindbrain electrosensory neurons providing afferent input to these midbrain neurons, suggesting that response invariance results from nonlinear integration of such input. To test this hypothesis, we built a model based on the Hodgkin-Huxley formalism that received realistic afferent input. We found that multiple combinations of parameter values could give rise to invariant responses matching those seen experimentally. Our model thus shows that there are multiple solutions towards achieving invariant responses and reveals how subthreshold membrane conductances help promote robust and invariant firing in response to heterogeneous stimulus waveforms associated with behaviorally relevant stimuli. We discuss the implications of our findings for the electrosensory and other systems. PMID:26474395

  9. Neuronal responses in cat primary auditory cortex to natural and altered species-specific calls.

    PubMed

    Gehr, D D; Komiya, H; Eggermont, J J

    2000-12-01

    We investigated how natural and morphed cat vocalizations are represented in primary auditory cortex (AI). About 40% of the neurons showed time-locked responses to major peaks in the vocalization envelope, 60% only responded at the onset. Simultaneously recorded multi-unit (MU) activity of these peak-tracking neurons on separate electrodes was significantly more synchronous during stimulation than under silence. Thus, the representation of the vocalizations is likely synchronously distributed across the cortex. The sum of the responses to the low and high frequency part of the meow, with the boundary at 2.5 kHz, was larger than the neuronal response to the natural meow itself, suggesting that strong lateral inhibition is shaping the response to the natural meow. In this sense, the neurons are combination-sensitive. The frequency-tuning properties and the response to amplitude-modulated tones of the MU recordings can explain the responses to natural, and temporally and spectrally altered vocalizations. Analysis of the mutual information in the firing rate suggests that the activity of at least 95 recording sites in AI would be needed to reliably distinguish between the nine different vocalizations. This suggests that a distributed representation based on temporal stimulus aspects may be more efficient than one based on firing rate. PMID:11077191

  10. Serum Response Factor Mediated Gene Activity in Physiological and Pathological Processes of Neuronal Motility

    PubMed Central

    Knöll, Bernd

    2011-01-01

    In recent years, the transcription factor serum response factor (SRF) was shown to contribute to various physiological processes linked to neuronal motility. The latter include cell migration, axon guidance, and, e.g., synapse function relying on cytoskeletal dynamics, neurite outgrowth, axonal and dendritic differentiation, growth cone motility, and neurite branching. SRF teams up with myocardin related transcription factors (MRTFs) and ternary complex factors (TCFs) to mediate cellular actin cytoskeletal dynamics and the immediate-early gene (IEG) response, a bona fide indicator of neuronal activation. Herein, I will discuss how SRF and cofactors might modulate physiological processes of neuronal motility. Further, potential mechanisms engaged by neurite growth promoting molecules and axon guidance cues to target SRF’s transcriptional machinery in physiological neuronal motility will be presented. Of note, altered cytoskeletal dynamics and rapid initiation of an IEG response are a hallmark of injured neurons in various neurological disorders. Thus, SRF and its MRTF and TCF cofactors might emerge as a novel trio modulating peripheral and central axon regeneration. PMID:22164132

  11. Complete Firing-Rate Response of Neurons with Complex Intrinsic Dynamics.

    PubMed

    Puelma Touzel, Maximilian; Wolf, Fred

    2015-12-01

    The response of a neuronal population over a space of inputs depends on the intrinsic properties of its constituent neurons. Two main modes of single neuron dynamics-integration and resonance-have been distinguished. While resonator cell types exist in a variety of brain areas, few models incorporate this feature and fewer have investigated its effects. To understand better how a resonator's frequency preference emerges from its intrinsic dynamics and contributes to its local area's population firing rate dynamics, we analyze the dynamic gain of an analytically solvable two-degree of freedom neuron model. In the Fokker-Planck approach, the dynamic gain is intractable. The alternative Gauss-Rice approach lifts the resetting of the voltage after a spike. This allows us to derive a complete expression for the dynamic gain of a resonator neuron model in terms of a cascade of filters on the input. We find six distinct response types and use them to fully characterize the routes to resonance across all values of the relevant timescales. We find that resonance arises primarily due to slow adaptation with an intrinsic frequency acting to sharpen and adjust the location of the resonant peak. We determine the parameter regions for the existence of an intrinsic frequency and for subthreshold and spiking resonance, finding all possible intersections of the three. The expressions and analysis presented here provide an account of how intrinsic neuron dynamics shape dynamic population response properties and can facilitate the construction of an exact theory of correlations and stability of population activity in networks containing populations of resonator neurons. PMID:26720924

  12. Complete Firing-Rate Response of Neurons with Complex Intrinsic Dynamics

    PubMed Central

    Puelma Touzel, Maximilian; Wolf, Fred

    2015-01-01

    The response of a neuronal population over a space of inputs depends on the intrinsic properties of its constituent neurons. Two main modes of single neuron dynamics–integration and resonance–have been distinguished. While resonator cell types exist in a variety of brain areas, few models incorporate this feature and fewer have investigated its effects. To understand better how a resonator’s frequency preference emerges from its intrinsic dynamics and contributes to its local area’s population firing rate dynamics, we analyze the dynamic gain of an analytically solvable two-degree of freedom neuron model. In the Fokker-Planck approach, the dynamic gain is intractable. The alternative Gauss-Rice approach lifts the resetting of the voltage after a spike. This allows us to derive a complete expression for the dynamic gain of a resonator neuron model in terms of a cascade of filters on the input. We find six distinct response types and use them to fully characterize the routes to resonance across all values of the relevant timescales. We find that resonance arises primarily due to slow adaptation with an intrinsic frequency acting to sharpen and adjust the location of the resonant peak. We determine the parameter regions for the existence of an intrinsic frequency and for subthreshold and spiking resonance, finding all possible intersections of the three. The expressions and analysis presented here provide an account of how intrinsic neuron dynamics shape dynamic population response properties and can facilitate the construction of an exact theory of correlations and stability of population activity in networks containing populations of resonator neurons. PMID:26720924

  13. Direction-selective neurons in the optokinetic system with long-lasting after-responses.

    PubMed

    Price, Nicholas S C; Ibbotson, Michael R

    2002-11-01

    We describe the responses during and after motion of slow cells, which are a class of direction-selective neurons in the pretectal nucleus of the optic tract (NOT) of the wallaby. Neurons in the NOT respond to optic flow generated by head movements and drive compensatory optokinetic eye movements. Motion in the preferred direction produces increased firing rates in the cells, whereas motion in the opposite direction inhibits their high spontaneous activities. Neurons were stimulated with moving spatial sinusoidal gratings through a range of temporal and spatial frequencies. The slow cells were maximally stimulated at temporal frequencies <1 Hz and spatial frequencies of 0.13-1 cpd. During motion, the responses oscillate at the fundamental temporal frequency of the grating but not at higher-order harmonics. There is prolonged excitation after preferred direction motion and prolonged inhibition after anti-preferred direction motion, which are referred to as same-sign after-responses (SSARs). This is the first time that the response properties of neurons with SSARs have been reported and modeled in detail for neurons in the NOT. Slow cell responses during and after motion are modeled using an array of Reichardt-type motion detectors that include band-pass temporal prefilters. The oscillatory behavior during motion and the SSARs can be simulated accurately with the model by manipulating time constants associated with temporal filtering in the prefilters and motion detectors. The SSARs of slow cells are compared with those of previously described direction-selective neurons, which usually show transient inhibition or excitation after preferred or anti-preferred direction motion, respectively. Possible functional roles for slow cells are discussed in the context of eye movement control. PMID:12424264

  14. The Response of Retinal Neurons to High-Frequency Stimulation

    PubMed Central

    Cai, Changsi; Twyford, Perry; Fried, Shelley

    2013-01-01

    Objective High-rate pulse trains have proven to be effective in cochlear prosthetics and, more recently, have been shown to elicit a wide range of interesting response properties in axons of the PNS. Surprisingly, the effectiveness of such trains for use in retinal prostheses has not been explored. Approach Using cell-attached patch clamp methods, we measured the in vitro response of two rabbit retinal ganglion cell (RGC) types, OFF-Brisk Transient (OFF-BT) and ON-OFF Directionally Selective (DS), to trains of biphasic pulses delivered at 2000 pulses per second (PPS). Main Results For OFF-BT cells, response onset occurred at ~20 uA, and maximum response occurred at ~40 uA. Interestingly, spiking levels decreased for further increases in amplitude. In contrast, DS cells had a spiking onset at ~25 uA and maintained strong spiking as stimulus amplitude was increased, even at the highest levels tested. Thus, a low-amplitude stimulus train at 2000 PPS (~25 μA) will activate OFF-BT cells strongly, while simultaneously activating DS cells only weakly. In contrast, a high amplitude train (~75 μA) will activate DS cells strongly while suppressing responses in OFF-BT cells. Significance The response differences between cell types suggest some forms of preferential activation may be possible, and further testing is warranted. Further, the scope of the response differences found here suggests activation mechanisms that are more complex than those described in previous studies. PMID:23594620

  15. Influence of Probe Flexibility and Gelatin Embedding on Neuronal Density and Glial Responses to Brain Implants

    PubMed Central

    Köhler, Per; Wolff, Anette; Ejserholm, Fredrik; Wallman, Lars

    2015-01-01

    To develop long-term high quality communication between brain and computer, a key issue is how to reduce the adverse foreign body responses. Here, the impact of probe flexibility and gelatine embedding on long-term (6w) tissue responses, was analyzed. Probes of same polymer material, size and shape, flexible mainly in one direction, were implanted in rat cerebral cortex (nimplants = 3 x 8) in two orientations with respect to the major movement direction of the brain relative to the skull: parallel to (flex mode) or transverse to (rigid mode). Flex mode implants were either embedded in gelatin or non-embedded. Neurons, activated microglia and astrocytes were visualized using immunohistochemistry. The astrocytic reactivity, but not microglial response, was significantly lower to probes implanted in flex mode as compared to rigid mode. The microglial response, but not astrocytic reactivity, was significantly smaller to gelatin embedded probes (flex mode) than non-embedded. Interestingly, the neuronal density was preserved in the inner zone surrounding gelatin embedded probes. This contrasts to the common reports of reduced neuronal density close to implanted probes. In conclusion, sheer stress appears to be an important factor for astrocytic reactivity to implanted probes. Moreover, gelatin embedding can improve the neuronal density and reduce the microglial response close to the probe. PMID:25790172

  16. Mouse V1 population correlates of visual detection rely on heterogeneity within neuronal response patterns

    PubMed Central

    Montijn, Jorrit S; Goltstein, Pieter M; Pennartz, Cyriel MA

    2015-01-01

    Previous studies have demonstrated the importance of the primary sensory cortex for the detection, discrimination, and awareness of visual stimuli, but it is unknown how neuronal populations in this area process detected and undetected stimuli differently. Critical differences may reside in the mean strength of responses to visual stimuli, as reflected in bulk signals detectable in functional magnetic resonance imaging, electro-encephalogram, or magnetoencephalography studies, or may be more subtly composed of differentiated activity of individual sensory neurons. Quantifying single-cell Ca2+ responses to visual stimuli recorded with in vivo two-photon imaging, we found that visual detection correlates more strongly with population response heterogeneity rather than overall response strength. Moreover, neuronal populations showed consistencies in activation patterns across temporally spaced trials in association with hit responses, but not during nondetections. Contrary to models relying on temporally stable networks or bulk signaling, these results suggest that detection depends on transient differentiation in neuronal activity within cortical populations. DOI: http://dx.doi.org/10.7554/eLife.10163.001 PMID:26646184

  17. Increased cellular turnover in response to fluoxetine in neuronal precursors derived from human embryonic stem cells.

    PubMed

    Chang, Eun-Ah; Beyhan, Zeki; Yoo, Myung-Sik; Siripattarapravat, Kannika; Ko, Tak; Lookingland, Keith J; Madhukar, Burra V; Cibelli, Jose B

    2010-01-01

    Previous reports have shown that antidepressants increase neuronal cell proliferation and enhance neuroplasticity both in vivo and in vitro. This study investigated the direct effects of one such antidepressant, fluoxetine , on cell proliferation and on the production of neurotrophic factors in neuronal precursors derived from human embryonic stem cells (hESCs; H9). Fluoxetine induced the differentiation of neuronal precursors, strongly enhancing neuronal characteristics. The rate of proliferation was higher in fluoxetine -treated cells than in control cells, as determined by MTT [3(4,5-dimethylthiazol-2-yl) 2,5-diphenyltetrazolium bromide] assay. The CPDL (cumulative population doubling level) of the fluoxetine-treated cells was significantly increased in comparison to that of control cells (p<.001). Bromodeoxyuridine incorporation and staurosporine-induced apoptosis assays were elevated in fluoxetine-treated cells. Quantitative RT-PCR analysis revealed no significant differences in the expression of neurotrophic factors, brain-derived neurotrophic factor (BDNF);glial-derived neurotrophic factor (GDNF) and cAMP-responsive element-binding protein (CREB) between cells treated with fluoxetine for two weeks and their untreated counterparts. These results may help elucidate the mechanism of action of fluoxetine as a therapeutic drug for the treatment of depression. Data presented herein provide more evidence that, in addition to having a direct chemical effect on serotonin levels, fluoxetine can influence hESC-derived neuronal cells by increasing cell proliferation, while allowing them to maintain their neuronal characteristics. PMID:19598107

  18. Dual Electrophysiological Recordings of Synaptically-evoked Astroglial and Neuronal Responses in Acute Hippocampal Slices

    PubMed Central

    Rouach, Nathalie

    2012-01-01

    Astrocytes form together with neurons tripartite synapses, where they integrate and modulate neuronal activity. Indeed, astrocytes sense neuronal inputs through activation of their ion channels and neurotransmitter receptors, and process information in part through activity-dependent release of gliotransmitters. Furthermore, astrocytes constitute the main uptake system for glutamate, contribute to potassium spatial buffering, as well as to GABA clearance. These cells therefore constantly monitor synaptic activity, and are thereby sensitive indicators for alterations in synaptically-released glutamate, GABA and extracellular potassium levels. Additionally, alterations in astroglial uptake activity or buffering capacity can have severe effects on neuronal functions, and might be overlooked when characterizing physiopathological situations or knockout mice. Dual recording of neuronal and astroglial activities is therefore an important method to study alterations in synaptic strength associated to concomitant changes in astroglial uptake and buffering capacities. Here we describe how to prepare hippocampal slices, how to identify stratum radiatum astrocytes, and how to record simultaneously neuronal and astroglial electrophysiological responses. Furthermore, we describe how to isolate pharmacologically the synaptically-evoked astroglial currents. PMID:23222635

  19. Melatonin Ameliorates Injury and Specific Responses of Ischemic Striatal Neurons in Rats

    PubMed Central

    Ma, Yuxin; Feng, Qiqi; Ma, Jing; Feng, Zhibo; Zhan, Mali; OuYang, Lisi; Mu, Shuhua; Liu, Bingbing; Jiang, Zhuyi; Jia, Yu; Li, Youlan

    2013-01-01

    Studies have confirmed that middle cerebral artery occlusion (MCAO) causes striatal injury in which oxidative stress is involved in the pathological mechanism. Increasing evidence suggests that melatonin may have a neuroprotective effect on cerebral ischemic damage. This study aimed to examine the morphological changes of different striatal neuron types and the effect of melatonin on striatal injury by MCAO. The results showed that MCAO induced striatum-related dysfunctions of locomotion, coordination, and cognition, which were remarkably relieved with melatonin treatment. MCAO induced severe striatal neuronal apoptosis and loss, which was significantly decreased with melatonin treatment. Within the outer zone of the infarct, the number of Darpp-32+ projection neurons and the densities of dopamine-receptor-1 (D1)+ and dopamine-receptor-2 (D2)+ fibers were reduced; however, both parvalbumin (Parv)+ and choline acetyltransferase (ChAT)+ interneurons were not significantly decreased in number, and neuropeptide Y (NPY)+ and calretinin (Cr)+ interneurons were even increased. With melatonin treatment, the loss of projection neurons and characteristic responses of interneurons were notably attenuated. The present study demonstrates that the projection neurons are rather vulnerable to ischemic damage, whereas the interneurons display resistance and even hyperplasia against injury. In addition, melatonin alleviates striatal dysfunction, neuronal loss, and morphological transformation of interneurons resulting from cerebral ischemia. PMID:23686363

  20. Odorant response properties of individual neurons in an olfactory glomerular module

    PubMed Central

    Kikuta, Shu; Fletcher, Max L.; Homma, Ryota; Yamasoba, Tatsuya; Nagayama, Shin

    2013-01-01

    Summary Neuronal networks that are directly associated with glomeruli in the olfactory bulb are thought to comprise functional modules. However, this has not yet been experimentally proven. In this study, we explored the anatomical and functional architecture of glomerular modules using in vivo two-photon calcium imaging. Surprisingly, the deep portions of the glomerular modules showed considerable spatial overlap with other modules. Juxtaglomerular cells showed similar excitatory odorant response profiles to presynaptic olfactory sensory neuron inputs. Mitral cells exhibited a more sharply tuned molecular receptive range compared to juxtaglomerular cells, and their odorant response profiles varied depending on their interneuronal horizontal distances. These data suggest that glomerular modules are composed of functionally distinct neurons, and that homogenous odor inputs to each glomerulus may be parsed and processed in different fashions within the modules before being sent to higher olfactory centers. PMID:23522047

  1. Predicting every spike: a model for the responses of visual neurons.

    PubMed

    Keat, J; Reinagel, P; Reid, R C; Meister, M

    2001-06-01

    In the early visual system, neuronal responses can be extremely precise. Under a wide range of stimuli, cells in the retina and thalamus fire spikes very reproducibly, often with millisecond precision on subsequent stimulus repeats. Here we develop a mathematical description of the firing process that, given the recent visual input, accurately predicts the timing of individual spikes. The formalism is successful in matching the spike trains from retinal ganglion cells in salamander, rabbit, and cat, as well as from lateral geniculate nucleus neurons in cat. It adapts to many different response types, from very precise to highly variable. The accuracy of the model allows a compact description of how these neurons encode the visual stimulus. PMID:11430813

  2. Responses from two firing patterns in inferior colliculus neurons to stimulation of the lateral lemniscus dorsal nucleus.

    PubMed

    Li, Xiao-Ting; Wang, Ning-Yu; Wang, Yan-Jun; Xu, Zhi-Qing; Liu, Jin-Feng; Bai, Yun-Fei; Dai, Jin-Sheng; Zhao, Jing-Yi

    2016-05-01

    The γ-aminobutyric acid neurons (GABAergic neurons) in the inferior colliculus are classified into various patterns based on their intrinsic electrical properties to a constant current injection. Although this classification is associated with physiological function, the exact role for neurons with various firing patterns in acoustic processing remains poorly understood. In the present study, we analyzed characteristics of inferior colliculus neurons in vitro, and recorded responses to stimulation of the dorsal nucleus of the lateral lemniscus using the whole-cell patch clamp technique. Seven inferior colliculus neurons were tested and were classified into two firing patterns: sustained-regular (n = 4) and sustained-adapting firing patterns (n = 3). The majority of inferior colliculus neurons exhibited slight changes in response to stimulation and bicuculline. The responses of one neuron with a sustained-adapting firing pattern were suppressed after stimulation, but recovered to normal levels following application of the γ-aminobutyric acid receptor antagonist. One neuron with a sustained-regular pattern showed suppressed stimulation responses, which were not affected by bicuculline. Results suggest that GABAergic neurons in the inferior colliculus exhibit sustained-regular or sustained-adapting firing patterns. Additionally, GABAergic projections from the dorsal nucleus of the lateral lemniscus to the inferior colliculus are associated with sound localization. The different neuronal responses of various firing patterns suggest a role in sound localization. A better understanding of these mechanisms and functions will provide better clinical treatment paradigms for hearing deficiencies. PMID:27335563

  3. Responses from two firing patterns in inferior colliculus neurons to stimulation of the lateral lemniscus dorsal nucleus

    PubMed Central

    Li, Xiao-ting; Wang, Ning-yu; Wang, Yan-jun; Xu, Zhi-qing; Liu, Jin-feng; Bai, Yun-fei; Dai, Jin-sheng; Zhao, Jing-yi

    2016-01-01

    The γ-aminobutyric acid neurons (GABAergic neurons) in the inferior colliculus are classified into various patterns based on their intrinsic electrical properties to a constant current injection. Although this classification is associated with physiological function, the exact role for neurons with various firing patterns in acoustic processing remains poorly understood. In the present study, we analyzed characteristics of inferior colliculus neurons in vitro, and recorded responses to stimulation of the dorsal nucleus of the lateral lemniscus using the whole-cell patch clamp technique. Seven inferior colliculus neurons were tested and were classified into two firing patterns: sustained-regular (n = 4) and sustained-adapting firing patterns (n = 3). The majority of inferior colliculus neurons exhibited slight changes in response to stimulation and bicuculline. The responses of one neuron with a sustained-adapting firing pattern were suppressed after stimulation, but recovered to normal levels following application of the γ-aminobutyric acid receptor antagonist. One neuron with a sustained-regular pattern showed suppressed stimulation responses, which were not affected by bicuculline. Results suggest that GABAergic neurons in the inferior colliculus exhibit sustained-regular or sustained-adapting firing patterns. Additionally, GABAergic projections from the dorsal nucleus of the lateral lemniscus to the inferior colliculus are associated with sound localization. The different neuronal responses of various firing patterns suggest a role in sound localization. A better understanding of these mechanisms and functions will provide better clinical treatment paradigms for hearing deficiencies. PMID:27335563

  4. Responses of primate cortical neurons to unitary and binary taste stimuli.

    PubMed

    Miyaoka, Y; Pritchard, T C

    1996-01-01

    1. The responses of 126 neurons in primary gustatory cortices of two rhesus monkeys were recorded during sapid stimulation of the tongue with 18 taste stimuli. Ten of these stimuli were dissolved in distilled water (DW): 1.0 M sucrose (Suc), 0.1 M and 0.03 M sodium chloride (NaCl), 0.003 M hydrochloric acid (HCl), 0.001 M quinine hydrochloride (QHCl), 0.03 M monosodium glutamate (MSG), 0.03 M polycose, 0.3 M glycine, 0.1 M proline, and 0.1 M malic acid. Seven other stimuli were dissolved in 0.03 M MSG; the last stimulus was a mixture of 1.0 M Suc and 0.03 M NaCl. 2. The average spontaneous rate (2.2 +/- 0.2 spikes/s, mean +/- SE) and response to DW (2.5 +/- 0.2) of these 126 neurons was low but within the range previously reported for neurons in primate taste cortex. Suc was the most effective stimulus for 24.1% of the neurons tested followed by NaCl (15.7%), QHCl (14.8%), HCl (11.1%), MSG (10.2%), and other miscellaneous unitary gustatory stimuli (8.3%). Binary taste mixtures were the most effective stimuli for 15.7% of the sample. The net responses (corrected for DW, in spikes/s) for Suc-best (3.3), NaCl-best (4.3), HCl-best (3.4), QHCl-best (2.3), and MSG-best (4.1) were sluggish, but comparable with that reported previously. 3. The response breadth of the 82 neurons that responded best to either Suc, NaCl, HCl, or QHCl measured with the entropy coefficient indicated a moderate response breadth for these neurons (mean = 0.79; range = 0.30-0.98). According to the response criteria adopted in this experiment (water response +/- 1.96 SD), however, 81 of these 82 neurons (98.1%) responded to only one or two of the four basic taste stimuli. The disparity between the entropy- and criterion-based measures of response derive from the nature of the two statistics. Adjustments that would make the entropy statistic less inclusive and the definition of a response according to statistical criteria less exclusive would increase their concordance. 4. Three multivariate

  5. Corneal dry-responsive neurons in the spinal trigeminal nucleus respond to innocuous cooling in the rat.

    PubMed

    Kurose, Masayuki; Meng, Ian D

    2013-05-01

    Corneal primary afferent neurons that respond to drying of the ocular surface have been previously characterized and found to respond to innocuous cooling, menthol, and hyperosmotic stimuli. The purpose of the present study was to examine the receptive field properties of second-order neurons in the trigeminal nucleus that respond to drying of the ocular surface. Single-unit electrophysiological recordings were performed in anesthetized rats, and dry-responsive corneal units were isolated in the brain stem at the transition zone between the spinal trigeminal subnucleus caudalis and subnucleus interpolaris. Corneal units were characterized according to their responses to changes in temperature (cooling and heating), hyperosmotic artificial tears, menthol, and low pH. All dry-responsive neurons (n = 18) responded to cooling of the ocular surface. In addition, these neurons responded to hyperosmotic stimuli and menthol application to the cornea. One-half of the neurons were activated by low pH, and these acid-sensitive neurons were also activated by noxious heat. Furthermore, neurons that were activated by low pH had a significantly lower response to cooling and menthol. These results indicate that dry-responsive neurons recorded in the trigeminal nucleus receive input from cold, sensitive primary afferent neurons, with a subset of these neurons receiving input from corneal primary afferent neurons sensitive to acid and noxious heat. It is proposed that acid-insensitive corneal neurons represent a labeled line for lacrimation in response to evaporation of tears from the ocular surface, whereas acid-sensitive neurons are involved in tearing, elicited by damaging or potentially damaging stimuli. PMID:23446686

  6. The response of retinal neurons to high-frequency stimulation

    NASA Astrophysics Data System (ADS)

    Cai, Changsi; Twyford, Perry; Fried, Shelley

    2013-06-01

    Objective. High-rate pulse trains have proven to be effective in cochlear prosthetics and, more recently, have been shown to elicit a wide range of interesting response properties in axons of the peripheral nervous system. Surprisingly, the effectiveness of such trains for use in retinal prostheses has not been explored. Approach. Using cell-attached patch clamp methods, we measured the in vitro response of two rabbit retinal ganglion cell types, OFF-brisk transient (OFF-BT) and ON-OFF directionally selective (DS), to trains of biphasic pulses delivered at 2000 pulses per second (PPS). Main Results. For OFF-BT cells, response onset occurred at ˜20 µA, and maximum response occurred at ˜40 µA. Interestingly, spiking levels decreased for further increases in amplitude. In contrast, DS cells had a spiking onset at ˜25 µA and maintained strong spiking as stimulus amplitude was increased, even at the highest levels tested. Thus, a low-amplitude stimulus train at 2000 PPS (˜25 µA) will activate OFF-BT cells strongly, while simultaneously activating DS cells only weakly. In contrast, a high amplitude train (˜75 µA) will activate DS cells strongly while suppressing responses in OFF-BT cells. Significance. The response differences between cell types suggest some forms of preferential activation may be possible, and further testing is warranted. Further, the scope of the response differences found here suggests activation mechanisms that are more complex than those described in previous studies.

  7. The serotonin releaser fenfluramine alters the auditory responses of inferior colliculus neurons.

    PubMed

    Hall, Ian C; Hurley, Laura M

    2007-06-01

    Local direct application of the neuromodulator serotonin strongly influences auditory response properties of neurons in the inferior colliculus (IC), but endogenous stores of serotonin may be released in a distinct spatial or temporal pattern. To explore this issue, the serotonin releaser fenfluramine was iontophoretically applied to extracellularly recorded neurons in the IC of the Mexican free-tailed bat (Tadarida brasiliensis). Fenfluramine mimicked the effects of serotonin on spike count and first spike latency in most neurons, and its effects could be blocked by co-application of serotonin receptor antagonists, consistent with fenfluramine-evoked serotonin release. Responses to fenfluramine did not vary during single applications or across multiple applications, suggesting that fenfluramine did not deplete serotonin stores. A predicted gradient in the effects of fenfluramine with serotonin fiber density was not observed, but neurons with fenfluramine-evoked increases in latency occurred at relatively greater recording depths compared to other neurons with similar characteristic frequencies. These findings support the conclusion that there may be spatial differences in the effects of exogenous and endogenous sources of serotonin, but that other factors such as the identities and locations of serotonin receptors are also likely to play a role in determining the dynamics of serotonergic effects. PMID:17339086

  8. Neuronal response in Alzheimer's and Parkinson's disease: the effect of toxic proteins on intracellular pathways.

    PubMed

    Majd, Shohreh; Power, John H; Grantham, Hugh J M

    2015-01-01

    Accumulation of protein aggregates is the leading cause of cellular dysfunction in neurodegenerative disorders. Alzheimer's disease (AD), Parkinson's disease (PD), Huntington's disease, Prion disease and motor disorders such as amyotrophic lateral sclerosis, present with a similar pattern of progressive neuronal death, nervous system deterioration and cognitive impairment. The common characteristic is an unusual misfolding of proteins which is believed to cause protein deposition and trigger degenerative signals in the neurons. A similar clinical presentation seen in many neurodegenerative disorders suggests the possibility of shared neuronal responses in different disorders. Despite the difference in core elements of deposits in each neurodegenerative disorder, the cascade of neuronal reactions such as activation of glycogen synthase kinase-3 beta, mitogen-activated protein kinases, cell cycle re-entry and oxidative stress leading to a progressive neurodegeneration are surprisingly similar. This review focuses on protein toxicity in two neurodegenerative diseases, AD and PD. We reviewed the activated mechanisms of neurotoxicity in response to misfolded beta-amyloid and α-synuclein, two major toxic proteins in AD and PD, leading to neuronal apoptosis. The interaction between the proteins in producing an overlapping pathological pattern will be also discussed. PMID:26499115

  9. Minimal Peroxide Exposure of Neuronal Cells Induces Multifaceted Adaptive Responses

    PubMed Central

    Chadwick, Wayne; Zhou, Yu; Park, Sung-Soo; Wang, Liyun; Mitchell, Nicholas; Stone, Matthew D.; Becker, Kevin G.; Martin, Bronwen; Maudsley, Stuart

    2010-01-01

    Oxidative exposure of cells occurs naturally and may be associated with cellular damage and dysfunction. Protracted low level oxidative exposure can induce accumulated cell disruption, affecting multiple cellular functions. Accumulated oxidative exposure has also been proposed as one of the potential hallmarks of the physiological/pathophysiological aging process. We investigated the multifactorial effects of long-term minimal peroxide exposure upon SH-SY5Y neural cells to understand how they respond to the continued presence of oxidative stressors. We show that minimal protracted oxidative stresses induce complex molecular and physiological alterations in cell functionality. Upon chronic exposure to minimal doses of hydrogen peroxide, SH-SY5Y cells displayed a multifactorial response to the stressor. To fully appreciate the peroxide-mediated cellular effects, we assessed these adaptive effects at the genomic, proteomic and cellular signal processing level. Combined analyses of these multiple levels of investigation revealed a complex cellular adaptive response to the protracted peroxide exposure. This adaptive response involved changes in cytoskeletal structure, energy metabolic shifts towards glycolysis and selective alterations in transmembrane receptor activity. Our analyses of the global responses to chronic stressor exposure, at multiple biological levels, revealed a viable neural phenotype in-part reminiscent of aged or damaged neural tissue. Our paradigm indicates how cellular physiology can subtly change in different contexts and potentially aid the appreciation of stress response adaptations. PMID:21179406

  10. Ethanol withdrawal hyper-responsiveness mediated by NMDA receptors in spinal cord motor neurons

    PubMed Central

    Li, Hui-Fang; Kendig, Joan J

    2003-01-01

    Following ethanol (EtOH) exposure, population excitatory postsynaptic potentials (pEPSPs) in isolated spinal cord increase to a level above control (withdrawal hyper-responsiveness). The present studies were designed to characterize this phenomenon and in particular to test the hypothesis that protein kinases mediate withdrawal. Patch-clamp studies were carried out in motor neurons in rat spinal cord slices. Currents were evoked by brief pulses of glutamate, alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid (AMPA) or N-methyl-D-aspartic acid (NMDA). Of 15 EtOH-sensitive neurons in which currents were evoked by glutamate, four (27%) displayed withdrawal hyper-responsiveness in the washout period. Mean current area after washout was 129.6±5% of control. When currents were evoked by AMPA, two of 10 neurons (20%) displayed withdrawal hyper-responsiveness, with a mean current area 122±8% of control on washout. Of a group of 11 neurons in which currents were evoked by NMDA, nine (82%) displayed withdrawal hyper-responsiveness. Mean increase in current area at the end of the washout period was to 133±6% of control (n=9, P<0.001). When NMDA applications were stopped durithe period of EtOH exposure, mean area of NMDA-evoked responses on washout was only 98.0±5% of control (n=6, P>0.05). The tyrosine kinase inhibitor genistein (10–20 μM) blocked withdrawal hyper-responsiveness. Of six EtOH-sensitive neurons, the mean NMDA-evoked current area after washout was 89±6% of control, P>0.05. The protein kinase A (PKA) inhibitor Rp-cAMP (20–500 μM) did not block withdrawal hyper-responsiveness. On washout, the mean NMDA-evoked current area was 124±6% of control (n=5, P<0.05). Two broad-spectrum specific protein kinase C (PKC) inhibitors, GF-109203X (0.3 μM) and chelerythrine chloride (0.5–2 nM), blocked withdrawal hyper-responsiveness. Responses on washout were 108±7%, n=5 and 88±4%, n=4 of control, respectively, P>0.05. NMDA activation during EtOH exposure

  11. Responses of neurons in primary visual cortex to transient changes in local contrast and luminance.

    PubMed

    Geisler, Wilson S; Albrecht, Duane G; Crane, Alison M

    2007-05-01

    During normal saccadic inspection of natural images, the receptive fields of cortical neurons are bombarded with frequent simultaneous changes in local mean luminance and contrast, yet there have been no systematic studies of how cortical neurons respond to such stimulation. The responses of single neurons in the primary visual cortex of the cat were measured for 200 ms presentations of sine-wave gratings confined to the conventional receptive field. Both local mean luminance and contrast were parametrically and randomly varied over the 1-1.5 log unit ranges that are typical of natural images. We find that responses are strongly modulated by both the local mean luminance and contrast, but in an approximately separable manner: the contrast response function is approximately invariant except for a scale factor that depends on the local mean luminance. The shape of the temporal response profiles were found to be approximately invariant with contrast, but were strongly affected by the local mean luminance. The results suggest that most, if not all, cortical neurons carry substantial local luminance information. PMID:17494692

  12. Progressive loss of nigrostriatal dopaminergic neurons induced by inflammatory responses to fipronil.

    PubMed

    Park, Jae Hyeon; Park, Youn Sun; Koh, Hyun Chul

    2016-09-01

    Inflammatory responses are involved in mechanisms of neuronal cell damage in the pathogenesis of neurodegenerative diseases such as Parkinson's disease (PD). We investigated the mechanisms whereby inflammatory responses contribute to loss of dopaminergic neurons in fipronil (FPN)-treated rats. After stereotaxic injection of FPN in the substantia nigra (SN), the number of tyrosine hydroxylase (TH)-positive neurons and the levels of TH expression in the SN decreased at 7days, and a significant decrease was observed at 14days with a subsequent reduction in striatal TH expression. Decreases in dopamine (DA) levels, however, began at 3days post-injection, preceding the changes in TH expression. In contrast, glial fibrillary acidic protein (GFAP) expression was significantly increased at 3days and persisted for up to 14days post-lesion; these changes in GFAP expression appeared to be inversely correlated with TH expression. Furthermore, we found that FPN administration induced an inflammatory response characterized by increased levels of inducible NO synthase (iNOS), cyclooxygenase-2 (COX-2), and tumor necrosis factor-α (TNF-α), which was mediated by activated microglia following infusion of FPN unilaterally into the SN. Intranigral injection of FPN underwent an inflammatory response with a resultant ongoing loss of dopaminergic neurons, indicating that pesticides may have important implication for the study of PD. PMID:27313094

  13. Dietary Restriction Affects Neuronal Response Property and GABA Synthesis in the Primary Visual Cortex.

    PubMed

    Yang, Jinfang; Wang, Qian; He, Fenfen; Ding, Yanxia; Sun, Qingyan; Hua, Tianmiao; Xi, Minmin

    2016-01-01

    Previous studies have reported inconsistent effects of dietary restriction (DR) on cortical inhibition. To clarify this issue, we examined the response properties of neurons in the primary visual cortex (V1) of DR and control groups of cats using in vivo extracellular single-unit recording techniques, and assessed the synthesis of inhibitory neurotransmitter GABA in the V1 of cats from both groups using immunohistochemical and Western blot techniques. Our results showed that the response of V1 neurons to visual stimuli was significantly modified by DR, as indicated by an enhanced selectivity for stimulus orientations and motion directions, decreased visually-evoked response, lowered spontaneous activity and increased signal-to-noise ratio in DR cats relative to control cats. Further, it was shown that, accompanied with these changes of neuronal responsiveness, GABA immunoreactivity and the expression of a key GABA-synthesizing enzyme GAD67 in the V1 were significantly increased by DR. These results demonstrate that DR may retard brain aging by increasing the intracortical inhibition effect and improve the function of visual cortical neurons in visual information processing. This DR-induced elevation of cortical inhibition may favor the brain in modulating energy expenditure based on food availability. PMID:26863207

  14. Dietary Restriction Affects Neuronal Response Property and GABA Synthesis in the Primary Visual Cortex

    PubMed Central

    Sun, Qingyan; Hua, Tianmiao; Xi, Minmin

    2016-01-01

    Previous studies have reported inconsistent effects of dietary restriction (DR) on cortical inhibition. To clarify this issue, we examined the response properties of neurons in the primary visual cortex (V1) of DR and control groups of cats using in vivo extracellular single-unit recording techniques, and assessed the synthesis of inhibitory neurotransmitter GABA in the V1 of cats from both groups using immunohistochemical and Western blot techniques. Our results showed that the response of V1 neurons to visual stimuli was significantly modified by DR, as indicated by an enhanced selectivity for stimulus orientations and motion directions, decreased visually-evoked response, lowered spontaneous activity and increased signal-to-noise ratio in DR cats relative to control cats. Further, it was shown that, accompanied with these changes of neuronal responsiveness, GABA immunoreactivity and the expression of a key GABA-synthesizing enzyme GAD67 in the V1 were significantly increased by DR. These results demonstrate that DR may retard brain aging by increasing the intracortical inhibition effect and improve the function of visual cortical neurons in visual information processing. This DR-induced elevation of cortical inhibition may favor the brain in modulating energy expenditure based on food availability. PMID:26863207

  15. Modulation of Neuronal Responses by Exogenous Attention in Macaque Primary Visual Cortex.

    PubMed

    Wang, Feng; Chen, Minggui; Yan, Yin; Zhaoping, Li; Li, Wu

    2015-09-30

    Visual perception is influenced by attention deployed voluntarily or triggered involuntarily by salient stimuli. Modulation of visual cortical processing by voluntary or endogenous attention has been extensively studied, but much less is known about how involuntary or exogenous attention affects responses of visual cortical neurons. Using implanted microelectrode arrays, we examined the effects of exogenous attention on neuronal responses in the primary visual cortex (V1) of awake monkeys. A bright annular cue was flashed either around the receptive fields of recorded neurons or in the opposite visual field to capture attention. A subsequent grating stimulus probed the cue-induced effects. In a fixation task, when the cue-to-probe stimulus onset asynchrony (SOA) was <240 ms, the cue induced a transient increase of neuronal responses to the probe at the cued location during 40-100 ms after the onset of neuronal responses to the probe. This facilitation diminished and disappeared after repeated presentations of the same cue but recurred for a new cue of a different color. In another task to detect the probe, relative shortening of monkey's reaction times for the validly cued probe depended on the SOA in a way similar to the cue-induced V1 facilitation, and the behavioral and physiological cueing effects remained after repeated practice. Flashing two cues simultaneously in the two opposite visual fields weakened or diminished both the physiological and behavioral cueing effects. Our findings indicate that exogenous attention significantly modulates V1 responses and that the modulation strength depends on both novelty and task relevance of the stimulus. Significance statement: Visual attention can be involuntarily captured by a sudden appearance of a conspicuous object, allowing rapid reactions to unexpected events of significance. The current study discovered a correlate of this effect in monkey primary visual cortex. An abrupt, salient, flash enhanced neuronal

  16. Visual and noxious electrical stimulus-evoked membrane-potential responses in anterior cingulate cortical neurons.

    PubMed

    Ma, Li-Qing; Ning, Li; Wang, Zhiru; Wang, Ying-Wei

    2016-01-01

    Anterior cingulate cortex (ACC) is known to participate in numerous brain functions, such as memory storage, emotion, attention, as well as perception of acute and chronic pain. ACC-dependent brain functions often rely on ACC processing of various forms of environmental information. To understand the neural basis of ACC functions, previous studies have investigated ACC responses to environmental stimulation, particularly complex sensory stimuli as well as award and aversive stimuli, but this issue remains to be further clarified. Here, by performing whole-cell recording in vivo in anaesthetized adult rats, we examined membrane-potential (MP) responses of layer II/III ACC neurons that were evoked by a brief flash of visual stimulation and pain-related electrical stimulation delivered to hind paws. We found that ~54 and ~81 % ACC neurons exhibited excitatory MP responses, subthreshold or suprathreshold, to the visual stimulus and the electrical stimulus, respectively, with no cell showing inhibitory MP responses. We further found that the visually evoked ACC response could be greatly diminished by local lidocaine infusion in the visual thalamus, and only their temporal patterns but not amplitudes could be changed by large-scale visual cortical lesions. Our in vivo whole-cell recording data characterized in ACC neurons a visually evoked response, which was largely dependent on the visual thalamus but not visual cortex, as well as a noxious electrical stimulus-evoked response. These findings may provide potential mechanisms that are used for ACC functions on the basis of sensory information processing. PMID:27585569

  17. Receptive field size, chemical and thermal responses, and fiber conduction velocity of rat chorda tympani geniculate ganglion neurons.

    PubMed

    Yokota, Yusuke; Bradley, Robert M

    2016-06-01

    Afferent chorda tympani (CT) fibers innervating taste and somatosensory receptors in fungiform papillae have neuron cell bodies in the geniculate ganglion (GG). The GG/CT fibers branch in the tongue to innervate taste buds in several fungiform papillae. To investigate receptive field characteristics of GG/CT neurons, we recorded extracellular responses from GG cells to application of chemical and thermal stimuli. Receptive field size was mapped by electrical stimulation of individual fungiform papillae. Response latency to electrical stimulation was used to determine fiber conduction velocity. Responses of GG neurons to lingual application of stimuli representing four taste qualities, and water at 4°C, were used to classify neuron response properties. Neurons classified as SALT, responding only to NaCl and NH4Cl, had a mean receptive field size of six papillae. Neurons classified as OTHER responded to salts and other chemical stimuli and had smaller mean receptive fields of four papillae. Neurons that responded to salts and cold stimuli, classified as SALT/THERMAL, and neurons responding to salts, other chemical stimuli and cold, classified as OTHER/THERMAL, had mean receptive field sizes of six and five papillae, respectively. Neurons responding only to cold stimuli, categorized as THERMAL, had receptive fields of one to two papillae located at the tongue tip. Based on conduction velocity most of the neurons were classified as C fibers. Neurons with large receptive fields had higher conduction velocities than neurons with small receptive fields. These results demonstrate that GG neurons can be distinguished by receptive field size, response properties and afferent fiber conduction velocity derived from convergent input of multiple taste organs. PMID:27030734

  18. Responses of tectal neurons to contrasting stimuli: an electrophysiological study in the barn owl.

    PubMed

    Zahar, Yael; Wagner, Hermann; Gutfreund, Yoram

    2012-01-01

    The saliency of visual objects is based on the center to background contrast. Particularly objects differing in one feature from the background may be perceived as more salient. It is not clear to what extent this so called "pop-out" effect observed in humans and primates governs saliency perception in non-primates as well. In this study we searched for neural-correlates of pop-out perception in neurons located in the optic tectum of the barn owl. We measured the responses of tectal neurons to stimuli appearing within the visual receptive field, embedded in a large array of additional stimuli (the background). Responses were compared between contrasting and uniform conditions. In a contrasting condition the center was different from the background while in the uniform condition it was identical to the background. Most tectal neurons responded better to stimuli in the contrsating condition compared to the uniform condition when the contrast between center and background was the direction of motion but not when it was the orientation of a bar. Tectal neurons also preferred contrasting over uniform stimuli when the center was looming and the background receding but not when the center was receding and the background looming. Therefore, our results do not support the hypothesis that tectal neurons are sensitive to pop-out per-se. The specific sensitivity to the motion contrasting stimulus is consistent with the idea that object motion and not large field motion (e.g., self-induced motion) is coded in the neural responses of tectal neurons. PMID:22745787

  19. TEMPORAL RESPONSE OF NEURONS TO AMBIENT HEATING IN THE PREOPTIC AND SEPTAL AREA OF THE UNANESTHETIZED RABBIT

    EPA Science Inventory

    The firing rates of single neurons were recorded in the septal and preoptic areas of unanesthetized rabbits during brief periods of ambient heating. The temporal response for neurons responsive to ambient temperature were calculated as the interval of time between the onset of he...

  20. Prolonged noxious mechanical stimulation of the rat's tail: responses and encoding properties of dorsal horn neurones.

    PubMed Central

    Cervero, F; Handwerker, H O; Laird, J M

    1988-01-01

    1. Single-unit electrical activity has been recorded from dorsal horn neurones in the sacral (S1-S2) segments of the spinal cord of barbiturate-anaesthetized rats. Fifty-two neurones responding to a manually applied pinch of their receptive fields in the tail were selected. They were subsequently tested for their responses to four successive 2 min pinches at noxious intensities delivered by a feed-back-controlled mechanical device. 2. Neurones were tested with both innocuous (i.e. brushing and stroking) and noxious (i.e. pinching, pin-prick, and in some cases heating about 45 degrees C) stimulation of their cutaneous receptive fields. Three of the tested cells were driven exclusively by innocuous skin stimulation (mechanoreceptive or class 1), thirty-six were driven by both innocuous and noxious skin stimulation (multireceptive or class 2) and thirteen were driven exclusively by noxious skin stimulation (nocireceptive or class 3). 3. All of the multireceptive and nocireceptive neurones responded to the 2 min noxious pinch with an initial phasic discharge followed by sustained firing that showed little evidence of adaptation throughout the stimulus period. The three mechanoreceptive neurones responded to the 2 min noxious pinch with a short discharge at the stimulus onset, but were silent for the remainder of the stimulus period. 4. Thirty-one cells were tested with successive 2 min pinches of 4, 6 and 8 N (and in some cases, a further 4 N pinch) applied at 10 min intervals. Different encoding properties were observed during the sustained part of the neuronal response according to: (i) the afferent fibre input characteristics of the cell; (ii) whether or not the tail had received a test series of pinches earlier in the same experiment. 5. None of the multireceptive cells with only an A-fibre afferent input encoded the stimulus strength. However, the multireceptive cells with both an A- and a C-fibre afferent input and all nocireceptive cells did encode the stimulus

  1. On the dynamical mechanisms of influence of synaptic currents on the neuron model with response differentiation

    NASA Astrophysics Data System (ADS)

    Zakharov, D. G.; Kuznetsov, A. S.

    2015-08-01

    The combined effect of synaptic NMDA, AMPA, and GABA currents on the neuron model with response differentiation has been considered. It has been shown that the GABA and NMDA currents can compensate the effects of each other, whereas the AMPA current not only leads to the suppression of oscillations but also significantly amplifies the high-frequency activity of the neuron induced by the NMDA current. Two bifurcation scenarios underlying these effects have been revealed. It has been predicted which scenario takes place under the combined influence of all three currents.

  2. Effects of Dimethyl Sulfoxide on Neuronal Response Characteristics in Deep Layers of Rat Barrel Cortex

    PubMed Central

    Soltani, Narjes; Mohammadi, Elham; Allahtavakoli, Mohammad; Shamsizadeh, Ali; Roohbakhsh, Ali; Haghparast, Abbas

    2016-01-01

    Introduction: Dimethyl sulfoxide (DMSO) is a chemical often used as a solvent for water-insoluble drugs. In this study, we evaluated the effect of intracerebroventricular (ICV) administration of DMSO on neural response characteristics (in 1200–1500 μm depth) of the rat barrel cortex. Methods: DMSO solution was prepared in 10% v/v concentration and injected into the lateral ventricle of rats. Neuronal spontaneous activity and neuronal responses to deflection of the principal whisker (PW) and adjacent whisker (AW) were recorded in barrel cortex. A condition test ratio (CTR) was used to measure inhibitory receptive fields in barrel cortex. Results: The results showed that both PW and AW evoked ON and OFF responses, neuronal spontaneous activity and inhibitory receptive fields did not change following ICV administration of DMSO. Conclusion: Results of this study suggest that acute ICV administration of 10% DMSO did not modulate the electrophysiological characteristics of neurons in the l deep ayers of rat barrel cortex. PMID:27563414

  3. Dual depolarization responses generated within the same lateral septal neurons by TRPC4-containing channels

    PubMed Central

    Tian, Jinbin; Thakur, Dhananjay P.; Lu, Yungang; Zhu, Yingmin; Freichel, Marc; Flockerzi, Veit

    2013-01-01

    In the central nervous system, canonical transient receptor potential (TRPC) channels have been implicated in mediating neuronal excitation induced by stimulating metabotropic receptors, including group 1 metabotropic glutamate receptors (mGluRs). Lateral septal (LS) neurons express high levels of TRPC4 and group I mGluRs. However, to what extent native TRPC4-containing channels (TRPC4-cc) are activated as well as the impact of different levels of TRPC4-cc activation on neuronal excitability remain elusive. Here, we report that stimulating LS neurons with group I mGluR agonist, (S)-3,5-DHPG, causes either an immediate increase in firing rate or an initial burst followed by a pause of firing, which can be correlated with below-threshold-depolarization (BTD) or above-threshold-plateau-depolarization (ATPD), respectively, in whole-cell recordings. The early phase of BTD and the entire ATPD are completely absent in neurons from TRPC4−/− mice. Moreover, in the same LS neurons, BTD can be converted to ATPD at more depolarized potentials or with a brief current injection, suggesting that BTD and ATPD may represent partial and full activations of TRPC4-cc, respectively. We show that coincident mGluR stimulation and depolarization is required to evoke strong TRPC4-cc current, and Na+ and Ca2+ influx, together with dynamic changes of intracellular Ca2+, are essential for ATPD induction. Our results suggest that TRPC4-cc integrates metabotropic receptor stimulation with intracellular Ca2+ signals to generate two interconvertible depolarization responses to affect excitability of LS neurons in distinct fashions. PMID:24121765

  4. Gender differences in human single neuron responses to male emotional faces

    PubMed Central

    Newhoff, Morgan; Treiman, David M.; Smith, Kris A.; Steinmetz, Peter N.

    2015-01-01

    Well-documented differences in the psychology and behavior of men and women have spurred extensive exploration of gender's role within the brain, particularly regarding emotional processing. While neuroanatomical studies clearly show differences between the sexes, the functional effects of these differences are less understood. Neuroimaging studies have shown inconsistent locations and magnitudes of gender differences in brain hemodynamic responses to emotion. To better understand the neurophysiology of these gender differences, we analyzed recordings of single neuron activity in the human brain as subjects of both genders viewed emotional expressions. This study included recordings of single-neuron activity of 14 (6 male) epileptic patients in four brain areas: amygdala (236 neurons), hippocampus (n = 270), anterior cingulate cortex (n = 256), and ventromedial prefrontal cortex (n = 174). Neural activity was recorded while participants viewed a series of avatar male faces portraying positive, negative or neutral expressions. Significant gender differences were found in the left amygdala, where 23% (n = 15∕66) of neurons in men were significantly affected by facial emotion, vs. 8% (n = 6∕76) of neurons in women. A Fisher's exact test comparing the two ratios found a highly significant difference between the two (p < 0.01). These results show specific differences between genders at the single-neuron level in the human amygdala. These differences may reflect gender-based distinctions in evolved capacities for emotional processing and also demonstrate the importance of including subject gender as an independent factor in future studies of emotional processing by single neurons in the human amygdala. PMID:26441597

  5. Single-cell RNA-seq reveals distinct injury responses in different types of DRG sensory neurons

    PubMed Central

    Hu, Ganlu; Huang, Kevin; Hu, Youjin; Du, Guizhen; Xue, Zhigang; Zhu, Xianmin; Fan, Guoping

    2016-01-01

    Peripheral nerve injury leads to various injury-induced responses in sensory neurons including physiological pain, neuronal cell death, and nerve regeneration. In this study, we performed single-cell RNA-sequencing (scRNA-seq) analysis of mouse nonpeptidergic nociceptors (NP), peptidergic nociceptors (PEP), and large myelinated sensory neurons (LM) under both control and injury conditions at 3 days after sciatic nerve transection (SNT). After performing principle component and weighted gene co-expression network analysis, we categorized dorsal root ganglion (DRG) neurons into different subtypes and discovered co-regulated injury-response genes including novel regeneration associated genes (RAGs) in association with neuronal development, protein translation and cytoplasm transportation. In addition, we found significant up-regulation of the genes associated with cell death such as Pdcd2 in a subset of NP neurons after axotomy, implicating their actions in neuronal cell death upon nerve injury. Our study revealed the distinctive and sustained heterogeneity of transcriptomic responses to injury at single neuron level, implicating the involvement of different gene regulatory networks in nerve regeneration, neuronal cell death and neuropathy in different population of DRG neurons. PMID:27558660

  6. Single-cell RNA-seq reveals distinct injury responses in different types of DRG sensory neurons.

    PubMed

    Hu, Ganlu; Huang, Kevin; Hu, Youjin; Du, Guizhen; Xue, Zhigang; Zhu, Xianmin; Fan, Guoping

    2016-01-01

    Peripheral nerve injury leads to various injury-induced responses in sensory neurons including physiological pain, neuronal cell death, and nerve regeneration. In this study, we performed single-cell RNA-sequencing (scRNA-seq) analysis of mouse nonpeptidergic nociceptors (NP), peptidergic nociceptors (PEP), and large myelinated sensory neurons (LM) under both control and injury conditions at 3 days after sciatic nerve transection (SNT). After performing principle component and weighted gene co-expression network analysis, we categorized dorsal root ganglion (DRG) neurons into different subtypes and discovered co-regulated injury-response genes including novel regeneration associated genes (RAGs) in association with neuronal development, protein translation and cytoplasm transportation. In addition, we found significant up-regulation of the genes associated with cell death such as Pdcd2 in a subset of NP neurons after axotomy, implicating their actions in neuronal cell death upon nerve injury. Our study revealed the distinctive and sustained heterogeneity of transcriptomic responses to injury at single neuron level, implicating the involvement of different gene regulatory networks in nerve regeneration, neuronal cell death and neuropathy in different population of DRG neurons. PMID:27558660

  7. Neuronal migration in the murine rostral migratory stream requires serum response factor

    PubMed Central

    Alberti, Siegfried; Krause, Sven M.; Kretz, Oliver; Philippar, Ulrike; Lemberger, Thomas; Casanova, Emilio; Wiebel, Franziska F.; Schwarz, Heinz; Frotscher, Michael; Schütz, Günther; Nordheim, Alfred

    2005-01-01

    The central nervous system is fundamentally dependent on guided cell migration, both during development and in adulthood. We report an absolute requirement of the transcription factor serum response factor (SRF) for neuronal migration in the mouse forebrain. Conditional, late-prenatal deletion of Srf causes neurons to accumulate ectopically at the subventricular zone (SVZ), a prime neurogenic region in the brain. SRF-deficient cells of the SVZ exhibit impaired tangential chain migration along the rostral migratory stream into the olfactory bulb. SVZ explants display retarded chain migration in vitro. Regarding target genes, SRF deficiency impairs expression of the β-actin and gelsolin genes, accompanied by reduced cytoskeletal actin fiber density. At the posttranslational level, cofilin, a key regulator of actin dynamics, displays dramatically elevated inhibitory phosphorylation at Ser-3. Our studies indicate that SRF-controlled gene expression directs both the structure and dynamics of the actin microfilament, thereby determining cell-autonomous neuronal migration. PMID:15837932

  8. Visual response properties of neurons in four areas of the avian pallium.

    PubMed

    Scarf, Damian; Stuart, Michael; Johnston, Melissa; Colombo, Michael

    2016-03-01

    In the present study we investigate the visual responsiveness of neurons in the entopallium, arcopallium, nidopallium, and hippocampus of pigeons. Pigeons were presented with 12 different stimuli, including three stimuli of a pigeon (a portrait of a pigeon's face, a profile view of a pigeon's face, and a picture of a whole pigeon). A total of 53 cells were recorded from the entopallium, 65 from the arcopallium, 32 from the nidopallium, and 67 from the hippocampus. Although a number of neurons were selective for certain colours and shapes, no neurons were solely selective for the three pigeon stimuli. This finding contrasts with previous studies across a range of mammals demonstrating selective firing to images of conspecifics. Rather than reflecting an absence of these cells in pigeons, we argue our findings may reflect the difficulty pigeons have in understanding the correspondence between 2D representations of 3D stimuli. PMID:26868923

  9. Lateral orbitofrontal neurons acquire responses to upshifted, downshifted, or blocked cues during unblocking

    PubMed Central

    Lopatina, Nina; McDannald, Michael A; Styer, Clay V; Sadacca, Brian F; Cheer, Joseph F; Schoenbaum, Geoffrey

    2015-01-01

    The lateral orbitofrontal cortex (lOFC) has been described as signaling either outcome expectancies or value. Previously, we used unblocking to show that lOFC neurons respond to a predictive cue signaling a ‘valueless’ change in outcome features (McDannald, 2014). However, many lOFC neurons also fired to a cue that simply signaled more reward. Here, we recorded lOFC neurons in a variant of this task in which rats learned about cues that signaled either more (upshift), less (downshift) or the same (blocked) amount of reward. We found that neurons acquired responses specifically to one of the three cues and did not fire to the other two. These results show that, at least early in learning, lOFC neurons fire to valued cues in a way that is more consistent with signaling of the predicted outcome’s features than with signaling of a general, abstract or cached value that is independent of the outcome. DOI: http://dx.doi.org/10.7554/eLife.11299.001 PMID:26670544

  10. Single Cell Transcriptomics of Hypothalamic Warm Sensitive Neurons that Control Core Body Temperature and Fever Response

    PubMed Central

    Eberwine, James; Bartfai, Tamas

    2011-01-01

    We report on an ‘unbiased’ molecular characterization of individual, adult neurons, active in a central, anterior hypothalamic neuronal circuit, by establishing cDNA libraries from each individual, electrophysiologically identified warm sensitive neuron (WSN). The cDNA libraries were analyzed by Affymetrix microarray. The presence and frequency of cDNAs was confirmed and enhanced with Illumina sequencing of each single cell cDNA library. cDNAs encoding the GABA biosynthetic enzyme. GAD1 and of adrenomedullin, galanin, prodynorphin, somatostatin, and tachykinin were found in the WSNs. The functional cellular and in vivo studies on dozens of the more than 500 neurotransmitter -, hormone- receptors and ion channels, whose cDNA was identified and sequence confirmed, suggest little or no discrepancy between the transcriptional and functional data in WSNs; whenever agonists were available for a receptor whose cDNA was identified, a functional response was found.. Sequencing single neuron libraries permitted identification of rarely expressed receptors like the insulin receptor, adiponectin receptor2 and of receptor heterodimers; information that is lost when pooling cells leads to dilution of signals and mixing signals. Despite the common electrophysiological phenotype and uniform GAD1 expression, WSN- transcriptomes show heterogenity, suggesting strong epigenetic influence on the transcriptome. Our study suggests that it is well-worth interrogating the cDNA libraries of single neurons by sequencing and chipping. PMID:20970451

  11. Synaptic response patterns of neurons in the cortex of rat inferior colliculus.

    PubMed

    Li, Y; Evans, M S; Faingold, C L

    1999-11-01

    The present study examined synaptic potentials of neurons in inferior colliculus (IC) cortex slice and the roles of GABA and glutamate receptors in generating these potentials. Multipolar (82%) and elongated (18%) cells were observed with intracellular biocytin staining. Electrical stimulation of the IC commissure (CoIC) elicited only inhibitory postsynaptic potentials (IPSPs) (10% of cells), only excitatory postsynaptic potentials (EPSPs) (51%), or both (38%). IPSPs were elicited at lower thresholds and shorter latencies than EPSPs (mean: 1.6+/-1.2 ms) and IPSPs were observed in all neurons following membrane depolarization. Short-latency EPSPs were blocked by non-NMDA receptor antagonists, and longer-latency EPSPs were blocked by NMDA antagonists. CoIC stimulation evoked short-latency IPSPs (mean: 0.55+/-0.33 ms) in 48% of neurons, and the IPSPs persisted despite glutamate receptor blockade, which implies monosynaptic inhibitory input. A GABA(A) antagonist blocked IPSPs and paired pulse inhibition of EPSPs, suggesting GABA(A) receptor mediation. A GABA(B) antagonist reduced paired pulse inhibition of IPSPs, suggesting GABA(B) receptor modulation. Thus, GABA-mediated inhibition plays a critical role in shaping synaptic responses of IC cortex neurons. Normal GABAergic function in IC has been shown to be important in acoustic coding, and reduced efficacy of GABA function in IC neurons is critical in IC pathophysiology in presbycusis, tinnitus and audiogenic seizures. PMID:10545630

  12. Neuronal detection thresholds during vestibular compensation: contributions of response variability and sensory substitution

    PubMed Central

    Jamali, Mohsen; Mitchell, Diana E; Dale, Alexis; Carriot, Jerome; Sadeghi, Soroush G; Cullen, Kathleen E

    2014-01-01

    The vestibular system is responsible for processing self-motion, allowing normal subjects to discriminate the direction of rotational movements as slow as 1–2 deg s−1. After unilateral vestibular injury patients’ direction–discrimination thresholds worsen to ∼20 deg s−1, and despite some improvement thresholds remain substantially elevated following compensation. To date, however, the underlying neural mechanisms of this recovery have not been addressed. Here, we recorded from first-order central neurons in the macaque monkey that provide vestibular information to higher brain areas for self-motion perception. Immediately following unilateral labyrinthectomy, neuronal detection thresholds increased by more than two-fold (from 14 to 30 deg s−1). While thresholds showed slight improvement by week 3 (25 deg s−1), they never recovered to control values – a trend mirroring the time course of perceptual thresholds in patients. We further discovered that changes in neuronal response variability paralleled changes in sensitivity for vestibular stimulation during compensation, thereby causing detection thresholds to remain elevated over time. However, we found that in a subset of neurons, the emergence of neck proprioceptive responses combined with residual vestibular modulation during head-on-body motion led to better neuronal detection thresholds. Taken together, our results emphasize that increases in response variability to vestibular inputs ultimately constrain neural thresholds and provide evidence that sensory substitution with extravestibular (i.e. proprioceptive) inputs at the first central stage of vestibular processing is a neural substrate for improvements in self-motion perception following vestibular loss. Thus, our results provide a neural correlate for the patient benefits provided by rehabilitative strategies that take advantage of the convergence of these multisensory cues. PMID:24366259

  13. Heterogeneity of Voltage- and Chemosignal-Activated Response Profiles in Vomeronasal Sensory Neurons

    PubMed Central

    Labra, Antonieta; Brann, Jessica H.; Fadool, Debra A.

    2009-01-01

    Liolaemus lizards were explored to ascertain whether they would make an amenable model to study single-cell electrophysiology of neurons in the vomeronasal organ (VNO). Despite a rich array of chemosensory-related behaviors chronicled for this genus, no anatomical or functional data exist for the VNO, the organ mediating these types of behaviors. Two Liolaemus species (L. bellii and L. nigroviridis) were collected in Central Chile in the Farellones Mountains and transported to the United States. Lizards were subjected to hypothermia and then a lethal injection of sodium pentabarbitol prior to all experiments described in the following text. Retrograde dye perfusion combined with histological techniques demonstrated a compartmentalization of the proportionally large VNO from the main olfactory epithelium (MOE) in cryosections of L. bellii. SDS-PAGE analysis of the VNO of both species demonstrated the expression of three G protein subunits, namely, Gαo, Gαi2, and Gβ, and the absence of Gαolf, Gα11, and Gq, the latter of which are traditionally found in the MOE. Vomeronasal (VN) neurons were enzymatically isolated for whole cell voltage-clamp electrophysiology of single neurons. Both species demonstrated a tetrodotoxin (TTX)-sensitive, rapidly inactivating sodium current and a tetraethylammonium (TEA)-sensitive potassium current that had a transient and sustained component. VN neurons were classified into two types dependent on the ratio of sodium over sustained potassium current. VN neurons exhibited outward and inward chemosignal-evoked currents when stimulated with pheromone-containing secretions taken from the feces, skin, and precloacal pores. Fifty-nine percent of the neurons were responsive to at least one compound when presented with a battery of five different secretions. The breadth of responsiveness (H metric) demonstrated a heterogeneous population of tuning with a mean of 0.29. PMID:15972830

  14. Responses of neurons in rostral and caudal trigeminal nuclei to tooth pulp stimulation.

    PubMed

    Stephan, F K

    1976-01-01

    Using immobilized, lightly anesthetized cats, the responses of neurons in the nucleus principalis-subnucleus oralis and subnucleus caudalis regions of the sensory trigeminal complex were studied following electrical stimulation of the canine tooth pulp. Recording loci were verified histologically. Pulpal stimulation activated 122 cells in the rostral nuclei and 44 in the caudal one. Neurons in the two, spatially segregated, regions exhibited different, though overlapping distributions of response and receptive field properties. More specifically, the rostral region cells tended to have lower thresholds and to reach peak firing rates at lower stimulus intensities. Their peripheral fields were generally more restricted and more frequently homolateral. Following supra-maximal stimulation, they ordinarily had briefer initial spike latencies and their response bursts typically contained a greater number of spikes. These findings are consistent with the view that each of the regions operates in a different manner in the mediation of oro-facial pain. PMID:1009449

  15. Temporal response dynamics of Drosophila olfactory sensory neurons depends on receptor type and response polarity

    PubMed Central

    Getahun, Merid N.; Wicher, Dieter; Hansson, Bill S.; Olsson, Shannon B.

    2012-01-01

    Insect olfactory sensory neurons (OSN) express a diverse array of receptors from different protein families, i.e. ionotropic receptors (IR), gustatory receptors (GR) and odorant receptors (OR). It is well known that insects are exposed to a plethora of odor molecules that vary widely in both space and time under turbulent natural conditions. In addition to divergent ligand specificities, these different receptors might also provide an increased range of temporal dynamics and sensitivities for the olfactory system. To test this, we challenged different Drosophila OSNs with both varying stimulus durations (10–2000 ms), and repeated stimulus pulses of key ligands at various frequencies (1–10 Hz). Our results show that OR-expressing OSNs responded faster and with higher sensitivity to short stimulations as compared to IR- and Gr21a-expressing OSNs. In addition, OR-expressing OSNs could respond to repeated stimulations of excitatory ligands up to 5 Hz, while IR-expressing OSNs required ~5x longer stimulations and/or higher concentrations to respond to similar stimulus durations and frequencies. Nevertheless, IR-expressing OSNs did not exhibit adaptation to longer stimulations, unlike OR- and Gr21a-OSNs. Both OR- and IR-expressing OSNs were also unable to resolve repeated pulses of inhibitory ligands as fast as excitatory ligands. These differences were independent of the peri-receptor environment in which the receptors were expressed and suggest that the receptor expressed by a given OSN affects both its sensitivity and its response to transient, intermittent chemical stimuli. OR-expressing OSNs are better at resolving low dose, intermittent stimuli, while IR-expressing OSNs respond more accurately to long-lasting odor pulses. This diversity increases the capacity of the insect olfactory system to respond to the diverse spatiotemporal signals in the natural environment. PMID:23162431

  16. The adhesion-GPCR BAI3, a gene linked to psychiatric disorders, regulates dendrite morphogenesis in neurons.

    PubMed

    Lanoue, V; Usardi, A; Sigoillot, S M; Talleur, M; Iyer, K; Mariani, J; Isope, P; Vodjdani, G; Heintz, N; Selimi, F

    2013-08-01

    Adhesion-G protein-coupled receptors (GPCRs) are a poorly studied subgroup of the GPCRs, which have diverse biological roles and are major targets for therapeutic intervention. Among them, the Brain Angiogenesis Inhibitor (BAI) family has been linked to several psychiatric disorders, but despite their very high neuronal expression, the function of these receptors in the central nervous system has barely been analyzed. Our results, obtained using expression knockdown and overexpression experiments, reveal that the BAI3 receptor controls dendritic arborization growth and branching in cultured neurons. This role is confirmed in Purkinje cells in vivo using specific expression of a deficient BAI3 protein in transgenic mice, as well as lentivirus driven knockdown of BAI3 expression. Regulation of dendrite morphogenesis by BAI3 involves activation of the RhoGTPase Rac1 and the binding to a functional ELMO1, a critical Rac1 regulator. Thus, activation of the BAI3 signaling pathway could lead to direct reorganization of the actin cytoskeleton through RhoGTPase signaling in neurons. Given the direct link between RhoGTPase/actin signaling pathways, neuronal morphogenesis and psychiatric disorders, our mechanistic data show the importance of further studying the role of the BAI adhesion-GPCRs to understand the pathophysiology of such brain diseases. PMID:23628982

  17. The adhesion-GPCR BAI3, a gene linked to psychiatric disorders, regulates dendrite morphogenesis in neurons

    PubMed Central

    Lanoue, V; Usardi, A; Sigoillot, S M; Talleur, M; Iyer, K; Mariani, J; Isope, P; Vodjdani, G; Heintz, N; Selimi, F

    2013-01-01

    Adhesion-G protein-coupled receptors (GPCRs) are a poorly studied subgroup of the GPCRs, which have diverse biological roles and are major targets for therapeutic intervention. Among them, the Brain Angiogenesis Inhibitor (BAI) family has been linked to several psychiatric disorders, but despite their very high neuronal expression, the function of these receptors in the central nervous system has barely been analyzed. Our results, obtained using expression knockdown and overexpression experiments, reveal that the BAI3 receptor controls dendritic arborization growth and branching in cultured neurons. This role is confirmed in Purkinje cells in vivo using specific expression of a deficient BAI3 protein in transgenic mice, as well as lentivirus driven knockdown of BAI3 expression. Regulation of dendrite morphogenesis by BAI3 involves activation of the RhoGTPase Rac1 and the binding to a functional ELMO1, a critical Rac1 regulator. Thus, activation of the BAI3 signaling pathway could lead to direct reorganization of the actin cytoskeleton through RhoGTPase signaling in neurons. Given the direct link between RhoGTPase/actin signaling pathways, neuronal morphogenesis and psychiatric disorders, our mechanistic data show the importance of further studying the role of the BAI adhesion-GPCRs to understand the pathophysiology of such brain diseases. PMID:23628982

  18. Emotion processing fails to modulate putative mirror neuron response to trained visuomotor associations.

    PubMed

    Fitzgibbon, Bernadette M; Kirkovski, Melissa; Fornito, Alex; Paton, Bryan; Fitzgerald, Paul B; Enticott, Peter G

    2016-04-01

    Recent neuroimaging studies have demonstrated that activation of the putative human mirror neuron system (MNS) can be elicited via visuomotor training. This is generally interpreted as supporting an associative learning account of the mirror neuron system (MNS) that argues against the ontogeny of the MNS to be an evolutionary adaptation for social cognition. The current study assessed whether a central component of social cognition, emotion processing, would influence the MNS activity to trained visuomotor associations, which could support a broader role of the MNS in social cognition. Using functional magnetic resonance imaging (fMRI), we assessed repetition suppression to the presentation of stimulus pairs involving a simple hand action and a geometric shape that was either congruent or incongruent with earlier association training. Each pair was preceded by an image of positive, negative, or neutral emotionality. In support of an associative learning account of the MNS, repetition suppression was greater for trained pairs compared with untrained pairs in several regions, primarily supplementary motor area (SMA) and right inferior frontal gyrus (rIFG). This response, however, was not modulated by the valence of the emotional images. These findings argue against a fundamental role of emotion processing in the mirror neuron response, and are inconsistent with theoretical accounts linking mirror neurons to social cognition. PMID:26826520

  19. Imaging Light Responses of Targeted Neuron Populations in the Rodent Retina

    PubMed Central

    Borghuis, Bart G.; Tian, Lin; Xu, Ying; Nikonov, Sergei S.; Vardi, Noga; Zemelman, Boris V.; Looger, Loren L.

    2012-01-01

    Decoding the wiring diagram of the retina requires simultaneous observation of activity in identified neuron populations. Available recording methods are limited in their scope: electrodes can access only a small fraction of neurons at once, whereas synthetic fluorescent indicator dyes label tissue indiscriminately. Here, we describe a method for studying retinal circuitry at cellular and subcellular levels combining two-photon microscopy and a genetically encoded calcium indicator. Using specific viral and promoter constructs to drive expression of GCaMP3, we labeled all five major neuron classes in the adult mouse retina. Stimulus-evoked GCaMP3 responses as imaged by two-photon microscopy permitted functional cell type annotation. Fluorescence responses were similar to those measured with the small molecule dye OGB-1. Fluorescence intensity correlated linearly with spike rates >10 spikes/s, and a significant change in fluorescence always reflected a significant change in spike firing rate. GCaMP3 expression had no apparent effect on neuronal function. Imaging at subcellular resolution showed compartment-specific calcium dynamics in multiple identified cell types. PMID:21414907

  20. Seven cDNAs enriched following hippocampal lesion: possible roles in neuronal responses to injury.

    PubMed

    Price, Mitch; Lang, Molly G; Frank, Ami T; Goetting-Minesky, M Paula; Patel, Samip P; Silviera, Matthew L; Krady, J Kyle; Milner, Robert J; Ewing, Andrew G; Day, Jonathan R

    2003-09-10

    Synaptic plasticity is important for formation of long-term memories and in re-establishment of function following injury. Seven cDNAs enriched following lesion in the hippocampus of the rat have been isolated using a PCR-based cDNA suppression subtraction hybridization. Sequence analysis resulted in the identification of two genes with known roles in synaptic development and neuronal activities: astrotactin and calcineurin. These two neuron-specific genes have established roles in development or synaptogenesis. Sequence analysis of the other five additional genes shows that two are likely to be involved in G-protein signaling pathways, one is a WD repeat protein, and the remaining two are entirely novel. All seven candidates are expressed in the hippocampus and, in some cases, cortical layers of adult brains. RT-PCR data show that expression increases following synaptogenic lesion. Immunocytochemical analysis in primary hippocampal neurons showed that Calcineurin immunoreactivity was redistributed in neurons during 2 weeks in culture. This redistribution suggests that Calcineurin's role changes during neurite outgrowth immediately prior to synapse formation in vitro. In addition, inhibiting Calcineurin activity with cyclosporin A enhanced neurite outgrowth, suggesting that Calcineurin has a regulatory role in axon sprouting. The discovery of previously unknown genes involved in the response to neurodegeneration will contribute to our understanding of neural development, responses to CNS trauma, and neurodegenerative diseases. PMID:14499481

  1. Effects of Chronic Sleep Fragmentation on Wake-Active Neurons and the Hypercapnic Arousal Response

    PubMed Central

    Li, Yanpeng; Panossian, Lori A.; Zhang, Jing; Zhu, Yan; Zhan, Guanxia; Chou, Yu-Ting; Fenik, Polina; Bhatnagar, Seema; Piel, David A.; Beck, Sheryl G.; Veasey, Sigrid

    2014-01-01

    Study Objectives: Delayed hypercapnic arousals may occur in obstructive sleep apnea. The impaired arousal response is expected to promote more pronounced oxyhemoglobin desaturations. We hypothesized that long-term sleep fragmentation (SF) results in injury to or dysfunction of wake-active neurons that manifests, in part, as a delayed hypercapnic arousal response. Design: Adult male mice were implanted for behavioral state recordings and randomly assigned to 4 weeks of either orbital platform SF (SF4wk, 30 events/h) or control conditions (Ct4wk) prior to behavioral, histological, and locus coeruleus (LC) whole cell electrophysiological evaluations. Measurements and Results: SF was successfully achieved across the 4 week study, as evidenced by a persistently increased arousal index, P < 0.01 and shortened sleep bouts, P < 0.05, while total sleep/wake times and plasma corticosterone levels were unaffected. A multiple sleep latency test performed at the onset of the dark period showed a reduced latency to sleep in SF4wk mice (P < 0.05). The hypercapnic arousal latency was increased, Ct4wk 64 ± 5 sec vs. SF4wk 154 ± 6 sec, P < 0.001, and remained elevated after a 2 week recovery (101 ± 4 sec, P < 0.001). C-fos activation in noradrenergic, orexinergic, histaminergic, and cholinergic wake-active neurons was reduced in response to hypercapnia (P < 0.05-0.001). Catecholaminergic and orexinergic projections into the cingulate cortex were also reduced in SF4wk (P < 0.01). In addition, SF4wk resulted in impaired LC neuron excitability (P < 0.01). Conclusions: Four weeks of sleep fragmentation (SF4wk) impairs arousal responses to hypercapnia, reduces wake neuron projections and locus coeruleus neuronal excitability, supporting the concepts that some effects of sleep fragmentation may contribute to impaired arousal responses in sleep apnea, which may not reverse immediately with therapy. Citation: Li Y; Panossian LA; Zhang J; Zhu Y; Zhan G; Chou YT; Fenik P; Bhatnagar S; Piel

  2. Nerve Growth Factor Gene Therapy Activates Neuronal Responses in Alzheimer’s Disease

    PubMed Central

    Tuszynski, Mark H.; Yang, Jennifer H.; Barba, David; U, H S.; Bakay, Roy; Pay, Mary M.; Masliah, Eliezer; Conner, James M.; Kobalka, Peter; Roy, Subhojit; Nagahara, Alan H.

    2016-01-01

    IMPORTANCE Alzheimer’s disease (AD) is the most common neurodegenerative disorder, and lacks effective disease modifying therapies. In 2001 we initiated a clinical trial of Nerve Growth Factor (NGF) gene therapy in AD, the first effort at gene delivery in an adult neurodegenerative disorder. This program aimed to determine whether a nervous system growth factor prevents or reduces cholinergic neuronal degeneration in AD patients. We present post-mortem findings in 10 subjects with survival times ranging from 1 to 10 years post-treatment. OBJECTIVE To determine whether degenerating neurons in AD retain an ability to respond to a nervous system growth factor delivered after disease onset. DESIGN, SETTING, AND PARTICIPANTS 10 patients with early AD underwent NGF gene therapy using either ex vivo or in vivo gene transfer. The brains of all eight patients in the first Phase 1 ex vivo trial and two patients in a subsequent Phase 1 in vivo trial were examined. MAIN OUTCOME MEASURES Brains were immunolabeled to evaluate in vivo gene expression, cholinergic neuronal responses to NGF, and activation of NGF-related cell signaling. In two cases, NGF protein levels were measured by ELISA. RESULTS Degenerating neurons in the AD brain respond to NGF. All patients exhibited a trophic response to NGF, in the form of axonal sprouting toward the NGF source. Comparing treated and non-treated sides of the brain in three patients that underwent unilateral gene transfer, cholinergic neuronal hypertrophy occurred on the NGF-treated side (P>0.05). Activation of cellular signaling and functional markers were present in two patients that underwent AAV2-mediated NGF gene transfer. Neurons exhibiting tau pathology as well as neurons free of tau expressed NGF, indicating that degenerating cells can be infected with therapeutic genes with resulting activation of cell signaling. No adverse pathological effects related to NGF were observed. CONCLUSIONS AND RELEVANCE These findings indicate that

  3. In vivo responses of single olfactory receptor neurons of channel catfish to binary mixtures of amino acids.

    PubMed

    Kang, J; Caprio, J

    1997-01-01

    For the first time in any vertebrate, in vivo responses of single olfactory receptor neurons to odorant mixtures were studied quantitatively. Extracellular electrophysiological response of 54 single olfactory receptor neurons from 23 channel catfish, Ictalurus punctatus, to binary mixtures of amino acids and to their components were recorded simultaneously with the electroolfactogram (EOG). For 57% (73 of 128) of the tests, no significant change (N) from spontaneous activity occurred. Responses to the remaining 55 tests of binary mixtures were excitatory (E; 13%) or suppressive (S; 30%). No response type was associated with any specific mixture across the neurons sampled. Eighty-six percent of the responses of catfish olfactory receptor neurons to binary mixtures were classified similar to at least one of the component responses, a percentage comparable (i.e., 89%) with that observed for single olfactory bulb neurons in the same species to equivalent binary mixtures. The responses of single olfactory receptor neurons to component-similar binary mixtures (i.e., component responses were both E, both S, and both N, respectively) were generally (80% of 59 tests) classified similar to the responses to the components. For E+N and S+N binary mixtures, the N component often (66% of 58 tests) reduced or concealed (i.e., "masked") the excitatory and suppressive responses, respectively. For the majority (6 of 11 tests) of E + S binary mixtures, null activity resulted. Responses to the remaining five tests were either excitatory (n = 3) or suppressive (n = 2). PMID:9120550

  4. Global electrosensory oscillations enhance directional responses of midbrain neurons in eigenmannia.

    PubMed

    Ramcharitar, J U; Tan, E W; Fortune, E S

    2006-11-01

    Eigenmannia, a genus of weakly electric fish, exhibits a specialized behavior known as the jamming avoidance response (JAR). The JAR results in a categorical difference between Eigenmannia that are in groups of conspecifics and those that are alone. Fish in groups exhibit the JAR behavior and thereby experience ongoing, global synchronous 20- to 50-Hz electrosensory oscillations, whereas solitary fish do not. Although previous work has shown that these ongoing signals do not significantly degrade electrosensory behavior, these oscillations nevertheless elicit short-term synaptic depression in midbrain circuits. Because short-term synaptic depression can have profound effects on the transmission of information through synapses, we examined the differences in intracellularly recorded responses of midbrain neurons in awake, behaving fish to moving electrosensory images under electrosensory conditions that mimic solitary fish and fish in groups. In solitary conditions, moving objects elicited Gaussian or sinusoidal postsynaptic potentials (PSPs) that commonly exhibited preferential responses to a direction of motion. Surprisingly, when the same stimulus was presented in the presence of the global oscillations, directional selectivity was increased in all neurons tested. The magnitudes of the differences in PSP amplitude for preferred and nonpreferred directions were correlated with a measure of short-term synaptic depression in both conditions. The electrosensory consequences of the JAR appear to result in an enhancement of the representation of direction of motion in midbrain neurons. The data also support a role for short-term synaptic depression in the generation and modulation of directional responses. PMID:16790600

  5. Effect of autaptic activity on the response of a Hodgkin-Huxley neuron.

    PubMed

    Wang, Hengtong; Wang, Longfei; Chen, Yueling; Chen, Yong

    2014-09-01

    An autapse is a special synapse that connects a neuron to itself. In this study, we investigated the effect of an autapse on the responses of a Hodgkin-Huxley neuron to different forms of external stimuli. When the neuron was subjected to a DC stimulus, the firing frequencies and the interspike interval distributions of the output spike trains showed periodic behaviors as the autaptic delay time increased. When the input was a synaptic pulse-like train with random interspike intervals, we observed low-pass and band-pass filtering behaviors. Moreover, the region over which the output ISIs are distributed and the mean firing frequency display periodic behaviors with increasing autaptic delay time. When specific autaptic parameters were chosen, most of the input ISIs could be filtered, and the response spike trains were nearly regular, even with a highly random input. The background mechanism of these observed dynamics has been analyzed based on the phase response curve method. We also found that the information entropy of the output spike train could be modified by the autapse. These results also suggest that the autapse can serve as a regulator of information response in the nervous system. PMID:25273202

  6. Improved system identification using artificial neural networks and analysis of individual differences in responses of an identified neuron.

    PubMed

    Costalago Meruelo, Alicia; Simpson, David M; Veres, Sandor M; Newland, Philip L

    2016-03-01

    Mathematical modelling is used routinely to understand the coding properties and dynamics of responses of neurons and neural networks. Here we analyse the effectiveness of Artificial Neural Networks (ANNs) as a modelling tool for motor neuron responses. We used ANNs to model the synaptic responses of an identified motor neuron, the fast extensor motor neuron, of the desert locust in response to displacement of a sensory organ, the femoral chordotonal organ, which monitors movements of the tibia relative to the femur of the leg. The aim of the study was threefold: first to determine the potential value of ANNs as tools to model and investigate neural networks, second to understand the generalisation properties of ANNs across individuals and to different input signals and third, to understand individual differences in responses of an identified neuron. A metaheuristic algorithm was developed to design the ANN architectures. The performance of the models generated by the ANNs was compared with those generated through previous mathematical models of the same neuron. The results suggest that ANNs are significantly better than LNL and Wiener models in predicting specific neural responses to Gaussian White Noise, but not significantly different when tested with sinusoidal inputs. They are also able to predict responses of the same neuron in different individuals irrespective of which animal was used to develop the model, although notable differences between some individuals were evident. PMID:26717237

  7. Responses of neurons in the rat's ventral nucleus of the lateral lemniscus to amplitude-modulated tones.

    PubMed

    Zhang, Huiming; Kelly, Jack B

    2006-12-01

    Recordings were made from single neurons in the rat's ventral nucleus of the lateral lemniscus (VNLL) to determine responses to amplitude-modulated (AM) tones. The neurons were first characterized on the basis of their response to tone bursts presented to the contralateral ear and a distinction was made between those with transient onset responses and those with sustained responses. Sinusoidal AM tones were then presented to the contralateral ear with a carrier that matched the neuron's characteristic frequency (CF). Modulation transfer functions were generated on the basis of firing rate (MTF(FR)) and vector strength (MTF(VS)). Ninety-two percent of onset neurons that responded continuously to AM tones had band-pass MTF(FR)s with best modulation frequencies from 10 to 300 Hz. Fifty-four percent of sustained neurons had band-pass MTF(FR)s with best modulation frequencies from 10 to 500 Hz; other neurons had band-suppressed, all-pass, low-pass, or high-pass functions. Most neurons showed either band-pass or low-pass MTF(VS). Responses were well synchronized to the modulation cycle with maximum vector strengths ranging from 0.37 to 0.98 for sustained neurons and 0.78 to 0.99 for onset neurons. The upper frequency limit for response synchrony was higher than that reported for inferior colliculus, but lower than that seen in more peripheral structures. Results suggest that VNLL neurons, especially those with onset responses to tone bursts, are sensitive to temporal features of sounds and narrowly tuned to different modulation rates. However, there was no evidence of a topographic relation between dorsoventral position along the length of VNLL and best modulation frequency as determined by either firing rate or vector strength. PMID:16928797

  8. Response of pontomedullary reticulospinal neurons to vestibular stimuli in vertical planes. Role in vertical vestibulospinal reflexes of the decerebrate cat

    NASA Technical Reports Server (NTRS)

    Bolton, P. S.; Goto, T.; Schor, R. H.; Wilson, V. J.; Yamagata, Y.; Yates, B. J.

    1992-01-01

    1. To investigate the neural substrate of vestibulospinal reflexes in decerebrate cats, we studied the responses of pontomedullary reticulospinal neurons to natural stimulation of the labyrinth in vertical planes. Our principal aim was to determine whether reticulospinal neurons that terminate in, or are likely to give off collaterals to, the upper cervical segments had properties similar to those of the vestibulocollic reflex (VCR). 2. Antidromic stimulation was used to determine whether the neurons projected to the neck, lower cervical, thoracic, or lumbar levels. Dynamics of the responses of spontaneously firing neurons were studied with sinusoidal stimuli delivered at 0.05-1 Hz and aligned to the plane of body rotation, that produced maximal modulation of the neuron (response vector orientation). Each neuron was assigned a vestibular input classification of otolith, vertical canal, otolith + canal, or spatial-temporal convergence (STC). 3. We found, in agreement with previous studies, that the largest fraction of pontomedullary reticulospinal neurons projected to the lumbar cord, and that only a small number ended in the neck segments. Neurons projecting to all levels of the spinal cord had similar responses to labyrinth stimulation. 4. Reticulospinal neurons that received only vertical canal inputs were rare (1 of 67 units). Most reticulospinal neurons (48%) received predominant otolith inputs, 18% received otolith + canal input, and only 9% had STC behavior. These data are in sharp contrast to the results of our previous studies of vestibulospinal neurons. A considerable portion of vestibulospinal neurons receives vertical canal input (38%), fewer receive predominantly otolith input (22%), whereas the proportion that have otolith + canal input or STC behavior is similar to our present reticulospinal data. 5. The response vector orientations of our reticulospinal neurons, particularly those with canal inputs (canal, otolith + canal, STC) were predominantly in

  9. RBFOX1 and RBFOX2 are dispensable in iPSCs and iPSC-derived neurons and do not contribute to neural-specific paternal UBE3A silencing

    PubMed Central

    Chen, Pin-Fang; Hsiao, Jack S.; Sirois, Carissa L.; Chamberlain, Stormy J.

    2016-01-01

    Angelman Syndrome (AS) is a rare neurodevelopmental disorder caused by loss of function of the maternally inherited copy of UBE3A, an imprinted gene expressed biallelically in most tissues, but expressed exclusively from the maternal allele in neurons. Active transcription of the neuron-specific long non-coding RNA (lncRNA), UBE3A-ATS, has been shown to silence paternal UBE3A. We hypothesized that alternative splicing factors RBFOX2 and RBFOX1 might mediate splicing changes and result in the transcription of UBE3A-ATS in neurons. We found that RBFOX2 and RBFOX1 both bind to UBE3A-ATS transcript in neurons, but are not required for gene expression and/or neuron-specific processing in the SNURF/SNRPN-UBE3A region. However, we found that depletion of RBFOX2 causes a proliferation phenotype in immature neural cultures, suggesting that RBFOX2 is involved in division versus differentiation decisions in iPSC-derived neural progenitors. Absence of RBFOX2 also altered the expression of some genes that are important for glutamatergic neocortical development and Wnt-Frizzled signalling in mature neuronal cultures. Our data show that while RBFOX1 and RBFOX2 do not mediate neuron-specific processing of UBE3A-ATS, these proteins play important roles in developing neurons and are not completely functionally redundant. PMID:27146458

  10. Responses of neurones in the cat's visual cerebral cortex to relative movement of patterns

    PubMed Central

    Burns, B. Delisle; Gassanov, U.; Webb, A. C.

    1972-01-01

    1. We have investigated the responses of single neurones in the visual cerebral cortex of the unanaesthetized, isolated cat's forebrain to excitation of one retina with patterned light. The responses of twenty-six cells to the relative movement of two patterns in the visual field have been recorded. 2. We used several forms of relative movement for stimulation, but all of them involved a change in the separation of two parallel and straight light-dark edges. 3. Responses to this form of stimulation were compared with the responses of the same cells to simple movement, that is, movement of the same patterns without change of distance between their borders. 4. All cells showed a response to relative movement that differed from their response to simple movement. 5. The time-locked phasic response differed in 54% of the cells tested. Of cells responding in this way, 83% of tests produced an increased phasic response. 6. Relative movement brought about changes in the mean frequency of discharge in 96% of the cells tested. 82% of these cells responded with an increased rate of firing. 7. Movement relative to a coarse background pattern affected more neurones and produced a greater change in their behaviour than did movement relative to a fine-grained pattern. 8. The neurones tested represented the central part of the visual field (0-10°); while all were affected by relative movement, those representing points furthest from the optic axis appeared to be most susceptible (we found no correlation between size of receptive field and distance from the optic axis). PMID:5083167

  11. Orbital cortex neuronal responses during an odor-based conditioned associative task in rats.

    PubMed

    Yonemori, M; Nishijo, H; Uwano, T; Tamura, R; Furuta, I; Kawasaki, M; Takashima, Y; Ono, T

    2000-01-01

    Neuronal activity in the rat orbital cortex during discrimination of various odors [five volatile organic compounds (acetophenone, isoamyl acetate, cyclohexanone, p-cymene and 1,8-cineole), and food- and cosmetic-related odorants (black pepper, cheese, rose and perfume)] and other conditioned sensory stimuli (tones, light and air puff) was recorded and compared with behavioral responses to the same odors (black pepper, cheese, rose and perfume). In a neurophysiological study, the rats were trained to lick a spout that protruded close to its mouth to obtain sucrose or intracranial self-stimulation reward after presentation of conditioned stimuli. Of 150 orbital cortex neurons recorded during the task, 65 responded to one or more types of sensory stimuli. Of these, 73.8% (48/65) responded during presentation of an odor. Although the mean breadth of responsiveness (entropy) of the olfactory neurons based on the responses to five volatile organic compounds and air (control) was rather high (0.795), these stimuli were well discriminated in an odor space resulting from multidimensional scaling using Pearson's correlation coefficients between the stimuli. In a behavioral study, a rat was housed in an equilateral octagonal cage, with free access to food and choice among eight levers, four of which elicited only water (no odor, controls), and four of which elicited both water and one of four odors (black pepper, cheese, rose or perfume). Lever presses for each odor and control were counted. Distributions of these five stimuli (four odors and air) in an odor space derived from the multidimensional scaling using Pearson's correlation coefficients based on behavioral responses were very similar to those based on neuronal responses to the same five stimuli. Furthermore, Pearson's correlation coefficients between the same five stimuli based on the neuronal responses and those based on behavioral responses were significantly correlated. The results demonstrated a pivotal role of

  12. Plasma leptin inhibits the response of nucleus of the solitary tract neurons to aortic baroreceptor stimulation.

    PubMed

    Ciriello, John

    2013-08-01

    Leptin receptors have been identified within the nucleus of the solitary tract (NTS) and leptin injections into the caudal NTS inhibit the baroreceptor reflex. However, whether plasma leptin alters the discharge of NTS neurons mediating aortic baroreceptor reflex activity is not known. A series of electrophysiological single unit recording experiments was done in the urethane-chloralose anesthetized, paralyzed and artificially ventilated Wistar and Zucker obese rat with either their neuroaxis intact or with mid-collicular transections. Single units in NTS antidromically activated by electrical stimulation of depressor sites in the caudal ventrolateral medulla (CVLM) were found to display a cardiac cycle-related rhythmicity. These units were tested for their responses to stimulation of the aortic depressor nerve (ADN) and intra-carotid injections of leptin (50-200ng/0.1ml). Of 63 single units tested in NTS, 33 were antidromically activated by stimulation of CVLM depressor sites and 18 of these single units responded with a decrease in discharge rate after intracarotid injections of leptin. Thirteen of these leptin responsive neurons (∼72%) were excited by ADN stimulation. Furthermore, the excitatory response of these single units to ADN stimulation was attenuated by about 50% after the intracarotid leptin injection. Intracarotid injections of leptin (200ng/0.1ml) in the Zucker obese rat did not alter the discharge rate of NTS-CVLM projecting neurons. These data suggest that leptin exerts a modulatory effect on brainstem neuronal circuits that control cardiovascular responses elicited during the reflex activation of arterial baroreceptors. PMID:23792336

  13. Variability of visual responses of superior colliculus neurons depends on stimulus velocity.

    PubMed

    Mochol, Gabriela; Wójcik, Daniel K; Wypych, Marek; Wróbel, Andrzej; Waleszczyk, Wioletta J

    2010-03-01

    Visually responding neurons in the superficial, retinorecipient layers of the cat superior colliculus receive input from two primarily parallel information processing channels, Y and W, which is reflected in their velocity response profiles. We quantified the time-dependent variability of responses of these neurons to stimuli moving with different velocities by Fano factor (FF) calculated in discrete time windows. The FF for cells responding to low-velocity stimuli, thus receiving W inputs, increased with the increase in the firing rate. In contrast, the dynamics of activity of the cells responding to fast moving stimuli, processed by Y pathway, correlated negatively with FF whether the response was excitatory or suppressive. These observations were tested against several types of surrogate data. Whereas Poisson description failed to reproduce the variability of all collicular responses, the inclusion of secondary structure to the generating point process recovered most of the observed features of responses to fast moving stimuli. Neither model could reproduce the variability of low-velocity responses, which suggests that, in this case, more complex time dependencies need to be taken into account. Our results indicate that Y and W channels may differ in reliability of responses to visual stimulation. Apart from previously reported morphological and physiological differences of the cells belonging to Y and W channels, this is a new feature distinguishing these two pathways. PMID:20203179

  14. What Response Properties Do Individual Neurons Need to Underlie Position and Clutter “Invariant” Object Recognition?

    PubMed Central

    Li, Nuo; Cox, David D.; Zoccolan, Davide; DiCarlo, James J.

    2009-01-01

    Primates can easily identify visual objects over large changes in retinal position—a property commonly referred to as position “invariance.” This ability is widely assumed to depend on neurons in inferior temporal cortex (IT) that can respond selectively to isolated visual objects over similarly large ranges of retinal position. However, in the real world, objects rarely appear in isolation, and the interplay between position invariance and the representation of multiple objects (i.e., clutter) remains unresolved. At the heart of this issue is the intuition that the representations of nearby objects can interfere with one another and that the large receptive fields needed for position invariance can exacerbate this problem by increasing the range over which interference acts. Indeed, most IT neurons' responses are strongly affected by the presence of clutter. While external mechanisms (such as attention) are often invoked as a way out of the problem, we show (using recorded neuronal data and simulations) that the intrinsic properties of IT population responses, by themselves, can support object recognition in the face of limited clutter. Furthermore, we carried out extensive simulations of hypothetical neuronal populations to identify the essential individual-neuron ingredients of a good population representation. These simulations show that the crucial neuronal property to support recognition in clutter is not preservation of response magnitude, but preservation of each neuron's rank-order object preference under identity-preserving image transformations (e.g., clutter). Because IT neuronal responses often exhibit that response property, while neurons in earlier visual areas (e.g., V1) do not, we suggest that preserving the rank-order object preference regardless of clutter, rather than the response magnitude, more precisely describes the goal of individual neurons at the top of the ventral visual stream. PMID:19439676

  15. Cerebellar-responsive neurons in the thalamic ventroanterior-ventrolateral complex of rats: in vivo electrophysiology.

    PubMed

    Sawyer, S F; Young, S J; Groves, P M; Tepper, J M

    1994-12-01

    In vivo intracellular recordings were obtained from identified thalamocortical neurons in the ventroanterior-ventrolateral complex in urethane-anesthetized rats. This thalamic nucleus has few interneurons. Neurons that responded to cerebellar stimulation were injected intracellularly with horseradish peroxidase or biocytin and examined with light and electron microscopy (see companion paper). Intrinsic membrane properties and voltage-dependent rhythmic activity of cerebellar-responsive ventroanterior-ventrolateral neurons were similar to those described previously for thalamic neurons. Thus, in addition to conventional "fast" Na(+)-dependent spikes, rat ventroanterior-ventrolateral neurons had "slow" Ca(2+)-mediated low-threshold spikes and membrane conductances that supported rhythmic oscillations. Two modes of spontaneous activity were observed: (i) a tonic firing pattern that consisted of irregularly occurring fast spikes that predominated when the membrane potential was more positive than about -60 mV, and (ii) a rhythmic firing pattern, observed when the membrane potential was more negative than about -65 mV, composed of periodic (4-8 Hz) membrane hyperpolarizations and ramp depolarizations that often produced a low-threshold spike and a burst of fast spikes. In some neurons, spontaneous fast prepotentials were also observed, often with a relatively constant rate (up to 70 Hz). Cerebellar stimulation elicited excitatory postsynaptic potentials that in some cases appeared to be all-or-none and were similar in form to fast prepotentials. Stimulation of ipsilateral motor cortex elicited a short-latency antidromic response followed by a monosynaptic excitatory postsynaptic potential, which had a slower rise time than excitatory postsynaptic potentials evoked from cerebellum, suggesting that cortical inputs were electrotonically distal to cerebellar inputs. In the presence of moderate membrane hyperpolarization, the cortically evoked excitatory postsynaptic

  16. Effects of dynamic synapses on noise-delayed response latency of a single neuron.

    PubMed

    Uzuntarla, M; Ozer, M; Ileri, U; Calim, A; Torres, J J

    2015-12-01

    The noise-delayed decay (NDD) phenomenon emerges when the first-spike latency of a periodically forced stochastic neuron exhibits a maximum for a particular range of noise intensity. Here, we investigate the latency response dynamics of a single Hodgkin-Huxley neuron that is subject to both a suprathreshold periodic stimulus and a background activity arriving through dynamic synapses. We study the first-spike latency response as a function of the presynaptic firing rate f. This constitutes a more realistic scenario than previous works, since f provides a suitable biophysically realistic parameter to control the level of activity in actual neural systems. We first report on the emergence of classical NDD behavior as a function of f for the limit of static synapses. Second, we show that when short-term depression and facilitation mechanisms are included at the synapses, different NDD features can be found due to their modulatory effect on synaptic current fluctuations. For example, an intriguing double NDD (DNDD) behavior occurs for different sets of relevant synaptic parameters. Moreover, depending on the balance between synaptic depression and synaptic facilitation, single NDD or DNDD can prevail, in such a way that synaptic facilitation favors the emergence of DNDD whereas synaptic depression favors the existence of single NDD. Here we report the existence of the DNDD effect in the response latency dynamics of a neuron. PMID:26764730

  17. Spatiotemporal dynamics of neuronal population response in the primary visual cortex.

    PubMed

    Zhou, Douglas; Rangan, Aaditya V; McLaughlin, David W; Cai, David

    2013-06-01

    One of the fundamental questions in system neuroscience is how the brain encodes external stimuli in the early sensory cortex. It has been found in experiments that even some simple sensory stimuli can activate large populations of neurons. It is believed that information can be encoded in the spatiotemporal profile of these collective neuronal responses. Here, we use a large-scale computational model of the primary visual cortex (V1) to study the population responses in V1 as observed in experiments in which monkeys performed visual detection tasks. We show that our model can capture very well spatiotemporal activities measured by voltage-sensitive-dye-based optical imaging in V1 of the awake state. In our model, the properties of horizontal long-range connections with NMDA conductance play an important role in the correlated population responses and have strong implications for spatiotemporal coding of neuronal populations. Our computational modeling approach allows us to reveal intrinsic cortical dynamics, separating them from those statistical effects arising from averaging procedures in experiment. For example, in experiments, it was shown that there was a spatially antagonistic center-surround structure in optimal weights in signal detection theory, which was believed to underlie the efficiency of population coding. However, our study shows that this feature is an artifact of data processing. PMID:23696666

  18. Metabolic Communication between Astrocytes and Neurons via Bicarbonate-Responsive Soluble Adenylyl Cyclase

    PubMed Central

    Choi, Hyun B.; Gordon, Grant R.J.; Zhou, Ning; Tai, Chao; Rungta, Ravi L.; Martinez, Jennifer; Milner, Teresa A.; Ryu, Jae K.; McLarnon, James G.; Tresguerres, Martin; Levin, Lonny R.; Buck, Jochen; MacVicar, Brian A.

    2013-01-01

    SUMMARY Astrocytes are proposed to participate in brain energy metabolism by supplying substrates to neurons from their glycogen stores and from glycolysis. However, the molecules involved in metabolic sensing and the molecular pathways responsible for metabolic coupling between different cell types in the brain are not fully understood. Here we show that a recently cloned bicarbonate (HCO3−) sensor, soluble adenylyl cyclase (sAC), is highly expressed in astrocytes and becomes activated in response to HCO3− entry via the electrogenic NaHCO3 cotransporter (NBC). Activated sAC increases intracellular cAMP levels, causing glycogen breakdown, enhanced glycolysis, and the release of lactate into the extracellular space, which is subsequently taken up by neurons for use as an energy substrate. This process is recruited over a broad physiological range of [K+]ext and also during aglycemic episodes, helping to maintain synaptic function. These data reveal a molecular pathway in astrocytes that is responsible for brain metabolic coupling to neurons. PMID:22998876

  19. Cortical hypoexcitation defines neuronal responses in the immediate aftermath of traumatic brain injury.

    PubMed

    Johnstone, Victoria Philippa Anne; Yan, Edwin Bingbing; Alwis, Dasuni Sathsara; Rajan, Ramesh

    2013-01-01

    Traumatic brain injury (TBI) from a blow to the head is often associated with complex patterns of brain abnormalities that accompany deficits in cognitive and motor function. Previously we reported that a long-term consequence of TBI, induced with a closed-head injury method modelling human car and sporting accidents, is neuronal hyper-excitation in the rat sensory barrel cortex that receives tactile input from the face whiskers. Hyper-excitation occurred only in supra-granular layers and was stronger to complex than simple stimuli. We now examine changes in the immediate aftermath of TBI induced with same injury method. At 24 hours post-trauma significant sensorimotor deficits were observed and characterisation of the cortical population neuronal responses at that time revealed a depth-dependent suppression of neuronal responses, with reduced responses from supragranular layers through to input layer IV, but not in infragranular layers. In addition, increased spontaneous firing rate was recorded in cortical layers IV and V. We postulate that this early post-injury suppression of cortical processing of sensory input accounts for immediate post-trauma sensory morbidity and sets into train events that resolve into long-term cortical hyper-excitability in upper sensory cortex layers that may account for long-term sensory hyper-sensitivity in humans with TBI. PMID:23667624

  20. Effects of dynamic synapses on noise-delayed response latency of a single neuron

    NASA Astrophysics Data System (ADS)

    Uzuntarla, M.; Ozer, M.; Ileri, U.; Calim, A.; Torres, J. J.

    2015-12-01

    The noise-delayed decay (NDD) phenomenon emerges when the first-spike latency of a periodically forced stochastic neuron exhibits a maximum for a particular range of noise intensity. Here, we investigate the latency response dynamics of a single Hodgkin-Huxley neuron that is subject to both a suprathreshold periodic stimulus and a background activity arriving through dynamic synapses. We study the first-spike latency response as a function of the presynaptic firing rate f . This constitutes a more realistic scenario than previous works, since f provides a suitable biophysically realistic parameter to control the level of activity in actual neural systems. We first report on the emergence of classical NDD behavior as a function of f for the limit of static synapses. Second, we show that when short-term depression and facilitation mechanisms are included at the synapses, different NDD features can be found due to their modulatory effect on synaptic current fluctuations. For example, an intriguing double NDD (DNDD) behavior occurs for different sets of relevant synaptic parameters. Moreover, depending on the balance between synaptic depression and synaptic facilitation, single NDD or DNDD can prevail, in such a way that synaptic facilitation favors the emergence of DNDD whereas synaptic depression favors the existence of single NDD. Here we report the existence of the DNDD effect in the response latency dynamics of a neuron.

  1. Quantification of responses from proprioceptive neurons in the limbs of the crab, Cancer magister.

    PubMed

    Cooper, R L; Hartman, H B

    1999-11-01

    In the limbs of crustaceans, proprioception is monitored by chordotonal organs. One in particular, MC1, is arranged in a manner that is accessible for single unit recording of primary sensory neurons while simulating joint movement. The movement-sensitive cells are of two types, those sensitive to relaxation or to elongation of the chordotonal strand which corresponds to flexion or extension of the meropodite-carpopodite joint, respectively. A statistical method for the quantification of these movement-sensitive proprioceptive neuronal responses was implemented. This statistical index, eta(2), should allow neuronal responses recorded in different laboratories to be easily and quantitatively compared. In addition, an eta(2) value can be assigned to individual cells which represents a cell's consistency and degree to which the response is related to the stimulus. We found some cells to have a high eta(2) and to be consistent in their activity while other cells had a high degree of variability with low eta(2) values. J. Exp. Zool. 284:629-636, 1999. PMID:10531549

  2. Responses of Ventral Posterior Thalamus Neurons to Three-Dimensional Vestibular and Optic Flow Stimulation

    PubMed Central

    Meng, Hui

    2010-01-01

    Multisensory neurons tuned to both vestibular and visual motion (optic flow) signals are found in several cortical areas in the dorsal visual stream. Here we examine whether such convergence occurs subcortically in the macaque thalamus. We searched the ventral posterior nuclei, including the anterior pulvinar, as well as the ventro-lateral and ventral posterior lateral nuclei, areas that receive vestibular signals from brain stem and deep cerebellar nuclei. Approximately a quarter of cells responded to three-dimensional (3D) translational and/or rotational motion. More than half of the responsive cells were convergent, thus responded during both rotation and translation. The preferred axes of translation/rotation were distributed throughout 3D space. The majority of the neurons were excited, but some were inhibited, during rotation/translation in darkness. Only a couple of neurons were multisensory being tuned to both vestibular and optic flow stimuli. We conclude that multisensory vestibular/optic flow neurons, which are commonly found in cortical visual and visuomotor areas, are rare in the ventral posterior thalamus. PMID:19955294

  3. Charge-Tunable Silk-Tropoelastin Protein Alloys That Control Neuron Cell Responses

    PubMed Central

    Hu, Xiao; Tang-Schomer, Min D.; Huang, Wenwen; Xia, Xiao-Xia; Weiss, Anthony S.

    2014-01-01

    Tunable protein composites are important for constructing extracellular matrix mimics of human tissues with control of biochemical, structural, and mechanical properties. Molecular interaction mechanisms between silk fibroin protein and recombinant human tropoelastin, based on charge, are utilized to generate a new group of multifunctional protein alloys (mixtures of silk and tropoelastin) with different net charges. These new biomaterials are then utilized as a biomaterial platform to control neuron cell response. With a +38 net charge in water, tropoelastin molecules provide extraordinary elasticity and selective interactions with cell surface integrins. In contrast, negatively charged silk fibroin protein (net charge −36) provides remarkable toughness and stiffness with morphologic stability in material formats via autoclaving-induced beta-sheet crystal physical crosslinks. The combination of these properties in alloy format extends the versatility of both structural proteins, providing a new biomaterial platform. The alloys with weak positive charges (silk/tropoelastin mass ratio 75/25, net charge around +16) significantly improved the formation of neuronal networks and maintained cell viability of rat cortical neurons after 10 days in vitro. The data point to these protein alloys as an alternative to commonly used poly-L-lysine (PLL) coatings or other charged synthetic polymers, particularly with regard to the versatility of material formats (e.g., gels, sponges, films, fibers). The results also provide a practical example of physically designed protein materials with control of net charge to direct biological outcomes, in this case for neuronal tissue engineering. PMID:25093018

  4. The response of motor neurones to intramuscular injection of botulinum toxin

    PubMed Central

    Watson, W. E.

    1969-01-01

    1. The dry mass and nucleic acid content of both nerve cell bodies and their nucleoli were measured by interference microscopy and ultra-violet absorption microspectrography respectively: succinoxidase and acetylcholine hydrolase activities were also determined. Autoradiography was used to follow synthesis of deoxyribonucleic acid (DNA) by glial cells, and to follow nucleic acid and protein metabolism in muscle fibres. 2. After injection of botulinum toxin the synthesis of ribosomal RNA by the neurone followed closely the pattern found after axotomy. 3. After injection of toxin neuronal dry mass increased before the rate of ribosomal RNA synthesis was raised. This early increase, which was not due to increased protein synthesis, probably represents a `damming back' of proteins within the nerve cell body. 4. After injection of toxin no local accumulation of microglial cells synthesizing DNA was found around the affected neurones: it is suggested that this reflects the intact system for intra-axonal transport under these conditions. 5. The affected muscles show increased nucleic acid and protein synthesis. 6. It is suggested that the results obtained indicate that membrane expansion or synthesis which occurs both in muscle and in neurone under these circumstances is the factor responsible for inducing directly or indirectly the changes found in nucleic acid metabolism after injection of botulinum toxin and after axotomy. ImagesFig. 1Fig. 2 PMID:4892690

  5. The neuronal response at extended timescales: a linearized spiking input–output relation

    PubMed Central

    Soudry, Daniel; Meir, Ron

    2014-01-01

    Many biological systems are modulated by unknown slow processes. This can severely hinder analysis – especially in excitable neurons, which are highly non-linear and stochastic systems. We show the analysis simplifies considerably if the input matches the sparse “spiky” nature of the output. In this case, a linearized spiking Input–Output (I/O) relation can be derived semi-analytically, relating input spike trains to output spikes based on known biophysical properties. Using this I/O relation we obtain closed-form expressions for all second order statistics (input – internal state – output correlations and spectra), construct optimal linear estimators for the neuronal response and internal state and perform parameter identification. These results are guaranteed to hold, for a general stochastic biophysical neuron model, with only a few assumptions (mainly, timescale separation). We numerically test the resulting expressions for various models, and show that they hold well, even in cases where our assumptions fail to hold. In a companion paper we demonstrate how this approach enables us to fit a biophysical neuron model so it reproduces experimentally observed temporal firing statistics on days-long experiments. PMID:24765073

  6. Response functions for electrically coupled neuronal network: a method of local point matching and its applications.

    PubMed

    Yihe, Lu; Timofeeva, Yulia

    2016-06-01

    Neuronal networks connected by electrical synapses, also referred to as gap junctions, are present throughout the entire central nervous system. Many instances of gap-junctional coupling are formed between dendritic arbours of individual cells, and these dendro-dendritic gap junctions are known to play an important role in mediating various brain rhythms in both normal and pathological states. The dynamics of such neuronal networks modelled by passive or quasi-active (resonant) membranes can be described by the Green's function which provides the fundamental input-output relationships of the entire network. One of the methods for calculating this response function is the so-called 'sum-over-trips' framework which enables the construction of the Green's function for an arbitrary network as a convergent infinite series solution. Here we propose an alternative and computationally efficient approach for constructing the Green's functions on dendro-dendritic gap junction-coupled neuronal networks which avoids any infinite terms in the solutions. Instead, the Green's function is constructed from the solution of a system of linear algebraic equations. We apply this new method to a number of systems including a simple single cell model and two-cell neuronal networks. We also demonstrate that the application of this novel approach allows one to reduce a model with complex dendritic formations to an equivalent model with a much simpler morphological structure. PMID:26994016

  7. Osmotic and hormonal stimulation of the third ventricular region of ducks: antidiuretic, circulatory and local neuronal responses.

    PubMed

    Simon-Oppermann, C; Kanosue, K; Günther, O; Schmid, H

    1989-01-01

    By means of local microperfusion of the 3rd cerebral ventricle, antidiuretic and circulatory responses to stimulations with various hypertonic solutions and norepinephrine were analyzed in conscious ducks. The results suggest ionic rather than osmometric responsiveness of periventricular osmoreceptive elements, which is in line with single unit recordings of periventricular neurons tested in vitro for their osmoresponsiveness. These neurons were located subependymally at the site of greatest responsiveness in vivo, and corresponded to morphologically identified neurons projecting to the neuroendocrine hypothalamo-pituitary system. Antidiuresis was combined with increases in arterial pressure and heart rate in response to hypertonic stimulations with monovalent cations; divalent cations produced long-lasting antidiuresis and equivocal circulatory responses. Norepinephrine elicited antidiuresis which was accompanied by arterial hypotension and bradycardia. Osmotically and norepinephrine induced antidiuresis was combined with increases of plasma ADH concentration. Different modulatory actions of intrinsic adrenergic, angiotensinergic and vasotocinergic neurons are suggested in hypothalamic control of autonomic functions. PMID:2554682

  8. Responses of primate caudal parabrachial nucleus and Kolliker-fuse nucleus neurons to whole body rotation

    NASA Technical Reports Server (NTRS)

    Balaban, Carey D.; McGee, David M.; Zhou, Jianxun; Scudder, Charles A.

    2002-01-01

    The caudal aspect of the parabrachial (PBN) and Kolliker-Fuse (KF) nuclei receive vestibular nuclear and visceral afferent information and are connected reciprocally with the spinal cord, hypothalamus, amygdala, and limbic cortex. Hence, they may be important sites of vestibulo-visceral integration, particularly for the development of affective responses to gravitoinertial challenges. Extracellular recordings were made from caudal PBN cells in three alert, adult female Macaca nemestrina through an implanted chamber. Sinusoidal and position trapezoid angular whole body rotation was delivered in yaw, roll, pitch, and vertical semicircular canal planes. Sites were confirmed histologically. Units that responded during rotation were located in lateral and medial PBN and KF caudal to the trochlear nerve at sites that were confirmed anatomically to receive superior vestibular nucleus afferents. Responses to whole-body angular rotation were modeled as a sum of three signals: angular velocity, a leaky integration of angular velocity, and vertical position. All neurons displayed angular velocity and integrated angular velocity sensitivity, but only 60% of the neurons were position-sensitive. These responses to vertical rotation could display symmetric, asymmetric, or fully rectified cosinusoidal spatial tuning about a best orientation in different cells. The spatial properties of velocity and integrated velocity and position responses were independent for all position-sensitive neurons; the angular velocity and integrated angular velocity signals showed independent spatial tuning in the position-insensitive neurons. Individual units showed one of three different orientations of their excitatory axis of velocity rotation sensitivity: vertical-plane-only responses, positive elevation responses (vertical plane plus ipsilateral yaw), and negative elevation axis responses (vertical plane plus negative yaw). The interactions between the velocity and integrated velocity components

  9. Correlation of 125I-LSD autoradiographic labeling with serotonin voltage clamp responses in Aplysia neurons

    SciTech Connect

    Evans, M.L.; Kadan, M.J.; Hartig, P.R.; Carpenter, D.O. )

    1991-05-01

    Autoradiographic receptor binding studies using 125I-LSD (2-(125I)lysergic acid diethyamide) revealed intense labelling on the soma of a symmetrically located pair of cells in the abdominal ganglion of Aplysia californica. This binding was blocked by micromolar concentrations of serotonin and lower concentrations of the serotonergic antagonists, cyproheptadine and mianserin. Electrophysiological investigation of responses to serotonin of neurons in the left upper quadrant, where one of the labeled neurons is located, revealed a range of serotonin responses. Cells L3 and L6 have a K+ conductance increase in response to serotonin that is not blocked by cyproheptadine or mianserin. Cells L2 and L4 have a biphasic response to serotonin: a Na+ conductance increase, which can be blocked by cyproheptadine and mianserin, followed by a voltage dependent Ca2+ conductance which is blocked by Co2+ but not the serotonergic antagonists. Cell L1, and its symmetrical pair, R1, have in addition to the Na+ and Ca2+ responses observed in L2 and L4, a Cl- conductance increase blocked by LSD, cyproheptadine and mianserin. LSD had little effect on the other responses. The authors conclude that the symmetrically located cells L1 and R1 have a Cl- channel linked to a cyproheptadine- and mianserin-sensitive serotonin receptor that is selectively labelled by 125I-LSD. This receptor has many properties in common with the mammalian serotonin 1C receptor.

  10. Unique responses of midbrain CART neurons in macaques to ovarian steroids.

    PubMed

    Lima, F B; Henderson, J A; Reddy, A P; Tokuyama, Y; Hubert, G W; Kuhar, M J; Bethea, C L

    2008-08-28

    CART (cocaine and amphetamine regulated transcript) is a neuropeptide involved in the control of several physiological processes, such as response to psychostimulants, food intake, depressive diseases and neuroprotection. It is robustly expressed in the brain, mainly in regions that control emotional and stress responses and it is regulated by estrogen in the hypothalamus. There is a distinct population of CART neurons located in the vicinity of the Edinger-Westphal nucleus of the midbrain that also colocalize urocortin-1. The aims of this study were 1) to determine the distribution of CART immunoreactive neurons in the monkey midbrain, 2) to examine the effects of estrogen (E) and progesterone (P) on midbrain CART mRNA and peptide expression and 3) to determine whether midbrain CART neurons contain steroid receptors. Adult female rhesus monkeys (Macaca mulatta) were spayed and either treated with placebo (OVX), estrogen alone (E), progesterone alone (P) or E+P. Animals were prepared (a) for RNA extraction followed by microarray analysis and quantitative (q) RT-PCR (n=3/group); (b) for immunohistochemical analysis of CART and CART+tryptophan hydroxylase (TPH), CART+estrogen receptors (ER) or CART+progesterone receptors (n=5/group) and (c) for Western blots (n=3/group). Both E- and E+P-administration decreased CART gene expression on the microarray and with qRT-PCR. Stereological analysis of CART immunostaining at five levels of the Edinger-Westphal nucleus indicated little effect of E or E+P administration on the area of CART immunostaining. However, P administration increased CART-immunopositive area in comparison to the OVX control group with Student's t-test, but not with ANOVA. CART 55-102 detection on Western blot was unchanged by hormone administration. ERbeta and PR were detected in CART neurons and CART fibers appeared to innervate TPH-positive serotonin neurons in the dorsal raphe. In summary, E decreased CART mRNA, but this effect did not translate to the

  11. Responses of non-eye movement central vestibular neurons to sinusoidal horizontal translation in compensated macaques after unilateral labyrinthectomy

    PubMed Central

    Lin, Nan; Wei, Min

    2014-01-01

    After vestibular labyrinth injury, behavioral deficits partially recover through the process of vestibular compensation. The present study was performed to improve our understanding of the physiology of the macaque vestibular system in the compensated state (>7 wk) after unilateral labyrinthectomy (UL). Three groups of vestibular nucleus neurons were included: pre-UL control neurons, neurons ipsilateral to the lesion, and neurons contralateral to the lesion. The firing responses of neurons sensitive to linear acceleration in the horizontal plane were recorded during sinusoidal horizontal translation directed along six different orientations (30° apart) at 0.5 Hz and 0.2 g peak acceleration (196 cm/s2). This data defined the vector of best response for each neuron in the horizontal plane, along which sensitivity, symmetry, detection threshold, and variability of firing were determined. Additionally, the responses of the same cells to translation over a series of frequencies (0.25–5.0 Hz) either in the interaural or naso-occipital orientation were obtained to define the frequency response characteristics in each group. We found a decrease in sensitivity, increase in threshold, and alteration in orientation of best responses in the vestibular nuclei after UL. Additionally, the phase relationship of the best neural response to translational stimulation changed with UL. The symmetry of individual neuron responses in the excitatory and inhibitory directions was unchanged by UL. Bilateral central utricular neurons still demonstrated two-dimension tuning after UL, consistent with spatio-temporal convergence from a single vestibular end-organ. These neuronal data correlate with known behavioral deficits after unilateral vestibular compromise. PMID:24717349

  12. Repeated whisker stimulation evokes invariant neuronal responses in the dorsolateral striatum of anesthetized rats: a potential correlate of sensorimotor habits

    PubMed Central

    Mowery, Todd M.; Harrold, Jon B.

    2011-01-01

    The dorsolateral striatum (DLS) receives extensive projections from primary somatosensory cortex (SI), but very few studies have used somesthetic stimulation to characterize the sensory coding properties of DLS neurons. In this study, we used computer-controlled whisker deflections to characterize the extracellular responses of DLS neurons in rats lightly anesthetized with isoflurane. When multiple whiskers were synchronously deflected by rapid back-and-forth movements, whisker-sensitive neurons in the DLS responded to both directions of movement. The latency and magnitude of these neuronal responses displayed very little variation with changes in the rate (2, 5, or 8 Hz) of whisker stimulation. Simultaneous recordings in SI barrel cortex and the DLS revealed important distinctions in the neuronal responses of these serially connected brain regions. In contrast to DLS neurons, SI neurons were activated by the initial deflection of the whiskers but did not respond when the whiskers moved back to their original position. As the rate of whisker stimulation increased, SI responsiveness declined, and the latencies of the responses increased. In fact, when whiskers were deflected at 5 or 8 Hz, many neurons in the DLS responded before the SI neurons. These results and earlier anatomic findings suggest that a component of the sensory-induced response in the DLS is mediated by inputs from the thalamus. Furthermore, the lack of sensory adaptation in the DLS may represent a critical part of the neural mechanism by which the DLS encodes stimulus-response associations that trigger motor habits and other stimulus-evoked behaviors that are not contingent on rewarded outcomes. PMID:21389309

  13. Smooth pursuit preparation modulates neuronal responses in visual areas MT and MST.

    PubMed

    Ferrera, Vincent P

    2015-07-01

    Primates are able to track small moving visual targets using smooth pursuit eye movements. Target motion for smooth pursuit is signaled by neurons in visual cortical areas MT and MST. In this study, we trained monkeys to either initiate or withhold smooth pursuit in the presence of a moving target to test whether this decision was reflected in the relative strength of "go" and "no-go" processes. We found that the gain of the motor response depended strongly on whether monkeys were instructed to initiate or withhold pursuit, thus demonstrating voluntary control of pursuit initiation. We found that the amplitude of the neuronal response to moving targets in areas MT and MST was also significantly lower on no-go trials (by 2.1 spikes/s on average). The magnitude of the neural response reduction was small compared with the behavioral gain reduction. There were no significant differences in neuronal direction selectivity, spatial selectivity, or response reliability related to pursuit initiation or the absence thereof. Variability in eye speed was negatively correlated with firing rate variability after target motion onset during go trials but not during no-go trials, suggesting that MT and MST activity represents an error signal for a negative feedback controller. We speculate that modulation of the visual motion signals in areas MT and MST may be one of the first visual cortical events in the initiation of smooth pursuit and that the small early response modulation may be amplified to produce an all-or-none motor response by downstream areas. PMID:26019315

  14. Smooth pursuit preparation modulates neuronal responses in visual areas MT and MST

    PubMed Central

    2015-01-01

    Primates are able to track small moving visual targets using smooth pursuit eye movements. Target motion for smooth pursuit is signaled by neurons in visual cortical areas MT and MST. In this study, we trained monkeys to either initiate or withhold smooth pursuit in the presence of a moving target to test whether this decision was reflected in the relative strength of “go” and “no-go” processes. We found that the gain of the motor response depended strongly on whether monkeys were instructed to initiate or withhold pursuit, thus demonstrating voluntary control of pursuit initiation. We found that the amplitude of the neuronal response to moving targets in areas MT and MST was also significantly lower on no-go trials (by 2.1 spikes/s on average). The magnitude of the neural response reduction was small compared with the behavioral gain reduction. There were no significant differences in neuronal direction selectivity, spatial selectivity, or response reliability related to pursuit initiation or the absence thereof. Variability in eye speed was negatively correlated with firing rate variability after target motion onset during go trials but not during no-go trials, suggesting that MT and MST activity represents an error signal for a negative feedback controller. We speculate that modulation of the visual motion signals in areas MT and MST may be one of the first visual cortical events in the initiation of smooth pursuit and that the small early response modulation may be amplified to produce an all-or-none motor response by downstream areas. PMID:26019315

  15. Noradrenergic modulation of glutamate-induced excitatory responses in single neurons of the red nucleus: an electrophysiological study.

    PubMed

    Bronzi, D; Licata, F; Li Volsi, G

    2015-08-01

    The effect induced by noradrenaline (NA) on the spiking activity evoked by glutamate (Glu) on single neurons of the mesencephalic red nucleus (RN) of the rat was studied extracellularly. Long-lasting microiontophoretic applications of the amine induced a significant and reversible depression of the responsiveness of RN neurons to Glu. This effect was mediated by noradrenergic alpha2 receptors since it was mimicked by application of clonidine, an alpha2 adrenoceptor agonist, and blocked or at least reduced by application of yohimbine, an antagonist of NA for the same receptors. The effect appears homogeneously throughout the nucleus and is independent of the effect of NA on baseline firing rate. Application of isoproterenol, a beta adrenoceptor agonist, either enhanced or depressed neuronal responses to Glu in a high percentage (86%) of the tested neurons. Moreover, application of timolol, a beta adrenoceptor antagonist, was able to strengthen the depressive effects induced by NA application on neuronal responsiveness to Glu. Although these data suggest some involvement of beta adrenergic receptors in the modulation of neuronal responsiveness to Glu, the overall results indicate a short-term depressive action of NA, mediated by alpha2 receptors, on the responsiveness of RN neurons and suggest that stress initially leads to an attenuation of the relay function of the RN. PMID:26012489

  16. La3+ Alters the Response Properties of Neurons in the Mouse Primary Somatosensory Cortex to Low-Temperature Noxious Stimulation of the Dental Pulp

    PubMed Central

    Jin, Yanjiao

    2015-01-01

    Although dental pain is a serious health issue with high incidence among the human population, its cellular and molecular mechanisms are still unclear. Transient receptor potential (TRP) channels are assumed to be involved in the generation of dental pain. However, most of the studies were conducted with molecular biological or histological methods. In vivo functional studies on the role of TRP channels in the mechanisms of dental pain are lacking. This study uses in vivo cellular electrophysiological and neuropharmacological method to directly disclose the effect of LaCl3, a broad spectrum TRP channel blocker, on the response properties of neurons in the mouse primary somatosensory cortex to low-temperature noxious stimulation of the dental pulp. It was found that LaCl3 suppresses the high-firing-rate responses of all nociceptive neurons to noxious low-temperature stimulation and also inhibits the spontaneous activities in some nonnociceptive neurons. The effect of LaCl3 is reversible. Furthermore, this effect is persistent and stable unless LaCl3 is washed out. Washout of LaCl3 quickly revitalized the responsiveness of neurons to low-temperature noxious stimulation. This study adds direct evidence for the hypothesis that TRP channels are involved in the generation of dental pain and sensation. Blockade of TRP channels may provide a novel therapeutic treatment for dental pain. PMID:26604777

  17. Fractalkine receptor deficiency impairs microglial and neuronal responsiveness to chronic stress.

    PubMed

    Milior, Giampaolo; Lecours, Cynthia; Samson, Louis; Bisht, Kanchan; Poggini, Silvia; Pagani, Francesca; Deflorio, Cristina; Lauro, Clotilde; Alboni, Silvia; Limatola, Cristina; Branchi, Igor; Tremblay, Marie-Eve; Maggi, Laura

    2016-07-01

    Chronic stress is one of the most relevant triggering factors for major depression. Microglial cells are highly sensitive to stress and, more generally, to environmental challenges. However, the role of these brain immune cells in mediating the effects of stress is still unclear. Fractalkine signaling - which comprises the chemokine CX3CL1, mainly expressed by neurons, and its receptor CX3CR1, almost exclusively present on microglia in the healthy brain - has been reported to critically regulate microglial activity. Here, we investigated whether interfering with microglial function by deleting the Cx3cr1 gene affects the brain's response to chronic stress. To this purpose, we housed Cx3cr1 knockout and wild-type adult mice in either control or stressful environments for 2weeks, and investigated the consequences on microglial phenotype and interactions with synapses, synaptic transmission, behavioral response and corticosterone levels. Our results show that hampering neuron-microglia communication via the CX3CR1-CX3CL1 pathway prevents the effects of chronic unpredictable stress on microglial function, short- and long-term neuronal plasticity and depressive-like behavior. Overall, the present findings suggest that microglia-regulated mechanisms may underlie the differential susceptibility to stress and consequently the vulnerability to diseases triggered by the experience of stressful events, such as major depression. PMID:26231972

  18. Decreased Interleukin-4 Release from the Neurons of the Locus Coeruleus in Response to Immobilization Stress

    PubMed Central

    Park, Hyun-Jung; Starkweather, Angela; An, Kyungeh

    2016-01-01

    It has been demonstrated that immobilization (IMO) stress affects neuroimmune systems followed by alterations of physiology and behavior. Interleukin-4 (IL-4), an anti-inflammatory cytokine, is known to regulate inflammation caused by immune challenge but the effect of IMO on modulation of IL-4 expression in the brain has not been assessed yet. Here, it was demonstrated that IL-4 was produced by noradrenergic neurons in the locus coeruleus (LC) of the brain and release of IL-4 was reduced in response to IMO. It was observed that IMO groups were more anxious than nontreated groups. Acute IMO (2 h/day, once) stimulated secretion of plasma corticosterone and tyrosine hydroxylase (TH) in the LC whereas these increments were diminished in exposure to chronic stress (2 h/day, 21 consecutive days). Glucocorticoid receptor (GR), TH, and IL-4-expressing cells were localized in identical neurons of the LC, indicating that hypothalamic-pituitary-adrenal- (HPA-) axis and sympathetic-adrenal-medullary- (SAM-) axis might be involved in IL-4 secretion in the stress response. Accordingly, it was concluded that stress-induced decline of IL-4 concentration from LC neurons may be related to anxiety-like behavior and an inverse relationship exists between IL-4 secretion and HPA/SAM-axes activation. PMID:26903707

  19. Prostaglandin potentiates 5-HT responses in stomach and ileum innervating visceral afferent sensory neurons.

    PubMed

    Kim, Sojin; Jin, Zhenhua; Lee, Goeun; Park, Yong Seek; Park, Cheung-Seog; Jin, Young-Ho

    2015-01-01

    Gastrointestinal disorder is a common symptom induced by diverse pathophysiological conditions that include food tolerance, chemotherapy, and irradiation for therapy. Prostaglandin E2 (PGE2) level increase was often reported during gastrointestinal disorder and prostaglandin synthetase inhibitors has been used for ameliorate the symptoms. Exogenous administration of PGE2 induces gastrointestinal disorder, however, the mechanism of action is not known. Therefore, we tested PGE2 effect on visceral afferent sensory neurons of the rat. Interestingly, PGE2 itself did not evoked any response but enhanced serotonin (5-HT)-evoked currents up to 167% of the control level. The augmented 5-HT responses were completely inhibited by a 5-HT type 3 receptor antagonist, ondansetron. The PGE2-induced potentiation were blocked by a selective E-prostanoid type 4 (EP4) receptors antagonist, L-161,982, but type 1 and 2 receptor antagonist AH6809 has no effect. A membrane permeable protein kinase A (PKA) inhibitor, KT5720 also inhibited PGE2 effects. PGE2 induced 5-HT current augmentation was observed on 15% and 21% of the stomach and ileum projecting neurons, respectively. Current results suggest a synergistic signaling in visceral afferent neurons underlying gastrointestinal disorder involving PGE2 potentiation of 5-HT currents. Our findings may open a possibility for screen a new type drugs with lower side effects than currently using steroidal prostaglandin synthetase inhibitors by selectively targeting EP4 receptor/PKA pathway without interrupt prostaglandin synthesis. PMID:25446121

  20. Contribution of the T1r3 taste receptor to the response properties of central gustatory neurons.

    PubMed

    Lemon, Christian H; Margolskee, Robert F

    2009-05-01

    T1r3 is a critical subunit of T1r sweet taste receptors. Here we studied how the absence of T1r3 impacts responses to sweet stimuli by taste neurons in the nucleus tractus solitarius (NTS) of the mouse. The consequences bear on the multiplicity of sweet taste receptors and how T1r3 influences the distribution of central gustatory neurons. Taste responses to glycine, sucrose, NaCl, HCl, and quinine were electrophysiologically recorded from single NTS neurons in anesthetized T1r3 knockout (KO) and wild-type (WT) C57BL/6 mice. Other stimuli included l-proline, d-fructose, d-glucose, d-sorbitol, Na-saccharin, acesulfame-K, monosodium glutamate, NaNO(3), Na-acetate, citric acid, KCl, denatonium, and papaverine. Forty-one WT and 41 KO neurons were recorded. Relative to WT, KO responses to all sweet stimuli were significantly lower, although the degree of attenuation differed among stimuli, with near zero responses to sugars but salient residual activity to artificial sweeteners and glycine. Residual KO across-neuron responses to sweet stimuli were variably similar to nonsweet responses, as indexed by multivariate and correlation analyses. In some cases, this suggested that residual KO activity to "sweet" stimuli could be mediated by nonsweet taste receptors, implicating T1r3 receptors as primary contributors to NTS sweet processing. The influence of T1r3 on the distribution of NTS neurons was evaluated by comparing neuron types that emerged between WT and KO cells. Neurons tuned toward sweet stimuli composed 34% of the WT sample but did not appear among KO cells. Input from T1r3-containing receptors critically guides the normal development of NTS neurons oriented toward sweet tastants. PMID:19279151

  1. Nicotinic acetylcholine receptor-mediated responses in medial vestibular and prepositus hypoglossi nuclei neurons showing distinct neurotransmitter phenotypes.

    PubMed

    Zhang, Yue; Yanagawa, Yuchio; Saito, Yasuhiko

    2016-06-01

    Cholinergic transmission in both the medial vestibular nucleus (MVN) and prepositus hypoglossi nucleus (PHN) plays an important role in horizontal eye movements. We previously demonstrated that the current responses mediated via nicotinic acetylcholine receptors (nAChRs) were larger than those mediated via muscarinic acetylcholine receptors (mAChRs) in cholinergic MVN and PHN neurons that project to the cerebellum. In this study, to clarify the predominant nAChR responses and the expression patterns of nAChRs in MVN and PHN neurons that exhibit distinct neurotransmitter phenotypes, we identified cholinergic, inhibitory, and glutamatergic neurons using specific transgenic rats and investigated current responses to the application of acetylcholine (ACh) using whole cell recordings in brain stem slices. ACh application induced larger nAChR-mediated currents than mAChR-mediated currents in every neuronal phenotype. In the presence of an mAChR antagonist, we found three types of nAChR-mediated currents that exhibited different rise and decay times and designated these as fast (F)-, slow (S)-, and fast and slow (FS)-type currents. F-type currents were the predominant response in inhibitory MVN neurons, whereas S-type currents were observed in the majority of glutamatergic MVN and PHN neurons. No dominant response type was observed in cholinergic neurons. Pharmacological analyses revealed that the F-, S-, and FS-type currents were mainly mediated by α7, non-α7, and both α7 and non-α7 nAChRs, respectively. These findings suggest that cholinergic responses in the major neuronal populations of the MVN and PHN are predominantly mediated by nAChRs and that the expression of α7 and non-α7 nAChRs differ among the neuronal phenotypes. PMID:26936981

  2. Spatial Attention and Temporal Expectation Under Timed Uncertainty Predictably Modulate Neuronal Responses in Monkey V1.

    PubMed

    Sharma, Jitendra; Sugihara, Hiroki; Katz, Yarden; Schummers, James; Tenenbaum, Joshua; Sur, Mriganka

    2015-09-01

    The brain uses attention and expectation as flexible devices for optimizing behavioral responses associated with expected but unpredictably timed events. The neural bases of attention and expectation are thought to engage higher cognitive loci; however, their influence at the level of primary visual cortex (V1) remains unknown. Here, we asked whether single-neuron responses in monkey V1 were influenced by an attention task of unpredictable duration. Monkeys covertly attended to a spot that remained unchanged for a fixed period and then abruptly disappeared at variable times, prompting a lever release for reward. We show that monkeys responded progressively faster and performed better as the trial duration increased. Neural responses also followed monkey's task engagement-there was an early, but short duration, response facilitation, followed by a late but sustained increase during the time monkeys expected the attention spot to disappear. This late attentional modulation was significantly and negatively correlated with the reaction time and was well explained by a modified hazard function. Such bimodal, time-dependent changes were, however, absent in a task that did not require explicit attentional engagement. Thus, V1 neurons carry reliable signals of attention and temporal expectation that correlate with predictable influences on monkeys' behavioral responses. PMID:24836689

  3. Spatiotemporal activity patterns of rat cortical neurons predict responses in a conditioned task

    PubMed Central

    Villa, Alessandro E. P.; Tetko, Igor V.; Hyland, Brian; Najem, Abdellatif

    1999-01-01

    Precise and repeated spike-train timings within and across neurons define spatiotemporal patterns of activity. Although the existence of these patterns in the brain is well established in several species, there has been no direct evidence of their influence on behavioral output. To address this question, up to 15 neurons were recorded simultaneously in the auditory cortex of freely moving rats while animals waited for acoustic cues in a Go/NoGo task. A total of 235 significant patterns were detected during this interval from an analysis of 13 hr of recording involving over 1 million spikes. Of particular interest were 129 (55%) patterns that were significantly associated with the type of response the animal made later, independent of whether the response was that prompted by the cue because the response occurred later and the cue was chosen randomly. Of these behavior-predicting patterns, half (59/129) were associated with an enhanced tendency to go in response to the stimulus, and for 11 patterns of this subset, trials including the pattern were followed by significantly faster reaction time than those lacking the pattern. The remaining behavior-predicting patterns were associated with an enhanced NoGo tendency. Overall mean discharge rates did not vary across trials. Hence, these data demonstrate that particular spatiotemporal patterns predict future behavioral responses. Such presignal activity could form templates for extracting specific sensory information, motor programs prespecifying preference for a particular act, and/or some intermediate, associative brain process. PMID:9927701

  4. Pheromone responsiveness threshold depends on temporal integration by antennal lobe projection neurons

    PubMed Central

    Tabuchi, Masashi; Sakurai, Takeshi; Mitsuno, Hidefumi; Namiki, Shigehiro; Minegishi, Ryo; Shiotsuki, Takahiro; Uchino, Keiro; Sezutsu, Hideki; Tamura, Toshiki; Haupt, Stephan Shuichi; Nakatani, Kei; Kanzaki, Ryohei

    2013-01-01

    The olfactory system of male moths has an extreme sensitivity with the capability to detect and recognize conspecific pheromones dispersed and greatly diluted in the air. Just 170 molecules of the silkmoth (Bombyx mori) sex pheromone bombykol are sufficient to induce sexual behavior in the male. However, it is still unclear how the sensitivity of olfactory receptor neurons (ORNs) is relayed through the brain to generate high behavioral responsiveness. Here, we show that ORN activity that is subthreshold in terms of behavior can be amplified to suprathreshold levels by temporal integration in antennal lobe projection neurons (PNs) if occurring within a specific time window. To control ORN inputs with high temporal resolution, channelrhodopsin-2 was genetically introduced into bombykol-responsive ORNs. Temporal integration in PNs was only observed for weak inputs, but not for strong inputs. Pharmacological dissection revealed that GABAergic mechanisms inhibit temporal integration of strong inputs, showing that GABA signaling regulates PN responses in a stimulus-dependent fashion. Our results show that boosting of the PNs’ responses by temporal integration of olfactory information occurs specifically near the behavioral threshold, effectively defining the lower bound for behavioral responsiveness. PMID:24006366

  5. A Convolutional Subunit Model for Neuronal Responses in Macaque V1

    PubMed Central

    Vintch, Brett; Movshon, J. Anthony

    2015-01-01

    The response properties of neurons in the early stages of the visual system can be described using the rectified responses of a set of self-similar, spatially shifted linear filters. In macaque primary visual cortex (V1), simple cell responses can be captured with a single filter, whereas complex cells combine a set of filters, creating position invariance. These filters cannot be estimated using standard methods, such as spike-triggered averaging. Subspace methods like spike-triggered covariance can recover multiple filters but require substantial amounts of data, and recover an orthogonal basis for the subspace in which the filters reside, rather than the filters themselves. Here, we assume a linear-nonlinear-linear-nonlinear (LN-LN) cascade model in which the first LN stage consists of shifted (“convolutional”) copies of a single filter, followed by a common instantaneous nonlinearity. We refer to these initial LN elements as the “subunits” of the receptive field, and we allow two independent sets of subunits, each with its own filter and nonlinearity. The second linear stage computes a weighted sum of the subunit responses and passes the result through a final instantaneous nonlinearity. We develop a procedure to directly fit this model to electrophysiological data. When fit to data from macaque V1, the subunit model significantly outperforms three alternatives in terms of cross-validated accuracy and efficiency, and provides a robust, biologically plausible account of receptive field structure for all cell types encountered in V1. SIGNIFICANCE STATEMENT We present a new subunit model for neurons in primary visual cortex that significantly outperforms three alternative models in terms of cross-validated accuracy and efficiency, and provides a robust and biologically plausible account of the receptive field structure in these neurons across the full spectrum of response properties. PMID:26538653

  6. Imaging neuronal responses in slice preparations of vomeronasal organ expressing a genetically encoded calcium sensor.

    PubMed

    Ma, Limei; Haga-Yamanaka, Sachiko; Yu, Qingfeng Elden; Qiu, Qiang; Kim, Sangseong; Yu, C Ron

    2011-01-01

    The vomeronasal organ (VNO) detects chemosensory signals that carry information about the social, sexual and reproductive status of the individuals within the same species. These intraspecies signals, the pheromones, as well as signals from some predators, activate the vomeronasal sensory neurons (VSNs) with high levels of specificity and sensitivity. At least three distinct families of G-protein coupled receptors, V1R, V2R and FPR, are expressed in VNO neurons to mediate the detection of the chemosensory cues. To understand how pheromone information is encoded by the VNO, it is critical to analyze the response profiles of individual VSNs to various stimuli and identify the specific receptors that mediate these responses. The neuroepithelia of VNO are enclosed in a pair of vomer bones. The semi-blind tubular structure of VNO has one open end (the vomeronasal duct) connecting to the nasal cavity. VSNs extend their dendrites to the lumen part of the VNO, where the pheromone cues are in contact with the receptors expressed at the dendritic knobs. The cell bodies of the VSNs form pseudo-stratified layers with V1R and V2R expressed in the apical and basal layers respectively. Several techniques have been utilized to monitor responses of VSNs to sensory stimuli. Among these techniques, acute slice preparation offers several advantages. First, compared to dissociated VSNs, slice preparations maintain the neurons in their native morphology and the dendrites of the cells stay relatively intact. Second, the cell bodies of the VSNs are easily accessible in coronal slice of the VNO to allow electrophysiology studies and imaging experiments as compared to whole epithelium and whole-mount preparations. Third, this method can be combined with molecular cloning techniques to allow receptor identification. Sensory stimulation elicits strong Ca2+ influx in VSNs that is indicative of receptor activation. We thus develop transgenic mice that express G-CaMP2 in the olfactory sensory

  7. Prostaglandin potentiates 5-HT responses in stomach and ileum innervating visceral afferent sensory neurons

    SciTech Connect

    Kim, Sojin; Jin, Zhenhua; Lee, Goeun; Park, Yong Seek; Park, Cheung-Seog; Jin, Young-Ho

    2015-01-02

    Highlights: • Prostaglandin E2 (PGE{sub 2}) effect was tested on visceral afferent neurons. • PGE{sub 2} did not evoke response but potentiated serotonin (5-HT) currents up to 167%. • PGE{sub 2}-induced potentiation was blocked by E-prostanoid type 4 receptors antagonist. • PGE{sub 2} effect on 5-HT response was also blocked by protein kinase A inhibitor KT5720. • Thus, PGE{sub 2} modulate visceral afferent neurons via synergistic signaling with 5-HT. - Abstract: Gastrointestinal disorder is a common symptom induced by diverse pathophysiological conditions that include food tolerance, chemotherapy, and irradiation for therapy. Prostaglandin E{sub 2} (PGE{sub 2}) level increase was often reported during gastrointestinal disorder and prostaglandin synthetase inhibitors has been used for ameliorate the symptoms. Exogenous administration of PGE{sub 2} induces gastrointestinal disorder, however, the mechanism of action is not known. Therefore, we tested PGE{sub 2} effect on visceral afferent sensory neurons of the rat. Interestingly, PGE{sub 2} itself did not evoked any response but enhanced serotonin (5-HT)-evoked currents up to 167% of the control level. The augmented 5-HT responses were completely inhibited by a 5-HT type 3 receptor antagonist, ondansetron. The PGE{sub 2}-induced potentiation were blocked by a selective E-prostanoid type4 (EP{sub 4}) receptors antagonist, L-161,982, but type1 and 2 receptor antagonist AH6809 has no effect. A membrane permeable protein kinase A (PKA) inhibitor, KT5720 also inhibited PGE{sub 2} effects. PGE{sub 2} induced 5-HT current augmentation was observed on 15% and 21% of the stomach and ileum projecting neurons, respectively. Current results suggest a synergistic signaling in visceral afferent neurons underlying gastrointestinal disorder involving PGE{sub 2} potentiation of 5-HT currents. Our findings may open a possibility for screen a new type drugs with lower side effects than currently using steroidal prostaglandin

  8. Correlation of hippocampal theta rhythm with changes in cutaneous temperature. [evoked neuron response in thermoregulation

    NASA Technical Reports Server (NTRS)

    Horowitz, J. M.; Saleh, M. A.; Karem, R. D.

    1974-01-01

    A possible role for the hippocampus in alerting an animal to changes in cutaneous temperature was examined. Following local warming or cooling of the ears of unanesthetized, loosely restrained rabbits, theta waves (4-7 Hz EEG waves) were recorded from electrodes straddling the hippocampus. The onset of the hippocampal theta rhythm was correlated with changes in cutaneous temperature, an observation consistent with studies indicating that the theta rhythm is a nonspecific response evoked by stimulation of several sensory modalities. Additional data from cats and rabbits were correlated with specific neurons within the hippocampus, namely pyramidal cells. Post stimulus time histograms obtained by excitation of the dorsal fornix were interpreted in terms of excitatory and inhibitory inputs to pyramidal cells. Thus, the theta rhythm, which appears to be evoked by changes in cutaneous temperature, can be related to a specific type of hippocampal neuron which is in turn connected with other areas of the brain involved in temperature regulation.

  9. Visual Responsiveness of Neurons in the Secondary Somatosensory Area and its Surrounding Parietal Operculum Regions in Awake Macaque Monkeys

    PubMed Central

    Hihara, Sayaka; Taoka, Miki; Tanaka, Michio; Iriki, Atsushi

    2015-01-01

    Previous neurophysiological studies performed in macaque monkeys have shown that the secondary somatosensory cortex (SII) is essentially engaged in the processing of somatosensory information and no other sensory input has been reported. In contrast, recent human brain-imaging studies have revealed the effects of visual and auditory stimuli on SII activity, which suggest multisensory integration in the human SII. To determine whether multisensory responses of the SII also exist in nonhuman primates, we recorded single-unit activity in response to visual and auditory stimuli from the SII and surrounding regions in 8 hemispheres from 6 awake monkeys. Among 1157 recorded neurons, 306 neurons responded to visual stimuli. These visual neurons usually responded to rather complex stimuli, such as stimulation of the peripersonal space (40.5%), observation of human action (29.1%), and moving-object stimulation outside the monkey's reach (23.9%). We occasionally applied auditory stimuli to visual neurons and found 10 auditory-responsive neurons that exhibited somatosensory responses. The visual neurons were distributed continuously along the lateral sulcus covering the entire SII, along with other somatosensory neurons. These results highlight the need to investigate novel functional roles—other than somesthetic sensory processing—of the SII. PMID:25962920

  10. Cochlear nucleus neurons redistribute synaptic AMPA and glycine receptors in response to monaural conductive hearing loss

    PubMed Central

    Whiting, Brittany; Moiseff, Andrew; Rubio, María E.

    2009-01-01

    Neurons restore their function in response to external or internal perturbations and maintain neuronal or network stability through a homeostatic scaling mechanism. Homeostatic responses at synapses along the auditory system would be important for adaptation to normal and abnormal fluctuations in the sensory environment. We investigated at the electron microscopic level and after postembedding immunogold labeling whether projection neurons in the cochlear nucleus responded to modifications of auditory nerve activity. After unilaterally reducing the level of auditory inputs by ~ 20 dB by monaural earplugging, auditory nerve synapses on bushy cells somata and basal dendrites of fusiform cells of the ventral and dorsal cochlear nucleus, respectively, upregulated GluR3 AMPA receptor subunit, while inhibitory synapses decreased the expression of GlyRα1 subunit. These changes in expression levels were fully reversible once the earplug was removed, indicating that activity affects the trafficking of receptors at synapses. Excitatory synapses on apical dendrites of fusiform cells (parallel fibers) with different synaptic AMPA receptor subunit composition, were not affected by sound attenuation, as the expression levels of AMPA receptor subunits were the same as in normal hearing littermates. GlyRα1 subunit expression at inhibitory synapses on apical dendrites of fusiform cells was also found unaffected. Furthermore, fusiform and bushy cells of the contralateral side to the earplugging upregulated the GluR3 subunit at auditory nerve synapses. These results show that cochlear nucleus neurons innervated by the auditory nerve, are able to respond to small changes in sound levels by redistributing specific AMPA and glycine receptor subunits. PMID:19646510

  11. Impaired rRNA synthesis triggers homeostatic responses in hippocampal neurons

    PubMed Central

    Kiryk, Anna; Sowodniok, Katharina; Kreiner, Grzegorz; Rodriguez-Parkitna, Jan; Sönmez, Aynur; Górkiewicz, Tomasz; Bierhoff, Holger; Wawrzyniak, Marcin; Janusz, Artur K.; Liss, Birgit; Konopka, Witold; Schütz, Günther; Kaczmarek, Leszek; Parlato, Rosanna

    2013-01-01

    Decreased rRNA synthesis and nucleolar disruption, known as nucleolar stress, are primary signs of cellular stress associated with aging and neurodegenerative disorders. Silencing of rDNA occurs during early stages of Alzheimer's disease (AD) and may play a role in dementia. Moreover, aberrant regulation of the protein synthesis machinery is present in the brain of suicide victims and implicates the epigenetic modulation of rRNA. Recently, we developed unique mouse models characterized by nucleolar stress in neurons. We inhibited RNA polymerase I by genetic ablation of the basal transcription factor TIF-IA in adult hippocampal neurons. Nucleolar stress resulted in progressive neurodegeneration, although with a differential vulnerability within the CA1, CA3, and dentate gyrus (DG). Here, we investigate the consequences of nucleolar stress on learning and memory. The mutant mice show normal performance in the Morris water maze and in other behavioral tests, suggesting the activation of adaptive mechanisms. In fact, we observe a significantly enhanced learning and re-learning corresponding to the initial inhibition of rRNA transcription. This phenomenon is accompanied by aberrant synaptic plasticity. By the analysis of nucleolar function and integrity, we find that the synthesis of rRNA is later restored. Gene expression profiling shows that 36 transcripts are differentially expressed in comparison to the control group in absence of neurodegeneration. Additionally, we observe a significant enrichment of the putative serum response factor (SRF) binding sites in the promoters of the genes with changed expression, indicating potential adaptive mechanisms mediated by the mitogen-activated protein kinase pathway. In the DG a neurogenetic response might compensate the initial molecular deficits. These results underscore the role of nucleolar stress in neuronal homeostasis and open a new ground for therapeutic strategies aiming at preserving neuronal function. PMID:24273493

  12. Reduced expression of plasma membrane calcium ATPase 2 and collapsin response mediator protein 1 promotes death of spinal cord neurons.

    PubMed

    Kurnellas, M P; Li, H; Jain, M R; Giraud, S N; Nicot, A B; Ratnayake, A; Heary, R F; Elkabes, S

    2010-09-01

    The mechanisms underlying neuronal pathology and death in the spinal cord (SC) during inflammation remain elusive. We previously showed the important role of plasma membrane calcium ATPases (PMCAs) in the survival of SC neurons, in vitro. We also postulated that a decrease in PMCA2 expression could cause neuronal death during experimental autoimmune encephalomyelitis (EAE), an animal model of multiple sclerosis. The current studies were undertaken to define the specific contribution of PMCA2 to degeneration of SC neurons, the effectors downstream to PMCA2 mediating neuronal death and the triggers that reduce PMCA2 expression. We report that knockdown of PMCA2 in SC neurons decreases collapsin response mediator protein 1 (CRMP1) levels. This is followed by cell death. Silencing of CRMP1 expression also leads to neuronal loss. Kainic acid reduces both PMCA2 and CRMP1 levels and induces neuronal death. Administration of an alpha-amino-3-hydroxyl-5-methyl-4-isoxazole-propionate (AMPA)/kainate receptor antagonist, at onset or peak of EAE, restores the decreased PMCA2 and CRMP1 levels to control values and ameliorates clinical deficits. Thus, our data link the reduction in PMCA2 expression with perturbations in the expression of CRMP1 and the ensuing death of SC neurons. This represents an additional mechanism underlying AMPA/kainate receptor-mediated excitotoxicity with relevance to neurodegeneration in EAE. PMID:20489728

  13. Blocking miRNA Biogenesis in Adult Forebrain Neurons Enhances Seizure Susceptibility, Fear Memory, and Food Intake by Increasing Neuronal Responsiveness.

    PubMed

    Fiorenza, Anna; Lopez-Atalaya, Jose P; Rovira, Victor; Scandaglia, Marilyn; Geijo-Barrientos, Emilio; Barco, Angel

    2016-04-01

    The RNase Dicer is essential for the maturation of most microRNAs, a molecular system that plays an essential role in fine-tuning gene expression. To gain molecular insight into the role of Dicer and the microRNA system in brain function, we conducted 2 complementary RNA-seq screens in the hippocampus of inducible forebrain-restricted Dicer1 mutants aimed at identifying the microRNAs primarily affected by Dicer loss and their targets, respectively. Functional genomics analyses predicted the main biological processes and phenotypes associated with impaired microRNA maturation, including categories related to microRNA biology, signal transduction, seizures, and synaptic transmission and plasticity. Consistent with these predictions, we found that, soon after recombination, Dicer-deficient mice exhibited an exaggerated seizure response, enhanced induction of immediate early genes in response to different stimuli, stronger and more stable fear memory, hyperphagia, and increased excitability of CA1 pyramidal neurons. In the long term, we also observed slow and progressive excitotoxic neurodegeneration. Overall, our results indicate that interfering with microRNA biogenesis causes an increase in neuronal responsiveness and disrupts homeostatic mechanisms that protect the neuron against overactivation, which may explain both the initial and late phenotypes associated with the loss of Dicer in excitatory neurons. PMID:25595182

  14. Distinct physiologic and neuronal responses to decreased leptin and mild hyperleptinemia.

    PubMed

    Ahima, R S; Kelly, J; Elmquist, J K; Flier, J S

    1999-11-01

    Leptin acts on specific populations of hypothalamic neurons to regulate feeding behavior, energy expenditure, and neuroendocrine function. It is not known, however, whether the same neural circuits mediate leptin action across its full biologic dose-response curve, which extends over a broad range, from low levels seen during starvation to high levels characteristic of obesity. Here, we show that the characteristic fall in leptin with fasting causes a rise in neuropeptide Y (NPY) messenger RNA (mRNA), as well as a fall in POMC and cocaine and amphetamine-regulated transcript (CART) mRNAs. Sc infusion of leptin sufficient to maintain plasma levels within the physiologic range during the fast prevents changes in the expression of these peptides, as well as changes in neuroendocrine function, demonstrating that multiple neural circuits are highly sensitive to small changes in leptin within its low physiologic range. In contrast, a modest elevation of plasma leptin above the normal fed range by constant sc infusion, which produced marked reduction in food intake and body weight, decreased NPY mRNA in the arcuate hypothalamic nucleus but did not affect the levels of mRNAs encoding the anorexigenic peptides alpha-MSH, CART or CRH. These results suggest that the dose response characteristics of leptin on hypothalamic target neurons at the level of mRNA expression are variable, with some neurons (e.g. NPY) responding across a broad dose range and others (e.g. POMC and CART) showing a limited response within the low range. These results further suggest that the central targets of leptin that mediate the transition from starvation to the fed state may be distinct from those that mediate the response to overfeeding and obesity. PMID:10537115

  15. Ventral lamina terminalis mediates enhanced cardiovascular responses of rostral ventrolateral medulla neurons during increased dietary salt.

    PubMed

    Adams, Julye M; Bardgett, Megan E; Stocker, Sean D

    2009-08-01

    Increased dietary salt enhances sympathoexcitatory and sympathoinhibitory responses evoked from the rostral ventrolateral medulla (RVLM). The purpose of the present study was to determine whether neurons of the forebrain lamina terminalis (LT) mediated these changes in the RVLM. Male Sprague-Dawley rats with and without LT lesions were fed normal chow and given access to water or 0.9% NaCl for 14 to 15 days. Unilateral injection of l-glutamate into the RVLM produced significantly larger increases in renal sympathetic nerve activity and arterial blood pressure of sham rats ingesting 0.9% NaCl versus water. However, these differences were not observed between ventral LT-lesioned rats drinking 0.9% NaCl versus water. Similar findings were observed when angiotensin II or gamma-aminobutyric acid was injected into the RVLM. Interestingly, a subset of animals drinking 0.9% but with damage restricted to the organum vasculosum of the lamina terminalis did not show enhanced responses to l-glutamate or gamma-aminobutyric acid. In marked contrast, RVLM injection of l-glutamate or gamma-aminobutyric acid produced exaggerated sympathetic nerve activity and arterial blood pressure responses in animals drinking 0.9% NaCl versus water after an acute ventral LT lesion or chronic lesion of the subfornical organ. Additional experiments demonstrated that plasma sodium concentration and osmolality were increased at night in rats ingesting 0.9% NaCl. These findings suggest that neurons of the ventral LT mediate the ability of increased dietary salt to enhance the responsiveness of RVLM sympathetic neurons. PMID:19506102

  16. Loss of UBE3A from TH-expressing neurons suppresses GABA co-release and enhances VTA-NAc optical self-stimulation

    PubMed Central

    Berrios, Janet; Stamatakis, Alice M.; Kantak, Pranish A.; McElligott, Zoe A.; Judson, Matthew C.; Aita, Megumi; Rougie, Marie; Stuber, Garret D.; Philpot, Benjamin D.

    2016-01-01

    Motivated reward-seeking behaviours are governed by dopaminergic ventral tegmental area projections to the nucleus accumbens. In addition to dopamine, these mesoaccumbal terminals co-release other neurotransmitters including glutamate and GABA, whose roles in regulating motivated behaviours are currently being investigated. Here we demonstrate that loss of the E3-ubiquitin ligase, UBE3A, from tyrosine hydroxylase-expressing neurons impairs mesoaccumbal, non-canonical GABA co-release and enhances reward-seeking behaviour measured by optical self-stimulation. PMID:26869263

  17. Effects of attention and distractor contrast on the responses of middle temporal area neurons to transient motion direction changes.

    PubMed

    Khayat, Paul S; Martinez-Trujillo, Julio C

    2015-06-01

    The ability of primates to detect transient changes in a visual scene can be influenced by the allocation of attention, as well as by the presence of distractors. We investigated the neural substrates of these effects by recording the responses of neurons in the middle temporal area (MT) of two monkeys while they detected a transient motion direction change in a moving target. We found that positioning a distractor near the target impaired the change-detection performance of the animals. This impairment monotonically decreased as the distractor's contrast decreased. A neural correlate of this effect was a decrease in the ability of MT neurons to signal the direction change (detection sensitivity or DS) when a distractor was near the target, both located inside the neuron's receptive field. Moreover, decreasing distractor contrast increased neuronal DS. On the other hand, directing attention away from the target decreased neuronal DS. At the level of individual neurons, we found a negative correlation between the degree of response normalization and the DS. Finally, the intensity of a neuron's response to the change was predictive of the animal's reaction time, suggesting that the activity of our recorded neurons was linked to the animal's detection performance. Our results suggest that the ability of an MT neuron to signal a transient direction change is regulated by the degree of inhibitory drive into the cell. The presence of distractors, their contrast and the allocation of attention influence such inhibitory drive, therefore modulating the ability of the neurons to signal transient changes in stimulus features and consequently behavioral performance. PMID:25885809

  18. Enhancement of odorant-induced responses in olfactory receptor neurons by zinc nanoparticles.

    PubMed

    Viswaprakash, Nilmini; Dennis, John C; Globa, Ludmila; Pustovyy, Oleg; Josephson, Eleanor M; Kanju, Patrick; Morrison, Edward E; Vodyanoy, Vitaly J

    2009-09-01

    Zinc metal nanoparticles in picomolar concentrations strongly enhance odorant responses of olfactory sensory neurons. One- to 2-nm metallic particles contain 40-300 zinc metal atoms, which are not in an ionic state. We exposed rat olfactory epithelium to metal nanoparticles and measured odorant responses by electroolfactogram and whole-cell patch clamp. A small amount of zinc nanoparticles added to an odorant or an extracellular/intracellular particle perfusion strongly increases the odorant response in a dose-dependent manner. Zinc nanoparticles alone produce no odor effects. Copper, gold, or silver nanoparticles do not produce effects similar to those of zinc. If zinc nanoparticles are replaced by Zn(+2) ions in the same concentration range, we observed a reduction of the olfactory receptor neuron odorant response. Based on these observations, we hypothesize that zinc nanoparticles are closely located to the interface between the guanine nucleotide-binding protein and the receptor proteins and are involved in transferring signals in the initial events of olfaction. Our results suggest that zinc metal nanoparticles can be used to enhance and sustain the initial olfactory events. PMID:19525316

  19. Contrasting responses within a single neuron class enable sex-specific attraction in Caenorhabditis elegans.

    PubMed

    Narayan, Anusha; Venkatachalam, Vivek; Durak, Omer; Reilly, Douglas K; Bose, Neelanjan; Schroeder, Frank C; Samuel, Aravinthan D T; Srinivasan, Jagan; Sternberg, Paul W

    2016-03-01

    Animals find mates and food, and avoid predators, by navigating to regions within a favorable range of available sensory cues. How are these ranges set and recognized? Here we show that male Caenorhabditis elegans exhibit strong concentration preferences for sex-specific small molecule cues secreted by hermaphrodites, and that these preferences emerge from the collective dynamics of a single male-specific class of neurons, the cephalic sensory neurons (CEMs). Within a single worm, CEM responses are dissimilar, not determined by anatomical classification and can be excitatory or inhibitory. Response kinetics vary by concentration, suggesting a mechanism for establishing preferences. CEM responses are enhanced in the absence of synaptic transmission, and worms with only one intact CEM show nonpreferential attraction to all concentrations of ascaroside for which CEM is the primary sensor, suggesting that synaptic modulation of CEM responses is necessary for establishing preferences. A heterogeneous concentration-dependent sensory representation thus appears to allow a single neural class to set behavioral preferences and recognize ranges of sensory cues. PMID:26903633

  20. Sucralose Promotes Food Intake through NPY and a Neuronal Fasting Response.

    PubMed

    Wang, Qiao-Ping; Lin, Yong Qi; Zhang, Lei; Wilson, Yana A; Oyston, Lisa J; Cotterell, James; Qi, Yue; Khuong, Thang M; Bakhshi, Noman; Planchenault, Yoann; Browman, Duncan T; Lau, Man Tat; Cole, Tiffany A; Wong, Adam C N; Simpson, Stephen J; Cole, Adam R; Penninger, Josef M; Herzog, Herbert; Neely, G Gregory

    2016-07-12

    Non-nutritive sweeteners like sucralose are consumed by billions of people. While animal and human studies have demonstrated a link between synthetic sweetener consumption and metabolic dysregulation, the mechanisms responsible remain unknown. Here we use a diet supplemented with sucralose to investigate the long-term effects of sweet/energy imbalance. In flies, chronic sweet/energy imbalance promoted hyperactivity, insomnia, glucose intolerance, enhanced sweet taste perception, and a sustained increase in food and calories consumed, effects that are reversed upon sucralose removal. Mechanistically, this response was mapped to the ancient insulin, catecholamine, and NPF/NPY systems and the energy sensor AMPK, which together comprise a novel neuronal starvation response pathway. Interestingly, chronic sweet/energy imbalance promoted increased food intake in mammals as well, and this also occurs through an NPY-dependent mechanism. Together, our data show that chronic consumption of a sweet/energy imbalanced diet triggers a conserved neuronal fasting response and increases the motivation to eat. PMID:27411010

  1. Receptor expression and sympatric speciation: unique olfactory receptor neuron responses in F1 hybrid Rhagoletis populations.

    PubMed

    Olsson, Shannon B; Linn, Charles E; Michel, Andrew; Dambroski, Hattie R; Berlocher, Stewart H; Feder, Jeffrey L; Roelofs, Wendell L

    2006-10-01

    The Rhagoletis pomonella species complex is one of the foremost examples supporting the occurrence of sympatric speciation. A recent study found that reciprocal F(1) hybrid offspring from different host plant-infesting populations in the complex displayed significantly reduced olfactory host preference in flight-tunnel assays. Behavioral and electrophysiological studies indicate that olfactory cues from host fruit are important chemosensory signals for flies to locate fruit for mating and oviposition. The reduced olfactory abilities of hybrids could therefore constitute a significant post-mating barrier to gene flow among fly populations. The present study investigated the source of changes in the hybrid olfactory system by examining peripheral chemoreception in F(1) hybrid flies, using behaviorally relevant volatiles from the parent host fruit. Single-sensillum electrophysiological analyses revealed significant changes in olfactory receptor neuron (ORN) response specificities in hybrid flies when compared to parent ORN responses. We report that flies from F(1) crosses of apple-, hawthorn- and flowering dogwood-origin populations of R. pomonella exhibited distinct ORN response profiles absent from any parent population. These peripheral alterations in ORN response profiles could result from misexpression of multiple receptors in hybrid neurons as a function of genomic incompatibilities in receptor-gene pathways in parent populations. We conclude that these changes in peripheral chemoreception could impact olfactory host preference and contribute directly to reproductive isolation in the Rhagoletis complex, or could be genetically coupled to other host-associated traits. PMID:16985190

  2. On the Firing Rate Dependency of the Phase Response Curve of Rat Purkinje Neurons In Vitro

    PubMed Central

    Couto, João; Linaro, Daniele; De Schutter, E; Giugliano, Michele

    2015-01-01

    Synchronous spiking during cerebellar tasks has been observed across Purkinje cells: however, little is known about the intrinsic cellular mechanisms responsible for its initiation, cessation and stability. The Phase Response Curve (PRC), a simple input-output characterization of single cells, can provide insights into individual and collective properties of neurons and networks, by quantifying the impact of an infinitesimal depolarizing current pulse on the time of occurrence of subsequent action potentials, while a neuron is firing tonically. Recently, the PRC theory applied to cerebellar Purkinje cells revealed that these behave as phase-independent integrators at low firing rates, and switch to a phase-dependent mode at high rates. Given the implications for computation and information processing in the cerebellum and the possible role of synchrony in the communication with its post-synaptic targets, we further explored the firing rate dependency of the PRC in Purkinje cells. We isolated key factors for the experimental estimation of the PRC and developed a closed-loop approach to reliably compute the PRC across diverse firing rates in the same cell. Our results show unambiguously that the PRC of individual Purkinje cells is firing rate dependent and that it smoothly transitions from phase independent integrator to a phase dependent mode. Using computational models we show that neither channel noise nor a realistic cell morphology are responsible for the rate dependent shift in the phase response curve. PMID:25775448

  3. Sensitization of capsaicin and icilin responses in oxaliplatin treated adult rat DRG neurons

    PubMed Central

    2010-01-01

    Background Oxaliplatin chemotherapy induced neuropathy is a dose related cumulative toxicity that manifests as tingling, numbness, and chronic pain, compromising the quality of life and leading to discontinued chemotherapy. Patients report marked hypersensitivity to cold stimuli at early stages of treatment, when sensory testing reveals cold and heat hyperalgesia. This study examined the morphological and functional effects of oxaliplatin treatment in cultured adult rat DRG neurons. Results 48 hour exposure to oxaliplatin resulted in dose related reduction in neurite length, density, and number of neurons compared to vehicle treated controls, using Gap43 immunostaining. Neurons treated acutely with 20 μg/ml oxaliplatin showed significantly higher signal intensity for cyclic AMP immunofluorescence (160.5 ± 13 a.u., n = 3, P < 0.05), compared to controls (120.3 ± 4 a.u.). Calcium imaging showed significantly enhanced capsaicin (TRPV1 agonist), responses after acute 20 μg/ml oxaliplatin treatment where the second of paired capsaicin responses increased from 80.7 ± 0.6% without oxaliplatin, to 171.26 ± 29% with oxaliplatin, (n = 6 paired t test, P < 0.05); this was reduced to 81.42 ± 8.1% (P < 0.05), by pretretreatment with the cannabinoid CB2 receptor agonist GW 833972. Chronic oxaliplatin treatment also resulted in dose related increases in capsaicin responses. Similarly, second responses to icilin (TRPA1/TRPM8 agonist), were enhanced after acute (143.85 ± 7%, P = 0.004, unpaired t test, n = 3), and chronic (119.7 ± 11.8%, P < 0.05, n = 3) oxaliplatin treatment, compared to control (85.3 ± 1.7%). Responses to the selective TRPM8 agonist WS-12 were not affected. Conclusions Oxaliplatin treatment induces TRP sensitization mediated by increased intracellular cAMP, which may cause neuronal damage. These effects may be mitigated by co-treatment with adenylyl cyclase inhibitors, like CB2 agonists, to alleviate the neurotoxic effects of oxaliplatin. PMID:21106058

  4. Context-dependent place-selective responses of the neurons in the medial parietal region of macaque monkeys.

    PubMed

    Sato, Nobuya; Sakata, Hideo; Tanaka, Yuji L; Taira, Masato

    2010-04-01

    To investigate the role of the medial parietal region (MPR), comprising area 7 m and the retrosplenial and posterior cingulate cortices, in spatial navigation, we analyzed the spatial aspect of the responses of the MPR neurons in monkeys while they actively performed a navigation task in a virtual environment. One-third of the analyzed MPR neurons were activated depending on the location of the monkeys in the environment, that is, showed place-selective responses. Some neurons showed varying responses based on the starting point (SP) or destination. We further investigated the responses of the place-selective neurons when the monkeys were shown animations of the entire navigation route, including the preferred field, and a segment of the route, including an area around the preferred field, and a still image of the preferred field. We observed that the responses of some place-selective neurons reduced when the monkeys viewed the preferred field in the segmented animation or in the still image compared with when they viewed the entire animation. These results suggested that the knowledge about the SP or destination, that is, context, is necessary to activate place-selective neurons. The effect of such contextual information suggests that the MPR plays decisive roles in spatial processing such as navigation. PMID:19620622

  5. Spectrotemporal Response Properties of Core Auditory Cortex Neurons in Awake Monkey

    PubMed Central

    Massoudi, Roohollah; Van Wanrooij, Marc M.; Versnel, Huib; Van Opstal, A. John

    2015-01-01

    So far, most studies of core auditory cortex (AC) have characterized the spectral and temporal tuning properties of cells in non-awake, anesthetized preparations. As experiments in awake animals are scarce, we here used dynamic spectral-temporal broadband ripples to study the properties of the spectrotemporal receptive fields (STRFs) of AC cells in awake monkeys. We show that AC neurons were typically most sensitive to low ripple densities (spectral) and low velocities (temporal), and that most cells were not selective for a particular spectrotemporal sweep direction. A substantial proportion of neurons preferred amplitude-modulated sounds (at zero ripple density) to dynamic ripples (at non-zero densities). The vast majority (>93%) of modulation transfer functions were separable with respect to spectral and temporal modulations, indicating that time and spectrum are independently processed in AC neurons. We also analyzed the linear predictability of AC responses to natural vocalizations on the basis of the STRF. We discuss our findings in the light of results obtained from the monkey midbrain inferior colliculus by comparing the spectrotemporal tuning properties and linear predictability of these two important auditory stages. PMID:25680187

  6. Nucleus accumbens neuronal activity correlates to the animal’s behavioral response to acute and chronic methylphenidate

    PubMed Central

    Claussen, Catherine M; Chong, Samuel L; Dafny, Nachum

    2014-01-01

    Acute and chronic Methylphenidate (MPD) exposure was recorded simultaneously for the rat’s locomotor activity and the nucleus accumbens (NAc) neuronal activity. The evaluation of the neuronal events was based on the animal’s behavior response to chronic MPD administration: 1) Animals exhibiting behavioral sensitization 2) Animals exhibiting behavioral tolerance. The experiment lasted for 10 days with four groups of animals; saline, 0.6, 2.5, and 10.0mg/kg MPD. For the main behavioral findings, about half of the animals exhibited behavioral sensitization or behavioral tolerance to 0.6, 2.5, and/or 10 mg/kg MPD respectively. Three hundred and forty one NAc neuronal units were evaluated. Approximately 80% of NAc units responded to 0.6, 2.5, and 10.0 mg/kg MPD. When the neuronal activity was analyzed based on the animals behavioral response to chronic MPD exposure, significant differences were seen between the neuronal populations responses recorded from animals that expressed behavioral sensitization when compared to the NAc neuronal responses recorded from animals exhibiting behavioral tolerance. Three types of neurophysiological sensitization and neurophysiological tolerance can be recognized following chronic MPD administration to the neuronal populations. Collectively, these findings show that the same dose of chronic MPD can elicit either behavioral tolerance or behavioral sensitization. Differential statistical analysis were used to verify our hypothesis that the neuronal activity recorded from animals exhibiting behavioral sensitization will respond differently to MPD compared to those animals exhibiting behavioral tolerance. Thus, suggesting that it is essential to record the animals behavior concomitantly with neuronal recordings. PMID:24534179

  7. Differential innate immune response programs in neuronal subtypes determine susceptibility to infection in the brain by positive stranded RNA viruses

    PubMed Central

    Cho, Hyelim; Proll, Sean C.; Szretter, Kristy J.; Katze, Michael G.; Gale, Michael; Diamond, Michael S.

    2013-01-01

    Although susceptibility of neurons in the brain to microbial infection is a major determinant of clinical outcome, little is known about the molecular factors governing this. Here, we show that two types of neurons from distinct brain regions exhibited differential permissivity to replication of several positive-stranded RNA viruses. Granule cell neurons (GCN) of the cerebellum and cortical neurons (CN) from the cerebral cortex have unique innate immune programs that confer differential susceptibility to viral infection ex vivo and in vivo. By transducing CN with genes that were expressed more highly in GCN, we identified three interferon-stimulated genes (ISGs; Ifi27, Irg1, and Rsad2/Viperin) that mediated antiviral effects against different neurotropic viruses. Moreover, we found that the epigenetic state and microRNA-mediated regulation of ISGs correlates with enhanced antiviral response in GCN. Thus, neurons from evolutionarily distinct brain regions have unique innate immune signatures, which likely contribute to their relative permissiveness to infection. PMID:23455712

  8. [HOMOCYSTEINE-INDUCED MEMBRANE CURRENTS, CALCIUM RESPONSES AND CHANGES OF MITOCHONDRIAL POTENTIAL IN RAT CORTICAL NEURONS].

    PubMed

    Abushik, P A; Karelina, T V; Sibarov, D A; Stepanenko, J D; Giniatullin, R; Antonov, S M

    2015-01-01

    Homocysteine, a sulfur-containing amino acid, exhibits neurotoxic effects and is involved in the pathogenesis of several major neurodegenerative disorders. In contrast to well studied excitoxicity of glutamate, the mechanism of homocysteine neurotoxicity is not clearly understood. By using whole-cell patch-clamp, calcium imaging (fluo-3) and measurements of mitochondrial membrane potential (rhodamine 123) we studied transmembrane currents, calcium signals and changes in mitochondrial membrane potential induced by homocysteine versus responses induced by NMDA and glutamate in cultured rat cortical neurons. L-homocysteine (50 µM) induced inward currents that could be completely blocked by the selective antagonist of NMDA receptors - AP-5. In contrast to NMDA-induced currents, homocysteine-induced currents had a smaller steady-state amplitude. Comparison of calcium responses to homocysteine, NMDA or glutamate demonstrated that in all cortical neurons homocysteine elicited short, oscillatory-type calcium responses, whereas NMDA or glutamate induced sustained increase of intracellular calcium. Analysis of mitochondrial changes demonstrated that in contrast to NMDA homocysteine did not cause a drop of mitochondrial membrane potential at the early stages of action. However, after its long-term action, as in the case of NMDA and glutamate, the changes in mitochondrial membrane potential were comparable with the full drop of respiratory chain induced by protonophore FCCP. Our data suggest that in cultured rat cortical neuron homocysteine at the first stages of action induces neurotoxic effects through activation of NMDA-type ionotropic glutamate receptors with strong calcium influx through the channels of these receptors. The long-term action of homocysteine may lead to mitochondrial disfuction and appears as a drop of mitochondrial membrane potential. PMID:26547950

  9. Nicotine Dependence Reveals Distinct Responses from Neurons and Their Resident Nicotinic Receptors in Medial Habenula.

    PubMed

    Shih, Pei-Yu; McIntosh, J Michael; Drenan, Ryan M

    2015-12-01

    Nicotinic acetylcholine receptors (nAChRs) are the molecular target of nicotine. nAChRs in the medial habenula (MHb) have recently been shown to play a role in nicotine dependence, but it is not clear which nAChR subtypes or MHb neuron types are most important. To identify MHb nAChRs and/or cell types that play a role in nicotine dependence, we studied these receptors and cells with brain slice electrophysiology using both acute and chronic nicotine application. Cells in the ventroinferior (MHbVI) and ventrolateral MHb (MHbVL) subregions expressed functional nAChRs with different pharmacology. Further, application of nicotine to cells in these subregions led to different action potential firing patterns. The latter result was correlated with a differing ability of nicotine to induce nAChR desensitization. Chronic nicotine caused functional upregulation of nAChRs selectively in MHbVI cells, but did not change nAChR function in MHbVL. Importantly, firing responses were also differentially altered in these subregions following chronic nicotine. MHbVI neurons treated chronically with nicotine exhibited enhanced basal pacemaker firing but a blunted nicotine-induced firing response. MHbVL neurons did not change their firing properties in response to chronic nicotine. Together, these results suggest that acute and chronic nicotine differentially affect nAChR function and output of cells in MHb subregions. Because the MHb extensively innervates the interpeduncular nucleus, an area critical for both affective and somatic signs of withdrawal, these results could reflect some of the neurophysiological changes thought to occur in the MHb to the interpeduncular nucleus circuit in human smokers. PMID:26429939

  10. The iso-response method: measuring neuronal stimulus integration with closed-loop experiments

    PubMed Central

    Gollisch, Tim; Herz, Andreas V. M.

    2012-01-01

    Throughout the nervous system, neurons integrate high-dimensional input streams and transform them into an output of their own. This integration of incoming signals involves filtering processes and complex non-linear operations. The shapes of these filters and non-linearities determine the computational features of single neurons and their functional roles within larger networks. A detailed characterization of signal integration is thus a central ingredient to understanding information processing in neural circuits. Conventional methods for measuring single-neuron response properties, such as reverse correlation, however, are often limited by the implicit assumption that stimulus integration occurs in a linear fashion. Here, we review a conceptual and experimental alternative that is based on exploring the space of those sensory stimuli that result in the same neural output. As demonstrated by recent results in the auditory and visual system, such iso-response stimuli can be used to identify the non-linearities relevant for stimulus integration, disentangle consecutive neural processing steps, and determine their characteristics with unprecedented precision. Automated closed-loop experiments are crucial for this advance, allowing rapid search strategies for identifying iso-response stimuli during experiments. Prime targets for the method are feed-forward neural signaling chains in sensory systems, but the method has also been successfully applied to feedback systems. Depending on the specific question, “iso-response” may refer to a predefined firing rate, single-spike probability, first-spike latency, or other output measures. Examples from different studies show that substantial progress in understanding neural dynamics and coding can be achieved once rapid online data analysis and stimulus generation, adaptive sampling, and computational modeling are tightly integrated into experiments. PMID:23267315

  11. Response profiles of murine spiral ganglion neurons on multi-electrode arrays

    NASA Astrophysics Data System (ADS)

    Hahnewald, Stefan; Tscherter, Anne; Marconi, Emanuele; Streit, Jürg; Widmer, Hans Rudolf; Garnham, Carolyn; Benav, Heval; Mueller, Marcus; Löwenheim, Hubert; Roccio, Marta; Senn, Pascal

    2016-02-01

    Objective. Cochlear implants (CIs) have become the gold standard treatment for deafness. These neuroprosthetic devices feature a linear electrode array, surgically inserted into the cochlea, and function by directly stimulating the auditory neurons located within the spiral ganglion, bypassing lost or not-functioning hair cells. Despite their success, some limitations still remain, including poor frequency resolution and high-energy consumption. In both cases, the anatomical gap between the electrode array and the spiral ganglion neurons (SGNs) is believed to be an important limiting factor. The final goal of the study is to characterize response profiles of SGNs growing in intimate contact with an electrode array, in view of designing novel CI devices and stimulation protocols, featuring a gapless interface with auditory neurons. Approach. We have characterized SGN responses to extracellular stimulation using multi-electrode arrays (MEAs). This setup allows, in our view, to optimize in vitro many of the limiting interface aspects between CIs and SGNs. Main results. Early postnatal mouse SGN explants were analyzed after 6-18 days in culture. Different stimulation protocols were compared with the aim to lower the stimulation threshold and the energy needed to elicit a response. In the best case, a four-fold reduction of the energy was obtained by lengthening the biphasic stimulus from 40 μs to 160 μs. Similarly, quasi monophasic pulses were more effective than biphasic pulses and the insertion of an interphase gap moderately improved efficiency. Finally, the stimulation with an external electrode mounted on a micromanipulator showed that the energy needed to elicit a response could be reduced by a factor of five with decreasing its distance from 40 μm to 0 μm from the auditory neurons. Significance. This study is the first to show electrical activity of SGNs on MEAs. Our findings may help to improve stimulation by and to reduce energy consumption of CIs and

  12. Arsenic moiety in gallium arsenide is responsible for neuronal apoptosis and behavioral alterations in rats

    SciTech Connect

    Flora, Swaran J.S. Bhatt, Kapil; Mehta, Ashish

    2009-10-15

    Gallium arsenide (GaAs), an intermetallic semiconductor finds widespread applications in high frequency microwave and millimeter wave, and ultra fast supercomputers. Extensive use of GaAs has led to increased exposure to humans working in semiconductor industry. GaAs has the ability to dissociate into its constitutive moieties at physiological pH and might be responsible for the oxidative stress. The present study was aimed at evaluating, the principle moiety (Ga or As) in GaAs to cause neurological dysfunction based on its ability to cause apoptosis, in vivo and in vitro and if this neuronal dysfunction translated to neurobehavioral changes in chronically exposed rats. Result indicated that arsenic moiety in GaAs was mainly responsible for causing oxidative stress via increased reactive oxygen species (ROS) and nitric oxide (NO) generation, both in vitro and in vivo. Increased ROS further caused apoptosis via mitochondrial driven pathway. Effects of oxidative stress were also confirmed based on alterations in antioxidant enzymes, GPx, GST and SOD in rat brain. We noted that ROS induced oxidative stress caused changes in the brain neurotransmitter levels, Acetylcholinesterase and nitric oxide synthase, leading to loss of memory and learning in rats. The study demonstrates for the first time that the slow release of arsenic moiety from GaAs is mainly responsible for oxidative stress induced apoptosis in neuronal cells causing behavioral changes.

  13. Using Single Sensillum Recording to Detect Olfactory Neuron Responses of Bed Bugs to Semiochemicals.

    PubMed

    Liu, Feng; Liu, Nannan

    2016-01-01

    The insect olfactory system plays an important role in detecting semiochemicals in the environment. In particular, the antennal sensilla which house single or multiple neurons inside, are considered to make the major contribution in responding to the chemical stimuli. By directly recording action potential in the olfactory sensillum after exposure to stimuli, single sensillum recording (SSR) technique provides a powerful approach for investigating the neural responses of insects to chemical stimuli. For the bed bug, which is a notorious human parasite, multiple types of olfactory sensillum have been characterized. In this study, we demonstrated neural responses of bed bug olfactory sensilla to two chemical stimuli and the dose-dependent responses to one of them using the SSR method. This approach enables researchers to conduct early screening for individual chemical stimuli on the bed bug olfactory sensilla, which would provide valuable information for the development of new bed bug attractants or repellents and benefits the bed bug control efforts. PMID:26862929

  14. Cholinergic Responses and Intrinsic Membrane Properties of Developing Thalamic Parafascicular Neurons

    PubMed Central

    Ye, Meijun; Hayar, Abdallah; Garcia-Rill, Edgar

    2009-01-01

    Parafascicular (Pf) neurons receive cholinergic input from the pedunculopontine nucleus (PPN), which is active during waking and REM sleep. There is a developmental decrease in REM sleep in humans between birth and puberty and 10–30 days in rat. Previous studies have established an increase in muscarinic and 5-HT1 serotonergic receptor–mediated inhibition and a transition from excitatory to inhibitory GABAA responses in the PPN during the developmental decrease in REM sleep. However, no studies have been conducted on the responses of Pf cells to the cholinergic input from the PPN during development, which is a major target of ascending cholinergic projections and may be an important mechanism for the generation of rhythmic oscillations in the cortex. Whole cell patch-clamp recordings were performed in 9- to 20-day-old rat Pf neurons in parasagittal slices, and responses to the cholinergic agonist carbachol (CAR) were determined. Three types of responses were identified: inhibitory (55.3%), excitatory (31.1%), and biphasic (fast inhibitory followed by slow excitatory, 6.8%), whereas 6.8% of cells showed no response. The proportion of CAR-inhibited Pf neurons increased with development. Experiments using cholinergic antagonists showed that M2 receptors mediated the inhibitory response, whereas excitatory modulation involved M1, nicotinic, and probably M3 or M5 receptors, and the biphasic response was caused by the activation of multiple types of muscarinic receptors. Compared with CAR-inhibited cells, CAR-excited Pf cells showed 1) a decreased membrane time constant, 2) higher density of hyperpolarization-activated channels (Ih), 3) lower input resistance (Rin), 4) lower action potential threshold, and 5) shorter half-width duration of action potentials. Some Pf cells exhibited spikelets, and all were excited by CAR. During development, we observed decreases in Ih density, Rin, time constant, and action potential half-width. These results suggest that cholinergic

  15. Cholinergic responses and intrinsic membrane properties of developing thalamic parafascicular neurons.

    PubMed

    Ye, Meijun; Hayar, Abdallah; Garcia-Rill, Edgar

    2009-08-01

    Parafascicular (Pf) neurons receive cholinergic input from the pedunculopontine nucleus (PPN), which is active during waking and REM sleep. There is a developmental decrease in REM sleep in humans between birth and puberty and 10-30 days in rat. Previous studies have established an increase in muscarinic and 5-HT1 serotonergic receptor-mediated inhibition and a transition from excitatory to inhibitory GABA(A) responses in the PPN during the developmental decrease in REM sleep. However, no studies have been conducted on the responses of Pf cells to the cholinergic input from the PPN during development, which is a major target of ascending cholinergic projections and may be an important mechanism for the generation of rhythmic oscillations in the cortex. Whole cell patch-clamp recordings were performed in 9- to 20-day-old rat Pf neurons in parasagittal slices, and responses to the cholinergic agonist carbachol (CAR) were determined. Three types of responses were identified: inhibitory (55.3%), excitatory (31.1%), and biphasic (fast inhibitory followed by slow excitatory, 6.8%), whereas 6.8% of cells showed no response. The proportion of CAR-inhibited Pf neurons increased with development. Experiments using cholinergic antagonists showed that M2 receptors mediated the inhibitory response, whereas excitatory modulation involved M1, nicotinic, and probably M3 or M5 receptors, and the biphasic response was caused by the activation of multiple types of muscarinic receptors. Compared with CAR-inhibited cells, CAR-excited Pf cells showed 1) a decreased membrane time constant, 2) higher density of hyperpolarization-activated channels (I(h)), 3) lower input resistance (R(in)), 4) lower action potential threshold, and 5) shorter half-width duration of action potentials. Some Pf cells exhibited spikelets, and all were excited by CAR. During development, we observed decreases in I(h) density, R(in), time constant, and action potential half-width. These results suggest that

  16. Responses of spinal neurones to cutaneous and dorsal root stimuli in rats with mechanical allodynia after contusive spinal cord injury.

    PubMed

    Drew, G M; Siddall, P J; Duggan, A W

    2001-03-01

    The firing of neurones in spinal segments adjacent to a contusive T13 spinal cord injury was characterised in anaesthetised rats. Three groups of rats were examined: (1) allodynic spinally injured, (2) non-allodynic spinally injured and (3) normal, uninjured. Spinal cord field potentials evoked by electrical dorsal root stimulation and the responses of 207 dorsal horn neurones to mechanical stimuli applied to the skin were studied. Within the lesioned spinal segment few active neurones were encountered and field potentials were absent. Depolarising field potentials recorded rostral to the lesion were reduced in both allodynic and non-allodynic animals compared to uninjured controls, while those recorded in caudal segments were enhanced in allodynic animals. Neuronal recordings revealed that allodynia was associated with exaggerated responses, including afterdischarges, to innocuous and noxious mechanical stimuli in a proportion of wide dynamic range, but not low threshold, neurones. These changes were observed both rostral and caudal to the site of injury. The results suggest that an increased responsiveness of some dorsal horn neurones in segments neighbouring a contusive spinal cord injury may contribute to the expression of mechanical allodynia. It is proposed that a relative lack of inhibition underlies altered cell responses. PMID:11222993

  17. Response differences of intersegmental auditory neurons recorded close to or far away from the presumed spike-generating zone.

    PubMed

    Ostrowski, Tim D; Stumpner, Andreas

    2014-07-01

    Intracellular recordings may give valuable information about processing of a neuron and possibly its input from the network. Impalement with an electrode causes injury to the cell and depolarization from intrusion of extracellular fluid. Thus, penetration artefacts may contaminate recordings and conceal or even alter relevant information. These penetration artefacts may have the strongest impact close to the spike-generating zone near the dendrites. Recordings in axonal portions might therefore be less vulnerable while providing insufficient information about the synaptic input. In this study, we present data of five previously identified intersegmental auditory neurons of a bushcricket independently recorded in their dendrites (prothorax) and axon (brain). Generally, responses to acoustic pulses of the same parameter combination were similar within a neuronal class at the two recording sites. However, all neuronal classes showed significantly higher response variability and a tendency for higher spike activity when recorded in the dendrites. Unexpectedly, the combined activity of two neurons (Ascending Neurons 1 and 2) recorded in the brain provides a better fit to song recognition than when recorded in the thorax. Axonal recordings of T-shaped Neuron 1 revealed graded potentials originating in the brain and modulating its output in a potentially behaviourally relevant manner. PMID:24728380

  18. Modeling Neuronal Response to Simultaneous and Sequential Multi-Site Synaptic Stimulation

    NASA Astrophysics Data System (ADS)

    Johnston, David; Mekhail, Simon Peter; Go, Mary Ann; Daria, Vincent R.

    The flow of information in the brain theorizes that each neuron in a network receives synaptic inputs and sends off its processed signals to neighboring neurons. Here, we model these synaptic inputs to understand how each neuron processes these inputs and transmits neurotransmitters to neighboring neurons. We use the NEURON simulation package to stimulate a neuron at multiple synaptic locations along its dendritic tree. Accumulation of multiple synaptic inputs causes changes in the neuron's membrane potential leading to firing of an action potential. Our simulations show that simultaneous synaptic stimulation approaches firing of an action potential at lesser inputs compared to sequential stimulation at multiple sites distributed along several dendritic branches.

  19. GFRalpha-3, a protein related to GFRalpha-1, is expressed in developing peripheral neurons and ensheathing cells.

    PubMed

    Widenfalk, J; Tomac, A; Lindqvist, E; Hoffer, B; Olson, L

    1998-04-01

    We report here the identification of a gene, termed GFRalpha-3 (glial cell line-derived neurotrophic factor family receptor alpha-3), related to GFRalpha-1 and GFRalpha-2 (also known as GDNFR-alpha and GDNFR-beta), and describe distribution of GDNFalpha-3 in the nervous system and other parts of the mouse body during development and in the adult. GFRalpha-3 in situ hybridization signals were found mainly in the peripheral nervous system, with prominent signals in developing dorsal root and trigeminal ganglia. Sympathetic ganglia were also positive. Developing nerves manifested strong GFRalpha-3 mRNA signals, presumably generated by the Schwann cells. Olfactory ensheathing cells were also positive. Other non-neuronal cells appearing positive during development included chromaffin cells in the adrenal gland and small clusters of cells in the intestinal epithelium. In the central nervous system no robust signals could be detected at any stage investigated with the present probes. Compared with the previously described GFRalpha-1 and GFRalpha-2 mRNAs, which are widely distributed in the central nervous system and peripheral organs, the expression of GFRalpha-3 mRNA is much more restricted. The prominent expression in Schwann cells during development suggests a key role for GFRalpha-3 in the development of the peripheral nervous system. As Schwann cells are known to lack expression of the transducing RET receptor, we propose that a possible function of GFRalpha-3 during development could be to bind Schwann cell-derived GDNF-like ligands, thus presenting such molecules to growing axons. PMID:9749804

  20. The earliest neuronal responses to hypoxia in the neocortical circuit are glutamate-dependent.

    PubMed

    Revah, Omer; Lasser-Katz, Efrat; Fleidervish, Ilya A; Gutnick, Michael J

    2016-11-01

    Soon after exposure to hypoxia or ischemia, neurons in cortical tissues undergo massive anoxic depolarization (AD). This precipitous event is preceded by more subtle neuronal changes, including enhanced excitatory and inhibitory synaptic transmitter release. Here, we have used patch-in-slice techniques to identify the earliest effects of acute hypoxia on the synaptic and intrinsic properties of Layer 5 neurons, to determine their time course and to evaluate the role of glutamate receptors in their generation. Coronal slices of mouse somatosensory cortex were maintained at 36°C in an interface chamber and challenged with episodes of hypoxia. In recordings with cell-attached electrodes, the open probability of Ca(2+)-dependent BK channels began to increase within seconds of hypoxia onset, indicating a sharp rise in [Ca(2+)]i just beneath the membrane. By using a high concentration of K(+) in the pipette, we simultaneously monitored the membrane potential and showed that the [Ca(2+)]i rise was not associated with membrane depolarization. The earliest hypoxia-induced synaptic disturbance was a marked increase in the frequency of sPSCs, which also began soon after the removal of oxygen and long before AD. This synaptic effect was accompanied by depletion of the readily releasable transmitter pools, as demonstrated by a decreased response to hyperosmotic solutions. The early [Ca(2+)]i rise, the early increase in transmitter release and the subsequent AD itself were all prevented by bathing in a cocktail containing blockers of ionotropic glutamate receptors. We found no evidence for involvement of pannexin hemichannels or TRPM7 channels in the early responses to hypoxia in this experimental preparation. Our data indicate that the earliest cellular consequences of cortical hypoxia are triggered by activation of glutamate-gated channels. PMID:27443966

  1. Social Isolation Blunted the Response of Mesocortical Dopaminergic Neurons to Chronic Ethanol Voluntary Intake.

    PubMed

    Lallai, Valeria; Manca, Letizia; Dazzi, Laura

    2016-01-01

    Previous studies have shown that stress can increase the response of mesolimbic dopaminergic neurons to acute administration of drugs of abuse included ethanol. In this study, we investigated the possible involvement of the mesocortical dopaminergic pathway in the development of ethanol abuse under stress conditions. To this aim we trained both socially isolated (SI) and group housed (GH) rats to self administer ethanol which was made available only 2 ha day (from 11:00 to 13:00 h). Rats have been trained for 3 weeks starting at postnatal day 35. After training, rats were surgically implanted with microdialysis probes under deep anesthesia, and 24 hlater extracellular dopamine concentrations were monitored in medial prefrontal cortex (mPFC) for the 2 hpreceding ethanol administration (anticipatory phase), during ethanol exposure (consummatory phase) and for 2 hafter ethanol removal. Results show that, in GH animals, dopamine extracellular concentration in the mPFC increased as early as 80 min before ethanol presentation (+50% over basal values) and remained elevated for 80 min during ethanol exposure. In SI rats, on the contrary, dopamine extracellular concentration did not show any significant change at any time point. Ethanol consumption was significantly higher in SI than in GH rats. Moreover, mesocortical dopaminergic neurons in SI animals also showed a decreased sensitivity to an acute administration of ethanol with respect to GH rats. Our results show that prolonged exposure to stress, as in social isolation, is able to induce significant changes in the response of mesocortical dopaminergic neurons to ethanol exposure and suggest that these changes might play an important role in the compulsivity observed in ethanol addiction. PMID:27378852

  2. Social Isolation Blunted the Response of Mesocortical Dopaminergic Neurons to Chronic Ethanol Voluntary Intake

    PubMed Central

    Lallai, Valeria; Manca, Letizia; Dazzi, Laura

    2016-01-01

    Previous studies have shown that stress can increase the response of mesolimbic dopaminergic neurons to acute administration of drugs of abuse included ethanol. In this study, we investigated the possible involvement of the mesocortical dopaminergic pathway in the development of ethanol abuse under stress conditions. To this aim we trained both socially isolated (SI) and group housed (GH) rats to self administer ethanol which was made available only 2 ha day (from 11:00 to 13:00 h). Rats have been trained for 3 weeks starting at postnatal day 35. After training, rats were surgically implanted with microdialysis probes under deep anesthesia, and 24 hlater extracellular dopamine concentrations were monitored in medial prefrontal cortex (mPFC) for the 2 hpreceding ethanol administration (anticipatory phase), during ethanol exposure (consummatory phase) and for 2 hafter ethanol removal. Results show that, in GH animals, dopamine extracellular concentration in the mPFC increased as early as 80 min before ethanol presentation (+50% over basal values) and remained elevated for 80 min during ethanol exposure. In SI rats, on the contrary, dopamine extracellular concentration did not show any significant change at any time point. Ethanol consumption was significantly higher in SI than in GH rats. Moreover, mesocortical dopaminergic neurons in SI animals also showed a decreased sensitivity to an acute administration of ethanol with respect to GH rats. Our results show that prolonged exposure to stress, as in social isolation, is able to induce significant changes in the response of mesocortical dopaminergic neurons to ethanol exposure and suggest that these changes might play an important role in the compulsivity observed in ethanol addiction. PMID:27378852

  3. Light responses and morphology of bNOS-immunoreactive neurons in the mouse retina

    PubMed Central

    Pang, Ji-Jie; Gao, Fan; Wu, Samuel M.

    2010-01-01

    Nitric oxide (NO), produced by NO synthase (NOS), modulates the function of all retinal neurons and ocular blood vessels and participates in the pathogenesis of ocular diseases. To further understand the regulation of ocular NO release, we systematically studied the morphology, topography and light responses of NOS-containing amacrine cells (NOACs) in dark-adapted mouse retina. Immunohistological staining for neuronal NOS (bNOS), combined with retrograde labeling of ganglion cells (GCs) with Neurobiotin (NB, a gap junction permeable dye) and Lucifer yellow (LY, a less permeable dye), was used to identify NOACs. The light responses of ACs were recorded under whole-cell voltage clamp conditions and cell morphology was examined with a confocal microscope. We found that in dark-adapted conditions bNOS-immunoreactivity (IR) was present primarily in the inner nuclear layer and the ganglion cell layer. bNOS-IR somas were negative for LY, thus they were identified as ACs; nearly 6 % of the cells were labeled by NB but not by LY, indicating that they were dye-coupled with GCs. Three morphological subtypes of NOACs (NI, NII and displaced) were identified. The cell density, inter-cellular distance and the distribution of NOACs were studied in whole retinas. Light evoked depolarizing highly sensitive ON-OFF responses in NI cells and less sensitive OFF responses in NII cells. Frequent (1 to 2 Hz) or abrupt change of light-intensity evoked larger peak responses. The possibility for light to modify NO release from NOACs is discussed. PMID:20503422

  4. Amygdalar neuronal activity mediates the cardiovascular responses evoked from the dorsolateral periaqueductal gray in conscious rats.

    PubMed

    de Abreu, A R; Abreu, A R; Santos, L T; de Souza, A A; da Silva, L G; Chianca, D A; de Menezes, R C

    2015-01-22

    There is ample evidence that both lateral/dorsolateral periaqueductal gray (l/dlPAG) and basolateral amygdala (BLA) are essential for the regulation of the autonomic responses evoked during innate reactions to threatening stimuli. However, it is not well established to what extent the BLA regulates the upstream functional connection from the l/dlPAG. Here we evaluated the role of the BLA and its glutamatergic receptors in the cardiovascular responses induced by l/dlPAG stimulation in rats. We examined the influence of acute inhibition of the BLA, unilaterally, by injecting muscimol on the cardiovascular responses evoked by the injection of N-methyl D-aspartate (NMDA) into the l/dlPAG. We also evaluated the role of BLA ionotropic glutamate receptors in these responses by injecting antagonists of NMDA and AMPA/kainate receptor subtypes into the BLA. Our results show that the microinjection of NMDA in the BLA increased the mean arterial pressure (MAP) and heart rate (HR). Injection of NMDA into the l/dlPAG caused similar increases in these variables, which was prevented by the prior injection of muscimol, a GABAA agonist, into the BLA. Moreover, injection of glutamatergic antagonists (2-amino-5-phosphonopentanoate (AP5) and 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX)) into the BLA reduced the increase in MAP and HR induced by l/dlPAG activation. Finally, the inhibition of the central amygdala neurons failed to reduce the cardiovascular changes induced by l/dlPAG activation. These results indicate that physiological responses elicited by l/dlPAG activation require the neuronal activity in the BLA. This ascending excitatory pathway from the l/dlPAG to the BLA might ensure the expression of the autonomic component of the defense reaction. PMID:25451289

  5. Ventral premotor-motor cortex interactions in the macaque monkey during grasp: response of single neurons to intracortical microstimulation.

    PubMed

    Kraskov, Alexander; Prabhu, Gita; Quallo, Marsha M; Lemon, Roger N; Brochier, Thomas

    2011-06-15

    Recent stimulation studies in monkeys and humans have shown strong interactions between ventral premotor cortex (area F5) and the hand area of primary motor cortex (M1). These short-latency interactions usually involve facilitation from F5 of M1 outputs to hand muscles, although suppression has also been reported. This study, performed in three awake macaque monkeys, sought evidence that these interactions could be mediated by short-latency excitatory and inhibitory responses of single M1 neurons active during grasping tasks. We recorded responses of these M1 neurons to single low-threshold (≤40 μA) intracortical microstimuli delivered to F5 sites at which grasp-related neurons were recorded. In 29 sessions, we tested 232 M1 neurons with stimuli delivered to between one and four sites in F5. Of the 415 responses recorded, 142 (34%) showed significant effects. The most common type of response was pure excitation (53% of responses), with short latency (1.8-3.0 ms) and brief duration (∼1 ms); purely inhibitory responses had slightly longer latencies (2-5 ms) and were of small amplitude and longer duration (5-7 ms). They accounted for 13% of responses, whereas mixed excitation then inhibition was seen in 34%. Remarkably, a rather similar set of findings applied to 280 responses of 138 F5 neurons to M1 stimulation; 109 (34%) responses showed significant effects. Thus, with low-intensity stimuli, the dominant interaction between these two cortical areas is one of short-latency, brief excitation, most likely mediated by reciprocal F5-M1 connections. Some neurons were tested with stimuli at both 20 and 40 μA; inhibition tended to dominate at the higher intensity. PMID:21677165

  6. Responses of a Hodgkin-Huxley neuron to various types of spike-train inputs

    NASA Astrophysics Data System (ADS)

    Hasegawa, Hideo

    2000-01-01

    Numerical investigations have been made of responses of a Hodgkin-Huxley (HH) neuron to spike-train inputs whose interspike interval (ISI) is modulated by deterministic, semi-deterministic (chaotic), and stochastic signals. As deterministic one, we adopt inputs with the time-independent ISI and with time-dependent ISI modulated by sinusoidal signal. The Rössler and Lorentz models are adopted for chaotic modulations of ISI. Stochastic ISI inputs with the gamma distribution are employed. It is shown that distribution of output ISI data depends not only on the mean of ISIs of spike-train inputs but also on their fluctuations. The distinction of responses to the three kinds of inputs can be made by return maps of input and output ISIs, but not by their histograms. The relation between the variations of input and output ISIs is shown to be different from that of the integrate and fire (IF) model because of the refractory period in the HH neuron.

  7. Expression Patterns of Odorant Receptors and Response Properties of Olfactory Sensory Neurons in Aged Mice

    PubMed Central

    Lee, Anderson C.; Tian, Huikai; Grosmaitre, Xavier

    2009-01-01

    The sense of smell deteriorates in normal aging, but the underling mechanisms are still elusive. Here we investigated age-related alterations in expression patterns of odorant receptor (OR) genes and functional properties of olfactory sensory neurons (OSNs)—2 critical factors that define the odor detection threshold in the olfactory epithelium. Using in situ hybridization for 9 representative OR genes, we compared the cell densities of each OR in coronal nose sections at different ages (3–27 months). The cell density for different ORs peaked at different time points and a decline was observed for 6 of 9 ORs at advanced ages. Using patch clamp recordings, we then examined the odorant responses of individual OSNs coexpressing a defined OR (MOR23) and green fluorescent protein. The MOR23 neurons recorded from aged animals maintained a similar sensitivity and dynamic range in response to the cognate odorant (lyral) as those from younger mice. The results indicate that although the cell densities of OSNs expressing certain types of ORs decline at advanced ages, individual OSNs can retain their sensitivity. The implications of these findings in age-related olfactory deterioration are discussed. PMID:19759360

  8. The Anorectic Effect of CNTF Does Not Require Action in Leptin-Responsive Neurons

    PubMed Central

    Stefater, M. A.; MacLennan, A. J.; Lee, N.; Patterson, C. M.; Haller, A.; Sorrell, J.; Myers, M.; Woods, S. C.

    2012-01-01

    Leptin resistance is a feature of obesity that poses a significant therapeutic challenge. Any treatment that is effective to reduce body weight in obese patients must overcome or circumvent leptin resistance, which promotes the maintenance of excess body fat in obese individuals. Ciliary neurotrophic factor (CNTF) is unique in its ability to reduce food intake and body weight in obese, leptin-resistant humans and rodents. Although attempts to use CNTF as an obesity therapy failed due to the development of neutralizing antibodies to the drug, efforts to understand mechanisms for CNTF's anorectic effects provide an opportunity to develop new drugs for leptin-resistant individuals. CNTF and leptin share several structural, anatomic, and signaling properties, but it is not understood whether or how the two cytokines might interact to affect energy balance. Here, we conditionally deleted the CNTF receptor (CNTFR) subunit, CNTFRα, in cells expressing leptin receptors. We found that CNTFR signaling in leptin-responsive neurons is not required for endogenous maintenance of energy balance and is not required for the anorectic response to exogenous administration of a CNTF agonist. These results indicate that despite anatomical overlap for CNTF and leptin action, CNTF appears to act within a distinct neuronal population to elicit its potent anorectic effect. PMID:22518062

  9. Transient response in a dendritic neuron model for current injected at one branch.

    PubMed

    Rinzel, J; Rall, W

    1974-10-01

    Mathematical expressions are obtained for the response function corresponding to an instantaneous pulse of current injected to a single dendritic branch in a branched dendritic neuron model. The theoretical model assumes passive membrane properties and the equivalent cylinder constraint on branch diameters. The response function when used in a convolution formula enables one to compute the voltage transient at any specified point in the dendritic tree for an arbitrary current injection at a given input location. A particular numerical example, for a brief current injection at a branch terminal, illustrates the attenuation and delay characteristics of the depolarization peak as it spreads throughout the neuron model. In contrast to the severe attenuation of voltage transients from branch input sites to the soma, the fraction of total input charge actually delivered to the soma and other trees is calculated to be about one-half. This fraction is independent of the input time course. Other numerical examples, which compare a branch terminal input site with a soma input site, demonstrate that, for a given transient current injection, the peak depolarization is not proportional to the input resistance at the injection site and, for a given synaptic conductance transient, the effective synaptic driving potential can be significantly reduced, resulting in less synaptic current flow and charge, for a branch input site. Also, for the synaptic case, the two inputs are compared on the basis of the excitatory post-synaptic potential (EPSP) seen at the soma and the total charge delivered to the soma. PMID:4424185

  10. Biphasic plasticity of dendritic fields in layer V motor neurons in response to motor learning.

    PubMed

    Gloor, C; Luft, A R; Hosp, J A

    2015-11-01

    Motor learning is associated with plastic reorganization of neural networks in primary motor cortex (M1) that advances through stages. An initial increment in spine formation is followed by pruning and maturation one week after training ended. A similar biphasic course was described for the size of the forelimb representation in M1. This study investigates the evolution of the dendritic architecture in response to motor skill training using Golgy-Cox silver impregnation in rat M1. After learning of a unilateral forelimb-reaching task to plateau performance, an increase in dendritic length of layer V pyramidal neurons (i.e. motor neurons) was observed that peaked one month after training ended. This increment in dendritic length reflected an expansion of the distal dendritic compartment. After one month dendritic arborization shrinks even though animals retain task performance. This pattern of evolution was observed for apical and basal dendrites alike - although the increase in dendritic length occurs faster in basal than in apical dendrites. Dendritic plasticity in response to motor training follows a biphasic course with initial expansion and subsequent shrinkage. This evolution takes fourth as long as the biphasic reorganization of spines or motor representations. PMID:26318492

  11. Long Non-coding RNA in Neurons: New Players in Early Response to BDNF Stimulation

    PubMed Central

    Aliperti, Vincenza; Donizetti, Aldo

    2016-01-01

    Brain-derived neurotrophic factor (BDNF) is a neurotrophin family member that is highly expressed and widely distributed in the brain. BDNF is critical for neural survival and plasticity both during development and in adulthood, and dysfunction in its signaling may contribute to a number of neurodegenerative disorders. Deep understanding of the BDNF-activated molecular cascade may thus help to find new biomarkers and therapeutic targets. One interesting direction is related to the early phase of BDNF-dependent gene expression regulation, which is responsible for the activation of selective gene programs that lead to stable functional and structural remodeling of neurons. Immediate-early coding genes activated by BDNF are under investigation, but the involvement of the non-coding RNAs is largely unexplored, especially the long non-coding RNAs (lncRNAs). lncRNAs are emerging as key regulators that can orchestrate different aspects of nervous system development, homeostasis, and plasticity, making them attractive candidate markers and therapeutic targets for brain diseases. We used microarray technology to identify differentially expressed lncRNAs in the immediate response phase of BDNF stimulation in a neuronal cell model. Our observations on the putative functional role of lncRNAs provide clues to their involvement as master regulators of gene expression cascade triggered by BDNF. PMID:26973456

  12. Responses of neurons in the rostral ventrolateral medulla to whole body rotations: comparisons in decerebrate and conscious cats.

    PubMed

    Destefino, V J; Reighard, D A; Sugiyama, Y; Suzuki, T; Cotter, L A; Larson, M G; Gandhi, N J; Barman, S M; Yates, B J

    2011-06-01

    The responses to vestibular stimulation of brain stem neurons that regulate sympathetic outflow and blood flow have been studied extensively in decerebrate preparations, but not in conscious animals. In the present study, we compared the responses of neurons in the rostral ventrolateral medulla (RVLM), a principal region of the brain stem involved in the regulation of blood pressure, to whole body rotations of conscious and decerebrate cats. In both preparations, RVLM neurons exhibited similar levels of spontaneous activity (median of ∼17 spikes/s). The firing of about half of the RVLM neurons recorded in decerebrate cats was modulated by rotations; these cells were activated by vertical tilts in a variety of directions, with response characteristics suggesting that their labyrinthine inputs originated in otolith organs. The activity of over one-third of RVLM neurons in decerebrate animals was altered by stimulation of baroreceptors; RVLM units with and without baroreceptor signals had similar responses to rotations. In contrast, only 6% of RVLM neurons studied in conscious cats exhibited cardiac-related activity, and the firing of just 1% of the cells was modulated by rotations. These data suggest that the brain stem circuitry mediating vestibulosympathetic reflexes is highly sensitive to changes in body position in space but that the responses to vestibular stimuli of neurons in the pathway are suppressed by higher brain centers in conscious animals. The findings also raise the possibility that autonomic responses to a variety of inputs, including those from the inner ear, could be gated according to behavioral context and attenuated when they are not necessary. PMID:21493724

  13. Quantification of the response of rat medullary raphe neurones to independent changes in pHo and PCO2

    PubMed Central

    Wang, Wengang; Bradley, Stefania Risso; Richerson, George B

    2002-01-01

    The medullary raphe nuclei contain putative central respiratory chemoreceptor neurones that are highly sensitive to acidosis. To define the primary stimulus for chemosensitivity in these neurones, the response to hypercapnic acidosis was quantified and compared with the response to independent changes in PCO2 and extracellular pH (pHo). Neurones from the ventromedial medulla of neonatal rats (P0-P2) were dissociated and maintained in tissue culture for long enough to develop a mature response (up to 70 days). Perforated patch clamp recordings were used to record membrane potential and firing rate while changes were made in pHo, PCO2 and/or [NaHCO3]o from baseline values of 7.4, 5 % and 26 mm, respectively. Hypercapnic acidosis (PCO2 9 %; pHo 7.17) induced an increase in firing rate to 285 % of control in one subset of neurones (‘stimulated neurones’) and induced a decrease in firing rate to 21 % of control in a different subset of neurones (‘inhibited neurones’). Isocapnic acidosis (pHo 7.16; [NaHCO3]o 15 mm) induced an increase in firing rate of stimulated neurones to 309 % of control, and a decrease in firing rate of inhibited neurones to 38 % of control. In a different group of neurones, isohydric hypercapnia (9 % PCO2; [NaHCO3]o 40 mm) induced an increase in firing rate of stimulated neurones by the same amount (to 384 % of control) as in response to hypercapnic acidosis (to 327 % of control). Inhibited neurones also responded to isohydric hypercapnia in the same way as they did to hypercapnic acidosis. In Hepes-buffered solution, both types of neurone responded to changes in pHo in the same way as they responded to changes in pHo in bicarbonate-buffered Ringer solution. It has previously been shown that all acidosis-stimulated neurones in the medullary raphe are immunoreactive for tryptophan hydroxylase (TpOH-ir). Here it was found that TpOH-ir neurones in the medullary raphe were immunoreactive for carbonic anhydrase type II and type IV (CA II and CA

  14. Analysis and classification of delay-sensitive cortical neurons based on response to temporal parameters in echolocation signals.

    PubMed

    Chittajallu, S K; Palakal, M J; Wong, D

    1995-04-01

    Echolocating bats generate an acoustic image of their target by processing target-reflected echoes of their emitted biosonar pulses. Efforts in building computational models of auditory processing in the bat auditory system, using extensive neurophysiological data from cortical studies are challenged by the intrinsic complexity and the significant variability in neural response to stimuli. In this paper, we use a computerized method for the analysis and classification of delay-sensitive neurons to classify neurons from the auditory cortex of Myotis lucifugus, a species that echolocates with FM signals. The coefficients of the bi-linear fit to the best delay response surfaces (mean R2 = 0.01) were used in classifying the neurons. Six classes were derived that corresponded to the four previously characterized neurophysiologically. The first class corresponded to delay-tuned neurons which exhibited a constant best delay at different pulse repetition rates and pulse durations. Three other classes corresponded to the different subtypes of tracking neurons which changed their best delay to one or both of these stimulus temporal parameters. Two additional classes were differentiated although their best-delay response were similar to either the delay-tuned or the duration and pulse-repetition rate sensitive class. Artificial delay-sensitive neurons built from the parameters of the centroid of each class, will serve a key role in the FM bat auditory system model that we are building. PMID:7642448

  15. Neuronal Serotonin Release Triggers the Heat Shock Response in C. elegans in the Absence of Temperature Increase

    PubMed Central

    Tatum, Marcus C.; Ooi, Felicia K.; Chikka, Madhusudana Rao; Chauve, Laetitia; Martinez-Velazquez, Luis A.; Steinbusch, Harry W.M.; Morimoto, Richard I.; Prahlad, Veena

    2016-01-01

    Summary Background Cellular mechanisms aimed at repairing protein damage and maintaining homeostasis, widely understood to be triggered by the damage itself, have recently been shown to be under cell nonautonomous control in the metazoan C. elegans. The heat shock response (HSR) is one such conserved mechanism, activated by cells upon exposure to proteotoxic conditions such as heat. Previously, we had shown that this conserved cytoprotective response is regulated by the thermosensory neuronal circuitry of C. elegans. Here, we investigate the mechanisms and physiological relevance of neuronal control. Results By combining optogenetic methods with live visualization of the dynamics of the heat shock transcription factor (HSF1), we show that excitation of the AFD thermosensory neurons is sufficient to activate HSF1 in another cell, even in the absence of temperature increase. Excitation of the AFD thermosensory neurons enhances serotonin release. Serotonin release elicited by direct optogenetic stimulation of serotonergic neurons activates HSF1 and upregulates molecular chaperones through the metabotropic serotonin receptor SER-1. Consequently, excitation of serotonergic neurons alone can suppress protein misfolding in C. elegans peripheral tissue. Conclusions These studies imply that thermosensory activity coupled to serotonergic signaling is sufficient to activate the protective HSR prior to frank proteotoxic damage. The ability of neurosensory release of serotonin to control cellular stress responses and activate HSF1 has powerful implications for the treatment of protein conformation diseases. PMID:25557666

  16. Spontaneous dynamics and response properties of a Hodgkin-Huxley-type neuron model driven by harmonic synaptic noise

    PubMed Central

    Nguyen, Hoai; Neiman, Alexander B.

    2010-01-01

    We study statistical properties, response dynamics, and information transmission in a Hodgkin-Huxley–type neuron system, modeling peripheral electroreceptors in paddlefish. In addition to sodium and potassium currents, the neuron model includes fast calcium and slow afterhyperpolarization (AHP) potassium currents. The synaptic transmission from sensory epithelium is modeled by a Poission process with a rate modulated by narrow-band noise, mimicking stochastic epithelial oscillations observed experimentally. We study how the interplay of parameters of AHP current and synaptic noise affects the statistics of spontaneous dynamics and response properties of the system. In particular, we confirm predictions made earlier with perfect integrate and fire and phase neuron models that epithelial oscillations enhance stimulus–response coherence and thus information transmission in electroreceptor system. In addition, we consider a strong stimulus regime and show that coherent epithelial oscillations may reduce variability of electroreceptor responses to time-varying stimuli. PMID:20975925

  17. Social experience affects neuronal responses to male calls in adult female zebra finches.

    PubMed

    Menardy, F; Touiki, K; Dutrieux, G; Bozon, B; Vignal, C; Mathevon, N; Del Negro, C

    2012-04-01

    Plasticity studies have consistently shown that behavioural relevance can change the neural representation of sounds in the auditory system, but what occurs in the context of natural acoustic communication where significance could be acquired through social interaction remains to be explored. The zebra finch, a highly social songbird species that forms lifelong pair bonds and uses a vocalization, the distance call, to identify its mate, offers an opportunity to address this issue. Here, we recorded spiking activity in females while presenting distance calls that differed in their degree of familiarity: calls produced by the mate, by a familiar male, or by an unfamiliar male. We focused on the caudomedial nidopallium (NCM), a secondary auditory forebrain region. Both the mate's call and the familiar call evoked responses that differed in magnitude from responses to the unfamiliar call. This distinction between responses was seen both in single unit recordings from anesthetized females and in multiunit recordings from awake freely moving females. In contrast, control females that had not heard them previously displayed responses of similar magnitudes to all three calls. In addition, more cells showed highly selective responses in mated than in control females, suggesting that experience-dependent plasticity in call-evoked responses resulted in enhanced discrimination of auditory stimuli. Our results as a whole demonstrate major changes in the representation of natural vocalizations in the NCM within the context of individual recognition. The functional properties of NCM neurons may thus change continuously to adapt to the social environment. PMID:22512260

  18. Dynamic response of ensemble neurons to pulsed optical and electrical excitation in vivo and in vitro

    NASA Astrophysics Data System (ADS)

    Akchurin, Garif G.; Seleverstov, George A.; Kamenskih, Tatyana G.; Akchurin, George G.; Bondarenko, Olga A.

    2002-07-01

    The nonlinear response of the Hodgkin-Huxley model neuron with external electrical pulsed was investigated. Dynamic response of somatic frog nerve on electrical pulsed duration was study in vitro. Transcutaneous millisecond of excitation of the ganglion cell of the human retina by electric uses is used for diagnosis, determination of the extent of optic nerve damage, and also partial restoration of visual function in patients with glaucoma, myopia and different types of optic nerve atrophy. Correlation between the threshold of phosphen formation and duration of the stimulating electric pulses was determined experimentally in normal eyes and in eyes with various pathologies. Comparison of optical and electrical scintillating frequency gives information about the dynamic processes in the normal and pathological retina.

  19. Intensity invariant dynamics and odor-specific latencies in olfactory receptor neuron response

    PubMed Central

    Martelli, Carlotta; Carlson, John R.; Emonet, Thierry

    2013-01-01

    Odors elicit spatio-temporal patterns of activity in the brain. Spatial patterns arise from the specificity of the interaction between odorants and odorant receptors expressed in different olfactory receptor neurons (ORNs). But the origin of temporal patterns of activity and their role in odor coding remain unclear. We investigate how physiological aspects of ORN response and physical aspects of odor stimuli give rise to diverse responses in Drosophila ORNs. We show that odor stimuli have intrinsic dynamics that depend on odor type and strongly affect ORN response. Using linear-nonlinear modeling to remove the contribution of the stimulus dynamics from the ORN dynamics we study the physiological properties of the response to different odorants and concentrations. For several odorants and receptor types the ORN response dynamics normalized by the peak response are independent of stimulus intensity for a large portion of the neuron’s dynamic range. Adaptation to a background odor changes the gain and dynamic range of the response but does not affect normalized response dynamics. Stimulating ORNs with various odorants reveals significant odor-dependent delays in the ORN response functions. These differences however can be dominated by differences in stimulus dynamics. In one case the response of one ORN to two odorants is predicted solely from measurements of the odor signals. Within a large portion of their dynamic range ORNs can capture information about stimulus dynamics independently from intensity while introducing odor-dependent delays. How insects might use odor-specific stimulus dynamics and ORN dynamics in discrimination and navigation tasks remains an open question. PMID:23575828

  20. Potential confounds in estimating trial-to-trial correlations between neuronal response and behavior using choice probabilities

    PubMed Central

    Maunsell, John H. R.

    2012-01-01

    Correlations between trial-to-trial fluctuations in the responses of individual sensory neurons and perceptual reports, commonly quantified with choice probability (CP), have been widely used as an important tool for assessing the contributions of neurons to behavior. These correlations are usually weak and often require a large number of trials for a reliable estimate. Therefore, working with measures such as CP warrants care in data analysis as well as rigorous controls during data collection. Here we identify potential confounds that can arise in data analysis and lead to biased estimates of CP, and suggest methods to avoid the bias. In particular, we show that the common practice of combining neuronal responses across different stimulus conditions with z-score normalization can result in an underestimation of CP when the ratio of the numbers of trials for the two behavioral response categories differs across the stimulus conditions. We also discuss the effects of using variable time intervals for quantifying neuronal response on CP measurements. Finally, we demonstrate that serious artifacts can arise in reaction time tasks that use varying measurement intervals if the mean neuronal response and mean behavioral performance vary over time within trials. To emphasize the importance of addressing these concerns in neurophysiological data, we present a set of data collected from V1 cells in macaque monkeys while the animals performed a detection task. PMID:22993262

  1. Influence of stimulus and oral adaptation temperature on gustatory responses in central taste-sensitive neurons

    PubMed Central

    Li, Jinrong

    2015-01-01

    The temperature of taste stimuli can modulate gustatory processing. Perceptual data indicate that the adapted temperature of oral epithelia also influences gustation, although little is known about the neural basis of this effect. Here, we electrophysiologically recorded orosensory responses (spikes) to 25°C (cool) and 35°C (warm) solutions of sucrose (0.1 and 0.3 M), NaCl (0.004, 0.1, and 0.3 M), and water from taste-sensitive neurons in the nucleus of the solitary tract in mice under varied thermal adaptation of oral epithelia. Conditions included presentation of taste stimuli isothermal to adaptation temperatures of 25°C (constant cooling) and 35°C (constant warming), delivery of 25°C stimuli following 35°C adaptation (relative cooling), and presentation of 35°C stimuli following 25°C adaptation (relative warming). Responses to sucrose in sucrose-oriented cells (n = 15) were enhanced under the constant and relative warming conditions compared with constant cooling, where contiguous cooling across adaptation and stimulus periods induced the lowest and longest latency responses to sucrose. Yet compared with constant warming, cooling sucrose following warm adaptation (relative cooling) only marginally reduced activity to 0.1 M sucrose and did not alter responses to 0.3 M sucrose. Thus, warmth adaptation counteracted the attenuation in sucrose activity associated with stimulus cooling. Analysis of sodium-oriented (n = 25) neurons revealed adaptation to cool water, and cooling taste solutions enhanced unit firing to 0.004 M (perithreshold) NaCl, whereas warmth adaptation and stimulus warming could facilitate activity to 0.3 M NaCl. The concentration dependence of this thermal effect may reflect a dual effect of temperature on the sodium reception mechanism that drives sodium-oriented cells. PMID:25673737

  2. Dexamethasone Coated Neural Probes Elicit Attenuated Inflammatory Response and Neuronal Loss Compared to Uncoated Neural Probes

    PubMed Central

    Zhong, Yinghui; Bellamkonda, Ravi V.

    2007-01-01

    Glial scar formation around implanted silicon neural probes compromises their ability to facilitate long-term recordings. One approach to modulate the tissue reaction around implanted probes in the brain is to develop probe coatings that locally release antiinflammatory drugs. In this study, we developed a nitrocellulose-based coating for the local delivery of the anti-inflammatory drug dexamethasone (DEX). Silicon neural probes with and without nitrocellulose-DEX coatings were implanted into rat brains, and inflammatory response was evaluated 1 week and 4 weeks post implantation. DEX coatings significantly reduced the reactivity of microglia and macrophages one week post implantation as evidenced by ED1 immunostaining. CS56 staining demonstrated that DEX treatment significantly reduced chondroitin sulfate proteoglycan (CSPG) expression one week post implantation. Both at one week and at four week time points, GFAP staining for reactive astrocytes and neurofilament (NF) staining revealed that local DEX treatment significantly attenuated astroglial response and reduced neuronal loss in the vicinity of the probes. Weak ED1, neurocan, and NG2 positive signal was detected four weeks post implantation for both coated and uncoated probes, suggesting a stabilization of the inflammatory response over time in this implant model. In conclusion, this study demonstrates that the nitrocellulose-DEX coating can effectively attenuate the inflammatory response to the implanted neural probes, and reduce neuronal loss in the vicinity of the coated probes. Thus anti-inflammatory probe coatings may represent a promising approach to attenuate astroglial scar and reduce neural loss around implanted neural probes. PMID:17376408

  3. Sleep restriction increases the neuronal response to unhealthy food in normal-weight individuals

    PubMed Central

    St-Onge, M-P; Wolfe, S; Sy, M; Shechter, A; Hirsch, J

    2013-01-01

    Context Sleep restriction alters responses to food. However, the underlying neural mechanisms for this effect are not well understood. Objective The purpose of this study was to determine whether there is a neural system that is preferentially activated in response to unhealthy compared with healthy foods. Participants Twenty-five normal-weight individuals, who normally slept 7–9 h per night, completed both phases of this randomized controlled study. Intervention Each participant was tested after a period of five nights of either 4 or 9 h in bed. Functional magnetic resonance imaging (fMRI) was performed in the fasted state, presenting healthy and unhealthy food stimuli and objects in a block design. Neuronal responses to unhealthy, relative to healthy food stimuli after each sleep period were assessed and compared. Results After a period of restricted sleep, viewing unhealthy foods led to greater activation in the superior and middle temporal gyri, middle and superior frontal gyri, left inferior parietal lobule, orbitofrontal cortex, and right insula compared with healthy foods. These same stimuli presented after a period of habitual sleep did not produce marked activity patterns specific to unhealthy foods. Further, food intake during restricted sleep increased in association with a relative decrease in brain oxygenation level-dependent (BOLD) activity observed in the right insula. Conclusion This inverse relationship between insula activity and food intake and enhanced activation in brain reward and food-sensitive centers in response to unhealthy foods provides a model of neuronal mechanisms relating short sleep duration to obesity. PMID:23779051

  4. Response variability of frontal eye field neurons modulates with sensory input and saccade preparation but not visual search salience.

    PubMed

    Purcell, Braden A; Heitz, Richard P; Cohen, Jeremiah Y; Schall, Jeffrey D

    2012-11-01

    Discharge rate modulation of frontal eye field (FEF) neurons has been identified with a representation of visual search salience (physical conspicuity and behavioral relevance) and saccade preparation. We tested whether salience or saccade preparation are evident in the trial-to-trial variability of discharge rate. We quantified response variability via the Fano factor in FEF neurons recorded in monkeys performing efficient and inefficient visual search tasks. Response variability declined following stimulus presentation in most neurons, but despite clear discharge rate modulation, variability did not change with target salience. Instead, we found that response variability was modulated by stimulus luminance and the number of items in the visual field independently of attentional demands. Response variability declined to a minimum before saccade initiation, and presaccadic response variability was directionally tuned. In addition, response variability was correlated with the response time of memory-guided saccades. These results indicate that the trial-by-trial response variability of FEF neurons reflects saccade preparation and the strength of sensory input, but not visual search salience or attentional allocation. PMID:22956785

  5. A codimension-2 bifurcation controlling endogenous bursting activity and pulse-triggered responses of a neuron model.

    PubMed

    Barnett, William H; Cymbalyuk, Gennady S

    2014-01-01

    The dynamics of individual neurons are crucial for producing functional activity in neuronal networks. An open question is how temporal characteristics can be controlled in bursting activity and in transient neuronal responses to synaptic input. Bifurcation theory provides a framework to discover generic mechanisms addressing this question. We present a family of mechanisms organized around a global codimension-2 bifurcation. The cornerstone bifurcation is located at the intersection of the border between bursting and spiking and the border between bursting and silence. These borders correspond to the blue sky catastrophe bifurcation and the saddle-node bifurcation on an invariant circle (SNIC) curves, respectively. The cornerstone bifurcation satisfies the conditions for both the blue sky catastrophe and SNIC. The burst duration and interburst interval increase as the inverse of the square root of the difference between the corresponding bifurcation parameter and its bifurcation value. For a given set of burst duration and interburst interval, one can find the parameter values supporting these temporal characteristics. The cornerstone bifurcation also determines the responses of silent and spiking neurons. In a silent neuron with parameters close to the SNIC, a pulse of current triggers a single burst. In a spiking neuron with parameters close to the blue sky catastrophe, a pulse of current temporarily silences the neuron. These responses are stereotypical: the durations of the transient intervals-the duration of the burst and the duration of latency to spiking-are governed by the inverse-square-root laws. The mechanisms described here could be used to coordinate neuromuscular control in central pattern generators. As proof of principle, we construct small networks that control metachronal-wave motor pattern exhibited in locomotion. This pattern is determined by the phase relations of bursting neurons in a simple central pattern generator modeled by a chain of

  6. Expression of early growth response protein 1 in vasopressin neurones of the rat anterior olfactory nucleus following social odour exposure

    PubMed Central

    Wacker, Douglas W; Tobin, Vicky A; Noack, Julia; Bishop, Valerie R; Duszkiewicz, Adrian J; Engelmann, Mario; Meddle, Simone L; Ludwig, Mike

    2010-01-01

    The anterior olfactory nucleus (AON), a component of the main olfactory system, is a cortical region that processes olfactory information and acts as a relay between the main olfactory bulbs and higher brain regions such as the piriform cortex. Utilizing a transgenic rat in which an enhanced green fluorescent protein reporter gene is expressed in vasopressin neurones (eGFP-vasopressin), we have discovered a population of vasopressin neurones in the AON. These vasopressin neurones co-express vasopressin V1 receptors. They also co-express GABA and calbinin-D28k indicating that they are neurochemically different from the newly described vasopressin neurons in the main olfactory bulb. We utilized the immediate early gene product, early growth response protein 1 (Egr-1), to examine the functional role of these vasopressin neurons in processing social and non-social odours in the AON. Exposure of adult rats to a conspecific juvenile or a heterospecific predator odour leads to increases in Egr-1 expression in the AON in a subregion specific manner. However, only exposure to a juvenile increases Egr-1 expression in AON vasopressin neurons. These data suggest that vasopressin neurones in the AON may be selectively involved in the coding of social odour information. PMID:20921194

  7. Molecular Mechanisms Responsible for Neuron-Derived Conditioned Medium (NCM)-Mediated Protection of Ischemic Brain.

    PubMed

    Lin, Chi-Hsin; Wang, Chen-Hsuan; Hsu, Shih-Lan; Liao, Li-Ya; Lin, Ting-An; Hsueh, Chi-Mei

    2016-01-01

    The protective value of neuron-derived conditioned medium (NCM) in cerebral ischemia and the underlying mechanism(s) responsible for NCM-mediated brain protection against cerebral ischemia were investigated in the study. NCM was first collected from the neuronal culture growing under the in vitro ischemic condition (glucose-, oxygen- and serum-deprivation or GOSD) for 2, 4 or 6 h. Through the focal cerebral ischemia (bilateral CCAO/unilateral MCAO) animal model, we discovered that ischemia/reperfusion (I/R)-induced brain infarction was significantly reduced by NCM, given directly into the cistern magna at the end of 90 min of CCAO/MCAO. Immunoblocking and chemical blocking strategies were applied in the in vitro ischemic studies to show that NCM supplement could protect microglia, astrocytes and neurons from GOSD-induced cell death, in a growth factor (TGFβ1, NT-3 and GDNF) and p-ERK dependent manner. Brain injection with TGFβ1, NT3, GDNF and ERK agonist (DADS) alone or in combination, therefore also significantly decreased the infarct volume of ischemic brain. Moreover, NCM could inhibit ROS but stimulate IL-1β release from GOSD-treated microglia and limit the infiltration of IL-β-positive microglia into the core area of ischemic brain, revealing the anti-oxidant and anti-inflammatory activities of NCM. In overall, NCM-mediated brain protection against cerebral ischemia has been demonstrated for the first time in S.D. rats, due to its anti-apoptotic, anti-oxidant and potentially anti-glutamate activities (NCM-induced IL-1β can inhibit the glutamate-mediated neurotoxicity) and restriction upon the infiltration of inflammatory microglia into the core area of ischemic brain. The therapeutic potentials of NCM, TGFβ1, GDNF, NT-3 and DADS in the control of cerebral ischemia in human therefore have been suggested and require further investigation. PMID:26745377

  8. Prefrontal neurons encode context-based response execution and inhibition in reward seeking and extinction

    PubMed Central

    Moorman, David E.; Aston-Jones, Gary

    2015-01-01

    The prefrontal cortex (PFC) guides execution and inhibition of behavior based on contextual demands. In rodents, the dorsal/prelimbic (PL) medial PFC (mPFC) is frequently considered essential for execution of goal-directed behavior (“go”) whereas ventral/infralimbic (IL) mPFC is thought to control behavioral suppression (“stop”). This dichotomy is commonly seen for fear-related behaviors, and for some behaviors related to cocaine seeking. Overall, however, data for reward-directed behaviors are ambiguous, and few recordings of PL/IL activity have been performed to demonstrate single-neuron correlates. We recorded neuronal activity in PL and IL during discriminative stimulus driven sucrose seeking followed by multiple days of extinction of the reward-predicting stimulus. Contrary to a generalized PL-go/IL-stop hypothesis, we found cue-evoked activity in PL and IL during reward seeking and extinction. Upon analyzing this activity based on resultant behavior (lever press or withhold), we found that neurons in both areas encoded contextually appropriate behavioral initiation (during reward seeking) and withholding (during extinction), where context was dictated by response–outcome contingencies. Our results demonstrate that PL and IL signal contextual information for regulation of behavior, irrespective of whether that involves initiation or suppression of behavioral responses, rather than topographically encoding go vs. stop behaviors. The use of context to optimize behavior likely plays an important role in maximizing utility-promoting exertion of activity when behaviors are rewarded and conservation of energy when not. PMID:26170333

  9. Molecular Mechanisms Responsible for Neuron-Derived Conditioned Medium (NCM)-Mediated Protection of Ischemic Brain

    PubMed Central

    Lin, Chi-Hsin; Wang, Chen-Hsuan; Hsu, Shih-Lan; Liao, Li-Ya; Lin, Ting-An; Hsueh, Chi-Mei

    2016-01-01

    The protective value of neuron-derived conditioned medium (NCM) in cerebral ischemia and the underlying mechanism(s) responsible for NCM-mediated brain protection against cerebral ischemia were investigated in the study. NCM was first collected from the neuronal culture growing under the in vitro ischemic condition (glucose-, oxygen- and serum-deprivation or GOSD) for 2, 4 or 6 h. Through the focal cerebral ischemia (bilateral CCAO/unilateral MCAO) animal model, we discovered that ischemia/reperfusion (I/R)-induced brain infarction was significantly reduced by NCM, given directly into the cistern magna at the end of 90 min of CCAO/MCAO. Immunoblocking and chemical blocking strategies were applied in the in vitro ischemic studies to show that NCM supplement could protect microglia, astrocytes and neurons from GOSD-induced cell death, in a growth factor (TGFβ1, NT-3 and GDNF) and p-ERK dependent manner. Brain injection with TGFβ1, NT3, GDNF and ERK agonist (DADS) alone or in combination, therefore also significantly decreased the infarct volume of ischemic brain. Moreover, NCM could inhibit ROS but stimulate IL-1β release from GOSD-treated microglia and limit the infiltration of IL-β-positive microglia into the core area of ischemic brain, revealing the anti-oxidant and anti-inflammatory activities of NCM. In overall, NCM-mediated brain protection against cerebral ischemia has been demonstrated for the first time in S.D. rats, due to its anti-apoptotic, anti-oxidant and potentially anti-glutamate activities (NCM-induced IL-1β can inhibit the glutamate-mediated neurotoxicity) and restriction upon the infiltration of inflammatory microglia into the core area of ischemic brain. The therapeutic potentials of NCM, TGFβ1, GDNF, NT-3 and DADS in the control of cerebral ischemia in human therefore have been suggested and require further investigation. PMID:26745377

  10. DNA methyltransferase 3, a target of microRNA-29c, contributes to neuronal proliferation by regulating the expression of brain-derived neurotrophic factor.

    PubMed

    Yang, Guoshuai; Song, Yanmin; Zhou, Xiaoyan; Deng, Yidong; Liu, Tao; Weng, Guohu; Yu, Dan; Pan, Suyue

    2015-07-01

    Alzheimer's disease (AD), the most common form of dementia in the aged population, presents an increasing clinical challenge in terms of diagnosis and treatment. Neurodegeneration is one of the hallmarks of AD, which consequently induces cognitive impairment. Brain-derived neurotrophic factor (BDNF), a neuroprotective factor, has been implicated in neuronal survival and proliferation. The epigenetic mechanism of BDNF methylation may be responsible for the reduced expression of BDNF in patients with AD. DNA methyltransferase may contribute to the methylation of BDNF, which is involved in neuroprotection in AD. In addition, epigenetic modifications, including a combination of microRNAs (miRNAs/miRs) and DNA methylation, have been suggested as regulatory mechanisms in the control of neuronal survival. In the present study, the expression of miR-29c was determined in the cerebrospinal fluid (CSF) of patients with AD and of healthy control individuals. A marked decrease in the expression of miR-29c was observed in the AD group compared with the normal control group, accompanied by a decreased in the expression of BDNF. Additionally, a significant increase in the expression of DNA methyltransferase 3 (DNMT3) was observed in the CSF from the patients with AD. Correlation analysis revealed that the expression of miR-29c was positively correlated with BDNF and negatively correlated with DNMT3 protein in the CSF of patients with AD. In addition, the regulatory association between miR-29c, DNMT3 and BDNF were also examined in vitro. It was demonstrated that miR-29c directly targeted DNMT3 and contributed to neuronal proliferation by regulating the expression of BDNF, at least partially, through enhancing the activity of the tyrosine receptor kinase B/extracellular signal-regulated kinase signaling pathway. In conclusion, the present study suggested that miR-29c may be a promising potential therapeutic target in the treatment of AD. PMID:25815896

  11. In vivo responses of single olfactory receptor neurons in the channel catfish, Ictalurus punctatus.

    PubMed

    Kang, J; Caprio, J

    1995-01-01

    1. We report for the first time in any teleost, a quantitative in vivo study of recordings from single olfactory receptor neurons (ORNs) in the channel catfish, Ictalurus punctatus, with odorant stimuli. 2. Responses of 69 spontaneously active single ORNs were recorded simultaneously with the electroolfactogram (EOG). Recording times ranged from 10 to 72 min per receptor cell with an average of 24 +/- 15 (SD) min/cell. The averaged spontaneous frequency ranged from < 1 to 12 action potentials/s with a mean frequency of 4.7 +/- 2.5 action potentials/s. 3. Catfish ORNs responded to the odorant stimuli (amino acids, bile salts, and ATP) with either an excitation or suppression of the background neural activity. Suppressive responses were encountered more frequently than excitatory responses, suggesting that suppressive responses also play an important role in olfactory coding. 4. Excitatory and suppressive responses to the different odorants were elicited from the same ORN, suggesting that different olfactory receptor molecules and different transduction pathways exist in the same ORN. PMID:7714562

  12. Eugenol and carvacrol excite first- and second-order trigeminal neurons and enhance their heat-evoked responses

    PubMed Central

    Klein, Amanda H.; Joe, Christopher L.; Davoodi, Auva; Takechi, Kenichi; Carstens, Mirela Iodi; Carstens, E

    2014-01-01

    Eugenol and carvacrol from clove and oregano, respectively, are agonists of the warmth-sensitive transient receptor potential channel TRPV3 and the irritant-sensitive TRPA1. Eugenol and carvacrol induce oral irritation that rapidly desensitizes, accompanied by brief enhancement of innocuous warmth and heat pain in humans. We presently investigated if eugenol and carvacrol activate nociceptive primary afferent and higher-order trigeminal neurons and enhance their heat-evoked responses, using calcium imaging of cultured trigeminal ganglion (TG) and dorsal root ganglion (DRG) neurons, and in vivo single-unit recordings in trigeminal subnucleus caudalis (Vc) of rats. Eugenol and carvacrol activated 20-30% of TG and 7-20% of DRG cells, the majority of which additionally responded to menthol, mustard oil and/or capsaicin. TG cell responses to innocuous (39°) and noxious (42°C) heating were enhanced by eugenol and carvacrol. We identified dorsomedial Vc neurons responsive to noxious heating of the tongue in pentobarbital-anesthetized rats. Eugenol and carvacrol dose-dependently elicited desensitizing responses in 55% and 73% of heat-sensitive units, respectively. Responses to noxious heat were briefly enhanced by eugenol and carvacrol. Many eugenol- and carvacrol-responsive units also responded to menthol, cinnamaldehyde and capsaicin. These data support a peripheral site for eugenol and carvacrol to enhance warmth- and noxious heat-evoked responses of trigeminal neurons, and are consistent with the observation that these agonists briefly enhance warmth and heat pain on the human tongue. PMID:24759772

  13. Reactive Oxygen Species Donors Increase the Responsiveness of Dorsal Horn Neurons and Induce Mechanical Hyperalgesia in Rats

    PubMed Central

    Kim, Hee Young; Lee, Inhyung; Chun, Sang Woo; Kim, Hee Kee

    2015-01-01

    Our previous studies suggest that reactive oxygen species (ROS) scavengers have analgesic effect on neuropathic pain through spinal mechanisms in the rat. The studies suggest that superoxide in spinal cord is one of important mediators of persistent pain. To test the hypothesis that increase of superoxide-derived intermediates leads to central sensitization and pain, the effects of an intrathecal injection of chemical ROS donors releasing either OH∙, OCl−, or H2O2 were examined on pain behaviors. Following treatment with t-BOOH (OH∙ donor), dorsal horn neuron responses to mechanical stimuli in normal rats and the changes of neuronal excitability were explored on substantia gelatinosa (SG) neurons using whole-cell patch clamping recordings. Intrathecal administration of t-BOOH or NaOCl (OCl− donor), but not H2O2, significantly decreased mechanical thresholds of hind paws. The responses of wide dynamic range neurons to mechanical stimuli increased after a local application of t-BOOH. The t-BOOH increased the frequency and the amplitude of excitatory postsynaptic potentials, depolarized membrane potential in SG neurons, and increased the frequency of action potentials evoked by depolarizing current pulses. These results suggest that elevated ROS, especially OH∙, in the spinal cord sensitized dorsal horn neurons and produced hyperalgesia in normal rats. PMID:26457204

  14. The afferent signaling complex: Regulation of type I spiral ganglion neuron responses in the auditory periphery.

    PubMed

    Reijntjes, Daniël O J; Pyott, Sonja J

    2016-06-01

    The spiral ganglion neurons (SGNs) are the first action potential generating neurons in the auditory pathway. The type I SGNs contact the sensory inner hair cells via their peripheral dendrites and relay auditory information to the brainstem via their central axon fibers. Individual afferent fibers show differences in response properties that are essential for normal hearing. The mechanisms that give rise to the heterogeneity of afferent responses are very poorly understood but are likely already in place at the peripheral dendrites where synapses are formed and action potentials are generated. To identify these molecular mechanisms, this review synthesizes a variety of literature and comprehensively outlines the cellular and molecular components positioned to regulate SGN afferent dendrite excitability, especially following glutamate release. These components include 1) proteins of the SGN postsynapses and neighboring supporting cells that together shape glutamatergic signaling, 2) the ion channels and transporters that determine the intrinsic excitability of the SGN afferent dendrites, and 3) the neurotransmitter receptors that extrinsically modify this excitability via synaptic input from the lateral olivocochlear efferents. This cellular and molecular machinery, together with presynaptic specializations of the inner hair cells, can be collectively referred to as the type I afferent signaling complex. As this review underscores, interactions of this signaling complex determine excitability of the SGN afferent dendrites and the afferent fiber responses. Moreover, this complex establishes the environmental milieu critical for the development and maintenance of the SGN afferent dendrites and synapses. Motivated by these important functions, this review also indicates areas of future research to elucidate the contributions of the afferent signaling complex to both normal hearing and also hearing loss. PMID:27018296

  15. Transcriptome analysis reveals dysregulation of innate immune response genes and neuronal activity-dependent genes in autism

    PubMed Central

    Gupta, Simone; Ellis, Shannon E.; Ashar, Foram N.; Moes, Anna; Bader, Joel S.; Zhan, Jianan; West, Andrew B.; Arking, Dan E.

    2014-01-01

    Recent studies of genomic variation associated with autism have suggested the existence of extreme heterogeneity. Large-scale transcriptomics should complement these results to identify core molecular pathways underlying autism. Here we report results from a large-scale RNA sequencing effort, utilizing region-matched autism and control brains to identify neuronal and microglial genes robustly dysregulated in autism cortical brain. Remarkably, we note that a gene expression module corresponding to M2-activation states in microglia is negatively correlated with a differentially expressed neuronal module, implicating dysregulated microglial responses in concert with altered neuronal activity-dependent genes in autism brains. These observations provide pathways and candidate genes that highlight the interplay between innate immunity and neuronal activity in the aetiology of autism. PMID:25494366

  16. Visual Responses of Neurons in Somatosensory Cortex of Hamsters with Experimentally Induced Retinal Projections to Somatosensory Thalamus

    NASA Astrophysics Data System (ADS)

    Metin, Christine; Frost, Douglas O.

    1989-01-01

    These experiments investigate the capacity of thalamic and cortical structures in a sensory system to process information of a modality normally associated with another system. Retinal ganglion cells in newborn Syrian hamsters were made to project permanently to the main thalamic somatosensory (ventrobasal) nucleus. When the animals were adults, single unit recordings were made in the somatosensory cortices, the principal targets of the ventrobasal nucleus. The somatosensory neurons responded to visual stimulation of distinct receptive fields, and their response properties resembled, in several characteristic features, those of normal visual cortical neurons. In the visual cortex of normal animals and the somatosensory cortex of operated animals, the same functional categories of neurons occurred in similar proportions, and the neurons' selectivity for the orientation or direction of movement of visual stimuli was comparable. These results suggest that thalamic nuclei or cortical areas at corresponding levels in the visual and somatosensory pathways perform similar transformations on their inputs.

  17. Auto- and Crosscorrelograms for the Spike Response of Leaky Integrate-and-Fire Neurons with Slow Synapses

    NASA Astrophysics Data System (ADS)

    Moreno-Bote, Rubén; Parga, Néstor

    2006-01-01

    An analytical description of the response properties of simple but realistic neuron models in the presence of noise is still lacking. We determine completely up to the second order the firing statistics of a single and a pair of leaky integrate-and-fire neurons receiving some common slowly filtered white noise. In particular, the auto- and cross-correlation functions of the output spike trains of pairs of cells are obtained from an improvement of the adiabatic approximation introduced previously by Moreno-Bote and Parga [Phys. Rev. Lett.PRLTAO0031-9007 92, 028102 (2004)10.1103/PhysRevLett.92.028102]. These two functions define the firing variability and firing synchronization between neurons, and are of much importance for understanding neuron communication.

  18. Differential Tiam1/Rac1 activation in hippocampal and cortical neurons mediates differential spine shrinkage in response to oxygen/glucose deprivation

    PubMed Central

    Blanco-Suárez, Elena; Fiuza, Maria; Liu, Xun; Chakkarapani, Elavazhagan; Hanley, Jonathan G

    2014-01-01

    Distinct neuronal populations show differential sensitivity to global ischemia, with hippocampal CA1 neurons showing greater vulnerability compared to cortical neurons. The mechanisms that underlie differential vulnerability are unclear, and we hypothesize that intrinsic differences in neuronal cell biology are involved. Dendritic spine morphology changes in response to ischemic insults in vivo, but cell type-specific differences and the molecular mechanisms leading to such morphologic changes are unexplored. To directly compare changes in spine size in response to oxygen/glucose deprivation (OGD) in cortical and hippocampal neurons, we used separate and equivalent cultures of each cell type. We show that cortical neurons exhibit significantly greater spine shrinkage compared to hippocampal neurons. Rac1 is a Rho-family GTPase that regulates the actin cytoskeleton and is involved in spine dynamics. We show that Rac1 and the Rac guanine nucleotide exchange factor (GEF) Tiam1 are differentially activated by OGD in hippocampal and cortical neurons. Hippocampal neurons express more Tiam1 than cortical neurons, and reducing Tiam1 expression in hippocampal neurons by shRNA enhances OGD-induced spine shrinkage. Tiam1 knockdown also reduces hippocampal neuronal vulnerability to OGD. This work defines fundamental differences in signalling pathways that regulate spine morphology in distinct neuronal populations that may have a role in the differential vulnerability to ischemia. PMID:25248834

  19. Altered responsiveness of BNST and amygdala neurons in trauma-induced anxiety.

    PubMed

    Rodríguez-Sierra, O E; Goswami, S; Turesson, H K; Pare, D

    2016-01-01

    A highly conserved network of brain structures regulates the expression of fear and anxiety in mammals. Many of these structures display abnormal activity levels in post-traumatic stress disorder (PTSD). However, some of them, like the bed nucleus of the stria terminalis (BNST) and amygdala, are comprised of several small sub-regions or nuclei that cannot be resolved with human neuroimaging techniques. Therefore, we used a well-characterized rat model of PTSD to compare neuronal properties in resilient vs PTSD-like rats using patch recordings obtained from different BNST and amygdala regions in vitro. In this model, a persistent state of extreme anxiety is induced in a subset of susceptible rats following predatory threat. Previous animal studies have revealed that the central amygdala (CeA) and BNST are differentially involved in the genesis of fear and anxiety-like states, respectively. Consistent with these earlier findings, we found that between resilient and PTSD-like rats were marked differences in the synaptic responsiveness of neurons in different sectors of BNST and CeA, but whose polarity was region specific. In light of prior data about the role of these regions, our results suggest that control of fear/anxiety expression is altered in PTSD-like rats such that the influence of CeA is minimized whereas that of BNST is enhanced. A model of the amygdalo-BNST interactions supporting the PTSD-like state is proposed. PMID:27434491

  20. Disrupting astrocyte-neuron lactate transfer persistently reduces conditioned responses to cocaine.

    PubMed

    Boury-Jamot, B; Carrard, A; Martin, J L; Halfon, O; Magistretti, P J; Boutrel, B

    2016-08-01

    A central problem in the treatment of drug addiction is the high risk of relapse often precipitated by drug-associated cues. The transfer of glycogen-derived lactate from astrocytes to neurons is required for long-term memory. Whereas blockade of drug memory reconsolidation represents a potential therapeutic strategy, the role of astrocyte-neuron lactate transport in long-term conditioning has received little attention. By infusing an inhibitor of glycogen phosphorylase into the basolateral amygdala of rats, we report that disruption of astrocyte-derived lactate not only transiently impaired the acquisition of a cocaine-induced conditioned place preference but also persistently disrupted an established conditioning. The drug memory was rescued by L-Lactate co-administration through a mechanism requiring the synaptic plasticity-related transcription factor Zif268 and extracellular signal-regulated kinase (ERK) signalling pathway but not the brain-derived neurotrophic factor (Bdnf). The long-term amnesia induced by glycogenolysis inhibition and the concomitant decreased expression of phospho-ERK were both restored with L-Lactate co-administration. These findings reveal a critical role for astrocyte-derived lactate in positive memory formation and highlight a novel amygdala-dependent reconsolidation process, whose disruption may offer a novel therapeutic target to reduce the long-lasting conditioned responses to cocaine. PMID:26503760

  1. Disrupting astrocyte–neuron lactate transfer persistently reduces conditioned responses to cocaine

    PubMed Central

    Boury-Jamot, B; Carrard, A; Martin, J L; Halfon, O; Magistretti, P J; Boutrel, B

    2016-01-01

    A central problem in the treatment of drug addiction is the high risk of relapse often precipitated by drug-associated cues. The transfer of glycogen-derived lactate from astrocytes to neurons is required for long-term memory. Whereas blockade of drug memory reconsolidation represents a potential therapeutic strategy, the role of astrocyte–neuron lactate transport in long-term conditioning has received little attention. By infusing an inhibitor of glycogen phosphorylase into the basolateral amygdala of rats, we report that disruption of astrocyte-derived lactate not only transiently impaired the acquisition of a cocaine-induced conditioned place preference but also persistently disrupted an established conditioning. The drug memory was rescued by L-Lactate co-administration through a mechanism requiring the synaptic plasticity-related transcription factor Zif268 and extracellular signal-regulated kinase (ERK) signalling pathway but not the brain-derived neurotrophic factor (Bdnf). The long-term amnesia induced by glycogenolysis inhibition and the concomitant decreased expression of phospho-ERK were both restored with L-Lactate co-administration. These findings reveal a critical role for astrocyte-derived lactate in positive memory formation and highlight a novel amygdala-dependent reconsolidation process, whose disruption may offer a novel therapeutic target to reduce the long-lasting conditioned responses to cocaine. PMID:26503760

  2. Involvement of enteric neurones in the response of guinea-pig ileum preparations to metoclopramide.

    PubMed Central

    Bou, J.; Fernández, A. G.; Jauregui, J. M.; Massingham, R.

    1986-01-01

    The role of myenteric neurones in mediating the stimulant effects of metoclopramide in vitro in the guinea-pig ileum has been investigated using the non-ionic surfactant Triton X-100. Histological examination of the ileum 30 days after application of Triton X-100 to the serosal surface demonstrated a marked reduction in the number of ganglion cells and nerve elements in the myenteric plexus. Longitudinal muscle-myenteric plexus (LM-MP) preparations from Triton X-100-treated animals were unresponsive to dimethylphenylpiperazinium and responded poorly or not at all to electrical field stimulation. Metoclopramide (30 microM) elicited small contractions in LM-MP preparations from control and sham-operated animals but failed to contract Triton X-100-treated tissues. However, tissues responded in a similar manner to exogenous acetylcholine (ACh). These results demonstrate the importance of a prejunctional site of action for metoclopramide in this tissue and suggest that contractile responses to the drug are mediated indirectly, probably by increased release of ACh from myenteric neurones. Images Figure 1 PMID:3708227

  3. Post-spike hyperpolarization participates in the formation of auditory behavior-related response patterns of inferior collicular neurons in Hipposideros pratti.

    PubMed

    Li, Y-L; Fu, Z-Y; Yang, M-J; Wang, J; Peng, K; Yang, L-J; Tang, J; Chen, Q-C

    2015-03-19

    To probe the mechanism underlying the auditory behavior-related response patterns of inferior collicular neurons to constant frequency-frequency modulation (CF-FM) stimulus in Hipposideros pratti, we studied the role of post-spike hyperpolarization (PSH) in the formation of response patterns. Neurons obtained by in vivo extracellular (N=145) and intracellular (N=171) recordings could be consistently classified into single-on (SO) and double-on (DO) neurons. Using intracellular recording, we found that both SO and DO neurons have a PSH with different durations. Statistical analysis showed that most SO neurons had a longer PSH duration than DO neurons (p<0.01). These data suggested that the PSH directly participated in the formation of SO and DO neurons, and the PSH elicited by the CF component was the main synaptic mechanism underlying the SO and DO response patterns. The possible biological significance of these findings relevant to bat echolocation is discussed. PMID:25617651

  4. Early neuronal responses in right limbic structures mediate harmony incongruity processing in musical experts.

    PubMed

    James, Clara E; Britz, Juliane; Vuilleumier, Patrik; Hauert, Claude-Alain; Michel, Christoph M

    2008-10-01

    In western tonal music, musical phrases end with an explicit harmonic consequent which is highly expected. As such expectation is a consequence of musical background, cerebral processing of incongruities of musical grammar might be a function of expertise. We hypothesized that a subtle incongruity of standard closure should evoke a profound and rapid reaction in an expert's brain. If such a reaction is due to neuroplasticity as a consequence of musical training, it should be correlated with distinctive activations in sensory, motor and/or cognitive function related brain areas in response to the incongruent closure. Using event related potential (ERP) source imaging, we determined the temporal dynamics of neuronal activity in highly trained pianists and musical laymen in response to syntactic harmonic incongruities in expressive music, which were easily detected by the experts but not by the laymen. Our results revealed that closure incongruity evokes a selective early response in musical experts, characterized by a strong, right lateralized negative ERP component. Statistical source analysis could demonstrate putative contribution to the generation of this component in right temporal-limbic areas, encompassing hippocampal complex and amygdala, and in right insula. Its early onset (approximately 200 ms) preceded responses in frontal areas that may reflect more conscious processing. These results go beyond previous work demonstrating that musical training can change activity of sensory and motor areas during musical or audio-motor tasks, and suggest that functional plasticity in right medial-temporal structures and insula also modulates processing of subtle harmonic incongruities. PMID:18640279

  5. Phosphodiesterase 1C is dispensable for rapid response termination of olfactory sensory neurons

    PubMed Central

    Cygnar, Katherine D.; Zhao, Haiqing

    2009-01-01

    In the nose, odorants are detected on the cilia of olfactory sensory neurons (OSNs), where a cAMP-mediated signaling pathway transforms odor stimulation into electrical responses. Phosphodiesterase (PDE) activity in OSN cilia was long thought to account for rapid response termination by degrading odor-induced cAMP. Two PDEs with distinct cellular localization have been found in OSNs: PDE1C in cilia; PDE4A throughout the cell but absent from cilia. We disrupted both genes in mice and performed electroolfactogram analysis. Unexpectedly, eliminating PDE1C did not prolong response termination. Prolonged termination occurred only in mice lacking both PDEs, suggesting that cAMP degradation by PDE1C in cilia is not a rate-limiting factor for response termination in wildtype. Pde1c−/− OSNs instead displayed reduced sensitivity and attenuated adaptation to repeated stimulation, suggesting potential roles for PDE1C in regulating sensitivity and adaptation. These observations provide new perspectives in regulation of olfactory transduction. PMID:19305400

  6. Blockade of striatal neurone responses to morphine by aminophylline: evidence for adenosine mediation of opiate action.

    PubMed Central

    Perkins, M. N.; Stone, T. W.

    1980-01-01

    1 The responses of cortical and striatal neurones to morphine and adenosine applied iontophoretically have been studied in the male rat. 2 The majority of cells (57%) within the corpus striatum were profoundly inhibited, and a smaller proportion (18%) excited by morphine. Adenosine depressed the firing rate of 30/44 cells in the striatum, excitation never being observed. In contrast, the responses of cortical cells to morphine were typically weak and required longer ejection pulses to effect comparable changes in firing rate. 3 Aminophylline applied iontophoretically, as an anion, proved able to antagonize reversibly both morphine and adenosine in parallel. 4 On a number of cells, gamma-aminobutyric acid (GABA) was used as a control depressant but aminophylline did not appear to reduce these responses. 5 The responses to morphine (both inhibitory and excitatory) were not easily antagonized by naloxone. Typically, excitatory reponses were easier to antagonize than the inhibitory ones. 6 It is concluded that a consequence of the interaction of morphine with its receptors may be the release of adenosine which subsequently produces the inhibition observed with morphine. PMID:7378652

  7. Background complexity affects response of a looming-sensitive neuron to object motion.

    PubMed

    Silva, Ana C; McMillan, Glyn A; Santos, Cristina P; Gray, John R

    2015-01-01

    An increasing number of studies show how stimulus complexity affects the responses of looming-sensitive neurons across multiple animal taxa. Locusts contain a well-described, descending motion-sensitive pathway that is preferentially looming sensitive. However, the lobula giant movement detector/descending contralateral movement detector (LGMD/DCMD) pathway responds to more than simple objects approaching at constant, predictable trajectories. In this study, we presented Locusta migratoria with a series of complex three-dimensional visual stimuli presented while simultaneously recording DCMD activity extracellularly. In addition to a frontal looming stimulus, we used a combination of compound trajectories (nonlooming transitioning to looming) presented at different velocities and onto a simple, scattered, or progressive flow field background. Regardless of stimulus background, DCMD responses to looming were characteristic and related to previously described effects of azimuthal approach angle and velocity of object expansion. However, increasing background complexity caused reduced firing rates, delayed peaks, shorter rise phases, and longer fall phases. DCMD responded to transitions to looming with a characteristic drop in a firing rate that was relatively invariant across most stimulus combinations and occurred regardless of stimulus background. Spike numbers were higher in the presence of the scattered background and reduced in the flow field background. We show that DCMD response time to a transition depends on unique expansion parameters of the moving stimulus irrespective of background complexity. Our results show how background complexity shapes DCMD responses to looming stimuli, which is explained within a behavioral context. PMID:25274344

  8. Interactions between glutamate, dopamine, and the neuronal signature of response inhibition in the human striatum.

    PubMed

    Lorenz, Robert C; Gleich, Tobias; Buchert, Ralph; Schlagenhauf, Florian; Kühn, Simone; Gallinat, Jürgen

    2015-10-01

    Response inhibition is a basic mechanism in cognitive control and dysfunctional in major psychiatric disorders. The neuronal mechanisms are in part driven by dopamine in the striatum. Animal data suggest a regulatory role of glutamate on the level of the striatum. We used a trimodal imaging procedure of the human striatum including F18-DOPA positron emission tomography, proton magnetic resonance spectroscopy, and functional magnetic resonance imaging of a stop signal task. We investigated dopamine synthesis capacity and glutamate concentration in vivo and their relation to functional properties of response inhibition. A mediation analysis revealed a significant positive association between dopamine synthesis capacity and inhibition-related neural activity in the caudate nucleus. This relationship was significantly mediated by striatal glutamate concentration. Furthermore, stop signal reaction time was inversely related to striatal activity during inhibition. The data show, for the first time in humans, an interaction between dopamine, glutamate, and the neural signature of response inhibition in the striatum. This finding stresses the importance of the dopamine-glutamate interaction for behavior and may facilitate the understanding of psychiatric disorders characterized by impaired response inhibition. PMID:26177932

  9. Urethane anesthesia depresses activities of thalamocortical neurons and alters its response to nociception in terms of dual firing modes

    PubMed Central

    Huh, Yeowool; Cho, Jeiwon

    2013-01-01

    Anesthetics are often used to characterize the activity of single neurons in vivo for their advantages such as reduction of noise level and convenience in noxious stimulations. Urethane has been a widely used anesthetic in thalamic studies under the assumption that sensory signals are still relayed to the thalamus under urethane anesthesia and that thalamic response would therefore reflect the response of the awake state. We tested this assumption by comparing thalamic activity in terms of tonic and burst firing modes during “the awake state” or under “urethane anesthesia” using the extracellular single unit recording technique. We first tested how thalamic relay neurons respond to the introduction of urethane, and then tested how urethane influences thalamic discharges under formalin-induced nociception. Urethane significantly depressed overall firing rates of thalamic relay neurons, which was sustained despite the delayed increase of burst activity over a 4 h recording period. Thalamic response to nociception under anesthesia was also similar overall except for the slight and transient increase of burst activity. Overall, results demonstrated that urethane suppresses the activity of thalamic relay neurons and that, despite the slight fluctuation of burst firing, formalin-induced nociception cannot significantly change the firing pattern of thalamic relay neurons that was caused by urethane. PMID:24133420

  10. Electrophysiological properties of brain-natriuretic peptide- and gastrin-releasing peptide-responsive dorsal horn neurons in spinal itch transmission.

    PubMed

    Kusube, Fumiya; Tominaga, Mitsutoshi; Kawasaki, Hiroaki; Yamakura, Fumiyuki; Naito, Hisashi; Ogawa, Hideoki; Tomooka, Yasuhiro; Takamori, Kenji

    2016-08-01

    Spinal itch transmission has been reported to be mediated by at least two neuronal populations in spinal dorsal horn, neurons expressing brain-natriuretic peptide (BNP) receptor (Npra) and gastrin-releasing peptide (GRP) receptor (GRPR). Although Npra-expressing neurons were shown to be upstream of GRPR- expressing neurons in spinal itch transmission, the roles of BNP and GRP in the spinal neurotransmission of histamine-dependent and -independent itch remains unclear. Using in vivo electrophysiology and behavior analysis, this study examined the responses of chloroquine (histamine-independent pruritogen)-responsive and histamine-responsive dorsal horn neurons to spinal applications of BNP and GRP. Electrophysiologically, 9.5% of chloroquine-responsive neurons responded to BNP, 33.3% to GRP, and 4.8% to both, indicating that almost half of chloroquine-responsive neurons were unresponsive to both BNP and GRP. In contrast, histamine-responsive neurons did not respond to spinal BNP application, whereas 30% responded to spinal GRP application, indicating that 70% of histamine-responsive neurons were unresponsive to both BNP and GRP. Behavioral analyses showed differences in the time-course and frequency of scratching responses evoked by intrathecal BNP and GRP. These findings provide evidence that most BNP-Npra and GRP-GRPR signaling involve different pathways of spinal itch transmission, and that multiple neurotransmitters, in addition to BNP and GRP, are involved in spinal itch transmission. The electrophysiological results also suggest that spinal BNP contributes little to histaminergic itch directly. PMID:27235577

  11. The Effects of Energy Balance, Obesity-Proneness and Sex on the Neuronal Response to Sweet Taste

    PubMed Central

    Cornier, Marc-Andre; Shott, Megan E.; Thomas, Elizabeth A.; Bechtell, Jamie L.; Bessesen, Daniel H.; Tregellas, Jason R.; Frank, Guido K.

    2014-01-01

    We have previously shown that propensity for weight gain, energy balance state and sex are important determinants of the neuronal response to visual food cues. It is not clear, though, whether these factors also impact the neuronal response to taste. The objective of this study was to examine the neuronal response to sweet taste during energy imbalance in men and women recruited to be obesity-prone (OP) or obesity-resistant (OR). OP (13M, 12W) and OR (12M, 12W) subjects were studied after one day of eucaloric, overfed and underfed conditions in a randomized crossover design. On each test day, fMRI was performed in the respective acute fed state while subjects received in random order 60 trials each of 1M sucrose solution (SU), or artificial saliva (AS) following a visual cue predicting the taste. The neuronal response to SU vs AS expectation was significantly greater in the amygdala, orbitofrontal cortex, putamen and insula in OR versus OP; SU receipt was not different between groups. There were also sex-based differences with men having greater neuronal response to SU vs AS receipt in the caudate than women. The results, however, were not impacted by the state of energy balance. In summary, response to expectation but not receipt of basic sweet taste was different in OR compared to OP, highlighting the importance of learning and conditioning in the propensity to gain weight. Response to sucrose taste receipt was stronger in men than women, raising questions about the effect of sex hormones on brain response to food. PMID:25447301

  12. The effects of energy balance, obesity-proneness and sex on the neuronal response to sweet taste.

    PubMed

    Cornier, Marc-Andre; Shott, Megan E; Thomas, Elizabeth A; Bechtell, Jamie L; Bessesen, Daniel H; Tregellas, Jason R; Frank, Guido K

    2015-02-01

    We have previously shown that propensity for weight gain, energy balance state and sex are important determinants of the neuronal response to visual food cues. It is not clear, though, whether these factors also impact the neuronal response to taste. The objective of this study was to examine the neuronal response to sweet taste during energy imbalance in men and women recruited to be obesity-prone (OP) or obesity-resistant (OR). OP (13 men and 12 women) and OR (12 men and 12 women) subjects were studied after 1 day of eucaloric, overfed and underfed conditions in a randomized crossover design. On each test day, fMRI was performed in the respective acute fed state while subjects received in random order 60 trials each of 1M sucrose solution (SU), or artificial saliva (AS) following a visual cue predicting the taste. The neuronal response to SU versus AS expectation was significantly greater in the amygdala, orbitofrontal cortex, putamen and insula in OR versus OP; SU receipt was not different between groups. There were also sex-based differences with men having greater neuronal response to SU versus AS receipt in the caudate than women. The results, however, were not impacted by the state of energy balance. In summary, response to expectation but not receipt of basic sweet taste was different in OR compared to OP, highlighting the importance of learning and conditioning in the propensity to gain weight. Response to sucrose taste receipt was stronger in men than women, raising questions about the effect of sex hormones on brain response to food. PMID:25447301

  13. Layer-Specific fMRI Responses to Excitatory and Inhibitory Neuronal Activities in the Olfactory Bulb

    PubMed Central

    Poplawsky, Alexander John; Fukuda, Mitsuhiro; Murphy, Matthew

    2015-01-01

    High-resolution functional magnetic resonance imaging (fMRI) detects localized neuronal activity via the hemodynamic response, but it is unclear whether it accurately identifies neuronal activity specific to individual layers. To address this issue, we preferentially evoked neuronal activity in superficial, middle, and deep layers of the rat olfactory bulb: the glomerular layer by odor (5% amyl acetate), the external plexiform layer by electrical stimulation of the lateral olfactory tract (LOT), and the granule cell layer by electrical stimulation of the anterior commissure (AC), respectively. Electrophysiology, laser-Doppler flowmetry of cerebral blood flow (CBF), and blood oxygenation level-dependent (BOLD) and cerebral blood volume-weighted (CBV) fMRI at 9.4 T were performed independently. We found that excitation of inhibitory granule cells by stimulating LOT and AC decreased the spontaneous multi-unit activities of excitatory mitral cells and subsequently increased CBF, CBV, and BOLD signals. Odor stimulation also increased the hemodynamic responses. Furthermore, the greatest CBV fMRI responses were discretely separated into the same layers as the evoked neuronal activities for all three stimuli, whereas BOLD was poorly localized with some exception to the poststimulus undershoot. In addition, the temporal dynamics of the fMRI responses varied depending on the stimulation pathway, even within the same layer. These results indicate that the vasculature is regulated within individual layers and CBV fMRI has a higher fidelity to the evoked neuronal activity compared with BOLD. Our findings are significant for understanding the neuronal origin and spatial specificity of hemodynamic responses, especially for the interpretation of laminar-resolution fMRI. SIGNIFICANCE STATEMENT Functional magnetic resonance imaging (fMRI) is a noninvasive, in vivo technique widely used to map function of the entire brain, including deep structures, in animals and humans. However, it

  14. Differences in responsiveness of mediodorsal thalamic and medial prefrontal cortical neurons to social interaction and systemically administered phencyclidine in rats.

    PubMed

    Jodo, E; Katayama, T; Okamoto, M; Suzuki, Y; Hoshino, K; Kayama, Y

    2010-11-10

    Phencyclidine (PCP) is a psychotomimetic drug that induces schizophrenia-like symptoms in healthy individuals and behavioral abnormalities with corresponding symptoms of schizophrenia in non-human animals. Our previous studies showed that systemically administered PCP produces tonic activation of neurons in the medial prefrontal cortex (mPFC) of rats and that this activation is mainly via excitatory inputs from regions outside the mPFC. Such long-lasting activation of PFC neurons is now considered to be a pivotal factor in PCP-induced behavioral abnormalities. Although our previous study identified the ventral hippocampus as a possible source of the excitatory inputs, it is not the only source innervating the mPFC. Several regions such as the thalamus also have monosynaptic projections to the mPFC. Recently, increased c-fos expression by systemic PCP administration was reported in the mediodorsal nucleus of the thalamus (MD) and the centromedial nucleus of the thalamus (CM), which have strong reciprocal innervations with the mPFC. However, few studies have reported effects of PCP on the firing activity of MD/CM neurons in unanesthetized animals. In the current study in freely moving rats, we examined effects of systemically administered PCP on the spontaneous firing activity of the MD/CM, after identifying the response properties of recorded neurons in social interaction with an unfamiliar partner. About 30% of MD/CM neurons recorded exhibited tonic excitation following systemic PCP administration, whereas only a few neurons (7%) were inhibited by PCP. The proportion of MD neurons activated by systemic PCP administration was about half of that in the mPFC. Although the proportion of neurons responsive to social interaction did not differ between the two regions (40%), neurons activated during social interaction in the mPFC (90%) were more likely to be affected by systemic PCP administration than those in the MD/CM (45%). These results suggest that neurons

  15. Skin incision-induced receptive field responses of mechanosensitive peripheral neurons are developmentally regulated in the rat

    PubMed Central

    Gutierrez, Silvia; Giffear, Kelly; Eisenach, James C.; Ririe, Douglas G.

    2012-01-01

    Maturation of the nervous system results in changes in both central and peripheral processing. To better understand responses to injury in the young, developmental differences in the acute response to incision were investigated in both tactile and nociceptive myelinated peripheral mechanosensitive afferent neurons in vivo. Neuronal intrasomal recordings were performed in juvenile and infant rats in 34 L5 dorsal root ganglia, and each neuron was phenotypically defined. Neurons had a mechanosensitive receptive field in the glabrous skin on the plantar surface of the hind paw, which was characterized at baseline and for up to 45 min after incision. Fundamental maturational differences in the effect of incision were clear: in high-threshold nociceptive mechanoreceptors, the mechanical threshold decreased immediately and the receptive field size increased rapidly in juvenile rats but not in infant rats. Additionally, a divergence in changes in the instantaneous response frequency of tactile afferents occurred between the two ages. These differences may help explain maturational differences in responses to peripheral injury and suggest that differences in central nervous system responses may be partially mitigated by spatially confined and frequency-dependent differences resulting from tactile and nociceptive mechanosensitive input. PMID:22673323

  16. Reduction in host-finding behaviour in fungus-infected mosquitoes is correlated with reduction in olfactory receptor neuron responsiveness

    PubMed Central

    2011-01-01

    Background Chemical insecticides against mosquitoes are a major component of malaria control worldwide. Fungal entomopathogens formulated as biopesticides and applied as insecticide residual sprays could augment current control strategies and mitigate the evolution of resistance to chemical-based insecticides. Methods Anopheles stephensi mosquitoes were exposed to Beauveria bassiana or Metarhizium acridum fungal spores and sub-lethal effects of exposure to fungal infection were studied, especially the potential for reductions in feeding and host location behaviours related to olfaction. Electrophysiological techniques, such as electroantennogram, electropalpogram and single sensillum recording techniques were then employed to investigate how fungal exposure affected the olfactory responses in mosquitoes. Results Exposure to B. bassiana caused significant mortality and reduced the propensity of mosquitoes to respond and fly to a feeding stimulus. Exposure to M. acridum spores induced a similar decline in feeding propensity, albeit more slowly than B. bassiana exposure. Reduced host-seeking responses following fungal exposure corresponded to reduced olfactory neuron responsiveness in both antennal electroantennogram and maxillary palp electropalpogram recordings. Single cell recordings from neurons on the palps confirmed that fungal-exposed behavioural non-responders exhibited significantly impaired responsiveness of neurons tuned specifically to 1-octen-3-ol and to a lesser degree, to CO2. Conclusions Fungal infection reduces the responsiveness of mosquitoes to host odour cues, both behaviourally and neuronally. These pre-lethal effects are likely to synergize with fungal-induced mortality to further reduce the capacity of mosquito populations exposed to fungal biopesticides to transmit malaria. PMID:21812944

  17. Brainstem neurons responsible for postural, masseter or pharyngeal muscle atonia during paradoxical sleep in freely-moving cats.

    PubMed

    Sakai, K; Neuzeret, P-C

    2011-12-01

    In this mini review, we summarize our findings regarding the brainstem neurons responsible for the postural, masseter, or pharyngeal muscle atonia observed during paradoxical sleep (PS) in freely moving cats. Both the pons and medulla contain neurons showing tonic activation selective to PS and atonia, referred to as PS/atonia-on-neurons. The PS/atonia-on neurons, characterized by their most slow conducting property and located in the peri-locus coeruleus alpha (peri-LCa) and adjacent LCa of the mediodorsal pontine tegmentum, play a critical executive role in the somatic and orofacial muscle atonia observed during PS. Slow conducting medullary PS/atonia-on neurons located in the nuclei reticularis magnocellularis (Mc) and parvocellularis (Pc) may play a critical executive role in the generation of, respectively, antigravity or orofacial muscle atonia during PS. In addition, either tonic or phasic cessation of activity of medullary serotonergic neurons may play an important role in the atonia of genioglossus muscles during PS via a mechanism of disfacilitation. PMID:22205587

  18. Mitochondrial Cyclic AMP Response Element-binding Protein (CREB) Mediates Mitochondrial Gene Expression and Neuronal Survival*S

    PubMed Central

    Lee, Junghee; Kim, Chun-Hyung; Simon, David K.; Aminova, Lyaylya R.; Andreyev, Alexander Y.; Kushnareva, Yulia E.; Murphy, Anne N.; Lonze, Bonnie E.; Kim, Kwang-Soo; Ginty, David D.; Ferrante, Robert J.; Ryu, Hoon; Ratan, Rajiv R.

    2008-01-01

    Cyclic AMP response element-binding protein (CREB) is a widely expressed transcription factor whose role in neuronal protection is now well established. Here we report that CREB is present in the mitochondrial matrix of neurons and that it binds directly to cyclic AMP response elements (CREs) found within the mitochondrial genome. Disruption of CREB activity in the mitochondria decreases the expression of a subset of mitochondrial genes, including the ND5 subunit of complex I, down-regulates complex I-dependent mitochondrial respiration, and increases susceptibility to 3-nitropropionic acid, a mitochondrial toxin that induces a clinical and pathological phenotype similar to Huntington disease. These results demonstrate that regulation of mitochondrial gene expression by mitochondrial CREB, in part, underlies the protective effects of CREB and raise the possibility that decreased mitochondrial CREB activity contributes to the mitochondrial dysfunction and neuronal loss associated with neurodegenerative disorders. PMID:16207717

  19. Responses of Leaky Integrate-and-Fire Neurons to a Plurality of Stimuli in Their Receptive Fields.

    PubMed

    Li, Kang; Bundesen, Claus; Ditlevsen, Susanne

    2016-12-01

    A fundamental question concerning the way the visual world is represented in our brain is how a cortical cell responds when its classical receptive field contains a plurality of stimuli. Two opposing models have been proposed. In the response-averaging model, the neuron responds with a weighted average of all individual stimuli. By contrast, in the probability-mixing model, the cell responds to a plurality of stimuli as if only one of the stimuli were present. Here we apply the probability-mixing and the response-averaging model to leaky integrate-and-fire neurons, to describe neuronal behavior based on observed spike trains. We first estimate the parameters of either model using numerical methods, and then test which model is most likely to have generated the observed data. Results show that the parameters can be successfully estimated and the two models are distinguishable using model selection. PMID:27215548

  20. Response of a Hodgkin-Huxley neuron to a high-frequency input.

    PubMed

    Borkowski, L S

    2009-11-01

    We study the response of a Hodgkin-Huxley neuron stimulated by a periodic sequence of conductance pulses arriving through the synapse in the high-frequency regime. In addition to the usual excitation threshold there is a smooth crossover from the firing to the silent regime for increasing pulse amplitude gsyn. The amplitude of the voltage spikes decreases approximately linearly with gsyn. In some regions of parameter space the response is irregular, probably chaotic. In the chaotic regime between the mode-locked regions 3:1 and 2:1 near the lower excitation threshold, the output interspike interval histogram (ISIH) undergoes a sharp transition. If the driving period is below the critical value, TT* even multiples of Ti also appear in the histogram, starting from the largest values. Near T* the ISIH scales logarithmically on both sides of the transition. The coefficient of variation of ISIH has a cusp singularity at T*. The average response period has a maximum slightly above T*. Near the excitation threshold in the chaotic regime the average firing rate rises sublinearly from frequencies of order 1 Hz. PMID:20365013

  1. Influences of sensory input from the limbs on feline corticospinal neurons during postural responses

    PubMed Central

    Karayannidou, A; Deliagina, T G; Tamarova, Z A; Sirota, M G; Zelenin, P V; Orlovsky, G N; Beloozerova, I N

    2008-01-01

    The dorsal-side-up body posture of standing quadrupeds is maintained by coordinated activity of all limbs. Somatosensory input from the limbs evokes postural responses when the supporting surface is perturbed. The aim of this study was to reveal the contribution of sensory inputs from individual limbs to the posture-related modulation of pyramidal tract neurons (PTNs) arising in the primary motor cortex. We recorded the activity of PTNs from the limb representation of motor cortex in the cat maintaining balance on a platform periodically tilted in the frontal plane. Each PTN was recorded during standing on four limbs, and when two or three limbs were lifted from the platform and thus did not signal its displacement to motor cortex. By comparing PTN responses to tilts in different tests we found that the amplitude and the phase of the response in the majority of them were determined primarily by the sensory input from the corresponding contralateral limb. In a portion of PTNs, this input originated from afferents of the peripheral receptive field. Sensory input from the ipsilateral limb, as well as input from limbs of the other girdle made a much smaller contribution to the PTN modulation. These results show that, during postural activity, a key role of PTNs is the feedback control of the corresponding contralateral limb and, to a lesser extent, the coordination of posture within a girdle and between the two girdles. PMID:17974591

  2. The response of L5 pyramidal neurons of the PFC to magnetic stimulation from a micro-coil

    PubMed Central

    Lee, Seung Woo; Fried, Shelley I.

    2015-01-01

    Magnetic stimulation of the nervous system, e.g. transcranial magnetic stimulation (TMS), has been used both to unravel basic structure and function of the nervous system as well as to treat neurological diseases, i.e. clinical depression. Despite progress in both areas, ongoing advancements have been limited by a lack of understanding of the mechanism by which magnetic stimulation alters neural activity. Here, we report responses of cortical neurons to magnetic stimulation arising from a sub-millimeter coil. Cell attached patch clamp was used to record neural activity of layer 5/6 pyramidal neurons of the prefrontal cortex (PFC) in the in vitro mouse brain slice preparation. The fields arising from the small coil were quite different from those arising during clinical TMS but nevertheless allowed the responses of cortical neurons to magnetic stimulation to be probed. For example, the focal nature of induced fields allowed the sensitivity of different regions within targeted pyramidal neurons, e.g. apical dendrite, soma and axon hillock, to be compared. We found that PFC pyramidal neurons were not sensitive to single pulses of stimulation regardless of coil location. However, regions of the apical dendrite and proximal axon were both sensitive to repetitive stimulation as long as the orientation of the induced electric field was aligned with the long axis of the neuron. These results suggest that neurons of the PFC are sensitive to weak magnetic fields and further, that this type of approach may be useful for unraveling some of the mechanisms underlying TMS. PMID:25571395

  3. Relaxation oscillator-realized artificial electronic neurons, their responses, and noise

    NASA Astrophysics Data System (ADS)

    Lim, Hyungkwang; Ahn, Hyung-Woo; Kornijcuk, Vladimir; Kim, Guhyun; Seok, Jun Yeong; Kim, Inho; Hwang, Cheol Seong; Jeong, Doo Seok

    2016-05-01

    A proof-of-concept relaxation oscillator-based leaky integrate-and-fire (ROLIF) neuron circuit is realized by using an amorphous chalcogenide-based threshold switch and non-ideal operational amplifier (op-amp). The proposed ROLIF neuron offers biologically plausible features such as analog-type encoding, signal amplification, unidirectional synaptic transmission, and Poisson noise. The synaptic transmission between pre- and postsynaptic neurons is achieved through a passive synapse (simple resistor). The synaptic resistor coupled to the non-ideal op-amp realizes excitatory postsynaptic potential (EPSP) evolution that evokes postsynaptic neuron spiking. In an attempt to generalize our proposed model, we theoretically examine ROLIF neuron circuits adopting different non-ideal op-amps having different gains and slew rates. The simulation results indicate the importance of gain in postsynaptic neuron spiking, irrespective of the slew rate (as long as the rate exceeds a particular value), providing the basis for the ROLIF neuron circuit design. Eventually, the behavior of a postsynaptic neuron in connection to multiple presynaptic neurons via synapses is highlighted in terms of EPSP evolution amid simultaneously incident asynchronous presynaptic spikes, which in fact reveals an important role of the random noise in spatial integration.A proof-of-concept relaxation oscillator-based leaky integrate-and-fire (ROLIF) neuron circuit is realized by using an amorphous chalcogenide-based threshold switch and non-ideal operational amplifier (op-amp). The proposed ROLIF neuron offers biologically plausible features such as analog-type encoding, signal amplification, unidirectional synaptic transmission, and Poisson noise. The synaptic transmission between pre- and postsynaptic neurons is achieved through a passive synapse (simple resistor). The synaptic resistor coupled to the non-ideal op-amp realizes excitatory postsynaptic potential (EPSP) evolution that evokes postsynaptic

  4. Excitability and responsiveness of rat barrel cortex neurons in the presence and absence of spontaneous synaptic activity in vivo

    PubMed Central

    Altwegg-Boussac, Tristan; Chavez, Mario; Mahon, Séverine; Charpier, Stéphane

    2014-01-01

    The amplitude and temporal dynamics of spontaneous synaptic activity in the cerebral cortex vary as a function of brain states. To directly assess the impact of different ongoing synaptic activities on neocortical function, we performed in vivo intracellular recordings from barrel cortex neurons in rats under two pharmacological conditions generating either oscillatory or tonic synaptic drive. Cortical neurons membrane excitability and firing responses were compared, in the same neurons, before and after complete suppression of background synaptic drive following systemic injection of a high dose of anaesthetic. Compared to the oscillatory state, the tonic pattern resulted in a more depolarized and less fluctuating membrane potential (Vm), a lower input resistance (Rm) and steeper relations of firing frequency versus injected current (F–I). Whatever their temporal dynamics, suppression of background synaptic activities increased mean Vm, without affecting Rm, and induced a rightward shift of F–I curves. Both types of synaptic drive generated a high variability in current-induced firing rate and patterns in cortical neurons, which was much reduced after removal of spontaneous activity. These findings suggest that oscillatory and tonic synaptic patterns differentially facilitate the input–output function of cortical neurons but result in a similar moment-to-moment variability in spike responses to incoming depolarizing inputs. PMID:24732430

  5. Motor neurons in the escape response circuit of white shrimp (Litopenaeus setiferus)

    PubMed Central

    2015-01-01

    Many decapod crustaceans perform escape tailflips with a neural circuit involving giant interneurons, a specialized fast flexor motor giant (MoG) neuron, populations of larger, less specialized fast flexor motor neurons, and fast extensor motor neurons. These escape-related neurons are well described in crayfish (Reptantia), but not in more basal decapod groups. To clarify the evolution of the escape circuit, I examined the fast flexor and fast extensor motor neurons of white shrimp (Litopenaeus setiferus; Dendrobranchiata) using backfilling. In crayfish, the MoGs in each abdominal ganglion are a bilateral pair of separate neurons. In L. setiferus, the MoGs have massive, possibly syncytial, cell bodies and fused axons. The non-MoG fast flexor motor neurons and fast extensor motor neurons are generally found in similar locations to where they are found in crayfish, but the number of motor neurons in both the flexor and extensor pools is smaller than in crayfish. The loss of fusion in the MoGs and increased number of fast motor neurons in reptantian decapods may be correlated with an increased reliance on non-giant mediated tailflipping. PMID:26244117

  6. A point-process response model for spike trains from single neurons in neural circuits under optogenetic stimulation.

    PubMed

    Luo, X; Gee, S; Sohal, V; Small, D

    2016-02-10

    Optogenetics is a new tool to study neuronal circuits that have been genetically modified to allow stimulation by flashes of light. We study recordings from single neurons within neural circuits under optogenetic stimulation. The data from these experiments present a statistical challenge of modeling a high-frequency point process (neuronal spikes) while the input is another high-frequency point process (light flashes). We further develop a generalized linear model approach to model the relationships between two point processes, employing additive point-process response functions. The resulting model, point-process responses for optogenetics (PRO), provides explicit nonlinear transformations to link the input point process with the output one. Such response functions may provide important and interpretable scientific insights into the properties of the biophysical process that governs neural spiking in response to optogenetic stimulation. We validate and compare the PRO model using a real dataset and simulations, and our model yields a superior area-under-the-curve value as high as 93% for predicting every future spike. For our experiment on the recurrent layer V circuit in the prefrontal cortex, the PRO model provides evidence that neurons integrate their inputs in a sophisticated manner. Another use of the model is that it enables understanding how neural circuits are altered under various disease conditions and/or experimental conditions by comparing the PRO parameters. PMID:26411923

  7. Inverted optical intrinsic response accompanied by decreased cerebral blood flow are related to both neuronal inhibition and excitation

    PubMed Central

    Ma, Zengguang; Cao, Pengjia; Sun, Pengcheng; Zhao, Linna; Li, Liming; Tong, Shanbao; Lu, Yiliang; Yan, Yan; Chen, Yao; Chai, Xinyu

    2016-01-01

    Negative hemodynamic response has been widely reported in blood oxygenation level-dependent (BOLD) functional magnetic resonance imaging studies, however its origin is still controversial. Optical intrinsic signal (OIS) imaging can be used to study brain activity by simultaneously recording hemodynamic signals at different wavelengths with high spatial resolution. In this study, we found transcorneal electrical stimulation (TcES) could elicit both positive OIS response (POR) and negative OIS response (NOR) in cats’ visual cortex. We then investigated the property of this negative response to TcES and its relationship with cerebral blood flow (CBF) and neuronal activity. Results from laser speckle contrast imaging showed decreased CBF in the NOR region while increased CBF in the POR region. Both planar and laminar electrophysiological recordings in the middle (500–700 μm) cortical layers demonstrated that decreased and increased neuronal activities were coexisted in the NOR region. Furthermore, decreased neuronal activity was also detected in the deep cortical layers in the NOR region. This work provides evidence that the negative OIS together with the decreased CBF should be explained by mechanisms of both neuronal inhibition and excitation within middle cortical layers. Our results would be important for interpreting neurophysiological mechanisms underlying the negative BOLD signals. PMID:26860040

  8. Thiopental sodium preserves the responsiveness to glutamate but not acetylcholine in rat primary cultured neurons exposed to hypoxia.

    PubMed

    Morita, Tomotaka; Shibuta, Satoshi; Kosaka, Jun; Fujino, Yuji

    2016-06-15

    Although many in vitro studies demonstrated that thiopental sodium (TPS) is a promising neuroprotective agent, clinical attempts to use TPS showed mainly unsatisfactory results. We investigated the neuroprotective effects of TPS against hypoxic insults (HI), and the responses of the neurons to l-glutamate and acetylcholine application. Neurons prepared from E17 Wistar rats were used after 2weeks in culture. The neurons were exposed to 12-h HI with or without TPS. HI-induced neurotoxicity was evaluated morphologically. Moreover, we investigated the dynamics of the free intracellular calcium ([Ca(2+)]i) in the surviving neurons after HI with or without TPS pretreatment following the application of neurotransmitters. TPS was neuroprotective against HI according to the morphological examinations (0.73±0.06 vs. 0.52±0.07, P=0.04). While the response to l-glutamate was maintained (0.89±0.08 vs. 1.02±0.09, P=0.60), the [Ca(2+)]i response to acetylcholine was notably impaired (0.59±0.02 vs. 0.94±0.04, P<0.01). Though TPS to cortical cultures was neuroprotective against HI morphologically, the [Ca(2+)]i response not to l-glutamate but to acetylcholine was impaired. This may partially explain the inconsistent results regarding the neuroprotective effects of TPS between experimental studies and clinical settings. PMID:27206889

  9. Directional responses of visual wulst neurones to grating and plaid patterns in the awake owl.

    PubMed

    Baron, Jerome; Pinto, Lucas; Dias, Marcelo Oliveira; Lima, Bruss; Neuenschwander, Sergio

    2007-10-01

    The avian retinothalamofugal pathway reaches the telencephalon in an area known as visual wulst. A close functional analogy between this area and the early visual cortex of mammals has been established in owls. The goal of the present study was to assess quantitatively the directional selectivity and motion integration capability of visual wulst neurones, aspects that have not been previously investigated. We recorded extracellularly from a total of 101 cells in awake burrowing owls. From this sample, 88% of the units exhibited modulated directional responses to sinusoidal gratings, with a mean direction index of 0.74 +/- 0.03 and tuning bandwidth of 28 +/- 1.16 degrees . A direction index higher than 0.5 was observed in 66% of the cells, thereby qualifying them as direction selective. Motion integration was tested with moving plaids, made by adding two sinusoidal gratings of different orientations. We found that 80% of direction-selective cells responded optimally to the motion direction of the component gratings, whereas none responded to the global motion of plaids, whose direction was intermediate to that of the gratings. The remaining 20% were unclassifiable. The strength of component motion selectivity rapidly increased over a 200 ms period following stimulus onset, maintaining a relatively sustained profile thereafter. Overall, our data suggest that, as in the mammalian primary visual cortex, the visual wulst neurones of owls signal the local orientated features of a moving object. How and where these potentially ambiguous signals are integrated in the owl brain might be important for understanding the mechanisms underlying global motion perception. PMID:17897399

  10. Adult axolotls can regenerate original neuronal diversity in response to brain injury.

    PubMed

    Amamoto, Ryoji; Huerta, Violeta Gisselle Lopez; Takahashi, Emi; Dai, Guangping; Grant, Aaron K; Fu, Zhanyan; Arlotta, Paola

    2016-01-01

    The axolotl can regenerate multiple organs, including the brain. It remains, however, unclear whether neuronal diversity, intricate tissue architecture, and axonal connectivity can be regenerated; yet, this is critical for recovery of function and a central aim of cell replacement strategies in the mammalian central nervous system. Here, we demonstrate that, upon mechanical injury to the adult pallium, axolotls can regenerate several of the populations of neurons present before injury. Notably, regenerated neurons acquire functional electrophysiological traits and respond appropriately to afferent inputs. Despite the ability to regenerate specific, molecularly-defined neuronal subtypes, we also uncovered previously unappreciated limitations by showing that newborn neurons organize within altered tissue architecture and fail to re-establish the long-distance axonal tracts and circuit physiology present before injury. The data provide a direct demonstration that diverse, electrophysiologically functional neurons can be regenerated in axolotls, but challenge prior assumptions of functional brain repair in regenerative species. PMID:27156560

  11. Stress-Hyperresponsive WKY Rats Demonstrate Depressed Dorsal Raphe Neuronal Excitability and Dysregulated CRF-Mediated Responses

    PubMed Central

    Lemos, Julia C; Zhang, Guojun; Walsh, Teresa; Kirby, Lynn G; Akanwa, Adaure; Brooks-Kayal, Amy; Beck, Sheryl G

    2011-01-01

    Major depression is a debilitating psychiatric disease that may be precipitated by a dysregulation of stress neurocircuitry caused by chronic or severe stress exposure. Moreover, hyperresponsivity to stressors correlates with depressed mood and may contribute to the etiology of major depression. The serotonergic dorsal raphe nucleus (DRN) is an important site in the neurocircuitry underlying behavioral responses to stressors, and is tightly regulated, in part, by a combination of intrinsic cell properties, autoinhibition, and GABAergic synaptic transmission. The stress-related neurotransmitter corticotropin-releasing factor (CRF) modulates DRN neuronal excitability and subsequent 5-HT release in the forebrain. Wistar Kyoto (WKY) rats exhibit exaggerated behavioral responses to stressors, that is, stress hyperresponsivity, and are considered an animal model of depression. To better understand the neurobiological basis of the stress hyperresponsivity, we used a combination of mRNA analysis and whole-cell electrophysiological techniques to measure differences in intrinsic activity and receptor response, in 5-HT- and non-5-HT-containing neurons of the DRN in WKY rats compared with Sprague-Dawley controls. In the WKY rat, there was a decrease in the neuronal excitability of 5-HT neurons coupled with decreased TPH2 production. Additionally, we found that CRF did not increase GABAergic activity in 5-HT neurons as is normally seen in 5-HT neurons of Sprague-Dawley controls. The CRF modulation of 5-HT DRN neurotransmission at the single-cell level is selectively disrupted in the WKY animal model of depression and may be one of the cellular correlates underlying depression. PMID:21160465

  12. Modulatory Effects of Sex Steroids Progesterone and Estradiol on Odorant Evoked Responses in Olfactory Receptor Neurons

    PubMed Central

    Scholz, Paul; Mohrhardt, Julia; Gisselmann, Günter; Hatt, Hanns

    2016-01-01

    The influence of the sex steroid hormones progesterone and estradiol on physiology and behavior during menstrual cycles and pregnancy is well known. Several studies indicate that olfactory performance changes with cyclically fluctuating steroid hormone levels in females. Knowledge of the exact mechanisms behind how female sex steroids modulate olfactory signaling is limited. A number of different known genomic and non-genomic actions that are mediated by progesterone and estradiol via interactions with different receptors may be responsible for this modulation. Next generation sequencing-based RNA-Seq transcriptome data from the murine olfactory epithelium (OE) and olfactory receptor neurons (ORNs) revealed the expression of several membrane progestin receptors and the estradiol receptor Gpr30. These receptors are known to mediate rapid non-genomic effects through interactions with G proteins. RT-PCR and immunohistochemical staining results provide evidence for progestin and estradiol receptors in the ORNs. These data support the hypothesis that steroid hormones are capable of modulating the odorant-evoked activity of ORNs. Here, we validated this hypothesis through the investigation of steroid hormone effects by submerged electro-olfactogram and whole cell patch-clamp recordings of ORNs. For the first time, we demonstrate that the sex steroid hormones progesterone and estradiol decrease odorant-evoked signals in the OE and ORNs of mice at low nanomolar concentrations. Thus, both of these sex steroids can rapidly modulate the odor responsiveness of ORNs through membrane progestin receptors and the estradiol receptor Gpr30. PMID:27494699

  13. Neuronal networks and mediators of cortical neurovascular coupling responses in normal and altered brain states.

    PubMed

    Lecrux, C; Hamel, E

    2016-10-01

    Brain imaging techniques that use vascular signals to map changes in neuronal activity, such as blood oxygenation level-dependent functional magnetic resonance imaging, rely on the spatial and temporal coupling between changes in neurophysiology and haemodynamics, known as 'neurovascular coupling (NVC)'. Accordingly, NVC responses, mapped by changes in brain haemodynamics, have been validated for different stimuli under physiological conditions. In the cerebral cortex, the networks of excitatory pyramidal cells and inhibitory interneurons generating the changes in neural activity and the key mediators that signal to the vascular unit have been identified for some incoming afferent pathways. The neural circuits recruited by whisker glutamatergic-, basal forebrain cholinergic- or locus coeruleus noradrenergic pathway stimulation were found to be highly specific and discriminative, particularly when comparing the two modulatory systems to the sensory response. However, it is largely unknown whether or not NVC is still reliable when brain states are altered or in disease conditions. This lack of knowledge is surprising since brain imaging is broadly used in humans and, ultimately, in conditions that deviate from baseline brain function. Using the whisker-to-barrel pathway as a model of NVC, we can interrogate the reliability of NVC under enhanced cholinergic or noradrenergic modulation of cortical circuits that alters brain states.This article is part of the themed issue 'Interpreting BOLD: a dialogue between cognitive and cellular neuroscience'. PMID:27574304

  14. A kinetic model of the transient phase in the response of olfactory receptor neurons.

    PubMed

    Getz, W M

    1999-10-01

    A model is presented that predicts the instantaneous spike rate of an olfactory receptor neuron (ORN) in response to the quality and concentration of an odor stimulus. The model accounts for the chemical kinetics of ligand-receptor binding and activation processes, and implicitly the initiation of second messenger cascades that lead to depolarization and/or hyperpolarization of the ORN membrane. Both of these polarizing processes are included in the most general form of the model, as well as a process that restores the voltage to its negative resting state. The spike rate is assumed to be linearly proportional to the level of voltage depolarization above a critical negative voltage level. The model includes the simplifying assumption that activation of bound ligand-receptor complexes by G-proteins and other enabling molecules follows a Monod function that has the ratio of enabling molecules to bound unactivated ligand-receptor complexes as its argument. Parameters are selected that provide an excellent fit of the model to previously published empirical data on the response of cockroach ORNs to pulsed 1-hexanol stimuli. The sensitivity of model output to various model parameters is investigated and changes to parameters are discussed that would improve the ability of ORNs to follow rapidly pulsed stimuli. PMID:10576257

  15. Different expression domains for two closely related amphibian TAARs generate a bimodal distribution similar to neuronal responses to amine odors.

    PubMed

    Syed, Adnan S; Sansone, Alfredo; Röner, Sebastian; Bozorg Nia, Shahrzad; Manzini, Ivan; Korsching, Sigrun I

    2015-01-01

    Olfactory perception is mediated by a multitude of olfactory receptors, whose expression in the sensory surface, the olfactory epithelium, is spatially regulated. A common theme is the segregation of different olfactory receptors in different expression domains, which in turn leads to corresponding segregation in the neuronal responses to different odor groups. The amphibian olfactory receptor gene family of trace amine associated receptors, in short TAARs, is exceedingly small and allows a comprehensive analysis of spatial expression patterns, as well as a comparison with neuronal responses to the expected ligands for this receptor family, amines. Here we report that TAAR4b exhibits a spatial expression pattern characteristically different in two dimensions from that of TAAR4a, its close homolog. Together, these two genes result in a bimodal distribution resembling that of amine responses as visualized by calcium imaging. A stringent quantitative analysis suggests the involvement of additional olfactory receptors in amphibian responses to amine odors. PMID:26358883

  16. Different expression domains for two closely related amphibian TAARs generate a bimodal distribution similar to neuronal responses to amine odors

    PubMed Central

    Syed, Adnan S.; Sansone, Alfredo; Röner, Sebastian; Bozorg Nia, Shahrzad; Manzini, Ivan; Korsching, Sigrun I.

    2015-01-01

    Olfactory perception is mediated by a multitude of olfactory receptors, whose expression in the sensory surface, the olfactory epithelium, is spatially regulated. A common theme is the segregation of different olfactory receptors in different expression domains, which in turn leads to corresponding segregation in the neuronal responses to different odor groups. The amphibian olfactory receptor gene family of trace amine associated receptors, in short TAARs, is exceedingly small and allows a comprehensive analysis of spatial expression patterns, as well as a comparison with neuronal responses to the expected ligands for this receptor family, amines. Here we report that TAAR4b exhibits a spatial expression pattern characteristically different in two dimensions from that of TAAR4a, its close homolog. Together, these two genes result in a bimodal distribution resembling that of amine responses as visualized by calcium imaging. A stringent quantitative analysis suggests the involvement of additional olfactory receptors in amphibian responses to amine odors. PMID:26358883

  17. Relaxation oscillator-realized artificial electronic neurons, their responses, and noise.

    PubMed

    Lim, Hyungkwang; Ahn, Hyung-Woo; Kornijcuk, Vladimir; Kim, Guhyun; Seok, Jun Yeong; Kim, Inho; Hwang, Cheol Seong; Jeong, Doo Seok

    2016-05-14

    A proof-of-concept relaxation oscillator-based leaky integrate-and-fire (ROLIF) neuron circuit is realized by using an amorphous chalcogenide-based threshold switch and non-ideal operational amplifier (op-amp). The proposed ROLIF neuron offers biologically plausible features such as analog-type encoding, signal amplification, unidirectional synaptic transmission, and Poisson noise. The synaptic transmission between pre- and postsynaptic neurons is achieved through a passive synapse (simple resistor). The synaptic resistor coupled to the non-ideal op-amp realizes excitatory postsynaptic potential (EPSP) evolution that evokes postsynaptic neuron spiking. In an attempt to generalize our proposed model, we theoretically examine ROLIF neuron circuits adopting different non-ideal op-amps having different gains and slew rates. The simulation results indicate the importance of gain in postsynaptic neuron spiking, irrespective of the slew rate (as long as the rate exceeds a particular value), providing the basis for the ROLIF neuron circuit design. Eventually, the behavior of a postsynaptic neuron in connection to multiple presynaptic neurons via synapses is highlighted in terms of EPSP evolution amid simultaneously incident asynchronous presynaptic spikes, which in fact reveals an important role of the random noise in spatial integration. PMID:27103542

  18. Dynamic response and transfer characteristics of joint neurons in somatosensory thalamus of the cat.

    PubMed

    Yin, T C; Williams, W J

    1976-05-01

    1. The dynamic response of neurons sensitive to knee joint rotation in the cat somatosensory thalamus was studied during sinusoidal variation of joint angle. The input sine waves were applied with a precise voltage-controlled, electromechanical actuator. The average rate of discharge of a single cell was considered as the output parameter. Describing functions of the sensory system were extracted by correlation and spectral analysis techniques. The effects of anesthetic, bias angle, and excursion angle were investigated. Discrete and swept sinusoidal waveforms between 0.1 and 7.0 Hz were used as inputs.2. The majority of joint cells in the thalamus were rapidly adapting and had frequency-response curves that were characterized as highpass filters. Although the major features of the response curves for individual cells were very similar, they could not all be fit with a single transfer function. The describing function of all the rapidly adapting cells averaged together was well fit by a transfer function that could be termed velocity sensitive in the bandwidth between 0.1 and 6.5 Hz. Most of these phasic cells showed a phase-locking tendency, particularly at high frequencies.3. The dynamics of the response for the rapidly adapting cells was relatively independent of anesthetic, bias angle, and excursion angle. Threshold and saturation effects were exhibited by some cells for very small (less than 1 degree) and large (greater than 10 degrees) input amplitudes, respectively. In addition a few (17%) showed a bidirectional response, i.e., responded at both flexion and extension of the limb. The anesthetic had a strong effect in depressing the spontaneous discharge of the cells and seemed to change the character of the tonic response by introducing a bursting component.4. The transfer characteristic of the thalamic cells was found to be a single-pole low-pass filter plus a time delay. The optimized value for the filter was found to have a corner frequency of 6.0 Hz with

  19. Dissociation of response variability from firing rate effects in frontal eye field neurons during visual stimulation, working memory, and attention.

    PubMed

    Chang, Mindy H; Armstrong, Katherine M; Moore, Tirin

    2012-02-01

    Recent studies suggest that trial-to-trial variability of neuronal spiking responses may provide important information about behavioral state. Observed changes in variability during sensory stimulation, attention, motor preparation, and visual discrimination suggest that variability may reflect the engagement of neurons in a behavioral task. We examined changes in spiking variability of frontal eye field (FEF) neurons in a change detection task requiring monkeys to remember a visually cued location and direct attention to that location while ignoring distracters elsewhere. In this task, the firing rates (FRs) of FEF neurons not only continuously reflect the location of the remembered cue and select targets, but also predict detection performance on a trial-by-trial basis. Changes in FEF response variability, as measured by the Fano factor (FF), showed clear dissociations from changes in FR. The FF declined in response to visual stimulation at all tested locations, even in the opposite hemifield, indicating much broader spatial tuning of the FF compared with the FR. Furthermore, despite robust spatial modulation of the FR throughout all epochs of the task, spatial tuning of the FF did not persist throughout the delay period, nor did it show attentional modulation. These results indicate that changes in variability, at least in the FEF, are most effectively driven by visual stimulation, while behavioral engagement is not sufficient. Instead, changes in variability may reflect shifts in the balance between feedforward and recurrent sources of excitatory drive. PMID:22323732

  20. Responses of single corticospinal neurons to intracortical stimulation of primary motor and premotor cortex in the anesthetized macaque monkey.

    PubMed

    Maier, Marc A; Kirkwood, Peter A; Brochier, Thomas; Lemon, Roger N

    2013-06-01

    The responses of individual primate corticospinal neurons to localized electrical stimulation of primary motor (M1) and of ventral premotor cortex (area F5) are poorly documented. To rectify this and to study interactions between responses from these areas, we recorded corticospinal axons, identified by pyramidal tract stimulation, in the cervical spinal cord of three chloralose-anesthetized macaque monkeys. Single stimuli (≤400 μA) were delivered to the hand area of M1 or F5 through intracortical microwire arrays. Only 14/112 (13%) axons showed responses to M1 stimuli that indicated direct intracortical activation of corticospinal neurons (D-responses); no D-responses were seen from F5. In contrast, 62 axons (55%) exhibited consistent later responses to M1 stimulation, corresponding to indirect activation (I-responses), showing that single-pulse intracortical stimulation of motor areas can result in trans-synaptic activation of a high proportion of the corticospinal output. A combined latency histogram of all axon responses was nonperiodic, clearly different from the periodic surface-recorded corticospinal volleys. This was readily explained by correcting for conduction velocities of individual axons. D-responding axons, taken as originating in neurons close to the M1 stimulating electrodes, showed more I-responses from M1 than those without a D-response, and 8/10 of these axons also responded to F5 stimulation. Altogether, 33% of tested axons responded to F5 stimulation, most of which also showed I-responses from M1. These excitatory effects are in keeping with facilitation of hand muscles evoked from F5 being relayed via M1. This was further demonstrated by facilitation of test responses from M1 by conditioning F5 stimuli. PMID:23536718

  1. Spatiotemporal Changes of Neuronal Responses in the Primary Somatosensory Cortex to Noxious Tail Stimulation in Awake and Pentobarbital-Anesthetized Rats.

    PubMed

    Kuo, Chung-Chih; Lee, Jye-Chang; Chiou, Ruei-Jen; Tsai, Meng-Li; Yen, Chen-Tung

    2015-10-31

    Primary somatosensory cortex (SI) is a key area in the processing of nociceptor inputs to our consciousness. To clarify the columnar and laminar organization of SI for pain processing, we compared spatiotemporal changes in neuronal activities of the primary sensorimotor cortex (SmI) of the rat in response to noxious laser heat stimulation applied to the mid-tail. Longitudinal and vertical array microelectrodes were chronically implanted in the cerebral cortex. Evoked neuronal activities, including intracortical local field potentials (LFP) and ensemble single-unit activity (SU) around SmI were simultaneously recorded. The effect of pentobarbital on the neuronal responses was evaluated in comparison with the neuronal responses in conscious animals to explore the potential substrate of nociceptive processing in the conscious state. The results from the experiment with longitudinal microelectrode arrays indicated that noxious stimulation induced a neuronal response which was spread widely around the SmI of the conscious rat, and the range of neuronal responses was limited to the tail region of the SmI under anesthesia. The results from the experiment with vertical microelectrode arrays showed the universal neuronal responses through all cortical layers of the SmI in conscious rats, and sodium pentobarbital suppressed these neuronal responses in the supragranular layers significantly relative to the deeper layers and basal activity. These results imply that a wider range of cortical activation, both in the horizontal or vertical dimension, might be important for nociceptive processing in the conscious state. PMID:26387657

  2. Heterogeneous responses of nucleus incertus neurons to corticotrophin-releasing factor and coherent activity with hippocampal theta rhythm in the rat

    PubMed Central

    Ma, Sherie; Blasiak, Anna; Olucha-Bordonau, Francisco E; Verberne, Anthony J M; Gundlach, Andrew L

    2013-01-01

    The nucleus incertus (NI) of the rat hindbrain is a putative node in the ascending control of the septohippocampal system and hippocampal theta rhythm and is stress and arousal responsive. NI contains GABA neurons that express multiple neuropeptides, including relaxin-3 (RLN3) and neuropeptide receptors, including corticotrophin-releasing factor receptor-1 (CRF-R1), but the precise anatomical and physiological characteristics of NI neurons are unclear. Therefore, we examined the firing properties of NI neurons and their responses to CRF, the correlation of these responses with occurrence of relaxin-3, and NI neuron morphology in the rat. Most NI neurons excited by intracerebroventricular CRF infusion were RLN3-positive (9 of 10), whereas all inhibited cells were RLN3-negative (8 of 8). The spontaneous firing of RLN3 (n= 6) but not non-RLN3 neurons (n= 6) was strongly modulated and phase-locked with the initial ascending phase of hippocampal theta oscillations. In brain slices, the majority of recorded NI neurons (15 of 19) displayed excitatory responses to CRF, which uniformly increased action potential frequency and membrane potential depolarization in the presence of tetrodotoxin, indicating a direct, postsynaptic action of CRF on NI neurons. This excitation was associated with reduction in the slow component of afterhyperpolarization and a strong depolarization. Quantitative analysis in naïve rats of validated CRF-R1, RLN3 and neuronal nuclear antigen (NeuN) immunoreactivity revealed 52% of NI neurons as CRF-R1 positive, of which 53% were RLN3 positive, while 48% of NI neurons lacked CRF-R1 and RLN3. All RLN3 neurons expressed CRF-R1. CRF neurons that projected to the NI were identified in lateral preoptic hypothalamus, but not in paraventricular hypothalamus, bed nucleus of stria terminalis or central amygdala. Our findings suggest NI is an important site for CRF modulation of hippocampal theta rhythm via effects on GABA/RLN3 transmission. PMID:23671163

  3. Differential response of the central noradrenergic nervous system to the loss of locus coeruleus neurons in Parkinson's disease and Alzheimer's disease

    PubMed Central

    McMillan, Pamela J; White, Sylvia S; Franklin, Allyn; Greenup, J Lynne; Leverenz, James B; Raskind, Murray A; Szot, Patricia

    2011-01-01

    In Parkinson's disease (PD), there is a significant loss of noradrenergic neurons in the locus coeruleus (LC) in addition to the loss of dopaminergic neurons in the substantia nigra (SN). The goal of this study was to determine if the surviving LC noradrenergic neurons in PD demonstrate compensatory changes in response to the neuronal loss, as observed in Alzheimer's disease (AD). Tyrosine hydroxylase (TH) and dopamine β-hydroxylase (DBH) mRNA expression in postmortem LC tissue of control and age-matched PD subjects demonstrated a significant reduction in the number of noradrenergic neurons in the LC of PD subjects. TH mRNA expression/neuron did not differ between control and PD subjects, but DBH mRNA expression/neuron was significantly elevated in PD subjects compared to control. This increase in DBH mRNA expression in PD subjects is not a response to neuronal loss because the amount of DBH mRNA expression/neuron in AD subjects was not significantly different from control. Norepinephrine transporter (NET) binding site concentration in the LC of PD subjects was significantly reduced over the cell body region as well as the peri-LC dendritic zone. In PD subjects, the loss of dendrites from surviving noradrenergic neurons was also apparent with TH-immunoreactivity (IR). This loss of LC dendritic innervation in PD subjects as measured by TH-IR was not due to LC neuronal loss because TH-IR in AD subjects was robust, despite a similar loss of LC neurons. These data suggest that there is a differential response of the noradrenergic nervous system in PD compared to AD in response to the loss of LC neurons. PMID:21147074

  4. Differential response of the central noradrenergic nervous system to the loss of locus coeruleus neurons in Parkinson's disease and Alzheimer's disease.

    PubMed

    McMillan, Pamela J; White, Sylvia S; Franklin, Allyn; Greenup, J Lynne; Leverenz, James B; Raskind, Murray A; Szot, Patricia

    2011-02-10

    In Parkinson's disease (PD), there is a significant loss of noradrenergic neurons in the locus coeruleus (LC) in addition to the loss of dopaminergic neurons in the substantia nigra (SN). The goal of this study was to determine if the surviving LC noradrenergic neurons in PD demonstrate compensatory changes in response to the neuronal loss, as observed in Alzheimer's disease (AD). Tyrosine hydroxylase (TH) and dopamine β-hydroxylase (DBH) mRNA expression in postmortem LC tissue of control and age-matched PD subjects demonstrated a significant reduction in the number of noradrenergic neurons in the LC of PD subjects. TH mRNA expression/neuron did not differ between control and PD subjects, but DBH mRNA expression/neuron was significantly elevated in PD subjects compared to control. This increase in DBH mRNA expression in PD subjects is not a response to neuronal loss because the amount of DBH mRNA expression/neuron in AD subjects was not significantly different from control. Norepinephrine transporter (NET) binding site concentration in the LC of PD subjects was significantly reduced over the cell body region as well as the peri-LC dendritic zone. In PD subjects, the loss of dendrites from surviving noradrenergic neurons was also apparent with TH-immunoreactivity (IR). This loss of LC dendritic innervation in PD subjects as measured by TH-IR was not due to LC neuronal loss because TH-IR in AD subjects was robust, despite a similar loss of LC neurons. These data suggest that there is a differential response of the noradrenergic nervous system in PD compared to AD in response to the loss of LC neurons. PMID:21147074

  5. Connexin and pannexin hemichannels in inflammatory responses of glia and neurons

    PubMed Central

    Bennett, Michael V. L.; Garré, Juan M.; Orellana, Juan A.; Bukauskas, Felix F.; Nedergaard, Maiken; Sáez, Juan C.

    2013-01-01

    permeabilization is opening of Cx43 hemichannels, which can lead to cell death. Activated microglia secrete TNF-α and IL-1β, which open connexin hemichannels in astrocytes. Astrocytes release ATP and glutamate which can kill neurons in co-culture through activation of neuronal pannexin hemichannels. These studies implicate two kinds of gap junction hemichannel in inflammatory responses and cell death. PMID:22975435

  6. Neuronal Activation in the Medulla Oblongata during Selective Elicitation of the Laryngeal Adductor Response

    PubMed Central

    Ambalavanar, Ranjinidevi; Tanaka, Yasumasa; Selbie, W. Scott; Ludlow, Christy L.

    2008-01-01

    Swallow and cough are complex motor patterns elicited by rapid and intense electrical stimulation of the internal branch of the superior laryngeal nerve (ISLN). The laryngeal adductor response (LAR) includes only a laryngeal response, is elicited by single stimuli to the ISLN, and is thought to represent the brain stem pathway involved in laryngospasm. To identify which regions in the medulla are activated during elicitation of the LAR alone, single electrical stimuli were presented once every 2 s to the ISLN. Two groups of 5 cats each were studied; an experimental group with unilateral ISLN stimulation at 0.5 Hz and a surgical control group. Three additional cats were studied to evaluate whether other oral, pharyngeal or respiratory muscles were activated during ISLN stimulation eliciting LAR. We quantified up to 22 sections for each of 14 structures in the medulla to determine if regions had increased Fos-like immunoreactive neurons in the experimental group. Significant increases (p <0.0033) occurred with unilateral ISLN stimulation in the interstitial subnucleus, the ventrolateral subnucleus, the commissural subnucleus of the nucleus tractus solitarius, the lateral tegmental field of the reticular formation, the area postrema and the nucleus ambiguus. Neither the dorsal motor nucleus of the vagus, usually active for swallow, nor the nucleus retroambiguus, retrofacial nucleus, or the lateral reticular nucleus, usually active for cough, were active with elicitation of the laryngeal adductor response alone. The results demonstrate that the laryngeal adductor pathway is contained within the broader pathways for cough and swallow in the medulla. PMID:15212423

  7. Eugenol and carvacrol excite first- and second-order trigeminal neurons and enhance their heat-evoked responses.

    PubMed

    Klein, A H; Joe, C L; Davoodi, A; Takechi, K; Carstens, M I; Carstens, E

    2014-06-20

    Eugenol and carvacrol from clove and oregano, respectively, are agonists of the warmth-sensitive transient receptor potential channel TRPV3 and the irritant-sensitive transient receptor potential ankyrin (TRPA)-1. Eugenol and carvacrol induce oral irritation that rapidly desensitizes, accompanied by brief enhancement of innocuous warmth and heat pain in humans. We presently investigated if eugenol and carvacrol activate nociceptive primary afferent and higher order trigeminal neurons and enhance their heat-evoked responses, using calcium imaging of cultured trigeminal ganglion (TG) and dorsal root ganglion (DRG) neurons, and in vivo single-unit recordings in trigeminal subnucleus caudalis (Vc) of rats. Eugenol and carvacrol activated 20-30% of TG and 7-20% of DRG cells, the majority of which additionally responded to menthol, mustard oil and/or capsaicin. TG cell responses to innocuous (39°) and noxious (42 °C) heating were enhanced by eugenol and carvacrol. We identified dorsomedial Vc neurons responsive to noxious heating of the tongue in pentobarbital-anesthetized rats. Eugenol and carvacrol dose-dependently elicited desensitizing responses in 55% and 73% of heat-sensitive units, respectively. Responses to noxious heat were briefly enhanced by eugenol and carvacrol. Many eugenol- and carvacrol-responsive units also responded to menthol, cinnamaldehyde and capsaicin. These data support a peripheral site for eugenol and carvacrol to enhance warmth- and noxious heat-evoked responses of trigeminal neurons, and are consistent with the observation that these agonists briefly enhance warmth and heat pain on the human tongue. PMID:24759772

  8. Activation of TRPC channels contributes to OA-NO2-induced responses in guinea-pig dorsal root ganglion neurons

    PubMed Central

    Zhang, Xiulin; Beckel, Jonathan M; Daugherty, Stephanie L; Wang, Ting; Woodcock, Stephen R; Freeman, Bruce A; de Groat, William C

    2014-01-01

    Effects of nitro-oleic acid (OA-NO2) on TRP channels were examined in guinea-pig dissociated dorsal root ganglia (DRG) neurons using calcium imaging and patch clamp techniques. OA-NO2 increased intracellular Ca2+ in 60–80% DRG neurons. 1-Oleoyl-2acetyl-sn-glycerol (OAG), a TRPC agonist, elicited responses in 36% of OA-NO2-sensitive neurons while capsaicin (TRPV1 agonist) or allyl-isothiocyanate (AITC, TRPA1 agonist) elicited responses in only 16% and 10%, respectively, of these neurons. A TRPV1 antagonist (diarylpiperazine, 5 μm) in combination with a TRPA1 antagonist (HC-030031, 30 μm) did not change the amplitude of the Ca2+ transients or percentage of neurons responding to OA-NO2; however, a reducing agent DTT (50 mm) or La3+ (50 μm) completely abolished OA-NO2 responses. OA-NO2 also induced a transient inward current associated with a membrane depolarization followed by a prolonged outward current and hyperpolarization in 80% of neurons. The reversal potentials of inward and outward currents were approximately −20 mV and −60 mV, respectively. Inward current was reduced when extracellular Na+ was absent, but unchanged by niflumic acid (100 μm), a Cl− channel blocker. Outward current was abolished in the absence of extracellular Ca2+ or a combination of two Ca2+-activated K+ channel blockers (iberiotoxin, 100 nm and apamin, 1 μm). BTP2 (1 or 10 μm), a broad spectrum TRPC antagonist, or La3+ (50 μm) completely abolished OA-NO2 currents. RT-PCR performed on mRNA extracted from DRGs revealed the expression of all seven subtypes of TRPC channels. These results support the hypothesis that OA-NO2 activates TRPC channels other than the TRPV1 and TRPA1 channels already known to be targets in rat and mouse sensory neurons and challenge the prevailing view that electrophilic compounds act specifically on TRPA1 or TRPV1 channels. The modulation of sensory neuron excitability via actions on multiple TRP channels can contribute to the anti-inflammatory effect

  9. Cocaine attenuates blood flow but not neuronal responses to stimulation while preserving neurovascular coupling for resting brain activity

    PubMed Central

    Chen, Wei; Liu, Peng; Volkow, Nora D.; Pan, Yingtian; Du, Congwu

    2016-01-01

    Cocaine affects neuronal activity and constricts cerebral blood vessels, making it difficult to determine whether cocaine-induced changes in cerebral blood flow (CBF) reflect neuronal activation or its vasoactive effects. Here we assessed the effects of acute cocaine on both resting-state and stimulation responses to investigate cocaine’s effects on neurovascular coupling and to differentiate its effects on neuronal activity from its vasoactive actions. We concurrently measured cortical field potentials via thinned skull EEG recordings and CBF with laser Doppler flowmetry in the rat’s somatosensory cortex for both resting state and forepaw stimulation prior to and following cocaine administration (1mg/kg, i.v.). Results show both resting-state field potentials and CBF were depressed after cocaine administration (19.8±4.7% and 52.1±13.4%, respectively) and these changes were strongly correlated with each other (r=0.81, p<0.001) indicating that cocaine did not affect neurovascular coupling at rest and that the reduction in resting CBF reflected reduction in synchronized spontaneous neuronal activity rather than vasoconstriction. In contrast, the forepaw-stimulation-evoked neuronal activity was not changed by cocaine (p=0.244) whereas the CBF to the stimulation was reduced 49.9±2.6% (p=0.028) gradually recovering ~20min post cocaine injection, indicating that neurovascular coupling during stimulation was temporarily disrupted by cocaine. Neurovascular uncoupling by cocaine during stimulation but not during rest indicates that distinct processes might underlie regulation of neurovascular coupling for spontaneous than for stimulation-induced activity. The greater reductions by cocaine to the stimulation-induced CBF increases than to the background CBF should be considered when interpreting fMRI studies comparing activation responses between controls and cocaine abusers. Neurovascular uncoupling could contribute to cocaine’s neurotoxicity particularly for

  10. Catecholaminergic neurons in the comissural region of the nucleus of the solitary tract modulate hyperosmolality-induced responses.

    PubMed

    Freiria-Oliveira, Andre H; Blanch, Graziela T; Pedrino, Gustavo R; Cravo, Sergio L; Murphy, David; Menani, José V; Colombari, Débora S A

    2015-11-01

    Noradrenergic A2 neurons of the nucleus of the solitary tract (NTS) have been suggested to contribute to body fluid homeostasis and cardiovascular regulation. In the present study, we investigated the effects of lesions of A2 neurons of the commissural NTS (cNTS) on the c-Fos expression in neurons of the hypothalamic paraventricular (PVN) and supraoptic (SON) nuclei, arterial pressure, water intake, and urinary excretion in rats with plasma hyperosmolality produced by intragastric 2 M NaCl (2 ml/rat). Male Holtzman rats (280-320 g) received an injection of anti-dopamine-β-hydroxylase-saporin (12.6 ng/60 nl; cNTS/A2-lesion, n = 28) or immunoglobulin G (IgG)-saporin (12.6 ng/60 nl; sham, n = 24) into the cNTS. The cNTS/A2 lesions increased the number of neurons expressing c-Fos in the magnocellular PVN in rats treated with hypertonic NaCl (90 ± 13, vs. sham: 47 ± 20; n = 4), without changing the number of neurons expressing c-Fos in the parvocellular PVN or in the SON. Contrary to sham rats, intragastric 2 M NaCl also increased arterial pressure in cNTS/A2-lesioned rats (16 ± 3, vs. sham: 2 ± 2 mmHg 60 min after the intragastric load; n = 9), an effect blocked by the pretreatment with the vasopressin antagonist Manning compound (0 ± 3 mmHg; n = 10). In addition, cNTS/A2 lesions enhanced hyperosmolality-induced water intake (10.5 ± 1.4, vs. sham: 7.7 ± 0.8 ml/60 min; n = 8-10), without changing renal responses to hyperosmolality. The results suggest that inhibitory mechanisms dependent on cNTS/A2 neurons reduce water intake and vasopressin-dependent pressor response to an acute increase in plasma osmolality. PMID:26333788

  11. Neonatal seizures alter NMDA glutamate receptor GluN2A and 3A subunit expression and function in hippocampal CA1 neurons.

    PubMed

    Zhou, Chengwen; Sun, Hongyu; Klein, Peter M; Jensen, Frances E

    2015-01-01

    Neonatal seizures are commonly caused by hypoxic and/or ischemic injury during birth and can lead to long-term epilepsy and cognitive deficits. In a rodent hypoxic seizure (HS) model, we have previously demonstrated a critical role for seizure-induced enhancement of the AMPA subtype of glutamate receptor (GluA) in epileptogenesis and cognitive consequences, in part due to GluA maturational upregulation of expression. Similarly, as the expression and function of the N-Methyl-D-aspartate (NMDA) subtype of glutamate receptor (GluN) is also developmentally controlled, we examined how early life seizures during the critical period of synaptogenesis could modify GluN development and function. In a postnatal day (P)10 rat model of neonatal seizures, we found that seizures could alter GluN2/3 subunit composition of GluNs and physiological function of synaptic GluNs. In hippocampal slices removed from rats within 48-96 h following seizures, the amplitudes of synaptic GluN-mediated evoked excitatory postsynaptic currents (eEPSCs) were elevated in CA1 pyramidal neurons. Moreover, GluN eEPSCs showed a decreased sensitivity to GluN2B selective antagonists and decreased Mg(2+) sensitivity at negative holding potentials, indicating a higher proportion of GluN2A and GluN3A subunit function, respectively. These physiological findings were accompanied by a concurrent increase in GluN2A phosphorylation and GluN3A protein. These results suggest that altered GluN function and expression could potentially contribute to future epileptogenesis following neonatal seizures, and may represent potential therapeutic targets for the blockade of future epileptogenesis in the developing brain. PMID:26441533

  12. The cellular and Genomic response of rat dopaminergic neurons (N27) to coated nanosilver

    EPA Science Inventory

    This study examined if nanosilver (nanoAg) of different sizes and coatings were differentially toxic to oxidative stress-sensitive neurons. N27 rat dopaminergic neurons were exposed (0.5-5ppm) to a set of nanoAg of different sizes (10nm, 75nm) and coatings (PVP, citrate) and thei...

  13. Identification of neurons responsible for feeding behavior in the Drosophila brain.

    PubMed

    Sun, Fei; Wang, YiJin; Zhou, YanQiong; Van Swinderen, Bruno; Gong, ZheFeng; Liu, Li

    2014-04-01

    Drosophila melanogaster feeds mainly on rotten fruits, which contain many kinds of sugar. Thus, the sense of sweet taste has evolved to serve as a dominant regulator and driver of feeding behavior. Although several sugar receptors have been described, it remains poorly understood how the sensory input is transformed into an appetitive behavior. Here, we used a neural silencing approach to screen brain circuits, and identified neurons labeled by three Gal4 lines that modulate Drosophila feeding behavior. These three Gal4 lines labeled neurons mainly in the suboesophageal ganglia (SOG), which is considered to be the fly's primary taste center. When we blocked the activity of these neurons, flies decreased their sugar consumption significantly. In contrast, activation of these neurons resulted in enhanced feeding behavior and increased food consumption not only towards sugar, but to an array of food sources. Moreover, upon neuronal activation, the flies demonstrated feeding behavior even in the absence of food, which suggests that neuronal activation can replace food as a stimulus for feeding behavior. These findings indicate that these Gal4-labeled neurons, which function downstream of sensory neurons and regulate feeding behavior towards different food sources is necessary in Drosophila feeding control. PMID:24744088

  14. Neuronal response of the hippocampal formation to injury: blood flow, glucose metabolism, and protein synthesis

    SciTech Connect

    Kameyama, M.; Wasterlain, C.G.; Ackermann, R.F.; Finch, D.; Lear, J.; Kuhl, D.E.

    1983-02-01

    The reaction of the hippocampal formation to entorhinal lesions was studied from the viewpoints of cerebral blood flow ((/sup 123/I)isopropyl-iodoamphetamine(IMP))-glucose utilization ((/sup 14/C)2-deoxyglucose), and protein synthesis ((/sup 14/C)leucine), using single- and double-label autoradiography. Researchers' studies showed decreased glucose utilization in the inner part, and increased glucose utilization in the outer part of the molecular layer of the dentate gyrus, starting 3 days after the lesion; increased uptake of (/sup 123/I)IMP around the lesion from 1 to 3 days postlesion; and starting 3 days after the lesion, marked decrease in (/sup 14/C)leucine incorporation into proteins and cell loss in the dorsal CA1 and dorsal subiculum in about one-half of the rats. These changes were present only in animals with lesions which invaded the ventral hippocampal formation in which axons of CA1 cells travel. By contrast, transsection of the 3rd and 4th cranial nerves resulted, 3 to 9 days after injury, in a striking increase in protein synthesis in the oculomotor and trochlear nuclei. These results raise the possibility that in some neurons the failure of central regeneration may result from the cell's inability to increase its rate of protein synthesis in response to axonal injury.

  15. TGFβ induces GDNF responsiveness in neurons by recruitment of GFRα1 to the plasma membrane

    PubMed Central

    Peterziel, H.; Unsicker, K.; Krieglstein, K.

    2002-01-01

    We have previously shown that the neurotrophic effect of glial cell line–derived neurotrophic factor (GDNF) in vitro and in vivo requires the presence of transforming growth factor (TGF)β. Using primary neurons (chick E8 ciliary) we show that the combination of GDNF plus TGFβ promotes survival, whereas the single factors do not. This cooperative effect is inhibited by blocking the extracellular signal-regulated kinase (ERK)/MAPK pathway, but not by interfering with the PI3 kinase signaling cascade. Although there is no functional GDNF signaling in the absence of TGFβ, pretreatment with TGFβ confers GDNF responsiveness to the cells. This is not due to upregulation of GDNF receptors mRNA and protein, but to TGFβ-induced recruitment of the glycosyl-phosphatidylinositol-anchored GDNF receptor (GFR)α1 to the plasma membrane. This is supported by the fact that GDNF in the presence of a soluble GFRα1 can promote survival in the absence of TGFβ. Our data suggest that TGFβ is involved in GFRα1 membrane translocation, thereby permitting GDNF signaling and neurotrophic effects. PMID:12370242

  16. The mouse brain metabolome: region-specific signatures and response to excitotoxic neuronal injury.

    PubMed

    Jaeger, Christian; Glaab, Enrico; Michelucci, Alessandro; Binz, Tina M; Koeglsberger, Sandra; Garcia, Pierre; Trezzi, Jean-Pierre; Ghelfi, Jenny; Balling, Rudi; Buttini, Manuel

    2015-06-01

    Neurodegeneration is a multistep process characterized by a multitude of molecular entities and their interactions. Systems analyses, or omics approaches, have become an important tool in characterizing this process. Although RNA and protein profiling made their entry into this field a couple of decades ago, metabolite profiling is a more recent addition. The metabolome represents a large part or all metabolites in a tissue, and gives a snapshot of its physiology. By using gas chromatography coupled to mass spectrometry, we analyzed the metabolic profile of brain regions of the mouse, and found that each region is characterized by its own metabolic signature. We then analyzed the metabolic profile of the mouse brain after excitotoxic injury, a mechanism of neurodegeneration implicated in numerous neurological diseases. More important, we validated our findings by measuring, histologically and molecularly, actual neurodegeneration and glial response. We found that a specific global metabolic signature, best revealed by machine learning algorithms, rather than individual metabolites, was the most robust correlate of neuronal injury and the accompanying gliosis, and this signature could serve as a global biomarker for neurodegeneration. We also observed that brain lesioning induced several metabolites with neuroprotective properties. Our results deepen the understanding of metabolic changes accompanying neurodegeneration in disease models, and could help rapidly evaluate these changes in preclinical drug studies. PMID:25934215

  17. Lymphocytes modulate innate immune responses and neuronal damage in experimental meningitis.

    PubMed

    Hoffmann, Olaf; Rung, Olga; Held, Josephin; Boettcher, Chotima; Prokop, Stefan; Stenzel, Werner; Priller, Josef

    2015-01-01

    In bacterial meningitis, excessive immune responses carry significant potential for damage to brain tissue even after successful antibiotic therapy. Bacterial meningitis is regarded primarily as the domain of innate immunity, and the role of lymphocytes remains unclear. We studied the contribution of lymphocytes to acute inflammation and neurodegeneration in experimental Toll-like receptor 2-driven meningitis, comparing wild-type mice with RAG-1-deficient mice that have no mature T and B lymphocytes. At 24 h after intrathecal challenge with the synthetic bacterial lipopeptide Pam(3)CysSK(4), RAG-1-deficient mice displayed more pronounced clinical impairment and an increased concentration of neutrophils, reduced expression of interleukin-10 (IL-10) mRNA, and increased expression of CXCL1 mRNA in the cerebrospinal fluid. Conversely, neuronal loss in the dentate gyrus was reduced in RAG-1-deficient mice, and expression of IL-10, transforming growth factor β and CCL2 mRNA by microglia was increased compared to wild-type mice. Adoptive transfer of wild-type lymphocytes reversed the enhanced meningeal inflammation and functional impairment observed in RAG-1-deficient mice. Our findings suggest compartment-specific effects of lymphocytes during acute bacterial meningitis, including attenuation of meningeal inflammation and shifting of microglial activation toward a more neurotoxic phenotype. PMID:25348636

  18. Pooled, but not single-neuron, responses in macaque V4 represent a solution to the stereo correspondence problem.

    PubMed

    Abdolrahmani ا, Mohammad; Doi, Takahiro; Shiozaki, Hiroshi M; Fujita, Ichiro

    2016-04-01

    Binocular disparity is an important cue for depth perception. To correctly represent disparity, neurons must find corresponding visual features between the left- and right-eye images. The visual pathway ascending from V1 to inferior temporal cortex solves the correspondence problem. An intermediate area, V4, has been proposed to be a critical stage in the correspondence process. However, the distinction between V1 and V4 is unclear, because accumulating evidence suggests that the process begins within V1. In this article, we report that the pooled responses in macaque V4, but not responses of individual neurons, represent a solution to the correspondence problem. We recorded single-unit responses of V4 neurons to random-dot stereograms of varying degrees of anticorrelation. To achieve gradual anticorrelation, we reversed the contrast of an increasing proportion of dots as in our previous psychophysical studies, which predicted that the neural correlates of the solution to correspondence problem should gradually eliminate their disparity modulation as the level of anticorrelation increases. Inconsistent with this prediction, the tuning amplitudes of individual V4 neurons quickly decreased to a nonzero baseline with small anticorrelation. By contrast, the shapes of individual tuning curves changed more gradually so that the amplitude of population-pooled responses gradually decreased toward zero over the entire range of graded anticorrelation. We explain these results by combining multiple energy-model subunits. From a comparison with the population-pooled responses in V1, we suggest that disparity representation in V4 is distinctly advanced from that in V1. Population readout of V4 responses provides disparity information consistent with the correspondence solution. PMID:26843595

  19. Sensory nerve crush and regeneration and the receptive fields and response properties of neurons in the primary somatosensory cerebral cortex of cats.

    PubMed

    Brandenberg, G A; Mann, M D

    1989-03-01

    Extracellular recordings were made of activity evoked in neurons of the forepaw focus of somatosensory cerebral cortex by electrical stimulation of each paw in control cats and cats that had undergone crush injury of all cutaneous sensory nerves to the contralateral forepaw 31 to 63 days previously. Neurons responding only to stimulation of the contralateral forepaw were classified as sa; neurons responding to stimulation of both forepaws were classified as sb; neurons responding to stimulation of both contralateral paws were classified as sc; and neurons responding to stimulation of at least three paws were classified as m. The ratio sa:sb:sc:m neurons was 46:3:0:0 in control cats and 104:15:3:26 in cats that had undergone nerve crush 1-2 months prior to study. sa neurons from experimental cats had depth distributions similar to those in controls and responded to contralateral forepaw stimulation with more spikes per discharge, longer latency, and higher threshold than sa neurons in control cats. m neurons from experimental cats were distributed deeper in the cortex than sa neurons, and, when compared to experimental sa neurons, they responded with longer latency and poorer frequency-following ability; however, the number of spikes per discharge and threshold were not significantly different. The appearance of wide-field neurons in this tissue may be explained in terms of strengthening of previously sub-threshold inputs to neurons in the somatosensory system. If the neurons in sensory cortex play a requisite role in cutaneous sensations and if changes similar to those reported here occur and persist in human cortex after nerve crush, then "complete" recovery of sensation in such patients may occur against a background of changed cortical neuronal responsiveness. PMID:2920791

  20. Learning-dependent Changes in the Neuronal Correlates of Response Inhibition in the Prefrontal Cortex and Hippocampus

    PubMed Central

    Byeon, Jung Seop

    2014-01-01

    It has been suggested that the hippocampus and the prefrontal cortex (PFC) play key roles in representing contextual memory and utilizing contextual information for flexible response selection. During response selection, a correct response should be facilitated and an incorrect response should be inhibited flexibly in association with a cueing stimulus. However, it is poorly understood how the hippocampal and PFC networks behave during such flexible control of facilitation and inhibition of behavioral responses. To find neural correlates of context-cued flexible response selection, the current study employed an object-place paired-associate (OPPA) task in which object A is only rewarded in place 1 and object B is associated with reward in place 2 while recording single units simultaneously from the hippocampus and PFC. During the task, response inhibition in front of a contextually wrong object is required for successful performance and such inhibitory responses were observed before the rat learned the task. A significant proportion of neurons that fired differentially depending on the existence of inhibitory behavior in the PFC was observed during the pre-learning stage. By contrast, the proportion of such neurons in the hippocampus was significantly greater than chance during post-learning stage. The results suggest that the development of inhibitory behavior is a critical behavioral marker that foretells an upcoming acquisition of the task and the hippocampus and PFC are involved in learning contextual response selection by learning how to control the inhibition of behavior as learning progresses. PMID:24963284

  1. Cerebellar-responsive neurons in the thalamic ventroanterior-ventrolateral complex of rats: light and electron microscopy.

    PubMed

    Sawyer, S F; Tepper, J M; Groves, P M

    1994-12-01

    The morphology and synaptic organization of neurons in the ventroanterior-ventrolateral nucleus of rats was examined using in vivo intracellular staining techniques. Neurons were characterized electrophysiologically based on intrinsic membrane properties and synaptic responses to stimulation of motor cortex and cerebellar nuclei, as described in the companion paper. Cerebellar-responsive neurons were stained intracellularly with either horseradish peroxidase or biocytin. All stained ventroanterior-ventrolateral nucleus neurons were identified as thalamocortical neurons on anatomical (and often electrophysiological) grounds, consistent with previous findings that rat ventroanterior-ventrolateral nucleus is interneuron-sparse. Ventroanterior-ventrolateral nucleus neurons had three to eight thick primary dendrites. Proximal dendrites often exhibited a tufted branching pattern, from which many thinner, higher order dendrites arose. Dendrites branched to form a funnel-like infiltration of the neuropil that resulted in a spherical, roughly homogeneous dendritic field. The axon originated from the cell body or a proximal dendrite and coursed laterally and dorsally to innervate motor cortex. One to five axon collaterals were emitted in the rostral dorsolateral sector of the thalamic reticular nucleus; collaterals were not observed in the ventroanterior-ventrolateral nucleus or other nuclei in dorsal thalamus. The synaptic organization of the ventroanterior-ventrolateral nucleus was examined with electron microscopy, including two intracellularly labeled ventroanterior-ventrolateral nucleus neurons that were shown electrophysiologically to receive monosynaptic inputs from the cerebellum. The neuropil of rat ventroanterior-ventrolateral nucleus lacked the complexity and diversity found in corresponding thalamic nuclei of felines and primates, due to the paucity of interneurons. Vesicle-containing dendrites, dendrodendritic synapses and glomeruli were not observed. Three

  2. Elevated intraocular pressure decreases response sensitivity of inner retinal neurons in experimental glaucoma mice

    PubMed Central

    Pang, Ji-Jie; Frankfort, Benjamin J.; Gross, Ronald L.; Wu, Samuel M.

    2015-01-01

    Glaucoma is the second leading cause of blindness in the United States and the world, characterized by progressive degeneration of the optic nerve and retinal ganglion cells (RGCs). Glaucoma patients exhibit an early diffuse loss of retinal sensitivity followed by focal loss of RGCs in sectored patterns. Recent evidence has suggested that this early sensitivity loss may be associated with dysfunctions in the inner retina, but detailed cellular and synaptic mechanisms underlying such sensitivity changes are largely unknown. In this study, we use whole-cell voltage-clamp techniques to analyze light responses of individual bipolar cells (BCs), AII amacrine cells (AIIACs), and ON and sustained OFF alpha-ganglion cells (ONαGCs and sOFFαGCs) in dark-adapted mouse retinas with elevated intraocular pressure (IOP). We present evidence showing that elevated IOP suppresses the rod ON BC inputs to AIIACs, resulting in less sensitive AIIACs, which alter AIIAC inputs to ONαGCs via the AIIAC→cone ON BC→ONαGC pathway, resulting in lower ONαGC sensitivity. The altered AIIAC response also reduces sOFFαGC sensitivity via the AIIAC→sOFFαGC chemical synapses. These sensitivity decreases in αGCs and AIIACs were found in mice with elevated IOP for 3–7 wk, a stage when little RGC or optic nerve degeneration was observed. Our finding that elevated IOP alters neuronal function in the inner retina before irreversible structural damage occurs provides useful information for developing new diagnostic tools and treatments for glaucoma in human patients. PMID:25675503

  3. Cell type-specific transcriptomics of hypothalamic energy-sensing neuron responses to weight-loss

    PubMed Central

    Henry, Fredrick E; Sugino, Ken; Tozer, Adam; Branco, Tiago; Sternson, Scott M

    2015-01-01

    Molecular and cellular processes in neurons are critical for sensing and responding to energy deficit states, such as during weight-loss. Agouti related protein (AGRP)-expressing neurons are a key hypothalamic population that is activated during energy deficit and increases appetite and weight-gain. Cell type-specific transcriptomics can be used to identify pathways that counteract weight-loss, and here we report high-quality gene expression profiles of AGRP neurons from well-fed and food-deprived young adult mice. For comparison, we also analyzed Proopiomelanocortin (POMC)-expressing neurons, an intermingled population that suppresses appetite and body weight. We find that AGRP neurons are considerably more sensitive to energy deficit than POMC neurons. Furthermore, we identify cell type-specific pathways involving endoplasmic reticulum-stress, circadian signaling, ion channels, neuropeptides, and receptors. Combined with methods to validate and manipulate these pathways, this resource greatly expands molecular insight into neuronal regulation of body weight, and may be useful for devising therapeutic strategies for obesity and eating disorders. DOI: http://dx.doi.org/10.7554/eLife.09800.001 PMID:26329458

  4. Response properties of temporomandibular joint mechanosensitive neurons in the trigeminal sensory complex of the rabbit.

    PubMed

    Suzuki, Osuke; Tsuboi, Akito; Tabata, Takayoshi; Takafuji, Yasuo; Sakurai, Takeshi; Watanabe, Makoto

    2012-10-01

    The neurophysiological properties of neurons sensitive to TMJ movement (TMJ neurons) in the trigeminal sensory complex (Vcomp) during passive movement of the isolated condyle were examined in 46 rabbits. Discharges of TMJ neurons from the rostral part of the Vcomp were recorded with a microelectrode when the isolated condyle was moved manually and with a computer-regulated mechanostimulator. A total of 443 neurons responding to mechanical stimulation of the face and oral cavity were recorded from the brainstem. Twenty-one TMJ neurons were detected rostrocaudally from the dorsal part of the trigeminal principal sensory nucleus (NVsnpr), subnucleus oralis of the trigeminal spinal nucleus, and reticular formation surrounding the trigeminal motor nucleus. Most of the TMJ neurons were located in the dorso-rostral part of the NVsnpr. Of the TMJ units recorded, 90 % were slowly adapting and 26 % had an accompanying resting discharge. The majority (86 %) of the TMJ units responded to the movement of the isolated condyle in the anterior and/or ventral directions, and half were sensitive to the condyle movement in a single direction. The discharge frequencies of TMJ units increased as the condyle displacement and constant velocity (5 mm/s) increased within a 5-mm anterior displacement of the isolated condyle. Based on these results, we conclude that sensory information is processed by TMJ neurons encoding at least joint position and displacement in the physiological range of mandibular displacement. PMID:22855309

  5. Mediation of the fastigial pressor response and a somatosympathetic reflex by ventral medullary neurones in the cat.

    PubMed Central

    McAllen, R M

    1985-01-01

    In chloralose-anaesthetized, artificially ventilated cats, the effects have been studied of inactivating neurones of the 'glycine-sensitive area' of the rostral ventrolateral medulla on evoked renal sympathetic and vasomotor responses. Glycine applied topically and bilaterally to the 'glycine-sensitive area' besides markedly lowering blood pressure and heart rate, reversibly abolished or severely attenuated both the pressor response and the renal nerve volley produced by electrical stimulation of the fastigial nucleus as well as the tibial to renal nerve somatosympathetic reflex. Bilateral radio-frequency lesions of the 'glycine-sensitive area' similarly lowered blood pressure and heart rate, blocked the fastigial pressor response and abolished renal nerve responses to fastigial nucleus or tibial nerve stimulation. Effective lesions extended greater than or equal to 1 mm deep from the medullary surface. These results are discussed with reference to the view that the 'glycine-sensitive area' contains neurones constituting a final descending bulbo-spinal pathway to preganglionic vasomotor neurones. PMID:4078745

  6. The p38 MAP kinase pathway modulates the hypoxia response and glutamate receptor trafficking in aging neurons

    PubMed Central

    Park, Eun Chan; Rongo, Christopher

    2016-01-01

    Neurons are sensitive to low oxygen (hypoxia) and employ a conserved pathway to combat its effects. Here, we show that p38 MAP Kinase (MAPK) modulates this hypoxia response pathway in C. elegans. Mutants lacking p38 MAPK components pmk-1 or sek-1 resemble mutants lacking the hypoxia response component and prolyl hydroxylase egl-9, with impaired subcellular localization of Mint orthologue LIN-10, internalization of glutamate receptor GLR-1, and depression of GLR-1-mediated behaviors. Loss of p38 MAPK impairs EGL-9 protein localization in neurons and activates the hypoxia-inducible transcription factor HIF-1, suggesting that p38 MAPK inhibits the hypoxia response pathway through EGL-9. As animals age, p38 MAPK levels decrease, resulting in GLR-1 internalization; this age-dependent downregulation can be prevented through either p38 MAPK overexpression or removal of CDK-5, an antagonizing kinase. Our findings demonstrate that p38 MAPK inhibits the hypoxia response pathway and determines how aging neurons respond to hypoxia through a novel mechanism. DOI: http://dx.doi.org/10.7554/eLife.12010.001 PMID:26731517

  7. Increased responsiveness of rat dorsal horn neurons in vivo following prolonged intrathecal exposure to interferon-gamma.

    PubMed

    Vikman, K S; Siddall, P J; Duggan, A W

    2005-01-01

    Prolonged increases in the level of the pro-inflammatory cytokine interferon-gamma occur in the CNS during some disease states associated with persistent pain. Administration of interferon-gamma to both humans and rodents has produced pain or pain-related behavior but the underlying mechanisms are unknown. The present study examined the effects of repeated intrathecal administration of interferon-gamma on dorsal horn neuronal responses under in vivo conditions. In addition, behavioral effects of interferon-gamma treatment were studied. Intrathecal cannulae were implanted into anesthetized rats. Animals then received either 1000 U of recombinant rat interferon-gamma in 10 microl buffer intrathecally, repeated four times over 8 days, or similarly administered buffer (controls). Interferon-gamma-treated animals showed a significant reduction in paw withdrawal threshold to mechanical stimulation of the hind paw. Electrophysiological experiments were performed under halothane anesthesia. Extracellular recordings of spontaneous and evoked responses were obtained from dorsal horn neurons (n=64) in the lumbar spinal cord. There was a significantly higher proportion of spontaneously active neurons in the interferon-gamma-treated animals (50%) when compared with controls (19%). A significantly increased proportion of neurons from interferon-gamma-treated animals displayed afterdischarges following both innocuous and noxious mechanical stimulation of the receptive field (brush: 21% in interferon-gamma-treated, 3% in controls; pinch: 97% in interferon-gamma-treated, 50% in controls). Neurons from interferon-gamma-treated animals also showed significantly increased wind-up of action potentials in response to repeated electrical stimulation of the sciatic nerve at C-fiber strength at both 0.5 and 1 Hz. Paired-pulse inhibition, evoked through electrical stimulation of the cutaneous receptive field, was significantly decreased in neurons from interferon-gamma-treated animals at 50

  8. Non-oscillatory discharges of an F-prostaglandin responsive neuron population in the olfactory bulb-telencephalon transition area in lake whitefish.

    PubMed

    Laberge, F; Hara, T J

    2003-01-01

    Our previous studies on olfactory bulbar responses in salmonid fishes suggest that pheromone signals might be processed by a mechanism distinct from that of other odorants. Using in vivo single-unit and electroencephalographic recordings, we investigated response characteristics of olfactory neurons in lake whitefish, Coregonus clupeaformis, a species characterized by high electrophysiological and behavioral sensitivities to the reproductive pheromone candidates F-prostaglandins. We found a neuron population responsive to F-prostaglandins in the ventromedial brain tissue strip connecting the olfactory bulb to the telencephalon. Of the 64 neurons examined in this area, 33% showed excitatory and 11% inhibitory responses to F-prostaglandins, while 52% were non-responsive to all the stimuli tested. Both phasic and tonic F-prostaglandin neuron response patterns were observed during the 10-s stimulus period; some responses were delayed from the onset of stimulation, and some persisted for a long time following stimulus cessation. This neuron population did not induce synchronized oscillatory waves upon stimulation with F-prostaglandins, despite massive discharges. We demonstrate for the first time that the olfactory bulb-telencephalon area of the brain is a distinct neural structure through which putative reproductive pheromone signals are integrated. Amino acid and F-prostaglandin neuron population discharges have different temporal characteristics, suggesting different processing mechanisms exist for odorant and pheromone signals. The observed sustained neuron discharges may play a role in amplifying pheromone signals required for triggering stereotyped neuroendocrine and/or behavior changes. PMID:12617950

  9. Both Estrogen and Androgen Modify the Response to Activation of Neurokinin-3 and κ-Opioid Receptors in Arcuate Kisspeptin Neurons From Male Mice.

    PubMed

    Ruka, Kristen A; Burger, Laura L; Moenter, Suzanne M

    2016-02-01

    Gonadal steroids regulate the pattern of GnRH secretion. Arcuate kisspeptin (kisspeptin, neurokinin B, and dynorphin [KNDy]) neurons may convey steroid feedback to GnRH neurons. KNDy neurons increase action potential firing upon the activation of neurokinin B receptors (neurokinin-3 receptor [NK3R]) and decrease firing upon the activation of dynorphin receptors (κ-opioid receptor [KOR]). In KNDy neurons from intact vs castrated male mice, NK3R-mediated stimulation is attenuated and KOR-mediated inhibition enhanced, suggesting gonadal secretions are involved. Estradiol suppresses spontaneous GnRH neuron firing in male mice, but the mediators of the effects on firing in KNDy neurons are unknown. We hypothesized the same gonadal steroids affecting GnRH firing pattern would regulate KNDy neuron response to NK3R and KOR agonists. To test this possibility, extracellular recordings were made from KNDy neurons in brain slices from intact, untreated castrated or castrated adult male mice treated in vivo with steroid receptor agonists. As observed previously, the stimulation of KNDy neurons by the NK3R agonist senktide was attenuated in intact vs castrated mice and suppression by dynorphin was enhanced. In contrast to observations of steroid effects on the GnRH neuron firing pattern, both estradiol and DHT suppressed senktide-induced KNDy neuron firing and enhanced the inhibition caused by dynorphin. An estrogen receptor-α agonist but not an estrogen receptor-β agonist mimicked the effects of estradiol on NK3R activation. These observations suggest the steroid modulation of responses to activation of NK3R and KOR as mechanisms for negative feedback in KNDy neurons and support the contribution of these neurons to steroid-sensitive elements of a GnRH pulse generator. PMID:26562263

  10. Response surface methodology for the modelling of 85Sr adsorption on zeolite 3A and pumice.

    PubMed

    Ciçek, Ekrem; Cojocaru, Corneliu; Zakrzewska-Trznadel, Grazyna; Harasimowicz, Marian; Miskiewicz, Agnieszka

    2012-01-01

    The adsorption of 85Sr from aqueous solutions on to zeolite 3A and three types of pumice materials (i.e. Kayseri, Isparta and Nevsehir) was investigated in this study. Experiments with radioactive 85Sr were performed to test the sorption ability of the sorbents to remove this radioisotope from liquid radioactive wastes. The influence of sorbent dosage and initial activity of feed solution on the decontamination factor were analysed and optimized by means of response surface methodology. The parameters of the experiments, namely temperature, pH, time, stirring efficiency, were selected in preliminary tests. The experimental results showed that the most efficient pumice sorbent for 85Sr is Isparta, for which a maximal decontamination factor of 76.92 was obtained by using the sorbent dosage of 0.5% w/v. However, the commercial zeolite 3A was 2.71-fold more efficient than Isparta pumice for decontamination of strontium radioactive solutions. Isparta pumice is a low-cost natural sorbent, and its ability to effectively bind strontium radioisotope from water solutions suggests that this material has further applications for radioactive waste treatment. PMID:22519087

  11. Responses of bradykinin sensitive tooth-pulp driven neurons in cat cerebral cortex.

    PubMed

    Iwata, K; Itoga, H; Muramatsu, H; Toda, K; Sumino, R

    1987-01-01

    The properties of single cortical neurons responding to electrical stimulation of the tooth-pulp and to intrapulpal application of bradykinin were studied in the cat. The activities of tooth-pulp driven neurons (TPNs) were recorded from the middle and anterior parts of the coronal gyrus of the cerebral cortex. Bradykinin-sensitive tooth-pulp driven neurons (BK-TPNs) were located in layer IV of area 3b of the anterior part of the coronal gyrus. These neurons had a large cutaneous oro-facial receptive field and received a nociceptive input from the facial skin as well as from the tooth-pulp. The BK-TPNs had a higher threshold and longer latency to electrical stimulation than TPNs insensitive to bradykinin (non BK-TPNs). These findings suggest that BK-TPNs in this cortical area may be involved in sensory processing of noxious information from trigeminal regions. PMID:3595787

  12. Kv2 dysfunction after peripheral axotomy enhances sensory neuron responsiveness to sustained input.

    PubMed

    Tsantoulas, Christoforos; Zhu, Lan; Yip, Ping; Grist, John; Michael, Gregory J; McMahon, Stephen B

    2014-01-01

    Peripheral nerve injuries caused by trauma are associated with increased sensory neuron excitability and debilitating chronic pain symptoms. Axotomy-induced alterations in the function of ion channels are thought to largely underlie the pathophysiology of these phenotypes. Here, we characterise the mRNA distribution of Kv2 family members in rat dorsal root ganglia (DRG) and describe a link between Kv2 function and modulation of sensory neuron excitability. Kv2.1 and Kv2.2 were amply expressed in cells of all sizes, being particularly abundant in medium-large neurons also immunoreactive for neurofilament-200. Peripheral axotomy led to a rapid, robust and long-lasting transcriptional Kv2 downregulation in the DRG, correlated with the onset of mechanical and thermal hypersensitivity. The consequences of Kv2 loss-of-function were subsequently investigated in myelinated neurons using intracellular recordings on ex vivo DRG preparations. In naïve neurons, pharmacological Kv2.1/Kv2.2 inhibition by stromatoxin-1 (ScTx) resulted in shortening of action potential (AP) after-hyperpolarization (AHP). In contrast, ScTx application on axotomized neurons did not alter AHP duration, consistent with the injury-induced Kv2 downregulation. In accordance with a shortened AHP, ScTx treatment also reduced the refractory period and improved AP conduction to the cell soma during high frequency stimulation. These results suggest that Kv2 downregulation following traumatic nerve lesion facilitates greater fidelity of repetitive firing during prolonged input and thus normal Kv2 function is postulated to limit neuronal excitability. In summary, we have profiled Kv2 expression in sensory neurons and provide evidence for the contribution of Kv2 dysfunction in the generation of hyperexcitable phenotypes encountered in chronic pain states. PMID:24252178

  13. Internal Ca2+ stores involved in anoxic responses of rat hippocampal neurons.

    PubMed Central

    Belousov, A B; Godfraind, J M; Krnjević, K

    1995-01-01

    1. During whole-cell recordings from CA1 neurons of rat brain slices with electrodes containing only KMeSO4 and Hepes, brief anoxia (2-3 min) consistently evoked a hyperpolarization (delta V approximately 14 mV) and reduction in input resistance (delta R approximately -20%). 2. As in previous intracellular recordings, Dantrolene sodium (10 microM) suppressed the anoxic delta V and delta R, confirming the release of internal Ca2+ is a major component of the anoxic response. 3. To identify the relevant intracellular Ca2+ store, other blockers of Ca2+ release were applied either externally (in the bath) or internally, by addition to the contents of the recording electrode. 4. The anoxic hyperpolarization was abolished or much reduced by heparin (10-20 micrograms ml-1, internal), thapsigargin (10 microM, external), Ruthenium Red (50 microM, internal) and external procaine (0.5-2 mM), but not by internal procaine (0.5-1 mM) or ryanodine (10 microM, external). 5. The anoxic fall in resistance was also abolished or reduced by heparin, thapsigargin and external procaine, but not by ryanodine, internal procaine or Ruthenium Red. 6. In addition, external procaine (0.5-2 mM) eliminated the early (transient) depolarization and reduced the post-anoxic hyperpolarization by 60 +/- 22%. 7. None of these agents consistently changed the resting potential, but the input resistance was significantly increased by Dantrolene and external procaine. 8. In view of the marked effects of heparin and thapsigargin, but not ryanodine and internal procaine, we conclude that the anoxic response seen in such whole-cell recordings is initiated predominantly by Ca2+ release from an internal store that is InsP3 sensitive rather than Ca2+ sensitive. 9. Comparable but less pronounced effects of external procaine were seen during intracellular recordings with 3 M KCl-containing electrodes. The dose-dependent suppression of various features of the anoxic response by external procaine (EC50 approximately

  14. Adult axolotls can regenerate original neuronal diversity in response to brain injury

    PubMed Central

    Amamoto, Ryoji; Huerta, Violeta Gisselle Lopez; Takahashi, Emi; Dai, Guangping; Grant, Aaron K; Fu, Zhanyan; Arlotta, Paola

    2016-01-01

    The axolotl can regenerate multiple organs, including the brain. It remains, however, unclear whether neuronal diversity, intricate tissue architecture, and axonal connectivity can be regenerated; yet, this is critical for recovery of function and a central aim of cell replacement strategies in the mammalian central nervous system. Here, we demonstrate that, upon mechanical injury to the adult pallium, axolotls can regenerate several of the populations of neurons present before injury. Notably, regenerated neurons acquire functional electrophysiological traits and respond appropriately to afferent inputs. Despite the ability to regenerate specific, molecularly-defined neuronal subtypes, we also uncovered previously unappreciated limitations by showing that newborn neurons organize within altered tissue architecture and fail to re-establish the long-distance axonal tracts and circuit physiology present before injury. The data provide a direct demonstration that diverse, electrophysiologically functional neurons can be regenerated in axolotls, but challenge prior assumptions of functional brain repair in regenerative species. DOI: http://dx.doi.org/10.7554/eLife.13998.001 PMID:27156560

  15. Expression of α5 integrin rescues fibronectin responsiveness in NT2N CNS neuronal cells

    PubMed Central

    Meland, Marit N.; Herndon, Mary E.; Stipp, Christopher S.

    2010-01-01

    The extracellular matrix protein fibronectin is implicated in neuronal regeneration in the peripheral nervous system. In the central nervous system (CNS), fibronectin is upregulated at sites of penetrating injuries and stroke; however, CNS neurons downregulate the fibronectin receptor, α5β1 integrin, during differentiation and generally respond poorly to fibronectin. NT2N CNS neuron-like cells (derived from NT2 precursor cells) have been used in pre-clinical and clinical studies for treatment of stroke and a variety of CNS injury and disease models. Here we show that, like primary CNS neurons, NT2N cells downregulate α5β1 integrin during differentiation and respond poorly to fibronectin. The poor neurite outgrowth by NT2N cells on fibronectin can be rescued by transducing NT2 precursors with a retroviral vector expressing α5 integrin under the control of the Murine Stem Cell Virus 5′ long terminal repeat. Sustained α5 integrin expression is compatible with the CNS-like neuronal differentiation of NT2N cells and does not prevent robust neurite outgrowth on other integrin ligands. Thus, α5 integrin expression in CNS neuronal precursor cells may provide a strategy for enhancing the outgrowth and survival of implanted cells in cell replacement therapies for CNS injury and disease. PMID:19598247

  16. Attenuated inhibition by levofloxacin, l-isomer of ofloxacin, on GABA response in the dissociated rat hippocampal neurons.

    PubMed

    Imanishi, T; Akahane, K; Akaike, N

    1995-06-30

    The effects of ofloxacin (OFLX) and its isomers, levofloxacin (LVFX) and DR-3354, on the gamma-aminobutyric acid (GABA)-induced Cl- current in acutely dissociated rat hippocampal CA1 neurons were investigated using nystatin perforated patch recording configuration under voltage-clamp conditions. At 10(-5) M these 3 compounds themselves did not affect the GABA response. Biphenylacetic acid (BPA) at 10(-5) M also had no effect on the GABA response, but BPA greatly suppressed the GABA response in combination with these 3 compounds without affecting the reversal potential of GABA response. The inhibitory effects of OFLX and DR-3354 on the GABA response were stronger than that of LVFX. LVFX inhibited the response in a competitive and voltage-independent manner. The results suggest that LVFX has lower CNS adverse effects, such as convulsions, compared to OFLX. PMID:7478164

  17. The Cancer Chemotherapeutic Paclitaxel Increases Human and Rodent Sensory Neuron Responses to TRPV1 by Activation of TLR4

    PubMed Central

    Li, Yan; Adamek, Pavel; Zhang, Haijun; Tatsui, Claudio Esteves; Rhines, Laurence D.; Mrozkova, Petra; Li, Qin; Kosturakis, Alyssa K.; Cassidy, Ryan M.; Harrison, Daniel S.; Cata, Juan P.; Sapire, Kenneth; Zhang, Hongmei; Kennamer-Chapman, Ross M.; Jawad, Abdul Basit; Ghetti, Andre; Yan, Jiusheng; Palecek, Jiri

    2015-01-01

    Peripheral neuropathy is dose limiting in paclitaxel cancer chemotherapy and can result in both acute pain during treatment and chronic persistent pain in cancer survivors. The hypothesis tested was that paclitaxel produces these adverse effects at least in part by sensitizing transient receptor potential vanilloid subtype 1 (TRPV1) through Toll-like receptor 4 (TLR4) signaling. The data show that paclitaxel-induced behavioral hypersensitivity is prevented and reversed by spinal administration of a TRPV1 antagonist. The number of TRPV1+ neurons is increased in the dorsal root ganglia (DRG) in paclitaxel-treated rats and is colocalized with TLR4 in rat and human DRG neurons. Cotreatment of rats with lipopolysaccharide from the photosynthetic bacterium Rhodobacter sphaeroides (LPS-RS), a TLR4 inhibitor, prevents the increase in numbers of TRPV1+ neurons by paclitaxel treatment. Perfusion of paclitaxel or the archetypal TLR4 agonist LPS activated both rat DRG and spinal neurons directly and produced acute sensitization of TRPV1 in both groups of cells via a TLR4-mediated mechanism. Paclitaxel and LPS sensitize TRPV1 in HEK293 cells stably expressing human TLR4 and transiently expressing human TRPV1. These physiological effects also are prevented by LPS-RS. Finally, paclitaxel activates and sensitizes TRPV1 responses directly in dissociated human DRG neurons. In summary, TLR4 was activated by paclitaxel and led to sensitization of TRPV1. This mechanism could contribute to paclitaxel-induced acute pain and chronic painful neuropathy. SIGNIFICANCE STATEMENT In this original work, it is shown for the first time that paclitaxel activates peripheral sensory and spinal neurons directly and sensitizes these cells to transient receptor potential vanilloid subtype 1 (TRPV1)-mediated capsaicin responses via Toll-like receptor 4 (TLR4) in multiple species. A direct functional interaction between TLR4 and TRPV1 is shown in rat and human dorsal root ganglion neurons, TLR4/TRPV1

  18. The Cholinergic Signaling Responsible for the Expression of a Memory-Related Protein in Primary Rat Cortical Neurons.

    PubMed

    Chen, Tsan-Ju; Chen, Shun-Sheng; Wang, Dean-Chuan; Hung, Hui-Shan

    2016-11-01

    Cholinergic dysfunction in the brain is closely related to cognitive impairment including memory loss. In addition to the degeneration of basal forebrain cholinergic neurons, deficits in the cholinergic receptor signaling may also play an important role. In the present study, to examine the cholinergic signaling pathways responsible for the induction of a memory-related postsynaptic protein, a cholinergic agonist carbachol was used to induce the expression of activity-regulated cytoskeleton associated protein (Arc) in primary rat cortical neurons. After pretreating neurons with various antagonists or inhibitors, the levels of carbachol-induced Arc protein expression were detected by Western blot analysis. The results show that carbachol induces Arc protein expression mainly through activating M1 acetylcholine receptors and the downstream phospholipase C pathway, which may lead to the activation of the MAPK/ERK signaling pathway. Importantly, carbachol-mediated M2 receptor activation exerts negative effects on Arc protein expression and thus counteracts the enhanced effects of M1 activation. Furthermore, it is suggested for the first time that M1-mediated enhancement of N-methyl-D-aspartate receptor (NMDAR) responses, leading to Ca(2+) entry through NMDARs, contributes to carbachol-induced Arc protein expression. These findings reveal a more complete cholinergic signaling that is responsible for carbachol-induced Arc protein expression, and thus provide more information for developing treatments that can modulate cholinergic signaling and consequently alleviate cognitive impairment. J. Cell. Physiol. 231: 2428-2438, 2016. © 2016 Wiley Periodicals, Inc. PMID:26895748

  19. Arctigenin reduces neuronal responses in the somatosensory cortex via the inhibition of non-NMDA glutamate receptors.

    PubMed

    Borbély, Sándor; Jócsák, Gergely; Moldován, Kinga; Sedlák, Éva; Preininger, Éva; Boldizsár, Imre; Tóth, Attila; Atlason, Palmi T; Molnár, Elek; Világi, Ildikó

    2016-07-01

    Lignans are biologically active phenolic compounds related to lignin, produced in different plants. Arctigenin, a dibenzylbutyrolactone-type lignan, has been used as a neuroprotective agent for the treatment of encephalitis. Previous studies of cultured rat cerebral cortical neurones raised the possibility that arctigenin inhibits kainate-induced excitotoxicity. The aims of the present study were: 1) to analyse the effect of arctigenin on normal synaptic activity in ex vivo brain slices, 2) to determine its receptor binding properties and test the effect of arctigenin on AMPA/kainate receptor activation and 3) to establish its effects on neuronal activity in vivo. Arctigenin inhibited glutamatergic transmission and reduced the evoked field responses. The inhibitory effect of arctigenin on the evoked field responses proved to be substantially dose dependent. Our results indicate that arctigenin exerts its effects under physiological conditions and not only on hyper-excited neurons. Furthermore, arctigenin can cross the blood-brain barrier and in the brain it interacts with kainate sensitive ionotropic glutamate receptors. These results indicate that arctigenin is a potentially useful new pharmacological tool for the inhibition of glutamate-evoked responses in the central nervous system in vivo. PMID:26972612

  20. Photoperiod alters fear responses and basolateral amygdala neuronal spine density in white-footed mice (Peromyscus leucopus).

    PubMed

    Walton, James C; Haim, Achikam; Spieldenner, James M; Nelson, Randy J

    2012-08-01

    Photoperiodism is a biological phenomenon in which environmental day length is monitored to ascertain time of year to engage in seasonally appropriate adaptations. This trait is common among organisms living outside of the tropics. White-footed mice (Peromyscus leucopus) are small photoperiodic rodents which display a suite of adaptive responses to short day lengths, including reduced hippocampal volume, impairments in hippocampal-mediated memory, and enhanced hypothalamic-pituitary-adrenal axis reactivity. Because these photoperiodic changes in brain and behavior mirror some of the etiology of post-traumatic stress disorder (PTSD), we hypothesized that photoperiod may also alter fear memory and neuronal morphology within the hippocampus-basolateral amygdala-prefrontal cortex fear circuit. Ten weeks of exposure to short days increased fear memory in an auditory-cued fear conditioning test. Short days also increased dendritic spine density of the neurons of the basolateral amygdala, without affecting morphology of pyramidal neurons within the infralimbic region of the medial prefrontal cortex. Taken together, photoperiodic phenotypic changes in brain morphology and physiology induced by a single environmental factor, exposure to short day lengths, affect responses to fearful stimuli in white-footed mice. These results have potential implications for understanding seasonal changes in fear responsiveness, as well as for expanding translational animal models for studying gene-environment interactions underlying psychiatric diseases, such as PTSD. PMID:22652395

  1. 5-HT potentiation of the GABAA response in the rat sacral dorsal commissural neurones

    PubMed Central

    Xu, Tian-Le; Pang, Zhi-Ping; Li, Ji-Shuo; Akaike, Norio

    1998-01-01

    The modulatory effect of 5-hydroxytryptamine (5-HT) on the γ-aminobutyric acidA (GABAA) response was investigated in the neurones freshly dissociated from the rat sacral dorsal commissural nucleus (SDCN) using the nystatin perforated patch recording configuration under the voltage-clamp conditions.5-HT potentiated GABA-induced Cl− current (IGABA) without affecting the reversal potential of IGABA and the apparent affinity of GABA to its receptor.α-Methyl-5-HT mimicked the potentiation effect of 5-HT on IGABA while ketanserine blocked it. 1-Oleoyl-2-acetyl-glycerol (OAG) potentiated IGABA, and the effect of 5-HT on IGABA was occluded by OAG pretreatment. In the presence of chelerythrine, 5-HT failed to potentiate IGABA, suggesting that protein kinase C (PKC) is involved in the pathway through which the activation of the 5-HT2 receptor potentiates the IGABA.The facilitatory effect of 5-HT on IGABA remained in the presence of BAPTA-AM. LiCl also had no effect on 5-HT-induced potentiation of IGABA.H-89, genistein, okadaic acid and pervanadate all had no effects on 5-HT potentiation of IGABA. Pertussis toxin treatment for 6–8 h did not block the facilitatory effect of 5-HT on IGABA.The present results show that GABAA receptor in the rat SDCN could be modulated in situ by 5-HT, one of the major transmitters involved in the supraspinal control of nociception, and that the phosphorylation of GABAA receptor by PKC may be sufficient to support such modulation. The results also strongly support the hypothesis that the cotransmission by 5-HT and GABA has an important role in the spinal cord. PMID:9690871

  2. Neuron-specific enolase as a novel biomarker reflecting tuberculosis activity and treatment response

    PubMed Central

    Nam, Sung-Jin; Jeong, Jee-Yeong; Jang, Tae-Won; Jung, Mann-Hong; Chun, Bong-Kwon; Cha, Hee-Jae; Oak, Chul-Ho

    2016-01-01

    Background/Aims: It is not clear which tests are indicative of the activity and severity of tuberculosis (TB). This study aimed to investigate the predictive value of neuron-specific enolase (NSE) and to determine the origin of NSE in TB patients. Methods: A single-center retrospective analysis was conducted on newly diagnosed TB patients between January and December 2010. Patients were categorized into one of two disease groups (focal segmental or extensive) based on chest X-ray. Pre- and post-treatment NSE concentrations were evaluated. To determine the origin of serum NSE concentration, NSE staining was compared with macrophage-specific CD68 staining in lung tissues and with a tissue microarray using immunohistochemistry and immunofluorescence. Results: A total of 60 newly diagnosed TB patients were analyzed. In TB patients, NSE serum concentration was significantly increased and NSE level decreased after treatment (p < 0.001). In proportion to serum high-sensitivity C-reactive protein concentration, the mean serum concentration of NSE in the extensive group (25.12 ng/mL) was significantly higher than that in the focal segmental group (20.23 ng/mL, p = 0.04). Immunohistochemical staining revealed a large number of macrophages that stained positively for both NSE and CD68 in TB tissues. In addition, NSE signals mostly co-localized with CD68 signals in the tissue microarray of TB patients. Conclusions: Our results suggest that NSE may be a practical parameter that can be used to monitor TB activity and treatment response. Elevated serum NSE level originates, at least in part, from macrophages in granulomatous lesions. PMID:27271274

  3. PEDOT:PSS Interfaces Support the Development of Neuronal Synaptic Networks with Reduced Neuroglia Response In vitro

    PubMed Central

    Cellot, Giada; Lagonegro, Paola; Tarabella, Giuseppe; Scaini, Denis; Fabbri, Filippo; Iannotta, Salvatore; Prato, Maurizio; Salviati, Giancarlo; Ballerini, Laura

    2016-01-01

    The design of electrodes based on conductive polymers in brain-machine interface technology offers the opportunity to exploit variably manufactured materials to reduce gliosis, indeed the most common brain response to chronically implanted neural electrodes. In fact, the use of conductive polymers, finely tailored in their physical-chemical properties, might result in electrodes with improved adaptability to the brain tissue and increased charge-transfer efficiency. Here we interfaced poly(3,4-ethylenedioxythiophene):poly(styrene sulfonate) (PEDOT:PSS) doped with different amounts of ethylene glycol (EG) with rat hippocampal primary cultures grown for 3 weeks on these synthetic substrates. We used immunofluorescence and scanning electron microscopy (SEM) combined to single cell electrophysiology to assess the biocompatibility of PEDOT:PSS in terms of neuronal growth and synapse formation. We investigated neuronal morphology, density and electrical activity. We reported the novel observation that opposite to neurons, glial cell density was progressively reduced, hinting at the ability of this material to down regulate glial reaction. Thus, PEDOT:PSS is an attractive candidate for the design of new implantable electrodes, controlling the extent of glial reactivity without affecting neuronal viability and function. PMID:26834546

  4. The retrotrapezoid nucleus neurons expressing Atoh1 and Phox2b are essential for the respiratory response to CO2

    PubMed Central

    Ruffault, Pierre-Louis; D'Autréaux, Fabien; Hayes, John A; Nomaksteinsky, Marc; Autran, Sandra; Fujiyama, Tomoyuki; Hoshino, Mikio; Hägglund, Martin; Kiehn, Ole; Brunet, Jean-François; Fortin, Gilles; Goridis, Christo

    2015-01-01

    Maintaining constant CO2 and H+ concentrations in the arterial blood is critical for life. The principal mechanism through which this is achieved in mammals is the respiratory chemoreflex whose circuitry is still elusive. A candidate element of this circuitry is the retrotrapezoid nucleus (RTN), a collection of neurons at the ventral medullary surface that are activated by increased CO2 or low pH and project to the respiratory rhythm generator. Here, we use intersectional genetic strategies to lesion the RTN neurons defined by Atoh1 and Phox2b expression and to block or activate their synaptic output. Photostimulation of these neurons entrains the respiratory rhythm. Conversely, abrogating expression of Atoh1 or Phox2b or glutamatergic transmission in these cells curtails the phrenic nerve response to low pH in embryonic preparations and abolishes the respiratory chemoreflex in behaving animals. Thus, the RTN neurons expressing Atoh1 and Phox2b are a necessary component of the chemoreflex circuitry. DOI: http://dx.doi.org/10.7554/eLife.07051.001 PMID:25866925

  5. Physiological role of group III metabotropic glutamate receptors in visually responsive neurons of the rat superficial superior colliculus.

    PubMed

    Cirone, J; Salt, T E

    2000-03-01

    There is evidence from immunohistochemical and in situ hybridization studies for the presence of Group I, II and III metabotropic glutamate receptors (mGluRs) in the rat superficial superior colliculus (SSC). The purpose of this study was to investigate if manipulation of Group III mGluRs affects visual responses in the SSC. Drugs were applied by iontophoresis and single neuron activity was recorded extracellularly. L-AP4 (Group III agonist) resulted in a reduction of visual responses in most neurons, but also a potentiation in others. The effect of L-AP4 is drug- and stereospecific in that application of D-AP4 did not significantly affect visual responses. L-AP4 application also resulted in a potentiation of the response to iontophoretically applied NMDA. The effects of MPPG and CPPG (Group III antagonists) were compared with the effect of L-AP4 in the same neuron and were found to produce the opposite effect to L-AP4. Furthermore, the effect of L-AP4 could be blocked by coapplication of MPPG or CPPG. Presynaptic depression of glutamate release is a possible mechanism by which L-AP4 could reduce visual responses in the SSC whereas the potentiation of visual responses by L-AP4 could be due to a reduction of GABAergic inhibition. The finding that MPPG and CPPG, as well as antagonizing the L-AP4 effect, have a direct effect on visual responses suggests that Group III mGluRs are activated by endogenous transmitter released during visual stimulation. PMID:10762314

  6. Chandelier cells control excessive cortical excitation: characteristics of whisker-evoked synaptic responses of layer 2/3 nonpyramidal and pyramidal neurons.

    PubMed

    Zhu, Yinghua; Stornetta, Ruth L; Zhu, J Julius

    2004-06-01

    Chandelier cells form inhibitory axo-axonic synapses on pyramidal neurons with their characteristic candlestick-like axonal terminals. The functional role of chandelier cells is still unclear, although the preferential loss of this cell type at epileptic loci suggests a role in epilepsy. Here we report an examination of whisker- and spontaneous activity-evoked responses in chandelier cells and other fast-spiking nonpyramidal neurons and regular-spiking pyramidal neurons in layer 2/3 of the barrel cortex. Fast-spiking nonpyramidal neurons, including chandelier cells, basket cells, neurogliaform cells, double bouquet cells, net basket cells, bitufted cells, and regular-spiking pyramidal neurons all respond to stimulation of multiple whiskers on the contralateral face. Whisker stimulation, however, evokes small, delayed EPSPs preceded by an earlier IPSP and no action potentials in chandelier cells, different from other nonpyramidal and pyramidal neurons. In addition, chandelier cells display a larger receptive field with lower acuity than other fast-spiking nonpyramidal neurons and pyramidal neurons. Notably, simultaneous dual whole-cell in vivo recordings show that chandelier cells, which rarely fire action potentials spontaneously, fire more robustly than other types of cortical neurons when the overall cortical excitation increases. Thus, chandelier cells may not process fast ascending sensory information but instead may be reserved to prevent excessive excitatory activity in neuronal networks. PMID:15175379

  7. Comparison of somatostatin and corticotrophin releasing hormone immunoreactivity in forebrain neurons projecting to taste responsive and non responsive regions of the parabrachial nucleus in rat

    PubMed Central

    Panguluri, Siva; Saggu, Shalini; Lundy, Robert

    2009-01-01

    Several forebrain areas have been shown to project to the parabrachial nucleus (PBN) and exert inhibitory and excitatory influences on taste processing. The neurochemicals by which descending forebrain inputs modulate neural taste-evoked responses remain to be established. This study investigated the existence of somatostatin (SS) and corticotrophin releasing factor (CRF) in forebrain neurons that project to caudal regions of the PBN responsive to chemical stimulation of the anterior tongue as well as more rostral unresponsive regions. Retrograde tracer was iontophoretically or pressure ejected from glass micropipettes, and seven days later the animals were euthanized for subsequent immunohistochemical processing for co-localization of tracer with SS and CRF in tissue sections containing the lateral hypothalamus (LH), central nucleus of the amygdala (CeA), bed nucleus of the stria terminalis (BNST), and insular cortex (IC). In each forebrain site, robust labeling of cells with distinguishable nuclei and short processes was observed for SS and CRF. The results indicate that CRF neurons in each forebrain site send projections throughout the rostral caudal extent of the PBN with a greater percentage terminating in regions rostral to the anterior tongue responsive area. For SS, the percentage of double-labeled neurons was more forebrain site specific in that only BNST and CeA exhibited significant numbers of double labeled neurons. Few retrogradely labeled cells in LH co-expressed SS, while no double labeled cells were observed in IC. Again, tracer injections into rostral PBN resulted in a greater percentage of double labeled neurons in BNST and CeA compared to caudal injections. The present results suggest that some sources of descending forebrain input might utilize somatostatin and/or CRF to exert a broad influence on sensory information processing in the PBN. PMID:19699720

  8. Deficiency of PTP1B in POMC neurons leads to alterations in energy balance and homeostatic response to cold exposure

    PubMed Central

    De Jonghe, Bart C.; Hayes, Matthew R.; Banno, Ryoichi; Skibicka, Karolina P.; Zimmer, Derek J.; Bowen, Kerisha A.; Leichner, Theresa M.; Alhadeff, Amber L.; Kanoski, Scott E.; Cyr, Nicole E.; Nillni, Eduardo A.; Grill, Harvey J.

    2011-01-01

    The adipose tissue-derived hormone leptin regulates energy balance through catabolic effects on central circuits, including proopiomelanocortin (POMC) neurons. Leptin activation of POMC neurons increases thermogenesis and locomotor activity. Protein tyrosine phosphatase 1B (PTP1B) is an important negative regulator of leptin signaling. POMC neuron-specific deletion of PTP1B in mice results in reduced high-fat diet-induced body weight and adiposity gain due to increased energy expenditure and greater leptin sensitivity. Mice lacking the leptin gene (ob/ob mice) are hypothermic and cold intolerant, whereas leptin delivery to ob/ob mice induces thermogenesis via increased sympathetic activity to brown adipose tissue (BAT). Here, we examined whether POMC PTP1B mediates the thermoregulatory response of CNS leptin signaling by evaluating food intake, body weight, core temperature (TC), and spontaneous physical activity (SPA) in response to either exogenous leptin or 4-day cold exposure (4°C) in male POMC-Ptp1b-deficient mice compared with wild-type controls. POMC-Ptp1b−/− mice were hypersensitive to leptin-induced food intake and body weight suppression compared with wild types, yet they displayed similar leptin-induced increases in TC. Interestingly, POMC-Ptp1b−/− mice had increased BAT weight and elevated plasma triiodothyronine (T3) levels in response to a 4-day cold challenge, as well as reduced SPA 24 h after cold exposure, relative to controls. These data show that PTP1B in POMC neurons plays a role in short-term cold-induced reduction of SPA and may influence cold-induced thermogenesis via enhanced activation of the thyroid axis. PMID:21406615

  9. Female Mice Lacking Estrogen Receptor-α in Hypothalamic Proopiomelanocortin (POMC) Neurons Display Enhanced Estrogenic Response on Cortical Bone Mass

    PubMed Central

    Farman, H. H.; Windahl, S. H.; Westberg, L.; Isaksson, H.; Egecioglu, E.; Schele, E.; Ryberg, H.; Jansson, J. O.; Tuukkanen, J.; Koskela, A.; Xie, S. K.; Hahner, L.; Zehr, J.; Clegg, D. J.; Lagerquist, M. K.

    2016-01-01

    Estrogens are important regulators of bone mass and their effects are mainly mediated via estrogen receptor (ER)α. Central ERα exerts an inhibitory role on bone mass. ERα is highly expressed in the arcuate (ARC) and the ventromedial (VMN) nuclei in the hypothalamus. To test whether ERα in proopiomelanocortin (POMC) neurons, located in ARC, is involved in the regulation of bone mass, we used mice lacking ERα expression specifically in POMC neurons (POMC-ERα−/−). Female POMC-ERα−/− and control mice were ovariectomized (OVX) and treated with vehicle or estradiol (0.5 μg/d) for 6 weeks. As expected, estradiol treatment increased the cortical bone thickness in femur, the cortical bone mechanical strength in tibia and the trabecular bone volume fraction in both femur and vertebrae in OVX control mice. Importantly, the estrogenic responses were substantially increased in OVX POMC-ERα−/− mice compared with the estrogenic responses in OVX control mice for cortical bone thickness (+126 ± 34%, P < .01) and mechanical strength (+193 ± 38%, P < .01). To test whether ERα in VMN is involved in the regulation of bone mass, ERα was silenced using an adeno-associated viral vector. Silencing of ERα in hypothalamic VMN resulted in unchanged bone mass. In conclusion, mice lacking ERα in POMC neurons display enhanced estrogenic response on cortical bone mass and mechanical strength. We propose that the balance between inhibitory effects of central ERα activity in hypothalamic POMC neurons in ARC and stimulatory peripheral ERα-mediated effects in bone determines cortical bone mass in female mice. PMID:27254004

  10. Interaction of myenteric neurons and extrinsic nerves in the intestinal inhibitory response induced by mesenteric nerve stimulation.

    PubMed

    Yamasato, T; Nakayama, S

    1991-04-01

    Effects of the mesenteric nerve stimulation (MNS) on the twitch contraction induced by field stimulation were investigated regarding the relationship between myenteric neurons and extrinsic cholinergic nerves in the guinea-pig mesenteric nerve-ileal preparation. The twitch contraction was inhibited after MNS. The inhibition of the twitch contraction after MNS was induced twice, just after MNS (1st inhibition) and 2-3 min later (2nd inhibition) (type I), or once, just after MNS (1st inhibition) (type II), in recovery course of twitch contraction for 6-8 min. The 1st inhibition was slightly decreased by guanethidine and hexamethonium. The inhibitory response (1st inhibition) in both types I and II was recovered to the control level by pretreatment with naloxone (recovered twitch contraction), but the late inhibitory response (2nd inhibition) was markedly observed after 2-3 min in types I and II. Either the 1st or the 2nd inhibition was not altered by capsaicin, desensitization to calcitonin gene-related polypeptide (CGRP), vasoactive intestinal polypeptide (VIP), somatostatin, or galanin. The recovered twitch contraction in types I and II was decreased by CGRP-desensitization, or capsaicin. These results suggest that the first inhibitory response was induced by enteric opioid neurons connected with extrinsic cholinergic nerves, but the 2nd inhibition was induced by unknown substances other than CGRP, VIP, somatostatin, and galanin. The twitch contraction may partly be induced by endogenous neurokinin-like substances. And, some CGRP containing neurons, which connect with extrinsic cholinergic nerves, probably activate the intrinsic excitatory neurons. PMID:1678243

  11. Female Mice Lacking Estrogen Receptor-α in Hypothalamic Proopiomelanocortin (POMC) Neurons Display Enhanced Estrogenic Response on Cortical Bone Mass.

    PubMed

    Farman, H H; Windahl, S H; Westberg, L; Isaksson, H; Egecioglu, E; Schele, E; Ryberg, H; Jansson, J O; Tuukkanen, J; Koskela, A; Xie, S K; Hahner, L; Zehr, J; Clegg, D J; Lagerquist, M K; Ohlsson, C

    2016-08-01

    Estrogens are important regulators of bone mass and their effects are mainly mediated via estrogen receptor (ER)α. Central ERα exerts an inhibitory role on bone mass. ERα is highly expressed in the arcuate (ARC) and the ventromedial (VMN) nuclei in the hypothalamus. To test whether ERα in proopiomelanocortin (POMC) neurons, located in ARC, is involved in the regulation of bone mass, we used mice lacking ERα expression specifically in POMC neurons (POMC-ERα(-/-)). Female POMC-ERα(-/-) and control mice were ovariectomized (OVX) and treated with vehicle or estradiol (0.5 μg/d) for 6 weeks. As expected, estradiol treatment increased the cortical bone thickness in femur, the cortical bone mechanical strength in tibia and the trabecular bone volume fraction in both femur and vertebrae in OVX control mice. Importantly, the estrogenic responses were substantially increased in OVX POMC-ERα(-/-) mice compared with the estrogenic responses in OVX control mice for cortical bone thickness (+126 ± 34%, P < .01) and mechanical strength (+193 ± 38%, P < .01). To test whether ERα in VMN is involved in the regulation of bone mass, ERα was silenced using an adeno-associated viral vector. Silencing of ERα in hypothalamic VMN resulted in unchanged bone mass. In conclusion, mice lacking ERα in POMC neurons display enhanced estrogenic response on cortical bone mass and mechanical strength. We propose that the balance between inhibitory effects of central ERα activity in hypothalamic POMC neurons in ARC and stimulatory peripheral ERα-mediated effects in bone determines cortical bone mass in female mice. PMID:27254004

  12. Spinal dorsal horn neuron response to mechanical stimuli is decreased by electrical stimulation of the primary motor cortex.

    PubMed

    Senapati, Arun K; Huntington, Paula J; Peng, Yuan B

    2005-03-01

    Motor cortex stimulation (MCS) has been used clinically as a tool for the control for central post-stroke pain and neuropathic facial pain. The underlying mechanisms involved in the antinociceptive effect of MCS are not clearly understood. We hypothesize that the antinociceptive effect is through the modulation of the spinal dorsal horn neuron activity. Thirty-two wide dynamic range spinal dorsal horn neurons were recorded, in response to graded mechanical stimulation (brush, pressure, and pinch) at their respective receptive fields, while a stepwise electrical stimulation was applied simultaneously in the motor cortex. The responses to brush at control, 10 V, 20 V, and 30 V, and recovery were 11.5+/-1.6, 12.1+/-2.6, 11.1+/-2.2, 10.5+/-2.1, and 13.2+/-2.5 spikes/s, respectively. The responses to pressure at control, 10 V, 20 V, and 30 V, and recovery were 33.2+/-6.1, 22.9+/-5.3, 20.5+/-5.0, 17.3+/-3.8, and 27.0+/-4.0 spikes/s, respectively. The responses to pinch at control, 10 V, 20 V, and 30 V, and recovery were 37.2+/-6.4, 26.3+/-4.7, 25.9+/-4.7, 22.5+/-4.3, and 35.0+/-6.2 spikes/s, respectively. It is concluded that, in the rat, electrical stimulation of the motor cortex produces significant transient inhibition of the responses of spinal cord dorsal horn neurons to higher intensity mechanical stimuli without affecting their response to an innocuous stimulus. PMID:15725415

  13. Bilateral inhibition generates neuronal responses tuned to interaural level differences in the auditory brainstem of the barn owl.

    PubMed

    Adolphs, R

    1993-09-01

    I investigated the neural algorithms by which neurons gain selectivity for interaural level difference in the brainstem of the barn owl (Tyto alba). Differences in the timing and in the level of sounds at the ears are used by this owl to encode, respectively, azimuthal and vertical position of sound sources in space. These two cues are processed in two parallel neural pathways. Below the level of the inferior colliculus, all neurons in the pathway that processes level differences show responses to this cue that are monotonic, and thus not selective for a particular level difference. Only in the inferior colliculus, which contains a map of auditory space, are neurons sharply tuned to specific interaural level differences. How are these response properties generated from those of the nuclei that provide input to the inferior colliculus? I show that the posterior subdivision of the nucleus ventralis lemnisci lateralis (VLVp) projects bilaterally to the lateral shell of the central nucleus of the inferior colliculus, the input stage to the map of auditory space. Both these nuclei are part of the pathway that processes interaural level differences. Manipulations of the responses in VLVp affected the responses to level differences in the inferior colliculus; responses to time differences were unaffected. By systematically increasing or decreasing neural activity in VLVp, I show that the VLVp on each side provides inhibition to the colliculus at large level differences. This results in a peaked response that is tuned to level differences in the inferior colliculus. Some cells in the lateral shell of the inferior colliculus appear to receive direct GABAergic inhibition from VLVp. I suggest that this circuitry and the algorithms it supports are the neural substrates that allow the barn owl to exploit level differences for computation of sound source elevation. PMID:7690063

  14. A temperature rise reduces trial-to-trial variability of locust auditory neuron responses.

    PubMed

    Eberhard, Monika J B; Schleimer, Jan-Hendrik; Schreiber, Susanne; Ronacher, Bernhard

    2015-09-01

    The neurophysiology of ectothermic animals, such as insects, is affected by environmental temperature, as their body temperature fluctuates with ambient conditions. Changes in temperature alter properties of neurons and, consequently, have an impact on the processing of information. Nevertheless, nervous system function is often maintained over a broad temperature range, exhibiting a surprising robustness to variations in temperature. A special problem arises for acoustically communicating insects, as in these animals mate recognition and mate localization typically rely on the decoding of fast amplitude modulations in calling and courtship songs. In the auditory periphery, however, temporal resolution is constrained by intrinsic neuronal noise. Such noise predominantly arises from the stochasticity of ion channel gating and potentially impairs the processing of sensory signals. On the basis of intracellular recordings of locust auditory neurons, we show that intrinsic neuronal variability on the level of spikes is reduced with increasing temperature. We use a detailed mathematical model including stochastic ion channel gating to shed light on the underlying biophysical mechanisms in auditory receptor neurons: because of a redistribution of channel-induced current noise toward higher frequencies and specifics of the temperature dependence of the membrane impedance, membrane potential noise is indeed reduced at higher temperatures. This finding holds under generic conditions and physiologically plausible assumptions on the temperature dependence of the channels' kinetics and peak conductances. We demonstrate that the identified mechanism also can explain the experimentally observed reduction of spike timing variability at higher temperatures. PMID:26041833

  15. Flattening plasma corticosterone levels increases the prevalence of serotonergic dorsal raphe neurons inhibitory responses to nicotine in adrenalectomised rats.

    PubMed

    Frías-Domínguez, Carmen; Garduño, Julieta; Hernández, Salvador; Drucker-Colin, René; Mihailescu, Stefan

    2013-09-01

    Major depression is characterized by a diminished activity of the brain serotonergic system as well as by the flattening of plasma cortisol levels. Nicotine improves mood in patients with major depression and in experimentally depressed animals by increasing brain serotonin (5-HT), noradrenaline and dopamine levels. The present study was directed to determine if flattening plasma glucocorticoid levels changes nicotine's stimulatory effects upon 5-HT DRN neurons. The experiments were performed in brain slices obtained from rats previously (14 days) adrenalectomised and implanted subcutaneously with one pellet containing 75mg of corticosterone (Adx+CSR rats). Whole cell voltage and current clamp techniques were used to study the activity of immunocitochemically identified 5-HT DRN neurons. Administration of nicotine (1μM) in sham-operated animals produced stimulatory effects in all 5-HT DRN neurons studied. In Adx+CSR rats however, nicotine inhibited 75% of 5-HT DRN neurons and increased the potassium-dependent inward rectifying current. The inhibitory effect of nicotine upon 5-HT DRN neurons was dependent on serotonin release inside the DRN, since it was converted into a stimulatory response by the selective antagonist of 5-HT1A receptors N-[2-[4-(2-methoxyphenyl)-1-piperazinyl]ethyl]-N-(2-pyridyl)cyclohexanecarboxamide (WAY100635, 25nM). Adx+CSR rats also presented an increased function of 5-HT1A autoreceptors, since, in these rats, serotonin (1-10μM) produced a higher increase in the potassium dependent inward rectifying current in comparison with sham-operated animals. Serotonin release inside DRN was mediated by α4β2 nicotinic acetylcholine receptors since the selective antagonist of these receptors dihydro-β-erytroidine hydrobromide (DHβE, 100nM) blocked the inhibitory effects of nicotine 5-HT DRN neurons. These data indicate that, in the experimental model of adrenalectomised rats implanted with corticosterone pellets, nicotine increases the function of

  16. Comparison of anterior cingulate and primary somatosensory neuronal responses to noxious laser-heat stimuli in conscious, behaving rats.

    PubMed

    Kuo, Chung-Chih; Yen, Chen-Tung

    2005-09-01

    In this study, we investigated single-unit responses of the primary sensorimotor cortex (SmI) and anterior cingulate cortex (ACC) to noxious stimulation of the tail of the rat. The influences of morphine on these nociceptive responses were also compared. Multiple single-unit activities were recorded from two eight-channel microwire arrays chronically implanted in the tail region of the SmI and ACC, respectively. CO2 laser-heat irradiation of the middle part of the tail at an intensity slightly higher than that causing a maximal tail flick response was used as a specific noxious stimulus. Examined individually, ACC neurons were less responsive than SmI neurons to laser-heat stimulus, in that only 51% of the ACC units (n = 125) responded compared with 88% of the SmI units (n = 74). Among these responsive ACC units, many had a very long latency and long-lasting excitatory type of response that was seldom found in the SmI. When ensemble activities were examined, laser heat evoked both short- (60 approximately 150 ms) and long-latency (151 approximately 600 ms) responses in the SmI and ACC. Latencies of both responses were longer in the ACC. Furthermore, a single dose of 2.5-10 mg/kg morphine intraperitoneally suppressed only the long latency response in the SmI, but significantly attenuated both responses in the ACC. These effects of morphine were completely blocked by prior treatment with the opiate receptor blocker, naloxone. These results provide further evidence suggesting that the SmI and ACC may play different roles in processing noxious information. PMID:16105955

  17. The reducing agent dithiothreitol (DTT) does not abolish the inhibitory nicotinic response recorded from rat dorsolateral septal neurons

    NASA Technical Reports Server (NTRS)

    Sorenson, E. M.; Gallagher, J. P.

    1993-01-01

    Previous intracellular recordings have demonstrated that dorsolateral septal nucleus (DLSN) neurons express a novel nicotinic receptor which produces a direct membrane hyperpolarization when activated by nicotinic agonists. Activation of the classical excitatory nicotinic receptors has been shown to require a disulfide bond involving the cysteines at positions 192 and 193 of the alpha subunits of the receptor. Reduction of this cystine bond with dithiothreitol (DTT) abolishes agonist activation of excitatory nicotinic receptors. We have now examined whether DTT treatment of the inhibitory nicotinic receptor on DLSN neurons also abolishes the inhibitory nicotinic response. We find that the inhibitory response persists after treatment of the neurons with 1 mM DTT, even if the reduction is followed by alkylation of the receptor with bromoacetylcholine to prevent possible reformation of disulfide bonds. This result suggests that the agonist binding site on the inhibitory nicotinic receptor does not require an intact disulfide bond, similar to the bond on the alpha subunit of the excitatory nicotinic receptor, for agonist activation of the receptor. Some of these results have been previously reported in abstract form.

  18. Environmental enrichment causes a global potentiation of neuronal responses across stimulus complexity and lamina of sensory cortex

    PubMed Central

    Alwis, Dasuni S.; Rajan, Ramesh

    2013-01-01

    Enriched social and physical housing produces many molecular, anatomical, electrophysiological and behavior benefits even in adult animals. Much less is known of its effects on cortical electrophysiology, especially in how sensory cortex encodes the altered environment, and extant studies have generally been restricted to neurons in input laminae in sensory cortex. To extend the understanding of how an enriched environment alters the way in which cortex views the world, we investigated enrichment-induced changes in neuronal encoding of sensory stimuli across all laminae of the rat barrel cortex receiving input from the face whisker tactile system. Animals were housed in Enriched (n = 13) or Isolated housing (n = 13) conditions for 8 weeks before extracellular recordings were obtained from barrel cortex in response to simple whisker deflections and whisker motions modeling movements seen in awake animals undertaking a variety of different tasks. Enrichment resulted in increases in neuronal responses to all stimuli, ranging from those modeling exploratory behavior through to discrimination behaviors. These increases were seen throughout the cortex from supragranular layers through to input Layer 4 and for some stimuli, in infragranular Layer 5. The observed enrichment-induced effect is consistent with the postulate that enrichment causes shift in cortical excitatory/inhibitory balance, and we demonstrate this is greatest in supragranular layers. However, we also report that the effects are non-selective for stimulus parameters across a range of stimuli except for one modeling the likely use of whiskers by the rats in the enriched housing. PMID:23964199

  19. Visual responses of neurones in the second visual area of flying foxes (Pteropus poliocephalus) after lesions of striate cortex

    PubMed Central

    Funk, Agnes P; Rosa, Marcello G P

    1998-01-01

    The first (V1) and second (V2) cortical visual areas exist in all mammals. However, the functional relationship between these areas varies between species. While in monkeys the responses of V2 cells depend on inputs from V1, in all non-primates studied so far V2 cells largely retain responsiveness to photic stimuli after destruction of V1.We studied the visual responsiveness of neurones in V2 of flying foxes after total or partial lesions of the primary visual cortex (V1). The main finding was that visual responses can be evoked in the region of V2 corresponding, in visuotopic co-ordinates, to the lesioned portion of V1 (‘lesion projection zone’; LPZ).The visuotopic organization of V2 was not altered by V1 lesions.The proportion of neurones with strong visual responses was significantly lower within the LPZs (31.5 %) than outside these zones, or in non-lesioned control hemispheres (> 70 %). LPZ cells showed weak direction and orientation bias, and responded consistently only at low spatial and temporal frequencies.The data demonstrate that the functional relationship between V1 and V2 of flying foxes resembles that observed in non-primate mammals. This observation contrasts with the ‘primate-like’ characteristics of the flying fox visual system reported by previous studies. PMID:9806999

  20. The response of neurons in the bed nucleus of the stria terminalis to serotonin: implications for anxiety.

    PubMed

    Hammack, Sayamwong E; Guo, Ji-Dong; Hazra, Rimi; Dabrowska, Joanna; Myers, Karyn M; Rainnie, Donald G

    2009-11-13

    Substantial evidence has suggested that the activity of the bed nucleus of the stria terminalis (BNST) mediates many forms of anxiety-like behavior in human and non-human animals. These data have led many investigators to suggest that abnormal processing within this nucleus may underlie anxiety disorders in humans, and effective anxiety treatments may restore normal BNST functioning. Currently some of the most effective treatments for anxiety disorders are drugs that modulate serotonin (5-HT) systems, and several decades of research have suggested that the activation of 5-HT can modulate anxiety-like behavior. Despite these facts, relatively few studies have examined how activity within the BNST is modulated by 5-HT. Here we review our own investigations using in vitro whole-cell patch-clamp electrophysiological methods on brain sections containing the BNST to determine the response of BNST neurons to exogenous 5-HT application. Our data suggest that the response of BNST neurons to 5-HT is complex, displaying both inhibitory and excitatory components, which are mediated by 5-HT(1A), 5-HT(2A), 5-HT(2C) and 5-HT(7) receptors. Moreover, we have shown that the selective activation of the inhibitory response to 5-HT reduces anxiety-like behavior, and we describe data suggesting that the activation of the excitatory response to 5-HT may be anxiogenic. We propose that in the normal state, the function of 5-HT is to dampen activity within the BNST (and consequent anxiety-like behavior) during exposure to threatening stimuli; however, we suggest that changes in the balance of the function of BNST 5-HT receptor subtypes could alter the response of BNST neurons to favor excitation and produce a pathological state of increased anxiety. PMID:19467288

  1. Cat vestibular neurons that exhibit different responses to active and passive yaw head rotations

    NASA Technical Reports Server (NTRS)

    Robinson, F. R.; Tomko, D. L.

    1987-01-01

    Neurons in the vestibular nuclei were recorded in alert cats during voluntary yaw rotations of the head and during the same rotations delivered with a turntable driven from a record of previous voluntary movements. During both voluntary and passive rotations, 35 percent (6/17) of neurons tested responded at higher rates or for a larger part of the movement during voluntary movements than during the same rotations delivered with the turntable. Neck sensory input was evaluated separately in many of these cells and can account qualitatively for the extra firing present during active movement.

  2. Neuropeptide co-release with GABA may explain functional non-monotonic uncertainty responses in dopamine neurons.

    PubMed

    Tan, Can Ozan; Bullock, Daniel

    2008-01-17

    Co-release of the inhibitory neurotransmitter GABA and the neuropeptide substance-P (SP) from single axons is a conspicuous feature of the basal ganglia, yet its computational role, if any, has not been resolved. In a new learning model, co-release of GABA and SP from axons of striatal projection neurons emerges as a highly efficient way to compute the uncertainty responses that are exhibited by dopamine (DA) neurons when animals adapt to probabilistic contingencies between rewards and the stimuli that predict their delivery. Such uncertainty-related dopamine release appears to be an adaptive phenotype, because it promotes behavioral switching at opportune times. Understanding the computational linkages between SP and DA in the basal ganglia is important, because Huntington's disease is characterized by massive SP depletion, whereas Parkinson's disease is characterized by massive DA depletion. PMID:18053647

  3. Responses of neurons in the marmoset primary auditory cortex to interaural level differences: comparison of pure tones and vocalizations

    PubMed Central

    Lui, Leo L.; Mokri, Yasamin; Reser, David H.; Rosa, Marcello G. P.; Rajan, Ramesh

    2015-01-01

    Interaural level differences (ILDs) are the dominant cue for localizing the sources of high frequency sounds that differ in azimuth. Neurons in the primary auditory cortex (A1) respond differentially to ILDs of simple stimuli such as tones and noise bands, but the extent to which this applies to complex natural sounds, such as vocalizations, is not known. In sufentanil/N2O anesthetized marmosets, we compared the responses of 76 A1 neurons to three vocalizations (Ock, Tsik, and Twitter) and pure tones at cells' characteristic frequency. Each stimulus was presented with ILDs ranging from 20 dB favoring the contralateral ear to 20 dB favoring the ipsilateral ear to cover most of the frontal azimuthal space. The response to each stimulus was tested at three average binaural levels (ABLs). Most neurons were sensitive to ILDs of vocalizations and pure tones. For all stimuli, the majority of cells had monotonic ILD sensitivity functions favoring the contralateral ear, but we also observed ILD sensitivity functions that peaked near the midline and functions favoring the ipsilateral ear. Representation of ILD in A1 was better for pure tones and the Ock vocalization in comparison to the Tsik and Twitter calls; this was reflected by higher discrimination indices and greater modulation ranges. ILD sensitivity was heavily dependent on ABL: changes in ABL by ±20 dB SPL from the optimal level for ILD sensitivity led to significant decreases in ILD sensitivity for all stimuli, although ILD sensitivity to pure tones and Ock calls was most robust to such ABL changes. Our results demonstrate differences in ILD coding for pure tones and vocalizations, showing that ILD sensitivity in A1 to complex sounds cannot be simply extrapolated from that to pure tones. They also show A1 neurons do not show level-invariant representation of ILD, suggesting that such a representation of auditory space is likely to require population coding, and further processing at subsequent hierarchical stages

  4. Systemically administered cocaine selectively enhances long-latency responses of rat barrel field cortical neurons to vibrissae stimulation.

    PubMed

    Bekavac, I; Waterhouse, B D

    1995-01-01

    Prominent among cocaine's psychostimulant actions are its abilities to heighten awareness of the sensory surround and induce sensory hallucinations. Although many studies have examined the cellular actions