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Sample records for alters motor behavior

  1. Deficient Grip Force Control in Schizophrenia: Behavioral and Modeling Evidence for Altered Motor Inhibition and Motor Noise

    PubMed Central

    Teremetz, Maxime; Amado, Isabelle; Bendjemaa, Narjes; Krebs, Marie-Odile; Lindberg, Pavel G.; Maier, Marc A.

    2014-01-01

    Whether upper limb sensorimotor control is affected in schizophrenia and how underlying pathological mechanisms may potentially intervene in these deficits is still being debated. We tested voluntary force control in schizophrenia patients and used a computational model in order to elucidate potential cerebral mechanisms underlying sensorimotor deficits in schizophrenia. A visuomotor grip force-tracking task was performed by 17 medicated and 6 non-medicated patients with schizophrenia (DSM-IV) and by 15 healthy controls. Target forces in the ramp-hold-and-release paradigm were set to 5N and to 10% maximal voluntary grip force. Force trajectory was analyzed by performance measures and Principal Component Analysis (PCA). A computational model incorporating neural control signals was used to replicate the empirically observed motor behavior and to explore underlying neural mechanisms. Grip task performance was significantly lower in medicated and non-medicated schizophrenia patients compared to controls. Three behavioral variables were significantly higher in both patient groups: tracking error (by 50%), coefficient of variation of force (by 57%) and duration of force release (up by 37%). Behavioral performance did not differ between patient groups. Computational simulation successfully replicated these findings and predicted that decreased motor inhibition, together with an increased signal-dependent motor noise, are sufficient to explain the observed motor deficits in patients. PCA also suggested altered motor inhibition as a key factor differentiating patients from control subjects: the principal component representing inhibition correlated with clinical severity. These findings show that schizophrenia affects voluntary sensorimotor control of the hand independent of medication, and suggest that reduced motor inhibition and increased signal-dependent motor noise likely reflect key pathological mechanisms of the sensorimotor deficit. PMID:25369465

  2. Prenatal chlorpyrifos exposure alters motor behavior and ultrasonic vocalization in cd-1 mouse pups

    PubMed Central

    2009-01-01

    Background Chlorpyrifos (CPF) is a non-persistent organophosphate (OP) largely used as pesticide. Studies from animal models indicate that CPF is a developmental neurotoxicant able to target immature central nervous system at dose levels well below the threshold of systemic toxicity. So far, few data are available on the potential short- and long-term adverse effects in children deriving from low-level exposures during prenatal life and infancy. Methods Late gestational exposure [gestational day (GD) 14–17] to CPF at the dose of 6 mg/kg was evaluated in CD-1 mice during early development, by assessment of somatic and sensorimotor maturation [reflex-battery on postnatal days (PNDs) 3, 6, 9, 12 and 15] and ultrasound emission after isolation from the mother and siblings (PNDs 4, 7 and 10). Pups' motor skills were assessed in a spontaneous activity test on PND 12. Maternal behavior of lactating dams in the home cage and in response to presentation of a pup previously removed from the nest was scored on PND 4, to verify potential alterations in maternal care directly induced by CPF administration. Results As for the effects on the offspring, results indicated that on PND 10, CPF significantly decreased number and duration of ultrasonic calls while increasing latency to emit the first call after isolation. Prenatal CPF also reduced motor behavior on PND 12, while a tendency to hyporeflexia was observed in CPF pups by means of reflex-battery scoring. Dams administered during gestation with CPF showed baseline levels of maternal care comparable to those of controls, but higher levels of both pup-directed (licking) and explorative (wall rearing) responses. Conclusion Overall our results are consistent with previous epidemiological data on OP neurobehavioral toxicity, and also indicate ultrasonic vocalization as an early marker of CPF exposure during development in rodent studies, with potential translational value to human infants. PMID:19331648

  3. Examination of Post-stroke Alteration in Motor Unit Firing Behavior Using High Density Surface EMG Decomposition

    PubMed Central

    Li, Xiaoyan; Holobar, Aleš; Gazzoni, Marco; Merletti, Roberto; Rymer, William Z.; Zhou, Ping

    2014-01-01

    Recent advances in high density surface electromyogram (EMG) decomposition have made it a feasible task to discriminate single motor unit activity from surface EMG interference patterns, thus providing a noninvasive approach for examination of motor unit control properties. In the current study we applied high density surface EMG recording and decomposition techniques to assess motor unit firing behavior alterations post-stroke. Surface EMG signals were collected using a 64-channel 2-dimensional electrode array from the paretic and contralateral first dorsal interosseous (FDI) muscles of nine hemiparetic stroke subjects at different isometric discrete contraction levels between 2 N to 10 N with a 2 N increment step. Motor unit firing rates were extracted through decomposition of the high density surface EMG signals, and compared between paretic and contralateral muscles. Across the nine tested subjects, paretic FDI muscles showed decreased motor unit firing rates compared with contralateral muscles at different contraction levels. Regression analysis indicated a linear relation between the mean motor unit firing rate and the muscle contraction level for both paretic and contralateral muscles (p < 0.001), with the former demonstrating a lower increment rate (0.32 pulses per second (pps)/N) compared with the latter (0.67 pps/N). The coefficient of variation (CoV, averaged over the contraction levels) of the motor unit firing rates for the paretic muscles (0.21 ± 0.012) was significantly higher than for the contralateral muscles (0.17 ± 0.014) (p < 0.05). This study provides direct evidence of motor unit firing behavior alterations post-stroke using surface EMG, which can be an important factor contributing to hemiparetic muscle weakness. PMID:25389239

  4. Lack of GPR88 enhances medium spiny neuron activity and alters motor- and cue-dependent behaviors.

    PubMed

    Quintana, Albert; Sanz, Elisenda; Wang, Wengang; Storey, Granville P; Güler, Ali D; Wanat, Matthew J; Roller, Bryan A; La Torre, Anna; Amieux, Paul S; McKnight, G Stanley; Bamford, Nigel S; Palmiter, Richard D

    2012-11-01

    The striatum regulates motor control, reward and learning. Abnormal function of striatal GABAergic medium spiny neurons (MSNs) is believed to contribute to the deficits in these processes that are observed in many neuropsychiatric diseases. The orphan G protein-coupled receptor GPR88 is robustly expressed in MSNs and is regulated by neuropharmacological drugs, but its contribution to MSN physiology and behavior is unclear. We found that, in the absence of GPR88, MSNs showed increased glutamatergic excitation and reduced GABAergic inhibition, which promoted enhanced firing rates in vivo, resulting in hyperactivity, poor motor coordination and impaired cue-based learning in mice. Targeted viral expression of GPR88 in MSNs rescued the molecular and electrophysiological properties and normalized behavior, suggesting that aberrant MSN activation in the absence of GPR88 underlies behavioral deficits and its dysfunction may contribute to behaviors observed in neuropsychiatric disease.

  5. Gonadotropin-releasing hormone receptor (Gnrhr) gene knock out: Normal growth and development of sensory, motor and spatial orientation behavior but altered metabolism in neonatal and prepubertal mice.

    PubMed

    Busby, Ellen R; Sherwood, Nancy M

    2017-01-01

    Gonadotropin-releasing hormone (GnRH) is important in the control of reproduction, but its actions in non-reproductive processes are less well known. In this study we examined the effect of disrupting the GnRH receptor in mice to determine if growth, metabolism or behaviors that are not associated with reproduction were affected. To minimize the effects of other hormones such as FSH, LH and sex steroids, the neonatal-prepubertal period of 2 to 28 days of age was selected. The study shows that regardless of sex or phenotype in the Gnrhr gene knockout line, there was no significant difference in the daily development of motor control, sensory detection or spatial orientation among the wildtype, heterozygous or null mice. This included a series of behavioral tests for touch, vision, hearing, spatial orientation, locomotory behavior and muscle strength. Neither the daily body weight nor the final weight on day 28 of the kidney, liver and thymus relative to body weight varied significantly in any group. However by day 28, metabolic changes in the GnRH null females compared with wildtype females showed a significant reduction in inguinal fat pad weight normalized to body weight; this was accompanied by an increase in glucose compared with wildtype females shown by Student-Newman-Keuls Multiple Comparison test and Student's unpaired t tests. Our studies show that the GnRH-GnRHR system is not essential for growth or motor/sensory/orientation behavior during the first month of life prior to puberty onset. The lack of the GnRH-GnRHR axis, however, did affect females resulting in reduced subcutaneous inguinal fat pad weight and increased glucose with possible insulin resistance; the loss of the normal rise of estradiol at postnatal days 15-28 may account for the altered metabolism in the prepubertal female pups.

  6. Gonadotropin-releasing hormone receptor (Gnrhr) gene knock out: Normal growth and development of sensory, motor and spatial orientation behavior but altered metabolism in neonatal and prepubertal mice

    PubMed Central

    Busby, Ellen R.; Sherwood, Nancy M.

    2017-01-01

    Gonadotropin-releasing hormone (GnRH) is important in the control of reproduction, but its actions in non-reproductive processes are less well known. In this study we examined the effect of disrupting the GnRH receptor in mice to determine if growth, metabolism or behaviors that are not associated with reproduction were affected. To minimize the effects of other hormones such as FSH, LH and sex steroids, the neonatal-prepubertal period of 2 to 28 days of age was selected. The study shows that regardless of sex or phenotype in the Gnrhr gene knockout line, there was no significant difference in the daily development of motor control, sensory detection or spatial orientation among the wildtype, heterozygous or null mice. This included a series of behavioral tests for touch, vision, hearing, spatial orientation, locomotory behavior and muscle strength. Neither the daily body weight nor the final weight on day 28 of the kidney, liver and thymus relative to body weight varied significantly in any group. However by day 28, metabolic changes in the GnRH null females compared with wildtype females showed a significant reduction in inguinal fat pad weight normalized to body weight; this was accompanied by an increase in glucose compared with wildtype females shown by Student-Newman-Keuls Multiple Comparison test and Student's unpaired t tests. Our studies show that the GnRH-GnRHR system is not essential for growth or motor/sensory/orientation behavior during the first month of life prior to puberty onset. The lack of the GnRH-GnRHR axis, however, did affect females resulting in reduced subcutaneous inguinal fat pad weight and increased glucose with possible insulin resistance; the loss of the normal rise of estradiol at postnatal days 15–28 may account for the altered metabolism in the prepubertal female pups. PMID:28346489

  7. The functional alterations associated with motor imagery training: a comparison between motor execution and motor imagery of sequential finger tapping

    NASA Astrophysics Data System (ADS)

    Zhang, Hang; Yao, Li; Long, Zhiying

    2011-03-01

    Motor imagery training, as an effective strategy, has been more and more applied to mental disorders rehabilitation and motor skill learning. Studies on the neural mechanism underlying motor imagery have suggested that such effectiveness may be related to the functional congruence between motor execution and motor imagery. However, as compared to the studies on motor imagery, the studies on motor imagery training are much fewer. The functional alterations associated with motor imagery training and the effectiveness of motor imagery training on motor performance improvement still needs further investigation. Using fMRI, we employed a sequential finger tapping paradigm to explore the functional alterations associated with motor imagery training in both motor execution and motor imagery task. We hypothesized through 14 consecutive days motor imagery training, the motor performance could be improved and the functional congruence between motor execution and motor imagery would be sustained form pre-training phase to post-training phase. Our results confirmed the effectiveness of motor imagery training in improving motor performance and demonstrated in both pre and post-training phases, motor imagery and motor execution consistently sustained the congruence in functional neuroanatomy, including SMA (supplementary motor cortex), PMA (premotor area); M1( primary motor cortex) and cerebellum. Moreover, for both execution and imagery tasks, a similar functional alteration was observed in fusiform through motor imagery training. These findings provided an insight into the effectiveness of motor imagery training and suggested its potential therapeutic value in motor rehabilitation.

  8. Adaptation to Leftward Shifting Prisms Alters Motor Interhemispheric Inhibition.

    PubMed

    Martín-Arévalo, Elisa; Schintu, Selene; Farnè, Alessandro; Pisella, Laure; Reilly, Karen T

    2016-12-18

    Adaptation to rightward shifting prisms (rightward prism adaptation, RPA) ameliorates neglect symptoms in patients while adaptation to leftward shifting prisms (leftward prism adaptation, LPA) induces neglect-like behaviors in healthy subjects. It has been hypothesized that prism adaptation (PA) modulates interhemispheric balance between the parietal cortices by inhibiting the posterior parietal cortex (PPC) contralateral to the prismatic deviation, but PA's effects on interhemispheric inhibition (IHI) have not been directly investigated. Since there are hyper-excitable connections between the PPC and primary motor cortex (M1) in the left hemisphere of neglect patients, we reasoned that LPA might mimic right hemisphere lesions by reducing parietal IHI, hyper-exciting the left PPC and PPC-M1 connections, and in turn altering IHI at the motor level. Namely, we hypothesized that LPA would increase IHI from the left to the right M1. We examined changes in left-to-right and right-to-left IHI between the 2 M1s using the ipsilateral silent period (iSP) (Meyer et al. 1995) before and after either LPA or RPA. The iSP was significantly longer after LPA but only from left-to-right and it did not change at all after RPA. This is the first physiological demonstration that LPA alters IHI in the healthy brain.

  9. Social Interaction and Repetitive Motor Behaviors

    ERIC Educational Resources Information Center

    Loftin, Rachel L.; Odom, Samuel L.; Lantz, Johanna F.

    2008-01-01

    Students with autism have difficulty initiating social interactions and may exhibit repetitive motor behavior (e.g., body rocking, hand flapping). Increasing social interaction by teaching new skills may lead to reductions in problem behavior, such as motor stereotypies. Additionally, self-monitoring strategies can increase the maintenance of…

  10. Alteration of Motor Network Function Following Injury

    DTIC Science & Technology

    2012-10-01

    unlikely system for spinal cord injury: namely crustacean motor networks such as the stomatogastric ganglion (STG)6. While the STG is an invertebrate...typically modify activity by regulating the properties or expression levels of subsets of ionic channels. In the stomatogastric system of crustaceans ...conductances preserves output in a computational model of a crustacean cardiac motor neuron. J Neurosci 30: 8637–8649, 2010. Baro DJ, Levini RM, Kim MT

  11. Alterations of motor evoked potentials by thalamotomy.

    PubMed

    van der Linden, C; Bruggeman, R; Goldman, W H

    1993-09-01

    To evaluate the effect of stereotactic thalamotomy on the function of the corticospinal tract, we studied motor evoked potentials (MEPs) recorded by surface electromyography (EMG) in the left extensor carpi radialis (ECR) and flexor carpi radialis (FCR) with magnetic stimulation of the contralateral motor cortex in a 43-year-old patient with a severe postural and resting tremor of the left hand. The patient was diagnosed eight years previously with left hemiparkinsonism. The tremor was unresponsive to various medications. After thalamotomy the tremor had disappeared, confirmed by EMG studies. MEP latencies at rest were normal and did not change after thalamotomy. Volitional contraction of either ECR or FCR shortened the latency of the corresponding MEP before and after thalamotomy. However, before thalamotomy responses at rest were less well synchronized and followed by EMG silence with subsequent long duration tonic after discharges. Furthermore, during voluntary contraction the responses only slightly enhanced. After surgery MEPs at rest in both muscles were more synchronized and after-discharges had disappeared. Moreover, with volitional contraction of either ECR of FCR, the MEPs enhanced more dramatically. The silent periods (SPs) following the MEP during sustained voluntary contraction were longer after thalamotomy. The consistent MEP latencies suggest that the conduction of the pyramidal tract is unaffected by thalamotomy. The better synchronized responses, the alleviation of after-discharges and the longer SPs in this patient with hemiparkinsonism following thalamotomy suggest an improved sensorimotor integration, which may be the result of a reduced thalamic input onto suprasegmental levels.

  12. Study of adaptation to altered gravity through systems analysis of motor control

    NASA Astrophysics Data System (ADS)

    Fox, R. A.; Daunton, N. G.; Corcoran, M. L.

    Maintenance of posture and production of functional, coordinated movement demand integration of sensory feedback with spinal and supra-spinal circuitry to produce adaptive motor control in altered gravity (G). To investigate neuroplastic processes leading to optimal performance in altered G we have studied motor control in adult rats using a battery of motor function tests following chronic exposure to various treatments (hyper-G, hindlimb suspension, chemical distruction of hair cells, space flight). These treatments differentially affect muscle fibers, vestibular receptors, and behavioral compensations and, in consequence, differentially disrupt air righting, swimming, posture and gait. The time-course of recovery from these disruptions varies depending on the function tested and the duration and type of treatment. These studies, with others (e.g., D'Amelio et al. in this volume), indicate that adaptation to altered gravity involves alterations in multiple sensory-motor systems that change at different rates. We propose that the use of parallel studies under different altered G conditions will most efficiently lead to an understanding of the modifications in central (neural) and peripheral (sensory and neuromuscular) systems that underlie sensory-motor adaptation in active, intact individuals.

  13. Modulation of brain development by morphine: effects on central motor systems and behavior.

    PubMed

    Handelmann, G E; Dow-Edwards, D

    1985-01-01

    Morphine administration to neonatal rats on days 1-7 after birth produced long-term changes in behavior and brain function. The pups were smaller than saline-treated littermates and showed retarded motor development. As adults, the morphine-treated rats had impaired motor coordination, altered gait, and altered patterns of activity in an open field. Several brain regions of the adult rats, including motor areas, had decreased metabolic activity as measured by the 2-deoxy-glucose technique, suggesting decreased functional activity in these areas. These results may be relevant to findings that children exposed in utero to narcotics tend to have impaired motor development.

  14. Rhythmic motor behavior of preambulatory motor impaired, Down syndrome and nondisabled children: a comparative analysis.

    PubMed

    MacLean, W E; Ellis, D N; Galbreath, H N; Halpern, L F; Baumeister, A A

    1991-06-01

    The developmental course of rhythmic motor behavior was followed longitudinally for three groups of preambulatory children--normally developing, Down syndrome, and those with profound motor impairment. The groups differed in chronological age but were comparable with respect to motor age. The motor impaired subjects displayed significantly less rhythmic motor behavior than the nondisabled and Down syndrome groups. In comparing particular subtypes of rhythmic motor behavior, differences were found in both the average number of bouts and duration of subtypes among the groups. Longitudinal analyses of the data over the entire observation period revealed that the rhythmic motor behavior of the children with Down syndrome was more similar to that exhibited by the nondisabled children than was the rhythmic motor behavior of the children with motor impairment. However, there was considerable variability among the groups in several particular subtypes.

  15. Motor Behavior Activates Bergmann Glial Networks

    PubMed Central

    Nimmerjahn, Axel; Mukamel, Eran A.; Schnitzer, Mark J.

    2010-01-01

    SUMMARY Although it is firmly established neuronal activity is a prime determinant of animal behavior, relationships between astrocytic excitation and animal behavior have remained opaque. Cerebellar Bergmann glia are radial astrocytes that are implicated in motor behavior and exhibit Ca2+-excitation. However, Ca2+-excitation in these cells has not previously been studied in behaving animals. Using two-photon microscopy we found that Bergmann glia exhibit three forms of Ca2+-excitation in awake behaving mice. Two of these are ongoing within the cerebellar vermis. During locomotor performance concerted Ca2+-excitation arises in networks of at least hundreds of Bergmann glia extending across several hundred microns or more. Concerted Ca2+-excitation was abolished by anesthesia or blockade of either neural activity or glutamatergic transmission. Thus, large networks of Bergmann glia can be activated by specific animal behaviors and undergo excitation of sufficient magnitude to potentially initiate macroscopic changes in brain dynamics or blood flow. PMID:19447095

  16. Motor Experience Reprograms Development of a Genetically-Altered Bilateral Corticospinal Motor Circuit

    PubMed Central

    Serradj, Najet

    2016-01-01

    Evidence suggests that motor experience plays a role in shaping development of the corticospinal system and voluntary motor control, which is a key motor function of the system. Here we used a mouse model with conditional forebrain deletion of the gene for EphA4 (Emx1-Cre:EphA4tm2Kldr), which regulates development of the laterality of corticospinal tract (CST). We combined study of Emx1-Cre:EphA4tm2Kldr with unilateral forelimb constraint during development to expand our understanding of experience-dependent CST development from both basic and translational perspectives. This mouse develops dense ipsilateral CST projections, a bilateral motor cortex motor representation, and bilateral motor phenotypes. Together these phenotypes can be used as readouts of corticospinal system organization and function and the changes brought about by experience. The Emx1-Cre:EphA4tm2Kldr mouse shares features with the common developmental disorder cerebral palsy: bilateral voluntary motor impairments and bilateral CST miswiring. Emx1-Cre:EphA4tm2Kldr mice with typical motor experiences during development display the bilateral phenotype of “mirror” reaching, because of a strongly bilateral motor cortex motor representation and a bilateral CST. By contrast, Emx1-Cre:EphA4tm2Kldr mice that experienced unilateral forelimb constraint from P1 to P30 and tested at maturity had a more contralateral motor cortex motor representation in each hemisphere; more lateralized CST projections; and substantially more lateralized/independent reaching movements. Changes in CST organization and function in this model can be explained by reduced synaptic competition of the CST from the side without developmental forelimb motor experiences. Using this model we show that unilateral constraint largely abrogated the effects of the genetic mutation on CST projections and thus demonstrates how robust and persistent experience-dependent development can be for the establishment of corticospinal system

  17. Hypergravity-induced altered behavior in Drosophila

    NASA Astrophysics Data System (ADS)

    Hosamani, Ravikumar; Wan, Judy; Marcu, Oana; Bhattacharya, Sharmila

    2012-07-01

    Microgravity and mechanical stress are important factors of the spaceflight environment, and affect astronaut health and behavior. Structural, functional, and behavioral mechanisms of all cells and organisms are adapted to Earth's gravitational force, 1G, while altered gravity can pose challenges to their adaptability to this new environment. On ground, hypergravity paradigms have been used to predict and complement studies on microgravity. Even small changes that take place at a molecular and genetic level during altered gravity may result in changes in phenotypic behavior. Drosophila provides a robust and simple, yet very reliable model system to understand the complexity of hypergravity-induced altered behavior, due to availability of a plethora of genetic tools. Locomotor behavior is a sensitive parameter that reflects the array of molecular adaptive mechanisms recruited during exposure to altered gravity. Thus, understanding the genetic basis of this behavior in a hypergravity environment could potentially extend our understanding of mechanisms of adaptation in microgravity. In our laboratory we are trying to dissect out the cellular and molecular mechanisms underlying hypergravity-induced oxidative stress, and its potential consequences on behavioral alterations by using Drosophila as a model system. In the present study, we employed pan-neuronal and mushroom body specific knock-down adult flies by using Gal4/UAS system to express inverted repeat transgenes (RNAi) to monitor and quantify the hypergravity-induced behavior in Drosophila. We established that acute hypergravity (3G for 60 min) causes a significant and robust decrease in the locomotor behavior in adult Drosophila, and that this change is dependent on genes related to Parkinson's disease, such as DJ-1α , DJ-1β , and parkin. In addition, we also showed that anatomically the control of this behavior is significantly processed in the mushroom body region of the fly brain. This work links a molecular

  18. Causal interaction following the alteration of target region activation during motor imagery training using real-time fMRI

    PubMed Central

    Zhao, Xiaojie; Zhang, Hang; Song, Sutao; Ye, Qing; Guo, Jia; Yao, Li

    2013-01-01

    Motor imagery training is an effective approach for motor skill learning and motor function rehabilitation. As a novel method of motor imagery training, real-time fMRI (rtfMRI) enables individuals to acquire self-control of localized brain activation, achieving desired changes in behavior. The regulation of target region activation by rtfMRI often alters the activation of related brain regions. However, the interaction between the target region and these related regions is unclear. The Granger causality model (GCM) is a data-driven method that can explore the causal interaction between brain regions. In this study, we employed rtfMRI to train subjects to regulate the activation of the ipsilateral dorsal premotor area (dPMA) during motor imagery training, and we calculated the causal interaction of the dPMA with other motor-related regions based on the GCM. The results demonstrated that as the activity of the dPMA changed during rtfMRI training, the interaction of the target region with other related regions became significantly altered, and behavioral performance was improved after training. The altered interaction primarily exhibited as an increased unidirectional interaction from the dPMA to the other regions. These findings support the dominant role of the dPMA in motor skill learning via rtfMRI training and may indicate how activation of the target region interacts with the activation of other related regions. PMID:24379775

  19. A Behavior Analytic Approach to Exploratory Motor Behavior: How Can Caregivers Teach EM Behavior to Infants with Down Syndrome?

    ERIC Educational Resources Information Center

    Bauer, Sara M.; Jones, Emily A.

    2014-01-01

    Impairment in exploratory motor (EM) behavior is part of the Down syndrome behavioral phenotype. Exploratory motor behavior may be a pivotal skill for early intervention with infants with Down syndrome. Exploratory motor impairments are often attributed to general delays in motor development in infants with Down syndrome. A behavior analytic…

  20. Repetitive motor behavior: further characterization of development and temporal dynamics.

    PubMed

    Muehlmann, Amber M; Bliznyuk, Nikolay; Duerr, Isaac; Lewis, Mark H

    2015-03-01

    Repetitive behaviors are diagnostic for autism spectrum disorders, common in related neurodevelopmental disorders, and normative in typical development. In order to identify factors that mediate repetitive behavior development, it is necessary to characterize the expression of these behaviors from an early age. Extending previous findings, we characterized further the ontogeny of stereotyped motor behavior both in terms of frequency and temporal organization in deer mice. A three group trajectory model provided a good fit to the frequencies of stereotyped behavior across eight developmental time points. Group based trajectory analysis using a measure of temporal organization of stereotyped behavior also resulted in a three group solution. Additionally, as the frequency of stereotyped behavior increased with age, the temporal distribution of stereotyped responses became increasingly regular or organized indicating a strong association between these measures. Classification tree and principal components analysis showed that accurate classification of trajectory group could be done with fewer observations. This ability to identify trajectory group membership earlier in development allows for examination of a wide range of variables, both experiential and biological, to determine their impact on altering the expected trajectory of repetitive behavior across development. Such studies would have important implications for treatment efforts in neurodevelopmental disorders such as autism.

  1. Static otolithic drive alters presynaptic inhibition in soleus motor pool.

    PubMed

    Fox, Apollonia; Koceja, David

    2017-02-01

    The vestibular system has both direct and indirect connections to the soleus motor pool via the vestibulospinal and reticulospinal tracts. The exact nature of how this vestibular information is integrated within the spinal cord is largely unknown. The purpose of this study was to identify whether changes in static otolithic drive altered the amount of presynaptic inhibition in the soleus H-reflex pathway. Changes in static otolithic drive were investigated in sixteen healthy participants using a tilt table. Two presynaptic pathways (common peroneal and femoral) to the soleus H-reflex were tested in three weight conditions (supine, non-weight bearing, and weight bearing). The dependent variable was the peak-to-peak amplitude of the soleus H-reflex. Inhibition to the soleus motor pool through the common peroneal nerve pathway differed significantly during weight conditions and tilt. During tilt and non-weight bearing there was greater inhibition of the soleus H-reflex compared to supine, however, this effect was reversed during tilt and weight bearing. Facilitation from the femoral nerve pathway was reduced by tilt compared to supine, but this reduction was unaffected by weight condition. This supports a role of the vestibular system as providing complex, task-dependent presynaptic input to motoneurons in the lower limbs.

  2. Altered motor control patterns in whiplash and chronic neck pain

    PubMed Central

    Woodhouse, Astrid; Vasseljen, Ottar

    2008-01-01

    Background Persistent whiplash associated disorders (WAD) have been associated with alterations in kinesthetic sense and motor control. The evidence is however inconclusive, particularly for differences between WAD patients and patients with chronic non-traumatic neck pain. The aim of this study was to investigate motor control deficits in WAD compared to chronic non-traumatic neck pain and healthy controls in relation to cervical range of motion (ROM), conjunct motion, joint position error and ROM-variability. Methods Participants (n = 173) were recruited to three groups: 59 patients with persistent WAD, 57 patients with chronic non-traumatic neck pain and 57 asymptomatic volunteers. A 3D motion tracking system (Fastrak) was used to record maximal range of motion in the three cardinal planes of the cervical spine (sagittal, frontal and horizontal), and concurrent motion in the two associated cardinal planes relative to each primary plane were used to express conjunct motion. Joint position error was registered as the difference in head positions before and after cervical rotations. Results Reduced conjunct motion was found for WAD and chronic neck pain patients compared to asymptomatic subjects. This was most evident during cervical rotation. Reduced conjunct motion was not explained by current pain or by range of motion in the primary plane. Total conjunct motion during primary rotation was 13.9° (95% CI; 12.2–15.6) for the WAD group, 17.9° (95% CI; 16.1–19.6) for the chronic neck pain group and 25.9° (95% CI; 23.7–28.1) for the asymptomatic group. As expected, maximal cervical range of motion was significantly reduced among the WAD patients compared to both control groups. No group differences were found in maximal ROM-variability or joint position error. Conclusion Altered movement patterns in the cervical spine were found for both pain groups, indicating changes in motor control strategies. The changes were not related to a history of neck trauma, nor

  3. Age-related decline in motor behavior and striatal dopamine transporter in cynomolgus monkeys.

    PubMed

    Yue, Feng; Zeng, Sien; Wu, Di; Yi, Deqiao; Alex Zhang, Y; Chan, Piu

    2012-08-01

    Advanced human aging is associated with progressive declines of motor function and a risk factor for Parkinson's disease, which mainly involves central nigrostriatal dopaminergic system. The present study investigated age-related changes in motor behaviors and alterations of the number of nigrostriatal dopaminergic terminals in non-human primates. A total of 30 cynomolgus monkeys (Macaca fascicularis) of age 3.5-15.5 years were studied. Motor behaviors including upper limb movement time and the amount of overall home cage activity were quantitatively assessed using a modified movement assessment panel and a newly developed webcam-based monitoring system. The function of the dopaminergic system was semi-quantitatively measured by (99m)Tc-TRODAT-1 uptake rates, a dopamine transporter (DAT) specific radiopharmaceutical with SPECT imaging. The results showed a significant decline in motor behaviors associated with aging which were significantly correlated with age-related decreases of (99m)Tc-TRODAT-1 uptake. A further partial correlation analysis independent of age indicated that age contributed to the relationship between striatal DAT levels and motor behaviors. Our results indicate that normal aging-related dopamine physiology influences certain aspects of motor behaviors and suggest that aging-associated dysfunction in the nigrostriatal dopaminergic system may be an important factor contributing to the decline of motor behaviors in aging cynomolgus monkeys.

  4. Motor control of Drosophila feeding behavior

    PubMed Central

    Schwarz, Olivia; Bohra, Ali Asgar; Liu, Xinyu; Reichert, Heinrich; VijayRaghavan, Krishnaswamy; Pielage, Jan

    2017-01-01

    The precise coordination of body parts is essential for survival and behavior of higher organisms. While progress has been made towards the identification of central mechanisms coordinating limb movement, only limited knowledge exists regarding the generation and execution of sequential motor action patterns at the level of individual motoneurons. Here we use Drosophila proboscis extension as a model system for a reaching-like behavior. We first provide a neuroanatomical description of the motoneurons and muscles contributing to proboscis motion. Using genetic targeting in combination with artificial activation and silencing assays we identify the individual motoneurons controlling the five major sequential steps of proboscis extension and retraction. Activity-manipulations during naturally evoked proboscis extension show that orchestration of serial motoneuron activation does not rely on feed-forward mechanisms. Our data support a model in which central command circuits recruit individual motoneurons to generate task-specific proboscis extension sequences. DOI: http://dx.doi.org/10.7554/eLife.19892.001 PMID:28211791

  5. Developmental Alterations in Motor Coordination and Medium Spiny Neuron Markers in Mice Lacking PGC-1α

    PubMed Central

    Lucas, Elizabeth K.; Dougherty, Sarah E.; McMeekin, Laura J.; Trinh, Alisa T.; Reid, Courtney S.; Cowell, Rita M.

    2012-01-01

    Accumulating evidence implicates the transcriptional coactivator peroxisome proliferator activated receptor γ coactivator 1α (PGC-1α) in the pathophysiology of Huntington Disease (HD). Adult PGC-1α −/− mice exhibit striatal neurodegeneration, and reductions in the expression of PGC-1α have been observed in striatum and muscle of HD patients as well as in animal models of the disease. However, it is unknown whether decreased expression of PGC-1α alone is sufficient to lead to the motor phenotype and striatal pathology characteristic of HD. For the first time, we show that young PGC-1α −/− mice exhibit severe rotarod deficits, decreased rearing behavior, and increased occurrence of tremor in addition to the previously described hindlimb clasping. Motor impairment and striatal vacuolation are apparent in PGC-1α −/− mice by four weeks of age and do not improve or decline by twelve weeks of age. The behavioral and pathological phenotype of PGC-1α −/− mice can be completely recapitulated by conditional nervous system deletion of PGC-1α, indicating that peripheral effects are not responsible for the observed abnormalities. Evaluation of the transcriptional profile of PGC-1α −/− striatal neuron populations and comparison to striatal neuron profiles of R6/2 HD mice revealed that PGC-1α deficiency alone is not sufficient to cause the transcriptional changes observed in this HD mouse model. In contrast to R6/2 HD mice, PGC-1α −/− mice show increases in the expression of medium spiny neuron (MSN) markers with age, suggesting that the observed behavioral and structural abnormalities are not primarily due to MSN loss, the defining pathological feature of HD. These results indicate that PGC-1α is required for the proper development of motor circuitry and transcriptional homeostasis in MSNs and that developmental disruption of PGC-1α leads to long-term alterations in motor functioning. PMID:22916173

  6. Cross-species assessments of motor and exploratory behavior related to bipolar disorder.

    PubMed

    Henry, Brook L; Minassian, Arpi; Young, Jared W; Paulus, Martin P; Geyer, Mark A; Perry, William

    2010-07-01

    Alterations in exploratory behavior are a fundamental feature of bipolar mania, typically characterized as motor hyperactivity and increased goal-directed behavior in response to environmental cues. In contrast, abnormal exploration associated with schizophrenia and depression can manifest as prominent withdrawal, limited motor activity, and inattention to the environment. While motor abnormalities are cited frequently as clinical manifestations of these disorders, relatively few empirical studies have quantified human exploratory behavior. This article reviews the literature characterizing motor and exploratory behavior associated with bipolar disorder and genetic and pharmacological animal models of the illness. Despite sophisticated assessment of exploratory behavior in rodents, objective quantification of human motor activity has been limited primarily to actigraphy studies with poor cross-species translational value. Furthermore, symptoms that reflect the cardinal features of bipolar disorder have proven difficult to establish in putative animal models of this illness. Recently, however, novel tools such as the human behavioral pattern monitor provide multivariate translational measures of motor and exploratory activity, enabling improved understanding of the neurobiology underlying psychiatric disorders.

  7. Haploinsufficiency of Dyrk1A in mice leads to specific alterations in the development and regulation of motor activity.

    PubMed

    Fotaki, V; Martínez De Lagrán, M; Estivill, X; Arbonés, M; Dierssen, M

    2004-08-01

    DYRK1A is a protein kinase proposed to be involved in neurogenesis. Gene-targeting disruption of Dyrk1A in mice leads to decreased body and brain size, with no severe disturbance of behavior. In this study, the authors focused on the motor profile of Dyrk1A(+/-) mice. These mice presented impairment of neuromotor development with decreased activity, suggesting a physiological role of Dyrk1A in the maturation of the neuromotor system. In the adult, a marked hypoactivity and alteration of specific motor parameters were detected. These results are in agreement with the significant expression of Dyrk1A in structures related to motor function and support a role of Dyrk1A in the control of motor function.

  8. Fetal grafts alter chronic behavioral outcome after contusion damage to the adult rat spinal cord.

    PubMed

    Stokes, B T; Reier, P J

    1992-04-01

    In the present experiments, we have examined the capacity of intraspinal transplants to effect alterations in certain locomotor behaviors after spinal contusion injuries. An electromechanical impactor that was sensitive to tissue biomechanical characteristics was used to produce rapid (20 ms) compression injuries to the thoracic spinal cord (T8). Suspensions of fetal spinal tissue (14-day) were placed at 10 days postinjury into the intraspinal cavity created by these reproducible spinal injuries. In the pre- and postinjury period, a number of general and sensitive motor behaviors were used to characterize the immediate and long-term progress of hindlimb behavioral recovery over an extended period of time (73 days). Our data reveal that a lasting alteration in some motor behaviors can be achieved by suspension grafts. While little improvement in some generalized motor tasks (inclined plane analysis, grid walking) takes place, fetal transplants precipitate a rapid and enduring change in certain motivated fine motor behaviors (gait analysis). The base of support and stride length of the hindlimbs were improved by 7 days post-transplantation and the effect was stable over time. The angle of rotation was, however, not altered. The lasting effect in two gait parameters noted was accompanied by the presence of well-developed spinal grafts that often fused with the host spinal parenchyma. These results provide the first documentation of an influence of fetal transplants on motivated locomotor capacity in a well-characterized spinal injury model that mimics lesions seen in the contused adult human spinal cord.

  9. Perinatal exposure to polychlorinated biphenyls alters social behaviors in rats

    PubMed Central

    Jolous-Jamshidi, Banafsheh; Cromwell, Howard C.; McFarland, Ashley M.; Meserve, Lee A.

    2014-01-01

    Perinatal exposure to polychlorinated biphenyls (PCBs) leads to significant alterations of neural and hormonal systems. These alterations have been shown to impair motor and sensory development. Less is known about the influence of PCB exposure on developing emotional and motivational systems involved in social interactions and social learning. The present study examined the impact of perinatal PCB exposure (mixture of congeners 47 and 77) on social recognition in juvenile animals, conspecific-directed investigation in adults and on neural and hormonal systems involved in social functions. We used a standard habituation–dishabituation paradigm to evaluate juvenile recognition and a social port paradigm to monitor adult social investigation. Areal measures of the periventricular nucleus (PVN) of the hypothalamus were obtained to provide correlations with related hormone and brain systems. PCB exposed rats were significantly impaired in social recognition as indicated by persistent conspecific-directed exploration by juvenile animals regardless of social experience. As adults, PCB exposure led to a dampening of the isolation-induced enhancement of social investigation. There was not a concomitant alteration of social investigation in pair-housed PCB exposed animals at this stage of development. Interestingly, PVN area was significantly decreased in juvenile animals exposed to PCB during the perinatal period. Shifts in hypothalamic regulation of hormones involved in social behavior and stress could be involved in the behavioral changes observed. Overall, the results suggest that PCB exposure impairs context or experience-dependent modulation of social approach and investigation. These types of social-context deficits are similar to behavioral deficits observed in social disorders such as autism and other pervasive developmental disorders. PMID:20813172

  10. Motor Stereotypies and Volumetric Brain Alterations in Children with Autistic Disorder

    ERIC Educational Resources Information Center

    Goldman, Sylvie; O'Brien, Liam M.; Filipek, Pauline A.; Rapin, Isabelle; Herbert, Martha R.

    2013-01-01

    Motor stereotypies are defined as patterned, repetitive, purposeless movements. These stigmatizing motor behaviors represent one manifestation of the third core criterion for an Autistic Disorder (AD) diagnosis, and are becoming viewed as potential early markers of autism. Moreover, motor stereotypies might be a tangible expression of the…

  11. REM sleep behavior disorder: motor manifestations and pathophysiology.

    PubMed

    Arnulf, Isabelle

    2012-05-01

    Patients with REM sleep behavior disorder (RBD) enact violent dreams during REM sleep in the absence of normal muscle atonia. This disorder is highly frequent in patients with synucleinopathies (60%-100% of patients) and rare in patients with other neurodegenerative disorders. The disorder is detected by interview plus video and sleep monitoring. Abnormal movements expose the patients and bed partners to a high risk of injury and sleep disruption. The disorder is usually alleviated with melatonin and clonazepam. Limb movements are mainly minor, jerky, fast, pseudohallucinatory, and repeated, with a limp wrist during apparently grasping movements, although body jerks and complex violent (fights) and nonviolent culturally acquired behaviors are also observed. Notably, parkinsonism disappears during RBD-associated complex behaviors in patients with Parkinson's disease and with multiple system atrophy, suggesting that the upper motor stream bypasses the basal ganglia during REM sleep. Longitudinal studies show that idiopathic RBD predisposes patients to later develop Parkinson's disease, dementia with Lewy bodies, and, more rarely, multiple system atrophy, with a rate of conversion of 46% within 5 years. During this time window, patients concomitantly develop nonmotor signs (decreased olfaction and color vision, orthostatic hypotension, altered visuospatial abilities, increased harm avoidance) and have abnormal test results (decreased putamen dopamine uptake, slower EEG). Patients with idiopathic RBD have higher and faster risk for conversion to Parkinson's disease and dementia with Lewy bodies if abnormalities in dopamine transporter imaging, transcranial sonography, olfaction, and color vision are found at baseline. They constitute a highly specific target for testing neuroprotective agents.

  12. Tactile stimulation during sleep alters slow oscillation and spindle densities but not motor skill.

    PubMed

    Pereira, Sofia Isabel Ribeiro; Beijamini, Felipe; Weber, Frederik D; Vincenzi, Roberta Almeida; da Silva, Felipe Augusto Cini; Louzada, Fernando Mazzilli

    2017-02-01

    Studies using targeted memory reactivation have shown that presentation of auditory or olfactory contextual cues during sleep can bias hippocampal reactivations towards the preferential replay of the cue-associated material, thereby resulting in enhanced consolidation of that information. If the same cortical ensembles are indeed used for encoding and storage of a given piece of information, forcing the sleeping brain to re-engage in task-intrinsic information processing should disturb the natural ongoing consolidation processes and therefore impair possible sleep benefits. Here we aimed at recreating an integral part of the sensory experience of a motor skill in a daytime nap, by means of a tactile stimulation. We hypothesized that tampering with the tactile component of a motor skill during sleep would result in hindered performance at retest, due to interference between the highly congruent incoming stimuli and the core skill trace. Contrary to our predictions, the tactile stimulation did not influence neither speed nor accuracy, when compared to natural sleep. However, an exploratory sleep EEG analysis revealed stimulation-induced alterations in the abundance and cortical topography of slow oscillations and spindles. These findings suggest that despite the lack of a significant effect on motor behavior, tactile stimulation induced changes in EEG features suggestive of a possible uncoupling between the sleep oscillations thought to underlie consolidation processes, i.e. slow oscillations and sleep spindles.

  13. Algal toxins alter copepod feeding behavior.

    PubMed

    Hong, Jiarong; Talapatra, Siddharth; Katz, Joseph; Tester, Patricia A; Waggett, Rebecca J; Place, Allen R

    2012-01-01

    Using digital holographic cinematography, we quantify and compare the feeding behavior of free-swimming copepods, Acartia tonsa, on nutritional prey (Storeatula major) to that occurring during exposure to toxic and non-toxic strains of Karenia brevis and Karlodinium veneficum. These two harmful algal species produce polyketide toxins with different modes of action and potency. We distinguish between two different beating modes of the copepod's feeding appendages-a "sampling beating" that has short durations (<100 ms) and involves little fluid entrainment and a longer duration "grazing beating" that persists up to 1200 ms and generates feeding currents. The durations of both beating modes have log-normal distributions. Without prey, A. tonsa only samples the environment at low frequency. Upon introduction of non-toxic food, it increases its sampling time moderately and the grazing period substantially. On mono algal diets for either of the toxic dinoflagellates, sampling time fraction is high but the grazing is very limited. A. tonsa demonstrates aversion to both toxic algal species. In mixtures of S. major and the neurotoxin producing K. brevis, sampling and grazing diminish rapidly, presumably due to neurological effects of consuming brevetoxins while trying to feed on S. major. In contrast, on mixtures of cytotoxin producing K. veneficum, both behavioral modes persist, indicating that intake of karlotoxins does not immediately inhibit the copepod's grazing behavior. These findings add critical insight into how these algal toxins may influence the copepod's feeding behavior, and suggest how some harmful algal species may alter top-down control exerted by grazers like copepods.

  14. Algal Toxins Alter Copepod Feeding Behavior

    PubMed Central

    Hong, Jiarong; Talapatra, Siddharth; Katz, Joseph; Tester, Patricia A.; Waggett, Rebecca J.; Place, Allen R.

    2012-01-01

    Using digital holographic cinematography, we quantify and compare the feeding behavior of free-swimming copepods, Acartia tonsa, on nutritional prey (Storeatula major) to that occurring during exposure to toxic and non-toxic strains of Karenia brevis and Karlodinium veneficum. These two harmful algal species produce polyketide toxins with different modes of action and potency. We distinguish between two different beating modes of the copepod’s feeding appendages–a “sampling beating” that has short durations (<100 ms) and involves little fluid entrainment and a longer duration “grazing beating” that persists up to 1200 ms and generates feeding currents. The durations of both beating modes have log-normal distributions. Without prey, A. tonsa only samples the environment at low frequency. Upon introduction of non-toxic food, it increases its sampling time moderately and the grazing period substantially. On mono algal diets for either of the toxic dinoflagellates, sampling time fraction is high but the grazing is very limited. A. tonsa demonstrates aversion to both toxic algal species. In mixtures of S. major and the neurotoxin producing K. brevis, sampling and grazing diminish rapidly, presumably due to neurological effects of consuming brevetoxins while trying to feed on S. major. In contrast, on mixtures of cytotoxin producing K. veneficum, both behavioral modes persist, indicating that intake of karlotoxins does not immediately inhibit the copepod’s grazing behavior. These findings add critical insight into how these algal toxins may influence the copepod’s feeding behavior, and suggest how some harmful algal species may alter top-down control exerted by grazers like copepods. PMID:22629336

  15. Alterations in the motor neuron-Renshaw cell circuit in the Sod1G93A mouse model

    PubMed Central

    Wootz, Hanna; FitzSimons-Kantamneni, Eileen; Larhammar, Martin; Rotterman, Travis M.; Enjin, Anders; Patra, Kalicharan; Andre, Elodie; van Zundert, Brigitte; Kullander, Klas; Alvarez, Francisco J.

    2012-01-01

    Motor neurons become hyperexcitable during progression of amyotrophic lateral sclerosis (ALS). This abnormal firing behavior has been explained by changes in their membrane properties, but more recently it has been suggested that changes in premotor circuits may also contribute to this abnormal activity. The specific circuits that may be altered during development of ALS have not been investigated. Here we examined the Renshaw cell recurrent circuit that exerts inhibitory feedback control on motor neuron firing. Using two markers for Renshaw cells (calbindin and Chrna2 , cholinergic nicotinic receptor subunit alpha2), two general markers for motor neurons (NeuN and VAChT, vesicular acethylcholine transporter ) and two markers for fast motor neurons (Chondrolectin and Calca, calcitonin-related polypeptide alpha), we analyzed the survival and connectivity of these cells during disease progression in the Sod1G93A mouse model. Most calbindin-immunoreactive (IR) Renshaw cells survive to end-stage but downregulate postsynaptic Chrna2 in presymptomatic animals. In motor neurons, some markers are downregulated early (NeuN, VAChT, Chondrolectin) and others at end-stage(Calca). Early downregulation of presynaptic VAChT and Chrna2 was correlated with disconnection from Renshaw cells as well as major structural abnormalities of motor axon synapses inside the spinal cord. Renshaw cell synapses on motor neurons underwent more complex changes, including transitional sprouting preferentially over remaining NeuN-IR motor neurons. We conclude that the loss of presynaptic motor axon input on Renshaw cells occurs at early stages of ALS and disconnects the recurrent inhibitory circuit, presumably resulting in a diminished control of motor neuron firing. PMID:23172249

  16. Exposure to Acetylcholinesterase Inhibitors Alters the Physiology and Motor Function of Honeybees

    PubMed Central

    Williamson, Sally M.; Moffat, Christopher; Gomersall, Martha A. E.; Saranzewa, Nastja; Connolly, Christopher N.; Wright, Geraldine A.

    2013-01-01

    Cholinergic signaling is fundamental to neuromuscular function in most organisms. Sub-lethal doses of neurotoxic pesticides that target cholinergic signaling can alter the behavior of insects in subtle ways; their influence on non-target organisms may not be readily apparent in simple mortality studies. Beneficial arthropods such as honeybees perform sophisticated behavioral sequences during foraging that, if influenced by pesticides, could impair foraging success and reduce colony health. Here, we investigate the behavioral effects on honeybees of exposure to a selection of pesticides that target cholinergic signaling by inhibiting acetylcholinesterase (AChE). To examine how continued exposure to AChE inhibitors affected motor function, we fed adult foraging worker honeybees sub-lethal concentrations of these compounds in sucrose solution for 24 h. Using an assay for locomotion in bees, we scored walking, stopped, grooming, and upside down behavior continuously for 15 min. At a 10 nM concentration, all the AChE inhibitors caused similar effects on behavior, notably increased grooming activity and changes in the frequency of bouts of behavior such as head grooming. Coumaphos caused dose-dependent effects on locomotion as well as grooming behavior, and a 1 μM concentration of coumaphos induced symptoms of malaise such as abdomen grooming and defecation. Biochemical assays confirmed that the four compounds we assayed (coumaphos, aldicarb, chlorpyrifos, and donepezil) or their metabolites acted as AChE inhibitors in bees. Furthermore, we show that transcript expression levels of two honeybee AChE inhibitors were selectively upregulated in the brain and in gut tissues in response to AChE inhibitor exposure. The results of our study imply that the effects of pesticides that rely on this mode of action have subtle yet profound effects on physiological effects on behavior that could lead to reduced survival. PMID:23386834

  17. tDCS-induced alterations in GABA concentration within primary motor cortex predict motor learning and motor memory: a 7 T magnetic resonance spectroscopy study.

    PubMed

    Kim, Soyoung; Stephenson, Mary C; Morris, Peter G; Jackson, Stephen R

    2014-10-01

    Transcranial direct current stimulation (tDCS) is a non-invasive brain stimulation technique that alters cortical excitability in a polarity specific manner and has been shown to influence learning and memory. tDCS may have both on-line and after-effects on learning and memory, and the latter are thought to be based upon tDCS-induced alterations in neurochemistry and synaptic function. We used ultra-high-field (7 T) magnetic resonance spectroscopy (MRS), together with a robotic force adaptation and de-adaptation task, to investigate whether tDCS-induced alterations in GABA and Glutamate within motor cortex predict motor learning and memory. Note that adaptation to a robot-induced force field has long been considered to be a form of model-based learning that is closely associated with the computation and 'supervised' learning of internal 'forward' models within the cerebellum. Importantly, previous studies have shown that on-line tDCS to the cerebellum, but not to motor cortex, enhances model-based motor learning. Here we demonstrate that anodal tDCS delivered to the hand area of the left primary motor cortex induces a significant reduction in GABA concentration. This effect was specific to GABA, localised to the left motor cortex, and was polarity specific insofar as it was not observed following either cathodal or sham stimulation. Importantly, we show that the magnitude of tDCS-induced alterations in GABA concentration within motor cortex predicts individual differences in both motor learning and motor memory on the robotic force adaptation and de-adaptation task.

  18. Interplay between glutamatergic and GABAergic neurotransmission alterations in cognitive and motor impairment in minimal hepatic encephalopathy.

    PubMed

    Llansola, Marta; Montoliu, Carmina; Agusti, Ana; Hernandez-Rabaza, Vicente; Cabrera-Pastor, Andrea; Gomez-Gimenez, Belen; Malaguarnera, Michele; Dadsetan, Sherry; Belghiti, Majedeline; Garcia-Garcia, Raquel; Balzano, Tiziano; Taoro, Lucas; Felipo, Vicente

    2015-09-01

    The cognitive and motor alterations in hepatic encephalopathy (HE) are the final result of altered neurotransmission and communication between neurons in neuronal networks and circuits. Different neurotransmitter systems cooperate to modulate cognitive and motor function, with a main role for glutamatergic and GABAergic neurotransmission in different brain areas and neuronal circuits. There is an interplay between glutamatergic and GABAergic neurotransmission alterations in cognitive and motor impairment in HE. This interplay may occur: (a) in different brain areas involved in specific neuronal circuits; (b) in the same brain area through cross-modulation of glutamatergic and GABAergic neurotransmission. We will summarize some examples of the (1) interplay between glutamatergic and GABAergic neurotransmission alterations in different areas in the basal ganglia-thalamus-cortex circuit in the motor alterations in minimal hepatic encephalopathy (MHE); (2) interplay between glutamatergic and GABAergic neurotransmission alterations in cerebellum in the impairment of cognitive function in MHE through altered function of the glutamate-nitric oxide-cGMP pathway. We will also comment the therapeutic implications of the above studies and the utility of modulators of glutamate and GABA receptors to restore cognitive and motor function in rats with hyperammonemia and hepatic encephalopathy.

  19. Dorsal anterior cingulate cortex modulates supplementary motor area in coordinated unimanual motor behavior

    PubMed Central

    Asemi, Avisa; Ramaseshan, Karthik; Burgess, Ashley; Diwadkar, Vaibhav A.; Bressler, Steven L.

    2015-01-01

    Motor control is integral to all types of human behavior, and the dorsal Anterior Cingulate Cortex (dACC) is thought to play an important role in the brain network underlying motor control. Yet the role of the dACC in motor control is under-characterized. Here we aimed to characterize the dACC’s role in adolescent brain network interactions during a simple motor control task involving visually coordinated unimanual finger movements. Network interactions were assessed using both undirected and directed functional connectivity analysis of functional Magnetic Resonance Imaging (fMRI) Blood-Oxygen-Level-Dependent (BOLD) signals, comparing the task with a rest condition. The relation between the dACC and Supplementary Motor Area (SMA) was compared to that between the dACC and Primary Motor Cortex (M1). The directed signal from dACC to SMA was significantly elevated during motor control in the task. By contrast, the directed signal from SMA to dACC, both directed signals between dACC and M1, and the undirected functional connections of dACC with SMA and M1, all did not differ between task and rest. Undirected coupling of dACC with both SMA and dACC, and only the dACC-to-SMA directed signal, were significantly greater for a proactive than a reactive task condition, suggesting that dACC plays a role in motor control by maintaining stimulus timing expectancy. Overall, these results suggest that the dACC selectively modulates the SMA during visually coordinated unimanual behavior in adolescence. The role of the dACC as an important brain area for the mediation of task-related motor control may be in place in adolescence, continuing into adulthood. The task and analytic approach described here should be extended to the study of healthy adults to examine network profiles of the dACC during basic motor behavior. PMID:26089783

  20. Behavioral and electromyographic assessment of oxaliplatin-induced motor dysfunctions: Evidence for a therapeutic effect of allopregnanolone.

    PubMed

    Taleb, O; Bouzobra, F; Tekin-Pala, H; Meyer, L; Mensah-Nyagan, A G; Patte-Mensah, C

    2017-03-01

    The antineoplastic oxaliplatin (OXAL) is pivotal for metastatic cancer treatments. However, OXAL evokes sensory and motor side-effects including pain, muscle weakness, motor nerve fiber dysfunctions/neuropathies that significantly impact patients' lives. Therefore, preclinical investigations are struggling to characterize effective analgesics against OXAL-induced painful/sensory symptoms but surprisingly, OXAL-evoked motor dysfunctions received little attention although these neurological symptoms are also disabling for patients. Here, we validated a rat model of OXAL-induced motor neuropathy by using (i) behavioral methods as the wire suspension and balance beam tests to assess muscle weakness and (ii) electrophysiological techniques to record the gastrocnemius electromyography (EMG). The conductance velocity of motor fibers was reduced and compound muscle action potential (CMAP) duration increased in OXAL-treated rats, leading to CMAP dispersion with no modification of the area under the curve, reflecting a heterogeneous demyelination of motor fibers. Functional motor unit analysis revealed a 50 % decrease of their estimated number which was compensated by a motor unit size increase. OXAL-induced motor weakness appeared as a combined consequence of motor fiber demyelination and motor axonopathy. Because we previously observed that allopregnanolone (AP) counteracted OXAL-evoked painful/sensory symptoms, we evaluated its action against OXAL-induced motor neurological dysfunctions. AP treatment successfully corrected motor behaviors, conductance velocity, CMAP duration, motor unit number (MUN) and motor unit size altered by OXAL-chemotherapy. These results, which are the first to show that AP efficiently rescues OXAL-induced motor neuropathy, consolidate the idea that AP-based therapy may be relevant for the treatment of both sensory and motor peripheral neuropathies.

  1. Attenuation of paraquat-induced motor behavior and neurochemical disturbances by L-valine in vivo.

    PubMed

    Chanyachukul, Thida; Yoovathaworn, Krongtong; Thongsaard, Watchareewan; Chongthammakun, Sukumal; Navasumrit, Panida; Satayavivad, Jutamaad

    2004-05-02

    Alterations of motor behavioral patterns and monoamine contents in the discrete rat brain areas after acute paraquat exposure (3, 5, 10, 20 mg/kg, s.c.) have been studied. The results showed that paraquat at the doses of 5, 10, and 20 mg/kg significantly reduced locomotive, stereotypic, and rotational behaviors. Significant decreases of norepinephrine (NE) contents in cortex and hypothalamus, as well as striatal contents of dopamine (DA) and its acidic metabolites, were detected. In addition, L-valine (200 mg/kg, i.p.) significantly attenuated paraquat-induced toxicity at moderate dose (5 mg/kg) but not at high dose (20 mg/kg). The results provide evidence that paraquat can enter the brain as illustrated by the alterations in the motor behavioral pattern and neurochemical contents. Furthermore, the attenuation effect of L-valine against systemic administration of paraquat-induced motor behaviors was detected, with a slightly protective effect on paraquat-induced neurochemical alterations.

  2. Behavioral motor dysfunction in Kv3-type potassium channel-deficient mice.

    PubMed

    Joho, R H; Street, C; Matsushita, S; Knöpfel, T

    2006-08-01

    The voltage-gated potassium channels Kv3.1 and Kv3.3 are expressed in several distinct neuronal subpopulations in brain areas known to be involved in motor control such as cortex, basal ganglia and cerebellum. Depending on the lack of Kv3.1 or Kv3.3 channel subunits, mutant mice show different Kv3-null allele-dependent behavioral alterations that include constitutive hyperactivity, sleep loss, impaired motor performance and, in the case of the Kv3.1/Kv3.3 double mutant, also severe ataxia, tremor and myoclonus (Espinosa et al. 2001, J Neurosci 21, 6657-6665, Genes, Brain Behav 3, 90-100). The lack of Kv3.1 channel subunits is mainly responsible for the constitutively increased locomotor activity and for sleep loss, whereas the absence of Kv3.3 subunits affects cerebellar function, in particular Purkinje cell discharges and olivocerebellar system properties (McMahon et al. 2004, Eur J Neurosci 19, 3317-3327). Here, we describe two sensitive and non-invasive tests to reliably quantify normal and abnormal motor functions, and we apply these tests to characterize motor dysfunction in Kv3-mutant mice. In contrast to wildtype and Kv3.1-single mutants, Kv3.3-single mutants and Kv3 mutants lacking three and four Kv3 alleles display Kv3-null allele-dependent gait alterations. Although the Kv3-null allele-dependent gait changes correlate with reduced motor performance, they appear to not affect the training-induced improvement of motor performance. These findings suggest that altered cerebellar physiology in the absence of Kv3.3 channels is responsible for impaired motor task execution but not motor task learning.

  3. Altered hippocampal-dependent memory and motor function in neuropilin 2–deficient mice

    PubMed Central

    Shiflett, M W; Gavin, M; Tran, T S

    2015-01-01

    Semaphorins have an important role in synapse refinement in the mammalian nervous system. The class 3 semaphorin-3F (Sema3F) acting through neuropilin 2/plexin-A3 (Nrp2/PlexA3) holoreceptor complex signals in vivo to restrain apical dendritic spine morphogenesis of cortical pyramidal neurons and hippocampal neurons during postnatal development and mediates excitatory synaptic transmission. Semaphorin signaling has been implicated in the etiology of a number of neurodevelopmental disorders; however, the effects on behavior and mental function of dysregulated Sema3F-Nrp2 signaling have not been fully addressed. The present study is the first behavioral investigation of mice harboring a mutation of the nrp2 gene. Given that loss of Nrp2 signaling alters cortical and hippocampal synaptic organization, we investigated performance of nrp2-deficient mice on learning and sensorimotor function that are known to depend on cortical and hippocampal circuitry. When compared with age-matched controls, nrp2 null mice showed striking impairments in object recognition memory and preference for social novelty. In addition, nrp2−/− mice displayed impaired motor function in the rotarod test and in observations of grooming behavior. Exploration of novel olfactory sensory stimuli and nociception were unaffected by the loss of Nrp2. Overall, loss of Nrp2 may induce aberrant processing within hippocampal and corticostriatal networks that may contribute to neurodevelopmental disease mechanisms. PMID:25734514

  4. Testosterone Enhances Risk Tolerance without Altering Motor Impulsivity in Male Rats

    PubMed Central

    Cooper, Sarah E.; Goings, Sydney P.; Kim, Jessica Y.; Wood, Ruth I.

    2014-01-01

    Summary Anabolic-androgenic steroids (AAS) increase impulsive and uncontrolled aggressive (‘roid rage) in humans and enhance agonistic behavior in animals. However, the underlying mechanisms for AAS-induced aggression remain unclear. Potential contributing elements include an increase risk-taking and/or motor impulsivity due to AAS. This study addressed the effects of chronic high-dose testosterone on risk tolerance using a risky decision-making task (RDT) and motor impulsivity with a go/no-go task in operant chambers. Male Long-Evans rats were treated for at least 4 weeks with testosterone (7.5mg/kg) or vehicle beginning in late adolescence. Testosterone was used because it is popular among human AAS users. In RDT testing, one lever was paired with delivery of a small “safe” food reward, while the other was paired with a large “risky” reward associated with an increasing risk of footshock (0, 25, 50, 75, 100%) in successive test blocks. Three shock intensities were used: 1.0, 1.2, and 1.4 mA/kg. As shock intensity and risk of shock increased, preference for the lever signifying a large reward significantly declined for both vehicle- and testosterone-treated rats (p<0.05). There was also a significant effect of drug (p<0.05), where testosterone-treated rats showed greater preference for the large reward, compared to vehicle- treated controls. Increased preference for the large reward, despite risk of footshock, is consistent with increased risk tolerance. In go/no-go testing, rats were trained to press a single lever if the go cue was presented (stimulus light) or to refrain from pressing during the no-go cue (tone). There was no effect of testosterone on pre-cue responses, or performance in go and no-go trials. These results suggest that AAS may increase risk-tolerance without altering motor impulsivity. PMID:24485492

  5. Exercise alters resting state functional connectivity of motor circuits in Parkinsonian rats

    PubMed Central

    Wang, Zhuo; Guo, Yumei; Myers, Kalisa G.; Heintz, Ryan; Peng, Yu-Hao; Maarek, Jean-Michel I.; Holschneider, Daniel P.

    2014-01-01

    Few studies have examined changes in functional connectivity after long-term aerobic exercise. We examined the effects of 4 weeks of forced running wheel exercise on the resting-state functional connectivity (rsFC) of motor circuits of rats subjected to bilateral 6-hydroxydopamine lesion of the dorsal striatum. Our results showed substantial similarity between lesion-induced changes in rsFC in the rats and alterations in rsFC reported in Parkinson’s disease subjects, including disconnection of the dorsolateral striatum. Exercise in lesioned rats resulted in: (a) normalization of many of the lesion-induced alterations in rsFC, including reintegration of the dorsolateral striatum into the motor network; (b) emergence of the ventrolateral striatum as a new broadly connected network hub; (c) increased rsFC among the motor cortex, motor thalamus, basal ganglia, and cerebellum. Our results showed for the first time that long-term exercise training partially reversed lesion-induced alterations in rsFC of the motor circuits, and in addition enhanced functional connectivity in specific motor pathways in the Parkinsonian rats, which could underlie recovery in motor functions observed in these rats. PMID:25219465

  6. Exercise alters resting-state functional connectivity of motor circuits in parkinsonian rats.

    PubMed

    Wang, Zhuo; Guo, Yumei; Myers, Kalisa G; Heintz, Ryan; Peng, Yu-Hao; Maarek, Jean-Michel I; Holschneider, Daniel P

    2015-01-01

    Few studies have examined changes in functional connectivity after long-term aerobic exercise. We examined the effects of 4 weeks of forced running wheel exercise on the resting-state functional connectivity (rsFC) of motor circuits of rats subjected to bilateral 6-hydroxydopamine lesion of the dorsal striatum. Our results showed substantial similarity between lesion-induced changes in rsFC in the rats and alterations in rsFC reported in Parkinson's disease subjects, including disconnection of the dorsolateral striatum. Exercise in lesioned rats resulted in: (1) normalization of many of the lesion-induced alterations in rsFC, including reintegration of the dorsolateral striatum into the motor network; (2) emergence of the ventrolateral striatum as a new broadly connected network hub; and (3) increased rsFC among the motor cortex, motor thalamus, basal ganglia, and cerebellum. Our results showed for the first time that long-term exercise training partially reversed lesion-induced alterations in rsFC of the motor circuits, and in addition enhanced functional connectivity in specific motor pathways in the parkinsonian rats, which could underlie recovery in motor functions observed in these animals.

  7. Chronic GABAergic blockade in the spinal cord in vivo induces motor alterations and neurodegeneration.

    PubMed

    Ramírez-Jarquín, Uri Nimrod; Tapia, Ricardo

    2017-05-01

    Inhibitory GABAergic and glycinergic neurotransmission in the spinal cord play a central role in the regulation of neuronal excitability, by maintaining a balance with the glutamate-mediated excitatory transmission. Glutamatergic agonists infusion in the spinal cord induce motor neuron death by excitotoxicity, leading to motor deficits and paralysis, but little is known on the effect of the blockade of inhibitory transmission. In this work we studied the effects of GABAergic and glycinergic blockade, by means of microdialysis perfusion (acute administration) and osmotic minipumps infusion (chronic administration) of GABA and glycine receptors antagonists directly in the lumbar spinal cord. We show that acute glycinergic blockade with strychnine or GABAergic blockade with bicuculline had no significant effects on motor activity and on motor neuron survival. However, chronic bicuculline infusion, but not strychnine, induced ipsilateral gait alterations, phalange flaccidity and significant motor neuron loss, and these effects were prevented by AMPA receptor blockade with CNQX but not by NMDA receptor blockade with MK801. In addition, we demonstrate that the chronic infusion of bicuculline enhanced the excitotoxic effect of AMPA, causing faster bilateral paralysis and increasing motor neuron loss. These findings indicate a relevant role of GABAergic inhibitory circuits in the regulation of motor neuron excitability and suggest that their alterations may be involved in the neurodegeneration processes characteristic of motor neuron diseases such as amyotrophic lateral sclerosis.

  8. Motor and cognitive integration: effect of bilateral behaviors on judgment.

    PubMed

    Cretenet, Joël; Mullet, Etienne; Dru, Vincent

    2015-10-01

    Performing approach vs. avoidance behaviors (arm flexion vs. arm extension) on the one hand, and lateralized peripheral activations (left side vs. right side) of the motivational systems of approach vs. avoidance, on the other hand, have been shown to impact on cognitive functioning (Cretenet, & Dru, 2009), mainly in judgment tasks. When a unilateral motor congruent behavior; that is, a behavior that activates the same motivational system (e.g., flexion of the right arm) was performed during a judgment task, participants' use of complex, interactive information integration rules was facilitated. No effect was, however, found when simpler, additive rules were involved (Mullet, Cretenet, & Dru, 2014). Three experiments are reported here that examined the effect of bilateral motor behaviors (e.g., flexion of the right arm and extension of the left arm) on the implementation of information integration rules. In Studies 1 and 2, two judgment tasks similar to the ones used by Mullet et al. (2014) were used: (a) a complex task in which participants judged a person's attractiveness from personality information, and (b) a simpler task in which they attributed blame according to bad deeds. It was found that similar motor behaviors performed by the two arms (e.g., flexion of both arms), in contrast to dissimilar ones, facilitated the use of complex, interactive information integration rules. No effect was found in the case of simpler integration rules. In Study 3, these results were replicated in a judgment task in which the complexity of the integration rule varied depending on the instructions given. Overall, when bilateral motor behaviors were performed during judgment, facilitation in the use of complex integration rules no longer depended on motivational congruence as in the case of unilateral motor behavior. It depended on symmetry/similarity of behaviors.

  9. Video analysis of motor events in REM sleep behavior disorder.

    PubMed

    Frauscher, Birgit; Gschliesser, Viola; Brandauer, Elisabeth; Ulmer, Hanno; Peralta, Cecilia M; Müller, Jörg; Poewe, Werner; Högl, Birgit

    2007-07-30

    In REM sleep behavior disorder (RBD), several studies focused on electromyographic characterization of motor activity, whereas video analysis has remained more general. The aim of this study was to undertake a detailed and systematic video analysis. Nine polysomnographic records from 5 Parkinson patients with RBD were analyzed and compared with sex- and age-matched controls. Each motor event in the video during REM sleep was classified according to duration, type of movement, and topographical distribution. In RBD, a mean of 54 +/- 23.2 events/10 minutes of REM sleep (total 1392) were identified and visually analyzed. Seventy-five percent of all motor events lasted <2 seconds. Of these events, 1,155 (83.0%) were classified as elementary, 188 (13.5%) as complex behaviors, 50 (3.6%) as violent, and 146 (10.5%) as vocalizations. In the control group, 3.6 +/- 2.3 events/10 minutes (total 264) of predominantly elementary simple character (n = 240, 90.9%) were identified. Number and types of motor events differed significantly between patients and controls (P < 0.05). This study shows a very high number and great variety of motor events during REM sleep in symptomatic RBD. However, most motor events are minor, and violent episodes represent only a small fraction.

  10. A Framework to Describe, Analyze and Generate Interactive Motor Behaviors

    PubMed Central

    Jarrassé, Nathanaël; Charalambous, Themistoklis; Burdet, Etienne

    2012-01-01

    While motor interaction between a robot and a human, or between humans, has important implications for society as well as promising applications, little research has been devoted to its investigation. In particular, it is important to understand the different ways two agents can interact and generate suitable interactive behaviors. Towards this end, this paper introduces a framework for the description and implementation of interactive behaviors of two agents performing a joint motor task. A taxonomy of interactive behaviors is introduced, which can classify tasks and cost functions that represent the way each agent interacts. The role of an agent interacting during a motor task can be directly explained from the cost function this agent is minimizing and the task constraints. The novel framework is used to interpret and classify previous works on human-robot motor interaction. Its implementation power is demonstrated by simulating representative interactions of two humans. It also enables us to interpret and explain the role distribution and switching between roles when performing joint motor tasks. PMID:23226231

  11. A framework to describe, analyze and generate interactive motor behaviors.

    PubMed

    Jarrassé, Nathanaël; Charalambous, Themistoklis; Burdet, Etienne

    2012-01-01

    While motor interaction between a robot and a human, or between humans, has important implications for society as well as promising applications, little research has been devoted to its investigation. In particular, it is important to understand the different ways two agents can interact and generate suitable interactive behaviors. Towards this end, this paper introduces a framework for the description and implementation of interactive behaviors of two agents performing a joint motor task. A taxonomy of interactive behaviors is introduced, which can classify tasks and cost functions that represent the way each agent interacts. The role of an agent interacting during a motor task can be directly explained from the cost function this agent is minimizing and the task constraints. The novel framework is used to interpret and classify previous works on human-robot motor interaction. Its implementation power is demonstrated by simulating representative interactions of two humans. It also enables us to interpret and explain the role distribution and switching between roles when performing joint motor tasks.

  12. Chronic hyperammonemia alters the circadian rhythms of corticosteroid hormone levels and of motor activity in rats.

    PubMed

    Ahabrach, Hanan; Piedrafita, Blanca; Ayad, Abdelmalik; El Mlili, Nisrin; Errami, Mohammed; Felipo, Vicente; Llansola, Marta

    2010-05-15

    Patients with liver cirrhosis may present hepatic encephalopathy with a wide range of neurological disturbances and alterations in sleep quality and in the sleep-wake circadian rhythm. Hyperammonemia is a main contributor to the neurological alterations in hepatic encephalopathy. We have assessed, in an animal model of chronic hyperammonemia without liver failure, the effects of hyperammonemia per se on the circadian rhythms of motor activity, temperature, and plasma levels of adrenal corticosteroid hormones. Chronic hyperammonemia alters the circadian rhythms of locomotor activity and of cortisol and corticosterone levels in blood. Different types of motor activity are affected differentially. Hyperammonemia significantly alters the rhythm of spontaneous ambulatory activity, reducing strongly ambulatory counts and slightly average velocity during the night (the active phase) but not during the day, resulting in altered circadian rhythms. In contrast, hyperammonemia did not affect wheel running at all, indicating that it affects spontaneous but not voluntary activity. Vertical activity was affected only very slightly, indicating that hyperammonemia does not induce anxiety. Hyperammonemia abolished completely the circadian rhythm of corticosteroid hormones in plasma, completely eliminating the peaks of cortisol and corticosterone present in control rats at the start of the dark period. The data reported show that chronic hyperammonemia, similar to that present in patients with liver cirrhosis, alters the circadian rhythms of corticosteroid hormones and of motor activity. This suggests that hyperammonemia would be a relevant contributor to the alterations in corticosteroid hormones and in circadian rhythms in patients with liver cirrhosis.

  13. The Feldenkrais Method: A Dynamic Approach to Changing Motor Behavior.

    ERIC Educational Resources Information Center

    Buchanan, Patricia A.; Ulrich, Beverly D.

    2001-01-01

    Describes the Feldenkrais Method of somatic education, noting parallels with a dynamic systems theory (DST) approach to motor behavior. Feldenkrais uses movement and perception to foster individualized improvement in function. DST explains that a human-environment system continually adapts to changing conditions and assembles behaviors…

  14. Supplementary motor area (SMA) volume is associated with psychotic aberrant motor behaviour of patients with schizophrenia.

    PubMed

    Stegmayer, Katharina; Horn, Helge; Federspiel, Andrea; Razavi, Nadja; Bracht, Tobias; Laimböck, Karin; Strik, Werner; Dierks, Thomas; Wiest, Roland; Müller, Thomas J; Walther, Sebastian

    2014-07-30

    We aimed to investigate whether aberrant motor behavior in schizophrenia was associated with structural alterations in the motor system. Whole brain voxel based morphometry of patients with different severity of motor symptoms identified altered gray matter volume in the supplementary motor area (SMA), a key region of the motor system.

  15. Motor effort alters changes of mind in sensorimotor decision making.

    PubMed

    Burk, Diana; Ingram, James N; Franklin, David W; Shadlen, Michael N; Wolpert, Daniel M

    2014-01-01

    After committing to an action, a decision-maker can change their mind to revise the action. Such changes of mind can even occur when the stream of information that led to the action is curtailed at movement onset. This is explained by the time delays in sensory processing and motor planning which lead to a component at the end of the sensory stream that can only be processed after initiation. Such post-initiation processing can explain the pattern of changes of mind by asserting an accumulation of additional evidence to a criterion level, termed change-of-mind bound. Here we test the hypothesis that physical effort associated with the movement required to change one's mind affects the level of the change-of-mind bound and the time for post-initiation deliberation. We varied the effort required to change from one choice target to another in a reaching movement by varying the geometry of the choice targets or by applying a force field between the targets. We show that there is a reduction in the frequency of change of mind when the separation of the choice targets would require a larger excursion of the hand from the initial to the opposite choice. The reduction is best explained by an increase in the evidence required for changes of mind and a reduced time period of integration after the initial decision. Thus the criteria to revise an initial choice is sensitive to energetic costs.

  16. Causal Role of Motor Simulation in Turn-Taking Behavior

    PubMed Central

    Novembre, Giacomo; Keller, Peter E.; Pickering, Martin J.

    2015-01-01

    Overlap between sensory and motor representations has been documented for a range of human actions, from grasping (Rizzolatti et al., 1996b) to playing a musical instrument (Novembre and Keller, 2014). Such overlap suggests that individuals use motor simulation to predict the outcome of observed actions (Wolpert, 1997). Here we investigate motor simulation as a basis of human communication. Using a musical turn-taking task, we show that pianists call on motor representations of their partner's part to predict when to come in for their own turn. Pianists played alternating solos with a videoed partner, and double-pulse transcranial magnetic stimulation was applied around the turn-switch to temporarily disrupt processing in two cortical regions implicated previously in different forms of motor simulation: (1) the dorsal premotor cortex (dPMC), associated with automatic motor resonance during passive observation of hand actions, especially when the actions are familiar (Lahav et al., 2007); and (2) the supplementary motor area (SMA), involved in active motor imagery, especially when the actions are familiar (Baumann et al., 2007). Stimulation of the right dPMC decreased the temporal accuracy of pianists' (right-hand) entries relative to sham when the partner's (left-hand) part had been rehearsed previously. This effect did not occur for dPMC stimulation without rehearsal or for SMA stimulation. These findings support the role of the dPMC in predicting the time course of observed actions via resonance-based motor simulation during turn-taking. Because turn-taking spans multiple modes of human interaction, we suggest that simulation is a foundational mechanism underlying the temporal dynamics of joint action. SIGNIFICANCE STATEMENT Even during passive observation, seeing or hearing somebody execute an action from within our repertoire activates motor cortices of our brain. But what is the functional relevance of such “motor simulation”? By combining a musical duet

  17. Adjustments of Motor Pattern for Load Compensation Via Modulated Activations of Muscle Synergies During Natural Behaviors

    PubMed Central

    Cheung, Vincent C. K.; d'Avella, Andrea; Bizzi, Emilio

    2009-01-01

    It has been suggested that the motor system may circumvent the difficulty of controlling many degrees of freedom in the musculoskeletal apparatus by generating motor outputs through a combination of discrete muscle synergies. How a discretely organized motor system compensates for diverse perturbations has remained elusive. Here, we investigate whether motor responses observed after an inertial-load perturbation can be generated by altering the recruitment of synergies normally used for constructing unperturbed movements. Electromyographic (EMG, 13 muscles) data were collected from the bullfrog hindlimb during natural behaviors before, during, and after the same limb was loaded by a weight attached to the calf. Kinematic analysis reveals the absence of aftereffect on load removal, suggesting that load-related EMG changes were results of immediate motor pattern adjustments. We then extracted synergies from EMGs using the nonnegative matrix factorization algorithm and developed a procedure for assessing the extent of synergy sharing across different loading conditions. Most synergies extracted were found to be activated in all loaded and unloaded conditions. However, for certain synergies, the amplitude, duration, and/or onset time of their activation bursts were up- or down-modulated during loading. Behavioral parameterizations reveal that load-related modulation of synergy activations depended on the behavioral variety (e.g., kick direction and amplitude) and the movement phase performed. Our results suggest that muscle synergies are robust across different dynamic conditions and immediate motor adjustments can be accomplished by modulating synergy activations. An appendix describes the novel procedure we developed, useful for discovering shared and specific features from multiple data sets. PMID:19091930

  18. Ethanol exposure during gastrulation alters neuronal morphology and behavior in zebrafish.

    PubMed

    Shan, Shubham D; Boutin, Savanna; Ferdous, Jannatul; Ali, Declan W

    2015-01-01

    Ethanol (EtOH) exposure during development has been shown to lead to deficits in fine and gross motor control. In this study we used zebrafish embryos to determine the effects of EtOH treatment during gastrulation. We treated embryos in the gastrulation stage (5.25 hours post fertilization (hpf) to 10.75 hpf) with 10 mM, 50 mM or 100 mM EtOH and examined the effects on general animal morphology, the c-start reflex behavior, Mauthner cell (M-cell) morphology and motor neuron morphology. EtOH treated fish exhibited a minor but significant increase in gross morphological deformities compared with untreated fish. Behavioral studies showed that EtOH treatment resulted in an increase in the peak speed of the tail during the escape response. Furthermore, there was a marked increase in abnormally directed c-starts, with treated fish showing greater incidences of c-starts in inappropriate directions. Immunolabeling of the M-cells, which are born during gastrulation, revealed that they were significantly smaller in fish treated with 100 mM EtOH compared with controls. Immunolabeling of primary motor neurons using anti-znp1, showed no significant effect on axonal branching, whereas secondary motor axons had a greater number of branches in ethanol treated fish compared with controls. Together these findings indicate that ethanol exposure during gastrulation can lead to alterations in behavior, neuronal morphology and possibly function.

  19. Effects of moderate prenatal ethanol exposure and age on social behavior, spatial response perseveration errors and motor behavior.

    PubMed

    Hamilton, Derek A; Barto, Daniel; Rodriguez, Carlos I; Magcalas, Christy M; Fink, Brandi C; Rice, James P; Bird, Clark W; Davies, Suzy; Savage, Daniel D

    2014-08-01

    Persistent deficits in social behavior are among the major negative consequences associated with exposure to ethanol during prenatal development. Prior work from our laboratory has linked deficits in social behavior following moderate prenatal alcohol exposure (PAE) in the rat to functional alterations in the ventrolateral frontal cortex [21]. In addition to social behaviors, the regions comprising the ventrolateral frontal cortex are critical for diverse processes ranging from orofacial motor movements to flexible alteration of behavior in the face of changing consequences. The broader behavioral implications of altered ventrolateral frontal cortex function following moderate PAE have, however, not been examined. In the present study we evaluated the consequences of moderate PAE on social behavior, tongue protrusion, and flexibility in a variant of the Morris water task that required modification of a well-established spatial response. PAE rats displayed deficits in tongue protrusion, reduced flexibility in the spatial domain, increased wrestling, and decreased investigation, indicating that several behaviors associated with ventrolateral frontal cortex function are impaired following moderate PAE. A linear discriminant analysis revealed that measures of wrestling and tongue protrusion provided the best discrimination of PAE rats from saccharin-exposed control rats. We also evaluated all behaviors in young adult (4-5 months) or older (10-11 months) rats to address the persistence of behavioral deficits in adulthood and possible interactions between early ethanol exposure and advancing age. Behavioral deficits in each domain persisted well into adulthood (10-11 months), however, there was no evidence that aging enhances the effects of moderate PAE within the age ranges that were studied.

  20. Distributed Effects of Biological Sex Define Sex-Typical Motor Behavior in Caenorhabditis elegans

    PubMed Central

    Mowrey, William R.; Bennett, Jessica R.

    2014-01-01

    Sex differences in shared behaviors (for example, locomotion and feeding) are a nearly universal feature of animal biology. Though these behaviors may share underlying neural programs, their kinematics can exhibit robust differences between males and females. The neural underpinnings of these differences are poorly understood because of the often-untested assumption that they are determined by sex-specific body morphology. Here, we address this issue in the nematode Caenorhabditis elegans, which features two sexes with distinct body morphologies but similar locomotor circuitry and body muscle. Quantitative behavioral analysis shows that C. elegans and related nematodes exhibit significant sex differences in the dynamics and geometry of locomotor body waves, such that the male is generally faster. Using a recently proposed model of locomotor wave propagation, we show that sex differences in both body mechanics and the intrinsic dynamics of the motor system can contribute to kinematic differences in distinct mechanical contexts. By genetically sex-reversing the properties of specific tissues and cells, however, we find that sex-specific locomotor frequency in C. elegans is determined primarily by the functional modification of shared sensory neurons. Further, we find that sexual modification of body wall muscle together with the nervous system is required to alter body wave speed. Thus, rather than relying on a single focus of modification, sex differences in motor dynamics require independent modifications to multiple tissue types. Our results suggest shared motor behaviors may be sex-specifically optimized though distributed modifications to several aspects of morphology and physiology. PMID:24478342

  1. Immunity and behavior: antibodies alter emotion.

    PubMed

    Huerta, Patricio T; Kowal, Czeslawa; DeGiorgio, Lorraine A; Volpe, Bruce T; Diamond, Betty

    2006-01-17

    Systemic lupus erythematosus is an autoimmune disease in which most patients express Abs that bind double-stranded DNA. Recent work has shown that a subset of lupus Abs can crossreact with the NR2A and NR2B subunits of the NMDA receptor. This receptor is expressed in neurons throughout the brain but is at highest density within cells of the hippocampus, amygdala, and hypothalamus. The neurons in the CNS are normally protected from brain-reactive Abs by the blood-brain barrier (BBB); however, a breach in the barrier's integrity exposes neurons to potentially pathogenic Abs. Previously, we have shown that mice that are immunized with a peptide mimetope of DNA produce lupus-like Abs that crossreact with DNA and the NMDA receptor. Moreover, after abrogation of the BBB by treatment with lipopolysaccharide, the immunized mice display hippocampal neuron damage with ensuing memory impairment. Given that rises in epinephrine can increase cerebral blood flow and can cause leaks in the BBB, we decided to investigate whether epinephrine could act as a permissive agent for Ab-mediated neurotoxicity. Here, we show that peptide-immunized mice, given epinephrine to open the BBB, lose neurons in the lateral amygdala and develop a behavioral disorder characterized by a deficient response to fear-conditioning paradigms. Thus, the agent used to open the BBB determines which brain region is made vulnerable to neurotoxic Abs, and Abs that penetrate brain tissue can cause changes not only in cognitive competence, but also in emotional behavior.

  2. Two distinct interneuron circuits in human motor cortex are linked to different subsets of physiological and behavioral plasticity.

    PubMed

    Hamada, Masashi; Galea, Joseph M; Di Lazzaro, Vincenzo; Mazzone, Paolo; Ziemann, Ulf; Rothwell, John C

    2014-09-17

    How does a single brain region participate in multiple behaviors? Here we argue that two separate interneuron circuits in the primary motor cortex (M1) contribute differently to two varieties of physiological and behavioral plasticity. To test this in human brain noninvasively, we used transcranial magnetic stimulation (TMS) of M1 hand area to activate two independent sets of synaptic inputs to corticospinal neurons by changing the direction of current induced in the brain: posterior-to-anterior current (PA inputs) and anterior-to-posterior current (AP inputs). We demonstrate that excitability changes produced by repetitive activation of AP inputs depend on cerebellar activity and selectively alter model-based motor learning. In contrast, the changes observed with repetitive stimulation of PA inputs are independent of cerebellar activity and specifically modulate model-free motor learning. The findings are highly suggestive that separate circuits in M1 subserve different forms of motor learning.

  3. Dynamical movement primitives: learning attractor models for motor behaviors.

    PubMed

    Ijspeert, Auke Jan; Nakanishi, Jun; Hoffmann, Heiko; Pastor, Peter; Schaal, Stefan

    2013-02-01

    Nonlinear dynamical systems have been used in many disciplines to model complex behaviors, including biological motor control, robotics, perception, economics, traffic prediction, and neuroscience. While often the unexpected emergent behavior of nonlinear systems is the focus of investigations, it is of equal importance to create goal-directed behavior (e.g., stable locomotion from a system of coupled oscillators under perceptual guidance). Modeling goal-directed behavior with nonlinear systems is, however, rather difficult due to the parameter sensitivity of these systems, their complex phase transitions in response to subtle parameter changes, and the difficulty of analyzing and predicting their long-term behavior; intuition and time-consuming parameter tuning play a major role. This letter presents and reviews dynamical movement primitives, a line of research for modeling attractor behaviors of autonomous nonlinear dynamical systems with the help of statistical learning techniques. The essence of our approach is to start with a simple dynamical system, such as a set of linear differential equations, and transform those into a weakly nonlinear system with prescribed attractor dynamics by means of a learnable autonomous forcing term. Both point attractors and limit cycle attractors of almost arbitrary complexity can be generated. We explain the design principle of our approach and evaluate its properties in several example applications in motor control and robotics.

  4. Targeting oxidative stress attenuates malonic acid induced Huntington like behavioral and mitochondrial alterations in rats.

    PubMed

    Kalonia, Harikesh; Kumar, Puneet; Kumar, Anil

    2010-05-25

    Objective of the present study was to explore the possible role of oxidative stress in the malonic acid induced behavioral, biochemical and mitochondrial alterations in rats. In the present study, unilateral single injections of malonic acid at different doses (1.5, 3 and 6 micromol) were made into the ipsilateral striatum in rats. Behavioral parameters were accessed on 1st, 7th and 14th day post malonic acid administration. Oxidative stress parameters and mitochondrial enzyme functions were assessed on day 14 after behavioral observations. Ipsilateral striatal malonic acid (3 and 6 micromol) administration significantly reduced body weight, locomotor activity, motor coordination and caused oxidative damage (lipid peroxidation, nitrite, superoxide dismutase, catalase and glutathione) in the striatum as compared to sham treated animal. Mitochondrial enzyme complexes and MTT (3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolinium bromide) activity were significantly inhibited by malonic acid. Vitamin E treatment (50 and 100 mg/kg, p.o.) significantly reversed the various behavioral, biochemical and mitochondrial alterations in malonic acid treated animals. Our findings show that targeting oxidative stress by vitamin E in malonic acid model, results in amelioration of behavioral and mitochondrial alterations are linked to inhibition of oxidative damage. Based upon these finding present study hypothesize that protection exerted by vitamin E on behavioral, mitochondrial markers indicates the possible preservation of the functional status of the striatal neurons by targeting the deleterious actions of oxidative stress.

  5. Type A behavior pattern and motor vehicle drivers' behavior.

    PubMed

    Perry, A R

    1986-10-01

    2 major components of the Type A coronary-prone behavior pattern are said to be a chronic sense of time urgency and impatience. The present study was done to determine whether these characteristics are associated with the driving performance of Type A individuals. 38 women and 32 men completed the Jenkins Activity Survey and a questionnaire concerning their driving. Those subjects exhibiting more Type A behavior tended to be more impatient, reported being involved in more accidents, and received more tickets for driving violations than those scoring lower on the Type A scale.

  6. Differential genetic regulation of motor activity and anxiety-related behaviors in mice using an automated home cage task.

    PubMed

    Kas, Martien J H; de Mooij-van Malsen, Annetrude J G; Olivier, Berend; Spruijt, Berry M; van Ree, Jan M

    2008-08-01

    Traditional behavioral tests, such as the open field test, measure an animal's responsiveness to a novel environment. However, it is generally difficult to assess whether the behavioral response obtained from these tests relates to the expression level of motor activity and/or to avoidance of anxiogenic areas. Here, an automated home cage environment for mice was designed to obtain independent measures of motor activity levels and of sheltered feeding preference during three consecutive days. Chronic treatment with the anxiolytic drug chlordiazepoxide (5 and 10 mg/kg/day) in C57BL/6J mice reduced sheltered feeding preference without altering motor activity levels. Furthermore, two distinct chromosome substitution strains, derived from C57BL/6J (host strain) and A/J (donor strain) inbred strains, expressed either increased sheltering preference in females (chromosome 15) or reduced motor activity levels in females and males (chromosome 1) when compared to C57BL/6J. Longitudinal behavioral monitoring revealed that these phenotypic differences maintained after adaptation to the home cage. Thus, by using new automated behavioral phenotyping approaches, behavior can be dissociated into distinct behavioral domains (e.g., anxiety-related and motor activity domains) with different underlying genetic origin and pharmacological responsiveness.

  7. Parathion alters incubation behavior of laughing gulls

    USGS Publications Warehouse

    White, D.H.; Mitchell, C.A.; Hill, E.F.

    1983-01-01

    One member of each pair of incubating laughing gulls at 9 nests was trapped, orally dosed with either 6 mg/kg parathion in corn oil or corn oil alone, and marked about the neck with red dye. Each nest was marked with a numbered stake and the treatment was recorded. A pilot study with captive laughing gulls had determined the proper dosage of parathion that would significantly inhibit their brain AChE activity (about 50% of normal) without overt signs of poisoning. After dosing, birds were released and the nests were observed for 2 1/2 days from a blind on the nesting island. The activities of the birds at each marked nest were recorded at 10-minute intervals. Results indicated that on the day of treatment there was no difference (P greater than 0.05, Chi-square test) in the proportion of time spent on the nest between treated and control birds. However, birds dosed with 6 mg/kg parathion spent significantly less time incubating on days 2 and 3 than did birds receiving only corn oil. By noon on the third day, sharing of nest duties between pair members in the treated group had approached normal, indicating recovery from parathion intoxication. These findings suggest that sublethal exposure of nesting birds to an organophosphate (OP) insecticide, such as parathion, may result in decreased nest attentiveness, thereby making the clutch more susceptible to predation or egg failure. Behavioral changes caused by sublethal OP exposure could be especially detrimental in avian species where only one pair member incubates or where both members are exposed in species sharing nest duties.

  8. Conservative motor systems, behavioral modulation and neural plasticity.

    PubMed

    Pellis, Sergio M

    2010-12-06

    Neural plasticity is a term that encompasses a vast array of changes in the nervous system in response to a wide range of environmental disturbances. The conservative manner in which nervous systems produce behavior is explored in the act of scratching the head. Whether the scratching is done with the hind leg (flamingos and axis deer) or the hand (spider monkey), it is shown that, when scratching their heads, animals follow a simple rule to avoid making multiple movements simultaneously with different parts of their bodies. Closer inspection of such a computational cost-saving scheme reveals that neural plasticity may best enhance motor performance when it occurs at higher levels of brain organization. The example of how complex social behavior, play fighting, is organized in rats shows that cortical systems can modify the contextual use of species-typical, or well-learned, behavior patterns, rather than producing new behavior patterns.

  9. Expression of Carbonic Anhydrase I in Motor Neurons and Alterations in ALS

    PubMed Central

    Liu, Xiaochen; Lu, Deyi; Bowser, Robert; Liu, Jian

    2016-01-01

    Carbonic anhydrase I (CA1) is the cytosolic isoform of mammalian α-CA family members which are responsible for maintaining pH homeostasis in the physiology and pathology of organisms. A subset of CA isoforms are known to be expressed and function in the central nervous system (CNS). CA1 has not been extensively characterized in the CNS. In this study, we demonstrate that CA1 is expressed in the motor neurons in human spinal cord. Unexpectedly, a subpopulation of CA1 appears to be associated with endoplasmic reticulum (ER) membranes. In addition, the membrane-associated CA1s are preferentially upregulated in amyotrophic lateral sclerosis (ALS) and exhibit altered distribution in motor neurons. Furthermore, long-term expression of CA1 in mammalian cells activates apoptosis. Our results suggest a previously unknown role for CA1 function in the CNS and its potential involvement in motor neuron degeneration in ALS. PMID:27809276

  10. Developmental exposure to methylmercury alters learning and induces depression-like behavior in male mice.

    PubMed

    Onishchenko, Natalia; Tamm, Christoffer; Vahter, Marie; Hökfelt, Tomas; Johnson, Jeffrey A; Johnson, Delinda A; Ceccatelli, Sandra

    2007-06-01

    To investigate the long-term effects of developmental exposure to methylmercury (MeHg), pregnant mice were exposed to at 0.5 mg MeHg/kg/day via drinking water from gestational day 7 until day 7 after delivery. The behavior of offspring was monitored at 5-15 and 26-36 weeks of age using an automated system (IntelliCage) designed for continuous long-term recording of the home cage behavior in social groups and complex analysis of basic activities and learning. In addition, spontaneous locomotion, motor coordination on the accelerating rotarod, spatial learning in Morris water maze, and depression-like behavior in forced swimming test were also studied. The analysis of behavior performed in the IntelliCage without social deprivation occurred to be more sensitive in detecting alterations in activity and learning paradigms. We found normal motor function but decreased exploratory activity in MeHg-exposed male mice, especially at young age. Learning disturbances observed in MeHg-exposed male animals suggest reference memory impairment. Interestingly, the forced swimming test revealed a predisposition to depressive-like behavior in the MeHg-exposed male offspring. This study provides novel evidence that the developmental exposure to MeHg can affect not only cognitive functions but also motivation-driven behaviors.

  11. Alterations of motor cortical excitability and anatomy in Unverricht-Lundborg disease.

    PubMed

    Danner, Nils; Julkunen, Petro; Hyppönen, Jelena; Niskanen, Eini; Säisänen, Laura; Könönen, Mervi; Koskenkorva, Päivi; Vanninen, Ritva; Kälviäinen, Reetta; Mervaala, Esa

    2013-11-01

    Unverricht-Lundborg disease is the most common form of progressive myoclonus epilepsies. In addition to generalized seizures, it is characterized by myoclonus, which usually is the most disabling feature of the disease. Classically, the myoclonus has been attributed to increased excitability of the primary motor cortex. However, inhibitory cortical phenomena have also been described along with anatomical alterations. We aimed to characterize the relationship between the excitability and anatomy of the motor cortex and their association with the severity of the clinical symptoms. Seventy genetically verified patients were compared with forty healthy controls. The symptoms were evaluated with the Unified Myoclonus Rating Scale. Navigated transcranial magnetic stimulation was applied to characterize the excitability of the primary motor cortex by determining the motor thresholds and cortical silent periods. In addition, the induced cortical electric fields were estimated using individual scalp-to-cortex distances measured from MRIs. A cortical thickness analysis was performed to elucidate possible disease-related anatomical alterations. The motor thresholds, cortical electric fields, and silent periods were significantly increased in the patients (P < 0.01). The silent periods correlated with the myoclonus scores (r = 0.48 to r = 0.49, P < 0.001). The scalp-to-cortex distance increased significantly with disease duration (r = 0.56, P < 0.001) and correlated inversely with cortical thickness. The results may reflect the refractory nature of the myoclonus and indicate a possible reactive cortical inhibitory mechanism to the underlying disease process. This is the largest clinical series on Unverricht-Lundborg disease and the first study describing parallel pathophysiological and structural alterations associated with the severity of the symptoms.

  12. Dissociating motivational direction and affective valence: specific emotions alter central motor processes.

    PubMed

    Coombes, Stephen A; Cauraugh, James H; Janelle, Christopher M

    2007-11-01

    We aimed to clarify the relation between affective valence and motivational direction by specifying how central and peripheral components of extension movements are altered according to specific unpleasant affective states. As predicted, premotor reaction time was quicker for extension movements initiated during exposure to attack than for extension movements initiated during exposure to all other valence categories (mutilation, erotic couples, opposite-sex nudes, neutral humans, household objects, blank). Exposure to erotic couples and mutilations yielded greater peak force than exposure to images of attack, neutral humans, and household objects. Finally, motor reaction time and peak electromyographic amplitude were not altered by valence. These findings indicate that unpleasant states do not unilaterally prime withdrawal movements, and that the quick execution of extension movements during exposure to threatening images is due to rapid premotor, rather than motor, reaction time. Collectively, our findings support the call for dissociating motivational direction and affective valence.

  13. Shared and specific muscle synergies in natural motor behaviors

    PubMed Central

    d'Avella, Andrea; Bizzi, Emilio

    2005-01-01

    Selecting the appropriate muscle pattern to achieve a given goal is an extremely complex task because of the dimensionality of the search space and because of the nonlinear and dynamical nature of the transformation between muscle activity and movement. To investigate whether the central nervous system uses a modular architecture to achieve motor coordination we characterized the motor output over a large set of movements. We recorded electromyographic activity from 13 muscles of the hind limb of intact and freely moving frogs during jumping, swimming, and walking in naturalistic conditions. We used multidimensional factorization techniques to extract invariant amplitude and timing relationships among the muscle activations. A decomposition of the instantaneous muscle activations as combinations of nonnegative vectors, synchronous muscle synergies, revealed a spatial organization in the muscle patterns. A decomposition of the same activations as a combination of temporal sequences of nonnegative vectors, time-varying muscle synergies, further uncovered specific characteristics in the muscle activation waveforms. A mixture of synergies shared across behaviors and synergies for specific behaviors captured the invariances across the entire dataset. These results support the hypothesis that the motor controller has a modular organization. PMID:15708969

  14. Altered bidirectional plasticity and reduced implicit motor learning in concussed athletes.

    PubMed

    De Beaumont, Louis; Tremblay, Sébastien; Poirier, Judes; Lassonde, Maryse; Théoret, Hugo

    2012-01-01

    Persistent motor/cognitive alterations and increased prevalence of Alzheimer's disease are known consequences of recurrent sports concussions, the most prevalent cause of mild traumatic brain injury (TBI) among youth. Animal models of TBI demonstrated that impaired learning was related to persistent synaptic plasticity suppression in the form of long-term potentiation (LTP) and depression (LTD). In humans, single and repeated concussive injuries lead to lifelong and cumulative enhancements of gamma-aminobutyric acid (GABA)-mediated inhibition, which is known to suppress LTP/LTD plasticity. To test the hypothesis that increased GABAergic inhibition after repeated concussions suppresses LTP/LTD and contributes to learning impairments, we used a paired associative stimulation (PAS) protocol to induce LTP/LTD-like effects in primary motor cortex (M1) jointly with an implicit motor learning task (serial reaction time task, SRTT). Our results indicate that repeated concussions induced persistent elevations of GABA(B)-mediated intracortical inhibition in M1, which was associated with suppressed PAS-induced LTP/LTD-like synaptic plasticity. This synaptic plasticity suppression was related to reduced implicit motor learning on the SRTT task relative to normal LTP/LTD-like synaptic plasticity in unconcussed teammates. These findings identify GABA neurotransmission alterations after repeated concussions and suggest that impaired learning after multiple concussions could at least partly be related to compromised GABA-dependent LTP/LTD synaptic plasticity.

  15. Locomotor activity and sensory-motor developmental alterations in rat offspring exposed to arsenic prenatally and via lactation.

    PubMed

    Gumilar, Fernanda; Lencinas, Ileana; Bras, Cristina; Giannuzzi, Leda; Minetti, Alejandra

    2015-01-01

    Arsenic (As) is one of the most toxic naturally occurring contaminants in the environment. The major source of human exposure to inorganic As (iAs) is through contaminated drinking water. Although both genotoxicity and carcinogenicity derived from this metalloid have been thoroughly studied, the effects of iAs on the development and function of the central nervous system (CNS) have received less attention and only a few studies have focused on neurobehavioral effects. Thus, in order to characterize developmental and behavioral alterations induced by iAs exposure, pregnant Wistar rats were exposed to 0.05 and 0.10 mg/L iAs through drinking water during gestation and lactation. Sensory-motor reflexes in each pup were analyzed and the postnatal day when righting reflex, cliff aversion and negative geotaxis were recorded. Functional Observational Battery (FOB) and locomotor activity in an open field were assessed in 90-day-old offspring. Results show that rats exposed to low iAs concentrations through drinking water during early development evidence a delay in the development of sensory-motor reflexes. Both FOB procedure and open-field tests showed a decrease in locomotor activity in adult rats. This study reveals that exposure to the above-mentioned iAs concentrations produces dysfunction in the CNS mechanisms whose role is to regulate motor and sensory development and locomotor activity.

  16. Altered motor unit discharge patterns in paretic muscles of stroke survivors assessed using surface electromyography

    NASA Astrophysics Data System (ADS)

    Hu, Xiaogang; Suresh, Aneesha K.; Rymer, William Z.; Suresh, Nina L.

    2016-08-01

    Objective. Hemispheric stroke survivors often show impairments in voluntary muscle activation. One potential source of these impairments could come from altered control of muscle, via disrupted motor unit (MU) firing patterns. In this study, we sought to determine whether MU firing patterns are modified on the affected side of stroke survivors, as compared with the analogous contralateral muscle. Approach. Using a novel surface electromyogram (EMG) sensor array, coupled with advanced template recognition software (dEMG) we recorded surface EMG signals over the first dorsal interosseous (FDI) muscle on both paretic and contralateral sides. Recordings were made as stroke survivors produced isometric index finger abductions over a large force range (20%-60% of maximum). Utilizing the dEMG algorithm, MU firing rates, recruitment thresholds, and action potential amplitudes were estimated for concurrently active MUs in each trial. Main results. Our results reveal significant changes in the firing rate patterns in paretic FDI muscle, in that the discharge rates, characterized in relation to recruitment force threshold and to MU size, were less clearly correlated with recruitment force than in contralateral FDI muscles. Firing rates in the affected muscle also did not modulate systematically with the level of voluntary muscle contraction, as would be expected in intact muscles. These disturbances in firing properties also correlated closely with the impairment of muscle force generation. Significance. Our results provide strong evidence of disruptions in MU firing behavior in paretic muscles after a hemispheric stroke, suggesting that modified control of the spinal motoneuron pool could be a contributing factor to muscular weakness in stroke survivors.

  17. Comparison of objectively measured motor behavior with ratings of the motor behavior domain of the Bern Psychopathology Scale (BPS) in schizophrenia.

    PubMed

    Bracht, Tobias; Heidemeyer, Kristine; Koschorke, Philipp; Horn, Helge; Razavi, Nadja; Wopfner, Alexander; Strik, Werner; Walther, Sebastian

    2012-07-30

    Motor symptoms in schizophrenia occur frequently and are relevant to diagnosis and antipsychotic therapy. To date motor symptoms are difficult to assess and their pathobiology is a widely unresolved issue. The Bern Psychopathology Scale for the assessment of system-specific psychotic symptoms (BPS) was designed to identify homogenous patient groups by focusing on three domains: language, affectivity and motor behavior. The present study aimed to validate the motor behavior domain of the BPS using wrist actigraphy. In total, 106 patients were rated with the BPS and underwent 24 h continuous actigraphy recording. The ratings of the global severity of the motor behavior domain (GSM) as well as the quantitative and the subjective items of the motor behavior domain of the BPS were significantly associated with actigraphic variables. In contrast, the qualitative items of the motor domain failed to show an association with actigraphy. Likewise, scores of the language and the affectivity domains were not related to actigraphic measures. In conclusion, we provided substantial external validity for global, quantitative and subjective ratings of the BPS motor behavior domain. Thus, the BPS is suitable to assess the dimension of quantitative motor behavior in the schizophrenia spectrum.

  18. Teacher Evaluation in Foreign Language Education: Behavior Alteration Techniques.

    ERIC Educational Resources Information Center

    Garrott, Carl L.

    A study examined the relationship between French teachers' use of behavior alteration techniques in the classroom, and the perceptions of individuals evaluating the teacher (students, peers, administrators) on the quality of instructional performance. Junior and community college French students, language teachers, and administrators responded to…

  19. Neonatal Stroke Causes Poor Midline Motor Behaviors and Poor Fine and Gross Motor Skills during Early Infancy

    ERIC Educational Resources Information Center

    Chen, Chao-Ying; Lo, Warren D.; Heathcock, Jill C.

    2013-01-01

    Upper extremity movements, midline behaviors, fine, and gross motor skills are frequently impaired in hemiparesis and cerebral palsy. We investigated midline toy exploration and fine and gross motor skills in infants at risk for hemiplegic cerebral palsy. Eight infants with neonatal stroke (NS) and thirteen infants with typical development (TD)…

  20. Mathematical modeling of bacterial track-altering motors: Track cleaving through burnt-bridge ratchets

    NASA Astrophysics Data System (ADS)

    Shtylla, Blerta; Keener, James P.

    2015-04-01

    The generation of directed movement of cellular components frequently requires the rectification of Brownian motion. Molecular motor enzymes that use ATP to walk on filamentous tracks are typically involved in cell transport, however, a track-altering motor can arise when an enzyme interacts with and alters its track. In Caulobacter crescentus and other bacteria, an active DNA partitioning (Par) apparatus is employed to segregate replicated chromosome regions to specific locations in dividing cells. The Par apparatus is composed of two proteins: ParA, an ATPase that can form polymeric structures on the nucleoid, and ParB, a protein that can bind and destabilize ParA structures. It has been proposed that the ParB-mediated alteration of ParA structures could be responsible for generating the directed movement of DNA during bacterial division. How precisely these actions are coordinated and translated into directed movement is not clear. In this paper we consider the C. crescentus segregation apparatus as an example of a track altering motor that operates using a so-called burnt-bridge mechanism. We develop and analyze mathematical models that examine how diffusion and ATP-hydrolysis-mediated monomer removal (or cleaving) can be combined to generate directed movement. Using a mean first passage approach, we analytically calculate the effective ParA track-cleaving velocities, effective diffusion coefficient, and other higher moments for the movement a ParB protein cluster that breaks monomers away at random locations on a single ParA track. Our model results indicate that cleaving velocities and effective diffusion constants are sensitive to ParB-induced ATP hydrolysis rates. Our analytical results are in excellent agreement with stochastic simulation results.

  1. Mathematical modeling of bacterial track-altering motors: Track cleaving through burnt-bridge ratchets.

    PubMed

    Shtylla, Blerta; Keener, James P

    2015-04-01

    The generation of directed movement of cellular components frequently requires the rectification of Brownian motion. Molecular motor enzymes that use ATP to walk on filamentous tracks are typically involved in cell transport, however, a track-altering motor can arise when an enzyme interacts with and alters its track. In Caulobacter crescentus and other bacteria, an active DNA partitioning (Par) apparatus is employed to segregate replicated chromosome regions to specific locations in dividing cells. The Par apparatus is composed of two proteins: ParA, an ATPase that can form polymeric structures on the nucleoid, and ParB, a protein that can bind and destabilize ParA structures. It has been proposed that the ParB-mediated alteration of ParA structures could be responsible for generating the directed movement of DNA during bacterial division. How precisely these actions are coordinated and translated into directed movement is not clear. In this paper we consider the C. crescentus segregation apparatus as an example of a track altering motor that operates using a so-called burnt-bridge mechanism. We develop and analyze mathematical models that examine how diffusion and ATP-hydrolysis-mediated monomer removal (or cleaving) can be combined to generate directed movement. Using a mean first passage approach, we analytically calculate the effective ParA track-cleaving velocities, effective diffusion coefficient, and other higher moments for the movement a ParB protein cluster that breaks monomers away at random locations on a single ParA track. Our model results indicate that cleaving velocities and effective diffusion constants are sensitive to ParB-induced ATP hydrolysis rates. Our analytical results are in excellent agreement with stochastic simulation results.

  2. Alterations of cortical excitability and central motor conduction time in Wilson's disease.

    PubMed

    Jhunjhunwala, Ketan; Prashanth, D K; Netravathi, M; Nagaraju, B C; Pal, Pramod Kr

    2013-10-11

    Wilson's disease (WD) leads to widespread structural alterations of central nervous system and our objectives were to determine the cortical excitability changes in WD by using transcranial magnetic stimulation (TMS). Thirteen patients with WD, diagnosed by the presence of Kayser-Fleischer ring and biochemical tests, were studied. TMS was performed using a figure-of-eight coil attached to Magstim 200 stimulator. Motor evoked potentials (MEP) were recorded from right first dorsal interosseous at rest. Resting motor threshold (RMT) was determined using standard techniques and central motor conduction time (CMCT) by 'F' wave method. Comparison was made with control data of our laboratory. Dysarthria was the presenting symptom in 5 patients (38.5%) and chorea, tremors, dystonia and abnormal gait in 2 patients each (15.4%). RMT was recordable in 10 patients and not recordable in 3. Compared to controls, patients in whom RMT was recordable, had significantly higher mean RMT (80.9 ± 14.8 vs. 41.1 ± 7, p<0.0001) and CMCT (6.7 ± 0.5 ms vs. 4.8 ± 0.6 ms; p<0.0001). In 2 of the 3 patients with non-recordable RMT, MEP could be obtained with active contraction. CMCT in these 2 patients was also prolonged. Patients with WD have reduced cortical excitability and prolonged CMCT which may be due to the intracortical presynaptic motor dysfunction.

  3. Localization of Motor Neurons and Central Pattern Generators for Motor Patterns Underlying Feeding Behavior in Drosophila Larvae

    PubMed Central

    Hückesfeld, Sebastian; Schoofs, Andreas; Schlegel, Philipp; Miroschnikow, Anton; Pankratz, Michael J.

    2015-01-01

    Motor systems can be functionally organized into effector organs (muscles and glands), the motor neurons, central pattern generators (CPG) and higher control centers of the brain. Using genetic and electrophysiological methods, we have begun to deconstruct the motor system driving Drosophila larval feeding behavior into its component parts. In this paper, we identify distinct clusters of motor neurons that execute head tilting, mouth hook movements, and pharyngeal pumping during larval feeding. This basic anatomical scaffold enabled the use of calcium-imaging to monitor the neural activity of motor neurons within the central nervous system (CNS) that drive food intake. Simultaneous nerve- and muscle-recordings demonstrate that the motor neurons innervate the cibarial dilator musculature (CDM) ipsi- and contra-laterally. By classical lesion experiments we localize a set of CPGs generating the neuronal pattern underlying feeding movements to the subesophageal zone (SEZ). Lesioning of higher brain centers decelerated all feeding-related motor patterns, whereas lesioning of ventral nerve cord (VNC) only affected the motor rhythm underlying pharyngeal pumping. These findings provide a basis for progressing upstream of the motor neurons to identify higher regulatory components of the feeding motor system. PMID:26252658

  4. Localization of Motor Neurons and Central Pattern Generators for Motor Patterns Underlying Feeding Behavior in Drosophila Larvae.

    PubMed

    Hückesfeld, Sebastian; Schoofs, Andreas; Schlegel, Philipp; Miroschnikow, Anton; Pankratz, Michael J

    2015-01-01

    Motor systems can be functionally organized into effector organs (muscles and glands), the motor neurons, central pattern generators (CPG) and higher control centers of the brain. Using genetic and electrophysiological methods, we have begun to deconstruct the motor system driving Drosophila larval feeding behavior into its component parts. In this paper, we identify distinct clusters of motor neurons that execute head tilting, mouth hook movements, and pharyngeal pumping during larval feeding. This basic anatomical scaffold enabled the use of calcium-imaging to monitor the neural activity of motor neurons within the central nervous system (CNS) that drive food intake. Simultaneous nerve- and muscle-recordings demonstrate that the motor neurons innervate the cibarial dilator musculature (CDM) ipsi- and contra-laterally. By classical lesion experiments we localize a set of CPGs generating the neuronal pattern underlying feeding movements to the subesophageal zone (SEZ). Lesioning of higher brain centers decelerated all feeding-related motor patterns, whereas lesioning of ventral nerve cord (VNC) only affected the motor rhythm underlying pharyngeal pumping. These findings provide a basis for progressing upstream of the motor neurons to identify higher regulatory components of the feeding motor system.

  5. Dynamics of behavioral organization and its alteration in major depression

    NASA Astrophysics Data System (ADS)

    Nakamura, Toru; Kiyono, Ken; Yoshiuchi, Kazuhiro; Nakahara, Rika; Struzik, Zbigniew R.; Yamamoto, Yoshiharu

    2007-07-01

    We describe the nature of human behavioral organization, specifically how resting and active periods are interwoven throughout daily life. Active period durations with physical activity counts successively above a predefined threshold follow a stretched exponential (gamma-type) cumulative distribution with characteristic time, both in healthy individuals and in patients with major depressive disorder. On the contrary, resting period durations below the threshold for both groups obey a scale free power law cumulative distribution over two decades, with significantly lower scaling exponents in the patients. We thus find underlying robust laws governing human behavioral organization, with a parameter altered in depression.

  6. Fishing indirectly structures macroalgal assemblages by altering herbivore behavior.

    PubMed

    Madin, Elizabeth M P; Gaines, Steven D; Madin, Joshua S; Warner, Robert R

    2010-12-01

    Fishing has clear direct effects on harvested species, but its cascading, indirect effects are less well understood. Fishing disproportionately removes larger, predatory fishes from marine food webs. Most studies of the consequent indirect effects focus on density-mediated interactions where predator removal alternately drives increases and decreases in abundances of successively lower trophic-level species. While prey may increase in number with fewer predators, they may also alter their behavior. When such behavioral responses impact the food resources of prey species, behaviorally mediated trophic cascades can dramatically shape landscapes. It remains unclear whether this pathway of change is typically triggered by ocean fishing. By coupling a simple foraging model with empirical observations from coral reefs, we provide a mechanistic basis for understanding and predicting how predator harvest can alter the landscape of risk for herbivores and consequently drive dramatic changes in primary producer distributions. These results broaden trophic cascade predictions for fisheries to include behavioral changes. They also provide a framework for detecting the presence and magnitude of behaviorally mediated cascades. This knowledge will help to reconcile the disparity between expected and observed patterns of fishing-induced cascades in the sea.

  7. Altered avoidance behavior of young black ducks fed cadmium

    USGS Publications Warehouse

    Heinz, G.H.; Haseltine, S.D.; Sileo, L.

    1983-01-01

    Pairs of adult black ducks (Anas rubripes) were fed a diet containing 0, 4 or 40 ppm cadmium as cadmium chloride. One-week-old ducklings that had been fed thc same dietary concentrations of cadmium as had their parents were tested for avoidance of a fright stimulus. Ducklings fed 4 ppm cadmium ran significantly farther from the stimulus than did controls or ducklings fed 40 ppm cadmium. Such an alteration in behavior could have harmful effects on wild birds.

  8. The role of spinal manipulation in addressing disordered sensorimotor integration and altered motor control.

    PubMed

    Haavik, Heidi; Murphy, Bernadette

    2012-10-01

    This review provides an overview of some of the growing body of research on the effects of spinal manipulation on sensory processing, motor output, functional performance and sensorimotor integration. It describes a body of work using somatosensory evoked potentials (SEPs), transcranial magnetic nerve stimulation, and electromyographic techniques to demonstrate neurophysiological changes following spinal manipulation. This work contributes to the understanding of how an initial episode(s) of back or neck pain may lead to ongoing changes in input from the spine which over time lead to altered sensorimotor integration of input from the spine and limbs.

  9. Motor Behavior: From Telegraph Keys and Twins to Linear Slides and Stepping

    ERIC Educational Resources Information Center

    Thomas, Jerry R.

    2006-01-01

    Motor behavior is a significant area of scholarship with 64 Fellows from the American Academy of Kinesiology and Physical Education engaged in that work since 1930. This paper provides a brief overview of the history of research in motor development and motor control/learning, particularly noting the contributions to scholarship of Academy…

  10. Methylglyoxal can mediate behavioral and neurochemical alterations in rat brain.

    PubMed

    Hansen, Fernanda; Pandolfo, Pablo; Galland, Fabiana; Torres, Felipe Vasconcelos; Dutra, Márcio Ferreira; Batassini, Cristiane; Guerra, Maria Cristina; Leite, Marina Concli; Gonçalves, Carlos-Alberto

    2016-10-01

    Diabetes is associated with loss of cognitive function and increased risk for Alzheimer's disease (AD). Advanced glycation end products (AGEs) are elevated in diabetes and AD and have been suggested to act as mediators of the cognitive decline observed in these pathologies. Methylglyoxal (MG) is an extremely reactive carbonyl compound that propagates glycation reactions and is, therefore, able to generate AGEs. Herein, we evaluated persistent behavioral and biochemical parameters to explore the hypothesis that elevated exogenous MG concentrations, induced by intracerebroventricular (ICV) infusion, lead to cognitive decline in Wistar rats. A high and sustained administration of MG (3μmol/μL; subdivided into 6days) was found to decrease the recognition index of rats, as evaluated by the object-recognition test. However, MG was unable to impair learning-memory processes, as shown by the habituation in the open field (OF) and Y-maze tasks. Moreover, a single high dose of MG induced persistent alterations in anxiety-related behavior, diminishing the anxiety-like parameters evaluated in the OF test. Importantly, MG did not alter locomotion behavior in the different tasks performed. Our biochemical findings support the hypothesis that MG induces persistent alterations in the hippocampus, but not in the cortex, related to glyoxalase 1 activity, AGEs content and glutamate uptake. Glial fibrillary acidic protein and S100B content, as well as S100B secretion (astroglial-related parameters of brain injury), were not altered by ICV MG administration. Taken together, our data suggest that MG interferes directly in brain function and that the time and the levels of exogenous MG determine the different features that can be seen in diabetic patients.

  11. Vibrissa motor cortex activity suppresses contralateral whisking behavior.

    PubMed

    Ebbesen, Christian Laut; Doron, Guy; Lenschow, Constanze; Brecht, Michael

    2017-01-01

    Anatomical, stimulation and lesion data implicate vibrissa motor cortex in whisker motor control. Work on motor cortex has focused on movement generation, but correlations between vibrissa motor cortex activity and whisking are weak. The exact role of vibrissa motor cortex remains unknown. We recorded vibrissa motor cortex neurons during various forms of vibrissal touch, which were invariably associated with whisker protraction and movement. Free whisking, object palpation and social touch all resulted in decreased cortical activity. To understand this activity decrease, we performed juxtacellular recordings, nanostimulation and in vivo whole-cell recordings. Social touch resulted in decreased spiking activity, decreased cell excitability and membrane hyperpolarization. Activation of vibrissa motor cortex by intracortical microstimulation elicited whisker retraction, as if to abort vibrissal touch. Various vibrissa motor cortex inactivation protocols resulted in contralateral protraction and increased whisker movements. These data collectively point to movement suppression as a prime function of vibrissa motor cortex activity.

  12. Motor Prediction at the Edge of Instability: Alteration of Grip Force Control during Changes in Bimanual Coordination

    ERIC Educational Resources Information Center

    Danion, Frederic; Jirsa, Viktor K.

    2010-01-01

    Predicting the consequences of actions is fundamental for skilled motor behavior. We investigated whether motor prediction is influenced by the fact that some movements are easier to perform and stabilize than others. Twelve subjects performed a bimanual rhythmical task either symmetrically or asymmetrically (the latter being more difficult and…

  13. Discharge behaviors of trapezius motor units during exposure to low and high levels of acute psychosocial stress

    PubMed Central

    Stephenson, Jennifer L; Maluf, Katrina S

    2010-01-01

    This study investigated the effects of acute psychosocial stress on trapezius single motor unit discharge behaviors. Twenty-one healthy women performed feedback-controlled isometric contractions under conditions of low and high psychosocial stress in the same experimental session. Psychosocial stress was manipulated using a verbal math task combined with social evaluative threat which significantly increased perceived anxiety, heart rate, and blood pressure (P<0.001). Motor unit discharge behaviors including the threshold and discharge rate at recruitment (7.7 (5.7) %MVC and 7.3 (6.8) pps, P>0.121, N=103) and derecruitment (6.0(4.4) %MVC and 6.5(4.1) pps, P>0.223, N=99), the mean (11.3 (2.3) pps, P=0.309, N=106) and variability (2.5 (0.91) pps, P=0.958, N=106) of discharge rate, and the proportion of motor units exhibiting double discharges (21%, P=0.446) did not change across stress conditions. Discharge rate modulation with changes in contraction intensity was highly variable and similar across stress conditions (P>0.308, N=89). Rate-rate modulation of concurrently active motor units was also highly variable (r=−0.84–1.00, N=75). Estimates of ΔF for motor unit pairs with rate-rate modulation ≥0.7 were positive and similar across stress conditions (4.7(2.0) pps, P=0.405, N=16). Results indicate that acute psychosocial stress does not alter trapezius motor unit discharge behaviors during a precisely controlled motor task in healthy women. PMID:20087201

  14. Motor planning modulates sensory-motor control of collision avoidance behavior in the bullfrog, Rana catesbeiana

    PubMed Central

    Nakagawa, Hideki; Nishida, Yuuya

    2012-01-01

    Summary In this study, we examined the collision avoidance behavior of the frog, Rana catesbeiana to an approaching object in the upper visual field. The angular velocity of the frog's escape turn showed a significant positive correlation with the turn angle (r2 = 0.5741, P<0.05). A similar mechanism of velocity control has been known in head movements of the owl and in human saccades. By analogy, this suggests that the frog planned its escape velocity in advance of executing the turn, to make the duration of the escape behavior relatively constant. For escape turns less than 60°, the positive correlation was very strong (r2 = 0.7097, P<0.05). Thus, the frog controlled the angular velocity of small escape turns very accurately and completed the behavior within a constant time. On the other hand, for escape turns greater than 60°, the same correlation was not significant (r2 = 0.065, P>0.05). Thus, the frog was not able to control the velocity of the large escape turns accurately and did not complete the behavior within a constant time. In the latter case, there was a small but significant positive correlation between the threshold angular size and the angular velocity (r2 = 0.1459, P<0.05). This suggests that the threshold is controlled to compensate for the insufficient escape velocity achieved during large turn angles, and could explain a significant negative correlation between the turn angle and the threshold angular size (r2 = 0.1145, P<0.05). Thus, it is likely that the threshold angular size is also controlled by the turn angle and is modulated by motor planning. PMID:23213389

  15. Motor planning modulates sensory-motor control of collision avoidance behavior in the bullfrog, Rana catesbeiana.

    PubMed

    Nakagawa, Hideki; Nishida, Yuuya

    2012-11-15

    In this study, we examined the collision avoidance behavior of the frog, Rana catesbeiana to an approaching object in the upper visual field. The angular velocity of the frog's escape turn showed a significant positive correlation with the turn angle (r(2) = 0.5741, P<0.05). A similar mechanism of velocity control has been known in head movements of the owl and in human saccades. By analogy, this suggests that the frog planned its escape velocity in advance of executing the turn, to make the duration of the escape behavior relatively constant. For escape turns less than 60°, the positive correlation was very strong (r(2) = 0.7097, P<0.05). Thus, the frog controlled the angular velocity of small escape turns very accurately and completed the behavior within a constant time. On the other hand, for escape turns greater than 60°, the same correlation was not significant (r(2) = 0.065, P>0.05). Thus, the frog was not able to control the velocity of the large escape turns accurately and did not complete the behavior within a constant time. In the latter case, there was a small but significant positive correlation between the threshold angular size and the angular velocity (r(2) = 0.1459, P<0.05). This suggests that the threshold is controlled to compensate for the insufficient escape velocity achieved during large turn angles, and could explain a significant negative correlation between the turn angle and the threshold angular size (r(2) = 0.1145, P<0.05). Thus, it is likely that the threshold angular size is also controlled by the turn angle and is modulated by motor planning.

  16. Structural Brain Alterations Associated with Rapid Eye Movement Sleep Behavior Disorder in Parkinson’s Disease

    PubMed Central

    Boucetta, Soufiane; Salimi, Ali; Dadar, Mahsa; Jones, Barbara E.; Collins, D. Louis; Dang-Vu, Thien Thanh

    2016-01-01

    Characterized by dream-enactment motor manifestations arising from rapid eye movement (REM) sleep, REM sleep behavior disorder (RBD) is frequently encountered in Parkinson’s disease (PD). Yet the specific neurostructural changes associated with RBD in PD patients remain to be revealed by neuroimaging. Here we identified such neurostructural alterations by comparing large samples of magnetic resonance imaging (MRI) scans in 69 PD patients with probable RBD, 240 patients without RBD and 138 healthy controls, using deformation-based morphometry (p < 0.05 corrected for multiple comparisons). All data were extracted from the Parkinson’s Progression Markers Initiative. PD patients with probable RBD showed smaller volumes than patients without RBD and than healthy controls in the pontomesencephalic tegmentum, medullary reticular formation, hypothalamus, thalamus, putamen, amygdala and anterior cingulate cortex. These results demonstrate that RBD is associated with a prominent loss of volume in the pontomesencephalic tegmentum, where cholinergic, GABAergic and glutamatergic neurons are located and implicated in the promotion of REM sleep and muscle atonia. It is additionally associated with more widespread atrophy in other subcortical and cortical regions whose loss also likely contributes to the altered regulation of sleep-wake states and motor activity underlying RBD in PD patients. PMID:27245317

  17. LRRK2 overexpression alters glutamatergic presynaptic plasticity, striatal dopamine tone, postsynaptic signal transduction, motor activity and memory.

    PubMed

    Beccano-Kelly, Dayne A; Volta, Mattia; Munsie, Lise N; Paschall, Sarah A; Tatarnikov, Igor; Co, Kimberley; Chou, Patrick; Cao, Li-Ping; Bergeron, Sabrina; Mitchell, Emma; Han, Heather; Melrose, Heather L; Tapia, Lucia; Raymond, Lynn A; Farrer, Matthew J; Milnerwood, Austen J

    2015-03-01

    Mutations in leucine-rich repeat kinase 2 (Lrrk2) are the most common genetic cause of Parkinson's disease (PD), a neurodegenerative disorder affecting 1-2% of those >65 years old. The neurophysiology of LRRK2 remains largely elusive, although protein loss suggests a role in glutamatergic synapse transmission and overexpression studies show altered dopamine release in aged mice. We show that glutamate transmission is unaltered onto striatal projection neurons (SPNs) of adult LRRK2 knockout mice and that adult animals exhibit no detectable cognitive or motor deficits. Basal synaptic transmission is also unaltered in SPNs of LRRK2 overexpressing mice, but they do exhibit clear alterations to D2-receptor-mediated short-term synaptic plasticity, behavioral hypoactivity and impaired recognition memory. These phenomena are associated with decreased striatal dopamine tone and abnormal dopamine- and cAMP-regulated phosphoprotein 32 kDa signal integration. The data suggest that LRRK2 acts at the nexus of dopamine and glutamate signaling in the adult striatum, where it regulates dopamine levels, presynaptic glutamate release via D2-dependent synaptic plasticity and dopamine-receptor signal transduction.

  18. Initial Observations of Fruit Fly;s Flight with its b1 Motor Neuron Altered

    NASA Astrophysics Data System (ADS)

    Wang, Z. Jane; Melfi, James, Jr.

    2015-11-01

    Recently we have suggested that one of the fly's 17 steering muscles, the first basalar muscle (b1) is responsible for maintaining flight stability. To test this, we compare the flight behavior of normal flies with genetically modified flies whose motor neuron to the b1 muscle is silenced. We report our initial observation of the difference and similarity between these two lines supplied by Janelia Farm. We also discuss the basic question for quantifying flight, what makes a good flier? Partly supported by the Visiting Scientist program at HHMI-Janelia Farm.

  19. Alterations of the Host Microbiome Affect Behavioral Responses to Cocaine

    PubMed Central

    Kiraly, Drew D.; Walker, Deena M.; Calipari, Erin S.; Labonte, Benoit; Issler, Orna; Pena, Catherine J.; Ribeiro, Efrain A.; Russo, Scott J.; Nestler, Eric J.

    2016-01-01

    Addiction to cocaine and other psychostimulants represents a major public health crisis. The development and persistence of addictive behaviors comes from a complex interaction of genes and environment - the precise mechanisms of which remain elusive. In recent years a surge of evidence has suggested that the gut microbiome can have tremendous impact on behavioral via the microbiota-gut-brain axis. In this study we characterized the influence of the gut microbiota on cocaine-mediated behaviors. Groups of mice were treated with a prolonged course of non-absorbable antibiotics via the drinking water, which resulted in a substantial reduction of gut bacteria. Animals with reduced gut bacteria showed an enhanced sensitivity to cocaine reward and enhanced sensitivity to the locomotor-sensitizing effects of repeated cocaine administration. These behavioral changes were correlated with adaptations in multiple transcripts encoding important synaptic proteins in the brain’s reward circuitry. This study represents the first evidence that alterations in the gut microbiota affect behavioral response to drugs of abuse. PMID:27752130

  20. Motor Circuit-Specific Burst Patterns Drive Different Muscle and Behavior Patterns

    PubMed Central

    Diehl, Florian; White, Rachel S.; Stein, Wolfgang

    2013-01-01

    In the isolated CNS, different modulatory inputs can enable one motor network to generate multiple output patterns. Thus far, however, few studies have established whether different modulatory inputs also enable a defined network to drive distinct muscle and movement patterns in vivo, much as they enable these distinctions in behavioral studies. This possibility is not a foregone conclusion, because additional influences present in vivo (e.g., sensory feedback, hormonal modulation) could alter the motor patterns. Additionally, rhythmic neuronal activity can be transformed into sustained muscle contractions, particularly in systems with slow muscle dynamics, as in the crab (Cancer borealis) stomatogastric system used here. We assessed whether two different versions of the biphasic (protraction, retraction) gastric mill (chewing) rhythm, triggered in the isolated stomatogastric system by the modulatory ventral cardiac neurons (VCNs) and postoesophageal commissure (POC) neurons, drive different muscle and movement patterns. One distinction between these rhythms is that the lateral gastric (LG) protractor motor neuron generates tonic bursts during the VCN rhythm, whereas its POC-rhythm bursts are divided into fast, rhythmic burstlets. Intracellular muscle fiber recordings and tension measurements show that the LG-innervated muscles retain the distinct VCN-LG and POC-LG neuron burst structures. Moreover, endoscope video recordings in vivo, during VCN-triggered and POC-triggered chewing, show that the lateral teeth protraction movements exhibit the same, distinct protraction patterns generated by LG in the isolated nervous system. Thus, the multifunctional nature of an identified motor network in the isolated CNS can be preserved in vivo, where it drives different muscle activity and movement patterns. PMID:23864688

  1. Coordination of Orofacial Motor Actions into Exploratory Behavior by Rat.

    PubMed

    Kurnikova, Anastasia; Moore, Jeffrey D; Liao, Song-Mao; Deschênes, Martin; Kleinfeld, David

    2017-03-06

    The delineation of sensorimotor circuits that guide exploration begins with an understanding of the pattern of motor outputs [1]. These motor patterns provide a clue to the form of the underlying circuits [2-4] (but see [5]). We focus on the behaviors that rodents use to explore their peripersonal space through goal-directed positioning of their nose, head, and vibrissae. Rodents sniff in response to novel odors, reward expectation, and as part of social interactions [6-12]. Sniffing serves olfaction [13, 14], while whisking synchronized to sniffing serves vibrissa-based touch [6, 15, 16]. We quantify the ethology of exploratory nose and head movements in relation to breathing. We find that sniffing is accompanied by prominent lateral and vertical deflections of the nose, i.e., twitches, which are driven by activation of the deflector nasi muscles [17]. On the timescale of individual breaths, nose motion is rhythmic and has a maximum deflection following the onset of inspiration. On a longer timescale, excursions of the nose persist for several breaths and are accompanied by an asymmetry in vibrissa positioning toward the same side of the face. Such directed deflections can be triggered by a lateralized source of odor. Lastly, bobbing of the head as the animal cranes and explores is phase-locked to sniffing and to movement of the nose. These data, along with prior results on the resetting of the whisk cycle at the onset of inspiration [15, 16, 18], reveal that the onset of each breath initiates a "snapshot" of the orofacial sensory environment. VIDEO ABSTRACT.

  2. Alterations of motor performance and brain cortex mitochondrial function during ethanol hangover.

    PubMed

    Bustamante, Juanita; Karadayian, Analia G; Lores-Arnaiz, Silvia; Cutrera, Rodolfo A

    2012-08-01

    Ethanol has been known to affect various behavioral parameters in experimental animals, even several hours after ethanol (EtOH) is absent from blood circulation, in the period known as hangover. The aim of this study was to assess the effects of acute ethanol hangover on motor performance in association with the brain cortex energetic metabolism. Evaluation of motor performance and brain cortex mitochondrial function during alcohol hangover was performed in mice 6 hours after a high ethanol dose (hangover onset). Animals were injected i.p. either with saline (control group) or with ethanol (3.8 g/kg BW) (hangover group). Ethanol hangover group showed a bad motor performance compared with control animals (p < .05). Oxygen uptake in brain cortex mitochondria from hangover animals showed a 34% decrease in the respiratory control rate as compared with the control group. Mitochondrial complex activities were decreased being the complex I-III the less affected by the hangover condition; complex II-III was markedly decreased by ethanol hangover showing 50% less activity than controls. Complex IV was 42% decreased as compared with control animals. Hydrogen peroxide production was 51% increased in brain cortex mitochondria from the hangover group, as compared with the control animals. Quantification of the mitochondrial transmembrane potential indicated that ethanol injected animals presented 17% less ability to maintain the polarized condition as compared with controls. These results indicate that a clear decrease in proton motive force occurs in brain cortex mitochondria during hangover conditions. We can conclude that a decreased motor performance observed in the hangover group of animals could be associated with brain cortex mitochondrial dysfunction and the resulting impairment of its energetic metabolism.

  3. Parkinson's Disease and REM Sleep Behavior Disorder Result in Increased Non-Motor Symptoms

    PubMed Central

    Neikrug, Ariel B.; Avanzino, Julie A.; Liu, Lianqi; Maglione, Jeanne E.; Natarajan, Loki; Corey-Bloom, Jody; Palmer, Barton W.; Loredo, Jose S.; Ancoli-Israel, Sonia

    2014-01-01

    Objective Rapid Eye Movement (REM) sleep behavior disorder is often co-morbid with Parkinson's disease (PD). The current study aimed to provide a detailed understanding of the impact of having REM sleep behavior disorder on multiple NMS in patients with PD. Methods 86 participants were evaluated for REM-sleep behavior disorder and assessed for multiple non-motor symptoms of PD. Principal component analysis was utilized to model multiple measures of non-motor symptoms in PD and a multivariate analysis of variance was used to assess the relationship between REM-sleep behavior disorder and the multiple non-motor symptoms measures. Seven non-motor symptoms measures were assessed: cognition, quality of life, fatigue, sleepiness, overall sleep, mood, and overall non-motor symptoms of PD. Results 36 PD patients were classified as having REM-sleep behavior disorder (objective polysomnography and subjective findings), 26 as not having REM-sleep behavior disorder (neither objective nor subjective findings), and 24 as probable REM-sleep behavior disorder (either subjective or objective findings). REM-sleep behavior disorder was a significant predictor of increased non-motor symptoms in PD while controlling for dopaminergic therapy and age (p=0.01). The REM-sleep behavior disorder group reported more non-motor symptoms of depression (p=0.012), fatigue (p=0.036), overall sleep (p=0.018), and overall non-motor symptoms (p=0.002). Conclusion In PD, REM-sleep behavior disorder is associated with more non-motor symptoms, particularly increased depressive symptoms, sleep disturbances, and fatigue. More research is needed to assess whether PD patients with REM-sleep behavior disorder represent a subtype of PD with different disease progression and phenomenological presentation. PMID:24938585

  4. Early exposure to dynamic environments alters patterns of motor exploration throughout the lifespan.

    PubMed

    Hong, S Lee; Estrada-Sánchez, Ana María; Barton, Scott J; Rebec, George V

    2016-04-01

    We assessed early rearing conditions on aging-related changes in mouse behavior. Two isolated-housing groups, running wheel (IHRW) and empty cage (IHEC), were compared against two enriched environments, static (EEST) and dynamic (EEDY), both of which included toys and other mice. For EEDY, the location of toys and sources of food and water changed daily, but remained constant for EEST. All mice, randomly assigned to one of the four groups at ∼4 weeks of age, remained in their respective environments for 25 weeks followed by single housing in empty cages. Beginning at ∼40 weeks of age, all mice were tested at monthly intervals in a plus-shaped maze in which we measured the number of arm entries and the probability of entering a perpendicular arm. Despite making significantly more arm entries than any other group, IHEC mice also were less likely to turn into the left or right arm, a sign of motor inflexibility. Both EEDY and EEST mice showed enhanced turning relative to IHRW and IHEC groups, but only EEDY mice maintained their turning performance for up to ∼100 weeks of age. EEDY and EEST mice also were unique in showing an increase in expression of the major glutamate transporter (GLT1) in striatum, but a decrease in motor cortex, suggesting a need for further assessment of environmental manipulations on long-term changes in forebrain glutamate transmission. Our behavioral results indicate that early exposure to continually changing environments, rather than socialization or exercise alone, results in life-long changes in patterns of motor exploration.

  5. Links between motor control and classroom behaviors: Moderation by low birth weight.

    PubMed

    Razza, Rachel A; Martin, Anne; Brooks-Gunn, Jeanne

    2016-08-01

    It is unclear from past research on effortful control whether one of its components, motor control, independently contributes to adaptive classroom behaviors. The goal of this study was to identify associations between early motor control, measured by the walk-a-line task at age 3, and teacher-reported learning-related behaviors (approaches to learning and attention problems) and behavior problems in kindergarten classrooms. Models tested whether children who were vulnerable to poorer learning behaviors and more behavior problems due to having been born low birth weight benefited more, less, or the same as other children from better motor control. Data were drawn from the national Fragile Families and Child-Wellbeing Study (n = 751). Regression models indicated that motor control was significantly associated with better approaches to learning and fewer behavior problems. Children who were low birth weight benefitted more than normal birth weight children from better motor control with respect to their approaches to learning, but equally with respect to behavior problems. Additionally, for low but not normal birth weight children, better motor control predicted fewer attention problems. These findings suggest that motor control follows a compensatory model of development for low birth weight children and classroom behaviors.

  6. Altered activation of the antagonist muscle during practice compromises motor learning in older adults.

    PubMed

    Chen, Yen-Ting; Kwon, MinHyuk; Fox, Emily J; Christou, Evangelos A

    2014-08-15

    Aging impairs the activation of muscle; however, it remains unclear whether it contributes to deficits in motor learning in older adults. The purpose of this study was to determine whether altered activation of antagonistic muscles in older adults during practice inhibits their ability to transfer a motor task ipsilaterally. Twenty young (25.1 ± 3.9 yr; 10 men, 10 women) and twenty older adults (71.5 ± 4.8 yr; 10 men, 10 women) participated. Half of the subjects practiced 100 trials of a rapid goal-directed task with ankle dorsiflexion and were tested 1 day later with elbow flexion (transfer). The rest did not perform any ankle practice and only performed the task with elbow flexion. The goal-directed task consisted of rapid movement (180 ms) to match a spatiotemporal target. For each limb, we recorded the EMG burst activity of the primary agonist and antagonist muscles. The rate of improvement during task acquisition (practice) was similar for young and older adults (P > 0.3). In contrast, only young adults were able to transfer the task to the upper limb. Specifically, young adults who practiced ankle dorsiflexion exhibited ∼30% (P < 0.05) lower movement error and ∼60% (P < 0.05) lower antagonist EMG burst activity compared with older adults who received equal practice and young adults who did not receive any ankle dorsiflexion practice. These results provide novel evidence that the deficient motor learning in older adults may be related to a differential activation of the antagonist muscle, which compromises their ability to acquire the task during practice.

  7. Cocaine Self-Administration Leads to Alterations in Temporal Responses to Cocaine Challenge in Limbic and Motor Circuitry

    PubMed Central

    Chen, Y. Iris; Famous, Katie; Xu, Haibo; Choi, Ji-Kyung; Mandeville, Joseph B.; Schmidt, Heath D.; Pierce, R. Christopher; Jenkins, Bruce G.

    2011-01-01

    Chronic use of cocaine is associated with lasting alterations in brain metabolism, circuitry and receptor properties. We used neuroimaging with pharmacologic MRI (phMRI) to assess alterations in response to cocaine (0.5mg/kg) in animals trained to self-administer (SA) cocaine on a fixed-ratio 5 schedule of reinforcement, as well as saline-yoked controls, after 28 days of cocaine abstinence. We fit the cerebral blood volume (CBV) curves for full-width half-maximum (FWHM) as well as peak CBV response. There were significant increases in the FWHM of the response curves in the cocaine-SA animals compared to saline-yoked controls in medial-prefrontal cortex (mPFC) and caudate/putamenm (CPu) and increases in peak CBV in M1 motor cortex, CPu and pedunculopontine tegmental nucleus. Functional connectivity analysis showed increased correlations in the SA rats upon acute cocaine challenge, especially in the S1, mPFC, and thalamus. Since D3 receptors are postulated to increase following chronic cocaine administration we also examined the response to 0.2 mg/kg of the D3 preferring agonist 7-OHDPAT. Cocaine SA animals showed a decreased overall CBV response to this drug, except in the globus pallidus. The hypothalamus showed a negative CBV change in response to cocaine challenge similar to that noted with the D3 agonist and showed a smaller response in the cocaine-SA animals than the controls. Given the good coupling of cerebral hemodynamics with dopamine dynamics previously observed with phMRI, these data suggest that increased persistence of dopamine in prefrontal cortex may be responsible for some of the behavioral alterations observed subsequent to chronic cocaine use. PMID:21896062

  8. Early life experience alters behavior during social defeat: focus on serotonergic systems.

    PubMed

    Gardner, K L; Thrivikraman, K V; Lightman, S L; Plotsky, P M; Lowry, C A

    2005-01-01

    Early life experience can have prolonged effects on neuroendocrine, autonomic, and behavioral responses to stress. The objective of this study was to investigate the effects of early life experience on behavior during social defeat, as well as on associated functional cellular responses in serotonergic and non-serotonergic neurons within the dorsal raphe nucleus, a structure which plays an important role in modulation of stress-related physiology and behavior. Male Long Evans rat pups were exposed to either normal animal facility rearing or 15 min or 180 min of maternal separation from postnatal days 2-14. As adults, these rats were exposed to a social defeat protocol. Differences in behavior were seen among the early life treatment groups during social defeat; rats exposed to 180 min of maternal separation from postnatal days 2-14 displayed more passive-submissive behaviors and less proactive coping behaviors. Analysis of the distribution of tryptophan hydroxylase and c-Fos-like immunoreactivity in control rats exposed to a novel cage and rats exposed to social defeat revealed that, independent of the early life experience, rats exposed to social defeat showed an increase in the number of c-Fos-like immunoreactive nuclei in serotonergic neurons in the middle and caudal parts of the dorsal dorsal raphe nucleus and caudal part of the ventral dorsal raphe nucleus, regions known to contain serotonergic neurons projecting to central autonomic and emotional motor control systems. This is the first study to show that the dorsomedial part of the mid-rostrocaudal dorsal raphe nucleus is engaged by a naturalistic stressor and supports the hypothesis that early life experience alters behavioral coping strategies during social conflict; furthermore, this study is consistent with the hypothesis that topographically organized subpopulations of serotonergic neurons principally within the mid-rostrocaudal and caudal part of the dorsal dorsal raphe nucleus modulate stress

  9. Altered directional connectivity between emotion network and motor network in Parkinson's disease with depression.

    PubMed

    Liang, Peipeng; Deshpande, Gopikrishna; Zhao, Sinan; Liu, Jiangtao; Hu, Xiaoping; Li, Kuncheng

    2016-07-01

    Depression is common in patients with Parkinson's disease (PD), which can make all the other symptoms of PD much worse. It is thus urgent to differentiate depressed PD (DPD) patients from non-depressed PD (NDPD).The purpose of the present study was to characterize alterations in directional brain connectivity unique to Parkinson's disease with depression, using resting state functional magnetic resonance imaging (rs-fMRI).Sixteen DPD patients, 20 NDPD patients, 17 patients with major depressive disorder (MDD) and 21 healthy control subjects (normal controls [NC]) underwent structural MRI and rs-fMRI scanning. Voxel-based morphometry and directional brain connectivity during resting-state were analyzed. Analysis of variance (ANOVA) and 2-sample t tests were used to compare each pair of groups, using sex, age, education level, structural atrophy, and/or HAMD, unified PD rating scale (UPDRS) as covariates.In contrast to NC, DPD showed significant gray matter (GM) volume abnormalities in some mid-line limbic regions including dorsomedial prefrontal cortex and precuneus, and sub-cortical regions including caudate and cerebellum. Relative to NC and MDD, both DPD and NDPD showed significantly increased directional connectivity from bilateral anterior insula and posterior orbitofrontal cortices to left inferior temporal cortex. As compared with NC, MDD and NDPD, alterations of directional connectivity in DPD were specifically observed in the pathway from bilateral anterior insula and posterior orbitofrontal cortices to right basal ganglia.Resting state directional connectivity alterations were observed between emotion network and motor network in DPD patients after controlling for age, sex, structural atrophy. Given that these alterations are unique to DPD, it may provide a potential differential biomarker for distinguishing DPD from NC, NDPD, and MDD.

  10. Altered directional connectivity between emotion network and motor network in Parkinson's disease with depression

    PubMed Central

    Liang, Peipeng; Deshpande, Gopikrishna; Zhao, Sinan; Liu, Jiangtao; Hu, Xiaoping; Li, Kuncheng

    2016-01-01

    Abstract Depression is common in patients with Parkinson's disease (PD), which can make all the other symptoms of PD much worse. It is thus urgent to differentiate depressed PD (DPD) patients from non-depressed PD (NDPD). The purpose of the present study was to characterize alterations in directional brain connectivity unique to Parkinson's disease with depression, using resting state functional magnetic resonance imaging (rs-fMRI). Sixteen DPD patients, 20 NDPD patients, 17 patients with major depressive disorder (MDD) and 21 healthy control subjects (normal controls [NC]) underwent structural MRI and rs-fMRI scanning. Voxel-based morphometry and directional brain connectivity during resting-state were analyzed. Analysis of variance (ANOVA) and 2-sample t tests were used to compare each pair of groups, using sex, age, education level, structural atrophy, and/or HAMD, unified PD rating scale (UPDRS) as covariates. In contrast to NC, DPD showed significant gray matter (GM) volume abnormalities in some mid-line limbic regions including dorsomedial prefrontal cortex and precuneus, and sub-cortical regions including caudate and cerebellum. Relative to NC and MDD, both DPD and NDPD showed significantly increased directional connectivity from bilateral anterior insula and posterior orbitofrontal cortices to left inferior temporal cortex. As compared with NC, MDD and NDPD, alterations of directional connectivity in DPD were specifically observed in the pathway from bilateral anterior insula and posterior orbitofrontal cortices to right basal ganglia. Resting state directional connectivity alterations were observed between emotion network and motor network in DPD patients after controlling for age, sex, structural atrophy. Given that these alterations are unique to DPD, it may provide a potential differential biomarker for distinguishing DPD from NC, NDPD, and MDD. PMID:27472694

  11. Differential behavioral and molecular alterations upon protracted abstinence from cocaine versus morphine, nicotine, THC and alcohol.

    PubMed

    Becker, Jérôme A J; Kieffer, Brigitte L; Le Merrer, Julie

    2016-04-28

    Unified theories of addiction are challenged by differing drug-seeking behaviors and neurobiological adaptations across drug classes, particularly for narcotics and psychostimulants. We previously showed that protracted abstinence to opiates leads to despair behavior and social withdrawal in mice, and we identified a transcriptional signature in the extended amygdala that was also present in animals abstinent from nicotine, Δ9-tetrahydrocannabinol (THC) and alcohol. Here we examined whether protracted abstinence to these four drugs would also share common behavioral features, and eventually differ from abstinence to the prototypic psychostimulant cocaine. We found similar reduced social recognition, increased motor stereotypies and increased anxiety with relevant c-fos response alterations in morphine, nicotine, THC and alcohol abstinent mice. Protracted abstinence to cocaine, however, led to strikingly distinct, mostly opposing adaptations at all levels, including behavioral responses, neuronal activation and gene expression. Together, these data further document the existence of common hallmarks for protracted abstinence to opiates, nicotine, THC and alcohol that develop within motivation/emotion brain circuits. In our model, however, these do not apply to cocaine, supporting the notion of unique mechanisms in psychostimulant abuse.

  12. Benefit on motor and non-motor behavior in a specialized unit for Parkinson's disease.

    PubMed

    Müller, Thomas; Öhm, Gabi; Eilert, Kathrin; Möhr, Katharina; Rotter, Stephanie; Haas, Thomas; Küchler, Matthias; Lütge, Sven; Marg, Marion; Rothe, Hartmut

    2017-02-28

    Treatment of patients with Parkinson's disease in specialized units is quite common in Germany. Data on the benefit of this hospitalization of patients with Parkinson's disease on motor and non-motor symptoms in conjunction with standardized tests are rare. Objective was to determine the efficacy of this therapeutic setting. We scored disease severity and performed clinical tests, respectively, instrumental procedures under standardized conditions in consecutively referred in-patients initially and at the end of their hospital stay. There was a decrease of motor and non-motor symptoms. The extent of improvement of non-motor and motor symptoms correlated to each other. Performance of complex movement sequences became better, whereas execution of simple movement series did not ameliorate. The interval for the timed up and go test went down. We demonstrate the effectiveness of an in-patient stay in a specialized unit for Parkinson's disease. Objective standardized testing supplements subjective clinical scoring with established rating scales.

  13. Galantamine reverses scopolamine-induced behavioral alterations in Dugesia tigrina.

    PubMed

    Ramakrishnan, Latha; Amatya, Christina; DeSaer, Cassie J; Dalhoff, Zachary; Eggerichs, Michael R

    2014-09-01

    In planaria (Dugesia tigrina), scopolamine, a nonselective muscarinic receptor antagonist, induced distinct behaviors of attenuated motility and C-like hyperactivity. Planarian locomotor velocity (pLMV) displayed a dose-dependent negative correlation with scopolamine concentrations from 0.001 to 1.0 mM, and a further increase in scopolamine concentration to 2.25 mM did not further decrease pLMV. Planarian hyperactivity counts was dose-dependently increased following pretreatment with scopolamine concentrations from 0.001 to 0.5 mM and then decreased for scopolamine concentrations ≥ 1 mM. Planarian learning and memory investigated using classical Pavlovian conditioning experiments demonstrated that scopolamine (1 mM) negatively influenced associative learning indicated by a significant decrease in % positive behaviors from 86 % (control) to 14 % (1 mM scopolamine) and similarly altered memory retention, which is indicated by a decrease in % positive behaviors from 69 % (control) to 27 % (1 mM scopolamine). Galantamine demonstrated a complex behavior in planarian motility experiments since co-application of low concentrations of galantamine (0.001 and 0.01 mM) protected planaria against 1 mM scopolamine-induced motility impairments; however, pLMV was significantly decreased when planaria were tested in the presence of 0.1 mM galantamine alone. Effects of co-treatment of scopolamine and galantamine on memory retention in planaria via classical Pavlovian conditioning experiments showed that galantamine (0.01 mM) partially reversed scopolamine (1 mM)-induced memory deficits in planaria as the % positive behaviors increased from 27 to 63 %. The results demonstrate, for the first time in planaria, scopolamine's effects in causing learning and memory impairments and galantamine's ability in reversing scopolamine-induced memory impairments.

  14. Cooperative behavior of molecular motors: Cargo transport and traffic phenomena

    NASA Astrophysics Data System (ADS)

    Lipowsky, Reinhard; Beeg, Janina; Dimova, Rumiana; Klumpp, Stefan; Müller, Melanie J. I.

    2010-01-01

    All eukaryotic cells including those of our own body contain complex transport systems based on molecular motors which walk along cytoskeletal filaments. These motors are rather small and make discrete mechanical steps with a step size of the order of 10 nm but are able to pull cargo particles over much larger distances, from micrometers up to meters. In vivo, the intracellular cargos include large membrane-bounded organelles, smaller vesicles, a subset of mRNAs, cytoskeletal filaments, and various protein building blocks, which are transported between different cell compartments. This cargo transport is usually performed by teams of motors. If all motors belong to the same molecular species, the cooperative action of the motors leads to uni-directional transport with a strongly increased run length and with a characteristic force dependence of the velocity distributions. If two antagonistic teams of motors pull on the same cargo particle, they perform a stochastic tug-of-war, which is characterized by a subtle force balance between the two motor teams and leads to several distinct patterns of bi-directional transport. So far, all experimental observations on bi-directional transport are consistent with such a tug-of-war. If many motors and/or cargo particles are transported along the filaments, one encounters various traffic phenomena. Depending on their mutual interactions and the compartment geometry, the motors form various spatio-temporal patterns such as traffic jams, and undergo nonequilibrium phase transitions between different patterns of transport.

  15. GABAergic influences on ORX receptor-dependent abnormal motor behaviors and neurodegenerative events in fish.

    PubMed

    Facciolo, Rosa Maria; Crudo, Michele; Giusi, Giuseppina; Canonaco, Marcello

    2010-02-15

    At date the major neuroreceptors i.e. gamma-aminobutyric acid(A) (GABA(A)R) and orexin (ORXR) systems are beginning to be linked to homeostasis, neuroendocrine and emotional states. In this study, intraperitoneal treatment of the marine teleost Thalassoma pavo with the highly selective GABA(A)R agonist (muscimol, MUS; 0.1 microg/g body weight) and/or its antagonist bicuculline (BIC; 1 microg/g body weight) have corroborated a GABA(A)ergic role on motor behaviors. In particular, MUS induced moderate (p<0.05) and great (p<0.01) increases of swimming towards food sources and resting states after 24 (1 dose) and 96 (4 doses) h treatment sessions, respectively, when compared to controls. Conversely, BIC caused a very strong (p<0.001) reduction of the former behavior and in some cases convulsive swimming. From the correlation of BIC-dependent behavioral changes to neuronal morphological and ORXR transcriptional variations, it appeared that the disinhibitory action of GABA(A)R was very likely responsible for very strong and strong ORXR mRNA reductions in cerebellum valvula and torus longitudinalis, respectively. Moreover these effects were linked to evident ultra-structural changes such as shrunken cell membranes and loss of cytoplasmic architecture. In contrast, MUS supplied a very low, if any, argyrophilic reaction in hypothalamic and mesencephalic regions plus a scarce level of ultra-structural damages. Interestingly, combined administrations of MUS+BIC were not related to consistent damages, aside mild neuronal alterations in motor-related areas such as optic tectum. Overall it is tempting to suggest, for the first time, a neuroprotective role of GABA(A)R inhibitory actions against the overexcitatory ORXR-dependent neurodegeneration and consequently abnormal swimming events in fish.

  16. GABAergic influences on ORX receptor-dependent abnormal motor behaviors and neurodegenerative events in fish

    SciTech Connect

    Facciolo, Rosa Maria; Crudo, Michele; Giusi, Giuseppina; Canonaco, Marcello

    2010-02-15

    At date the major neuroreceptors i.e. gamma-aminobutyric acid{sub A} (GABA{sub A}R) and orexin (ORXR) systems are beginning to be linked to homeostasis, neuroendocrine and emotional states. In this study, intraperitoneal treatment of the marine teleost Thalassoma pavo with the highly selective GABA{sub A}R agonist (muscimol, MUS; 0,1 mug/g body weight) and/or its antagonist bicuculline (BIC; 1 mug/g body weight) have corroborated a GABA{sub A}ergic role on motor behaviors. In particular, MUS induced moderate (p < 0.05) and great (p < 0.01) increases of swimming towards food sources and resting states after 24 (1 dose) and 96 (4 doses) h treatment sessions, respectively, when compared to controls. Conversely, BIC caused a very strong (p < 0.001) reduction of the former behavior and in some cases convulsive swimming. From the correlation of BIC-dependent behavioral changes to neuronal morphological and ORXR transcriptional variations, it appeared that the disinhibitory action of GABA{sub A}R was very likely responsible for very strong and strong ORXR mRNA reductions in cerebellum valvula and torus longitudinalis, respectively. Moreover these effects were linked to evident ultra-structural changes such as shrunken cell membranes and loss of cytoplasmic architecture. In contrast, MUS supplied a very low, if any, argyrophilic reaction in hypothalamic and mesencephalic regions plus a scarce level of ultra-structural damages. Interestingly, combined administrations of MUS + BIC were not related to consistent damages, aside mild neuronal alterations in motor-related areas such as optic tectum. Overall it is tempting to suggest, for the first time, a neuroprotective role of GABA{sub A}R inhibitory actions against the overexcitatory ORXR-dependent neurodegeneration and consequently abnormal swimming events in fish.

  17. Effect of Metasomatic Alteration on Frictional Behavior of Subduction Megathrusts

    NASA Astrophysics Data System (ADS)

    Hirauchi, K. I.; Yamamoto, Y.; Den Hartog, S. A. M.; Spiers, C. J.

    2014-12-01

    Along-strike variations in seismicity of subduction megathrusts can be attributed to the frictional properties of the fault-zone material, which is affected by the distribution of weak clays (smectite and illite) within sediments on the incoming plate. In addition, metasomatic alteration of the subducting sediments may result in significant changes in fault strength and slip stability of the megathrust. We examined an exhumed subduction thrust that separates serpentinite from tectonic mélange (argillite) of the Franciscan Complex, central California. The serpentinite represents a cataclastic shear zone, consisting of angular fragments in a fine-grained talc matrix. Talc schist also developed near the fault in beds up to 2 m thick. The argillite away from the fault displays a scaly fabric, composed of illite/muscovite and chlorite, while it is altered near the fault, characterized by the overgrowth of tremolite and minor chlorite along the previous foliation. We determined the frictional characteristics of these samples by performing rotary shear experiments at pore fluid pressures of 40-120 MPa, effective normal stresses (σneff) of 60-180 MPa, temperatures (T) of 20-400°C, and sliding velocities of 0.3-100 μm/s. The serpentinite was frictionally strong (friction coefficient, μ, 0.6) and exhibited velocity strengthening only at 150°C. The talc schist showed a low μ of 0.1-0.2, characterized by velocity-strengthening behavior at all experimental conditions tested. Argillite showed μ ranging from 0.4 to 0.6 with increasing T and σneff and a transition from velocity strengthening to velocity weakening behavior as T increased above 300°C. The tremolite schist had a weaker normal-stress dependence of μ than argillite, with μ of 0.4-0.5 and a velocity strengthening to velocity weakening transition occurring at 400°C. We propose that intense fluid-rock interactions took place during movement of the investigated fault. The serpentinite-argillite contact is

  18. Altered Dopamine and Serotonin Metabolism in Motorically Asymptomatic R6/2 Mice

    PubMed Central

    Mochel, Fanny; Durant, Brandon; Durr, Alexandra; Schiffmann, Raphael

    2011-01-01

    The pattern of cerebral dopamine (DA) abnormalities in Huntington disease (HD) is complex, as reflected by the variable clinical benefit of both DA antagonists and agonists in treating HD symptoms. In addition, little is known about serotonin metabolism despite the early occurrence of anxiety and depression in HD. Post-mortem enzymatic changes are likely to interfere with the in vivo profile of biogenic amines. Hence, in order to reliably characterize the regional and chronological profile of brain neurotransmitters in a HD mouse model, we used a microwave fixation system that preserves in vivo concentrations of dopaminergic and serotoninergic amines. DA was decreased in the striatum of R6/2 mice at 8 and 12 weeks of age while DA metabolites, 3-methoxytyramine and homovanillic acid, were already significantly reduced in 4-week-old motorically asymptomatic R6/2 mice. In the striatum, hippocampus and frontal cortex of 4, 8 and 12-week-old R6/2 mice, serotonin and its metabolite 5-hydroxyindoleacetic acid were significantly decreased in association with a decreased turnover of serotonin. In addition, automated high-resolution behavioural analyses displayed stress-like behaviours such as jumping and grooming and altered spatial learning in R6/2 mice at age 4 and 6 weeks respectively. Therefore, we describe the earliest alterations of DA and serotonin metabolism in a HD murine model. Our findings likely underpin the neuropsychological symptoms at time of disease onset in HD. PMID:21483838

  19. MicroRNA-128 governs neuronal excitability and motor behavior in mice.

    PubMed

    Tan, Chan Lek; Plotkin, Joshua L; Venø, Morten T; von Schimmelmann, Melanie; Feinberg, Philip; Mann, Silas; Handler, Annie; Kjems, Jørgen; Surmeier, D James; O'Carroll, Dónal; Greengard, Paul; Schaefer, Anne

    2013-12-06

    The control of motor behavior in animals and humans requires constant adaptation of neuronal networks to signals of various types and strengths. We found that microRNA-128 (miR-128), which is expressed in adult neurons, regulates motor behavior by modulating neuronal signaling networks and excitability. miR-128 governs motor activity by suppressing the expression of various ion channels and signaling components of the extracellular signal-regulated kinase ERK2 network that regulate neuronal excitability. In mice, a reduction of miR-128 expression in postnatal neurons causes increased motor activity and fatal epilepsy. Overexpression of miR-128 attenuates neuronal responsiveness, suppresses motor activity, and alleviates motor abnormalities associated with Parkinson's-like disease and seizures in mice. These data suggest a therapeutic potential for miR-128 in the treatment of epilepsy and movement disorders.

  20. Prenatal tactile stimulation attenuates drug-induced behavioral sensitization, modifies behavior, and alters brain architecture.

    PubMed

    Muhammad, Arif; Kolb, Bryan

    2011-07-11

    Based on the findings of postnatal tactile stimulation (TS), a favorable experience in rats, the present study examined the influence of prenatal TS on juvenile behavior, adult amphetamine (AMPH) sensitization, and structural alteration in the prefrontal cortex (PFC) and the striatum. Female rats received TS through a baby hair brush throughout pregnancy, and the pups born were tested for open field locomotion, elevated plus maze (EPM), novel object recognition (NOR), and play fighting behaviors. Development and persistence of drug-induced behavioral sensitization in adults were tested by repeated AMPH administration and a challenge, respectively. Structural plasticity in the brain was assessed from the prefrontal cortical thickness and striatum size from serial coronal sections. The results indicate that TS females showed enhanced exploration in the open field. TS decreased the frequency of playful attacks whereas the response to face or evade an attack was not affected. Anxiety-like behavior and cognitive performance were not influenced by TS. AMPH administration resulted in gradual increase in locomotor activity (i.e., behavioral sensitization) that persisted at least for 2 weeks. However, both male and female TS rats exhibited attenuated AMPH sensitization compared to sex-matched controls. Furthermore, the drug-associated alteration in the prefrontal cortical thickness and striatum size observed in controls were prevented by TS experience. In summary, TS during prenatal development modified juvenile behavior, attenuated drug-induced behavioral sensitization in adulthood, and reorganized brain regions implicated in drug addiction.

  1. Age-related Alterations in the Dynamic Behavior of Microglia

    PubMed Central

    Damani, Mausam R.; Zhao, Lian; Fontainhas, Aurora M.; Amaral, Juan; Fariss, Robert N.; Wong, Wai T.

    2010-01-01

    Summary Microglia, the primary resident immune cells of the CNS, exhibit dynamic behavior involving rapid process motility and cellular migration that is thought to underlie key functions of immune surveillance and tissue repair. Although age-related changes in microglial activation have been implicated in the pathogenesis of neurodegenerative diseases of aging, how dynamic behavior in microglia is influenced by aging is not fully understood. In this study, we employed live imaging of retinal microglia in situ to compare microglial morphology and behavioral dynamics in young and aged animals. We found that aged microglia in the resting state have significantly smaller and less branched dendritic arbors, and also slower process motilities, which likely compromise their ability to continuously survey and interact with their environment. We also found that dynamic microglial responses to injury were age-dependent. While young microglia responded to extracellular ATP, an injury-associated signal, by increasing their motility and becoming more ramified, aged microglia exhibited a contrary response, becoming less dynamic and ramified. In response to laser-induced focal tissue injury, aged microglia demonstrated slower acute responses with lower rates of process motility and cellular migration compared to young microglia. Interestingly, the longer term response of disaggregation from the injury site was retarded in aged microglia, indicating that senescent microglial responses, while slower to initiate, are more sustained. Together, these altered features of microglial behavior at rest and following injury reveal an age-dependent dysregulation of immune response in the CNS that may illuminate microglial contributions to age-related neuroinflammatory degeneration. PMID:21108733

  2. Alterations in the brain adenosine metabolism cause behavioral and neurological impairment in ADA-deficient mice and patients

    PubMed Central

    Sauer, Aisha V.; Hernandez, Raisa Jofra; Fumagalli, Francesca; Bianchi, Veronica; Poliani, Pietro L.; Dallatomasina, Chiara; Riboni, Elisa; Politi, Letterio S.; Tabucchi, Antonella; Carlucci, Filippo; Casiraghi, Miriam; Carriglio, Nicola; Cominelli, Manuela; Forcellini, Carlo Alberto; Barzaghi, Federica; Ferrua, Francesca; Minicucci, Fabio; Medaglini, Stefania; Leocani, Letizia; la Marca, Giancarlo; Notarangelo, Lucia D.; Azzari, Chiara; Comi, Giancarlo; Baldoli, Cristina; Canale, Sabrina; Sessa, Maria; D’Adamo, Patrizia; Aiuti, Alessandro

    2017-01-01

    Adenosine Deaminase (ADA) deficiency is an autosomal recessive variant of severe combined immunodeficiency (SCID) caused by systemic accumulation of ADA substrates. Neurological and behavioral abnormalities observed in ADA-SCID patients surviving after stem cell transplantation or gene therapy represent an unresolved enigma in the field. We found significant neurological and cognitive alterations in untreated ADA-SCID patients as well as in two groups of patients after short- and long-term enzyme replacement therapy with PEG-ADA. These included motor dysfunction, EEG alterations, sensorineural hypoacusia, white matter and ventricular alterations in MRI as well as a low mental development index or IQ. Ada-deficient mice were significantly less active and showed anxiety-like behavior. Molecular and metabolic analyses showed that this phenotype coincides with metabolic alterations and aberrant adenosine receptor signaling. PEG-ADA treatment corrected metabolic adenosine-based alterations, but not cellular and signaling defects, indicating an intrinsic nature of the neurological and behavioral phenotype in ADA deficiency. PMID:28074903

  3. Alterations in the brain adenosine metabolism cause behavioral and neurological impairment in ADA-deficient mice and patients.

    PubMed

    Sauer, Aisha V; Hernandez, Raisa Jofra; Fumagalli, Francesca; Bianchi, Veronica; Poliani, Pietro L; Dallatomasina, Chiara; Riboni, Elisa; Politi, Letterio S; Tabucchi, Antonella; Carlucci, Filippo; Casiraghi, Miriam; Carriglio, Nicola; Cominelli, Manuela; Forcellini, Carlo Alberto; Barzaghi, Federica; Ferrua, Francesca; Minicucci, Fabio; Medaglini, Stefania; Leocani, Letizia; la Marca, Giancarlo; Notarangelo, Lucia D; Azzari, Chiara; Comi, Giancarlo; Baldoli, Cristina; Canale, Sabrina; Sessa, Maria; D'Adamo, Patrizia; Aiuti, Alessandro

    2017-01-11

    Adenosine Deaminase (ADA) deficiency is an autosomal recessive variant of severe combined immunodeficiency (SCID) caused by systemic accumulation of ADA substrates. Neurological and behavioral abnormalities observed in ADA-SCID patients surviving after stem cell transplantation or gene therapy represent an unresolved enigma in the field. We found significant neurological and cognitive alterations in untreated ADA-SCID patients as well as in two groups of patients after short- and long-term enzyme replacement therapy with PEG-ADA. These included motor dysfunction, EEG alterations, sensorineural hypoacusia, white matter and ventricular alterations in MRI as well as a low mental development index or IQ. Ada-deficient mice were significantly less active and showed anxiety-like behavior. Molecular and metabolic analyses showed that this phenotype coincides with metabolic alterations and aberrant adenosine receptor signaling. PEG-ADA treatment corrected metabolic adenosine-based alterations, but not cellular and signaling defects, indicating an intrinsic nature of the neurological and behavioral phenotype in ADA deficiency.

  4. Can the Child Behavior Checklist Be Used to Screen for Motor Impairment?

    ERIC Educational Resources Information Center

    Piek, Jan P.; Barrett, Nicholas C.; Dyck, Murray J.; Reiersen, Angela M.

    2010-01-01

    Aim: It has been suggested that one approach to identifying motor impairment in children is to use the Child Behavior Checklist (CBCL) as a screening tool. The current study examined the validity of the CBCL in identifying motor impairment. Method: A total of 398 children, 206 females and 192 males, aged from 3 years 9 months to 14 years 10 months…

  5. A Model for the Transfer of Perceptual-Motor Skill Learning in Human Behaviors

    ERIC Educational Resources Information Center

    Rosalie, Simon M.; Muller, Sean

    2012-01-01

    This paper presents a preliminary model that outlines the mechanisms underlying the transfer of perceptual-motor skill learning in sport and everyday tasks. Perceptual-motor behavior is motivated by performance demands and evolves over time to increase the probability of success through adaptation. Performance demands at the time of an event…

  6. Decoding motor responses from the EEG during altered states of consciousness induced by propofol

    NASA Astrophysics Data System (ADS)

    Blokland, Yvonne; Farquhar, Jason; Lerou, Jos; Mourisse, Jo; Scheffer, Gert Jan; van Geffen, Geert-Jan; Spyrou, Loukianos; Bruhn, Jörgen

    2016-04-01

    Objective. Patients undergoing general anesthesia may awaken and become aware of the surgical procedure. Due to neuromuscular blocking agents, patients could be conscious yet unable to move. Using brain-computer interface (BCI) technology, it may be possible to detect movement attempts from the EEG. However, it is unknown how an anesthetic influences the brain response to motor tasks. Approach. We tested the offline classification performance of a movement-based BCI in 12 healthy subjects at two effect-site concentrations of propofol. For each subject a second classifier was trained on the subject’s data obtained before sedation, then tested on the data obtained during sedation (‘transfer classification’). Main results. At concentration 0.5 μg ml-1, despite an overall propofol EEG effect, the mean single trial classification accuracy was 85% (95% CI 81%-89%), and 83% (79%-88%) for the transfer classification. At 1.0 μg ml-1, the accuracies were 81% (76%-86%), and 72% (66%-79%), respectively. At the highest propofol concentration for four subjects, unlike the remaining subjects, the movement-related brain response had been largely diminished, and the transfer classification accuracy was not significantly above chance. These subjects showed a slower and more erratic task response, indicating an altered state of consciousness distinct from that of the other subjects. Significance. The results show the potential of using a BCI to detect intra-operative awareness and justify further development of this paradigm. At the same time, the relationship between motor responses and consciousness and its clinical relevance for intraoperative awareness requires further investigation.

  7. Adolescence as a vulnerable period to alter rodent behavior.

    PubMed

    Schneider, Miriam

    2013-10-01

    Adolescence and puberty are highly important periods for postnatal brain maturation. During adolescence, drastic changes of neuronal architecture and function occur that concomitantly lead to distinct behavioral alterations. Unsurprisingly in view of the multitude of ongoing neurodevelopmental processes in the adolescent brain, most adult neuropsychiatric disorders have their roots exactly during this time span. Adolescence and puberty are therefore crucial developmental periods in terms of understanding the causes and mechanisms of adult mental illness. Valid animal models for adolescent behavior and neurodevelopment might offer better insights into the underlying mechanisms and help to identify specific time windows with heightened susceptibility during development. In order to increase the translational value of such models, we urgently need to define the detailed timing of adolescence and puberty in laboratory rodents. The aim of the present review is to provide a more precise delineation of the time course of these developmental periods during postnatal life in rats and mice and to discuss the impact of adolescence and related neurodevelopmental processes on the heightened susceptibility for mental disorders.

  8. Brief Rewarming Blunts Hypothermia-Induced Alterations in Sensation, Motor Drive and Cognition

    PubMed Central

    Brazaitis, Marius; Paulauskas, Henrikas; Skurvydas, Albertas; Budde, Henning; Daniuseviciute, Laura; Eimantas, Nerijus

    2016-01-01

    hypothermia-induced alterations in neural drive transmission (4.3 ± 0.5 vs. 3.4 ± 0.8 mV H-reflex and 4.9 ± 0.2 vs. 4.4 ± 0.4 mV V-wave, P < 0.05), which increased central fatigue during a 2-min maximum load (P < 0.05). Furthermore, only in brief warm water rewarming cerebral alterations were restored to the control level and it was indicated by shortened reaction times (P < 0.05). Conclusions: Brief rewarming in warm water rather than the same duration rewarming in thermoneutral environment blunted the hypothermia-induced alterations for sensation, motor drive, and cognition, despite the fact that rectal and deep muscle temperature remained lowered. PMID:27990123

  9. Aniracetam Does Not Alter Cognitive and Affective Behavior in Adult C57BL/6J Mice

    PubMed Central

    Elston, Thomas W.; Pandian, Ashvini; Smith, Gregory D.; Holley, Andrew J.; Gao, Nanjing; Lugo, Joaquin N.

    2014-01-01

    There is a growing community of individuals who self-administer the nootropic aniracetam for its purported cognitive enhancing effects. Aniracetam is believed to be therapeutically useful for enhancing cognition, alleviating anxiety, and treating various neurodegenerative conditions. Physiologically, aniracetam enhances both glutamatergic neurotransmission and long-term potentiation. Previous studies of aniracetam have demonstrated the cognition-restoring effects of acute administration in different models of disease. No previous studies have explored the effects of aniracetam in healthy subjects. We investigated whether daily 50 mg/kg oral administration improves cognitive performance in naïve C57BL/6J mice in a variety of aspects of cognitive behavior. We measured spatial learning in the Morris water maze test; associative learning in the fear conditioning test; motor learning in the accelerating rotarod test; and odor discrimination. We also measured locomotion in the open field test, anxiety through the elevated plus maze test and by measuring time in the center of the open field test. We measured repetitive behavior through the marble burying test. We detected no significant differences between the naive, placebo, and experimental groups across all measures. Despite several studies demonstrating efficacy in impaired subjects, our findings suggest that aniracetam does not alter behavior in normal healthy mice. This study is timely in light of the growing community of healthy humans self-administering nootropic drugs. PMID:25099639

  10. Modulation of sensory-motor integration as a general mechanism for context dependence of behavior.

    PubMed

    Hoke, Kim Lisa; Pitts, Natalie Lynn

    2012-05-01

    Social communication is context-dependent, with both the production of signals and the responses of receivers tailored to each animal's internal needs and external environmental conditions. We propose that this context dependence arises because of neural modulation of the sensory-motor transformation that underlies the social behavior. Neural systems that are restricted to individual behaviors may be modulated at early stages of the sensory or motor pathways for optimal energy expenditure. However, when neural systems contribute to multiple important behaviors, we argue that the sensory-motor relay is the likely site of modulation. Plasticity in the sensory-motor relay enables subtle context dependence of the social behavior while preserving other functions of the sensory and motor systems. We review evidence that the robust responses of anurans to conspecific signals are dependent on reproductive state, sex, prior experience, and current context. A well-characterized midbrain sensory-motor relay establishes signal selectivity and gates locomotive responses to sound. The social decision-making network may modulate this auditory-motor transformation to confer context dependence of anuran reproductive responses to sound. We argue that similar modulation may be a general mechanism by which vertebrates prioritize their behaviors.

  11. Distinct motor impairments of dopamine D1 and D2 receptor knockout mice revealed by three types of motor behavior.

    PubMed

    Nakamura, Toru; Sato, Asako; Kitsukawa, Takashi; Momiyama, Toshihiko; Yamamori, Tetsuo; Sasaoka, Toshikuni

    2014-01-01

    Both D1R and D2R knock out (KO) mice of the major dopamine receptors show significant motor impairments. However, there are some discrepant reports, which may be due to the differences in genetic background and experimental procedures. In addition, only few studies directly compared the motor performance of D1R and D2R KO mice. In this paper, we examined the behavioral difference among N10 congenic D1R and D2R KO, and wild type (WT) mice. First, we examined spontaneous motor activity in the home cage environment for consecutive 5 days. Second, we examined motor performance using the rota-rod task, a standard motor task in rodents. Third, we examined motor ability with the Step-Wheel task in which mice were trained to run in a motor-driven turning wheel adjusting their steps on foothold pegs to drink water. The results showed clear differences among the mice of three genotypes in three different types of behavior. In monitoring spontaneous motor activities, D1R and D2R KO mice showed higher and lower 24 h activities, respectively, than WT mice. In the rota-rod tasks, at a low speed, D1R KO mice showed poor performance but later improved, whereas D2R KO mice showed a good performance at early days without further improvement. When first subjected to a high speed task, the D2R KO mice showed poorer rota-rod performance at a low speed than the D1R KO mice. In the Step-Wheel task, across daily sessions, D2R KO mice increased the duration that mice run sufficiently close to the spout to drink water, and decreased time to touch the floor due to missing the peg steps and number of times the wheel was stopped, which performance was much better than that of D1R KO mice. These incongruent results between the two tasks for D1R and D2R KO mice may be due to the differences in the motivation for the rota-rod and Step-Wheel tasks, aversion- and reward-driven, respectively. The Step-Wheel system may become a useful tool for assessing the motor ability of WT and mutant mice.

  12. VEGF induces sensory and motor peripheral plasticity, alters bladder function, and promotes visceral sensitivity

    PubMed Central

    2012-01-01

    Background This work tests the hypothesis that bladder instillation with vascular endothelial growth factor (VEGF) modulates sensory and motor nerve plasticity, and, consequently, bladder function and visceral sensitivity. In addition to C57BL/6J, ChAT-cre mice were used for visualization of bladder cholinergic nerves. The direct effect of VEGF on the density of sensory nerves expressing the transient receptor potential vanilloid subfamily 1 (TRPV1) and cholinergic nerves (ChAT) was studied one week after one or two intravesical instillations of the growth factor. To study the effects of VEGF on bladder function, mice were intravesically instilled with VEGF and urodynamic evaluation was assessed. VEGF-induced alteration in bladder dorsal root ganglion (DRG) neurons was performed on retrogradly labeled urinary bladder afferents by patch-clamp recording of voltage gated Na+ currents. Determination of VEGF-induced changes in sensitivity to abdominal mechanostimulation was performed by application of von Frey filaments. Results In addition to an overwhelming increase in TRPV1 immunoreactivity, VEGF instillation resulted in an increase in ChAT-directed expression of a fluorescent protein in several layers of the urinary bladder. Intravesical VEGF caused a profound change in the function of the urinary bladder: acute VEGF (1 week post VEGF treatment) reduced micturition pressure and longer treatment (2 weeks post-VEGF instillation) caused a substantial reduction in inter-micturition interval. In addition, intravesical VEGF resulted in an up-regulation of voltage gated Na+ channels (VGSC) in bladder DRG neurons and enhanced abdominal sensitivity to mechanical stimulation. Conclusions For the first time, evidence is presented indicating that VEGF instillation into the mouse bladder promotes a significant increase in peripheral nerve density together with alterations in bladder function and visceral sensitivity. The VEGF pathway is being proposed as a key modulator of

  13. Rescue of the Functional Alterations of Motor Cortical Circuits in Arginase Deficiency by Neonatal Gene Therapy

    PubMed Central

    Cantero, Gloria; Liu, Xiao-Bo; Mervis, Ronald F.; Lazaro, Maria T.; Cederbaum, Stephen D.; Golshani, Peyman

    2016-01-01

    Arginase 1 deficiency is a urea cycle disorder associated with hyperargininemia, spastic diplegia, loss of ambulation, intellectual disability, and seizures. To gain insight on how loss of arginase expression affects the excitability and synaptic connectivity of the cortical neurons in the developing brain, we used anatomical, ultrastructural, and electrophysiological techniques to determine how single-copy and double-copy arginase deletion affects cortical circuits in mice. We find that the loss of arginase 1 expression results in decreased dendritic complexity, decreased excitatory and inhibitory synapse numbers, decreased intrinsic excitability, and altered synaptic transmission in layer 5 motor cortical neurons. Hepatic arginase 1 gene therapy using adeno-associated virus rescued nearly all these abnormalities when administered to neonatal homozygous knock-out animals. Therefore, gene therapeutic strategies can reverse physiological and anatomical markers of arginase 1 deficiency and therefore may be of therapeutic benefit for the neurological disabilities in this syndrome. SIGNIFICANCE STATEMENT These studies are one of the few investigations to try to understand the underlying neurological dysfunction that occurs in urea cycle disorders and the only to examine arginase deficiency. We have demonstrated by multiple modalities that, in murine layer 5 cortical neurons, a gradation of abnormalities exists based on the functional copy number of arginase: intrinsic excitability is altered, there is decreased density in asymmetrical and perisomatic synapses, and analysis of the dendritic complexity is lowest in the homozygous knock-out. With neonatal administration of adeno-associated virus expressing arginase, there is near-total recovery of the abnormalities in neurons and cortical circuits, supporting the concept that neonatal gene therapy may prevent the functional abnormalities that occur in arginase deficiency. PMID:27335400

  14. SCH 23390 may alter dopamine-mediated motor behaviour via striatal D-1 receptors.

    PubMed

    Boyce, S; Kelly, E; Davis, A; Fleminger, S; Jenner, P; Marsden, C D

    1985-05-15

    SCH 23390 potently displaced the specific binding of 3H-piflutixol to D-1 sites in striatal membranes but haloperidol was only weakly effective. SCH 23390 weakly displaced specific 3H-spiperone binding to D-2 sites, but haloperidol was potent. SCH 23390 was more effective than haloperidol in inhibiting dopamine stimulated striatal adenylate cyclase activity. These results confirm the D-1 selectivity of SCH 23390. However, SCH 23390 inhibited apomorphine-induced stereotypy and climbing behaviour in rats with equal potency to haloperidol. Haloperidol dose-dependently increased striatal HVA and DOPAC concentrations without altering dopamine content. Low doses of SCH 23390 elevated striatal DOPAC concentrations but higher doses were without effect; striatal dopamine and HVA overall was unaffected by administration of SCH 23390. Haloperidol did not affect basal 3H-acetylcholine release from striatal slices but reversed the apomorphine-induced inhibition of 3H-acetylcholine release. SCH 23390 did not affect basal 3H-acetylcholine release nor did it reverse the apomorphine-induced inhibition of 3H-acetylcholine release. The ability of SCH 23390 to inhibit motor behaviour in the rat may be due to its action on D-1 receptors since the drug does not cause typical changes in parameters of striatal D-2 receptor function.

  15. Cerebellar sensory processing alterations impact motor cortical plasticity in Parkinson's disease: clues from dyskinetic patients.

    PubMed

    Kishore, Asha; Popa, Traian; Balachandran, Ammu; Chandran, Shyambabu; Pradeep, Salini; Backer, Febina; Krishnan, Syam; Meunier, Sabine

    2014-08-01

    The plasticity of primary motor cortex (M1) in patients with Parkinson's disease (PD) and levodopa-induced dyskinesias (LIDs) is severely impaired. We recently reported in young healthy subjects that inhibitory cerebellar stimulation enhanced the sensorimotor plasticity of M1 that was induced by paired associative stimulation (PAS). This study demonstrates that the deficient sensorimotor M1 plasticity in 16 patients with LIDs could be reinstated by a single session of real inhibitory cerebellar stimulation but not sham stimulation. This was evident only when a sensory component was involved in the induction of plasticity, indicating that cerebellar sensory processing function is involved in the resurgence of M1 plasticity. The benefit of inhibitory cerebellar stimulation on LIDs is known. To explore whether this benefit is linked to the restoration of sensorimotor plasticity of M1, we conducted an additional study looking at changes in LIDs and PAS-induced plasticity after 10 sessions of either bilateral, real inhibitory cerebellar stimulation or sham stimulation. Only real and not sham stimulation had an antidyskinetic effect and it was paralleled by a resurgence in the sensorimotor plasticity of M1. These results suggest that alterations in cerebellar sensory processing function, occurring secondary to abnormal basal ganglia signals reaching it, may be an important element contributing to the maladaptive sensorimotor plasticity of M1 and the emergence of abnormal involuntary movements.

  16. 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

  17. Altered motor activity, exploration and anxiety in heterozygous neuregulin 1 mutant mice: implications for understanding schizophrenia.

    PubMed

    Karl, T; Duffy, L; Scimone, A; Harvey, R P; Schofield, P R

    2007-10-01

    Human genetic studies have shown that neuregulin 1 (NRG1) is a potential susceptibility gene for schizophrenia. Nrg1 influences various neurodevelopmental processes, which are potentially related to schizophrenia. The neurodevelopmental theory of schizophrenia suggests that interactions between genetic and environmental factors are responsible for biochemical alterations leading to schizophrenia. To investigate these interactions and to match experimental design with the pathophysiology of schizophrenia, we applied a comprehensive behavioural phenotyping strategy for motor activity, exploration and anxiety in a heterozygous Nrg1 transmembrane domain mutant mouse model (Nrg1 HET) using different housing conditions and age groups. We observed a locomotion- and exploration-related hyperactive phenotype in Nrg1 HETs. Increased age had a locomotion- and exploration-inhibiting effect, which was significantly attenuated in mutant mice. Environmental enrichment (EE) had a stimulating influence on locomotion and exploration. The impact of EE was more pronounced in Nrg1 hypomorphs. Our study also showed a moderate task-specific anxiolytic-like phenotype for Nrg1 HETs, which was influenced by external factors. The behavioural phenotype detected in heterozygous Nrg1 mutant mice is not specific to schizophrenia per se, but the increased sensitivity of mutant mice to exogenous factors is consistent with the pathophysiology of schizophrenia and the neurodevelopmental theory. Our findings reinforce the importance of carefully controlling experimental designs for external factors and of comprehensive, integrative phenotyping strategies. Thus, Nrg1 HETs may, in combination with other genetic and drug models, help to clarify pathophysiological mechanisms behind schizophrenia.

  18. Opposing regulation of dopaminergic activity and exploratory motor behavior by forebrain and brainstem cholinergic circuits.

    PubMed

    Patel, Jyoti C; Rossignol, Elsa; Rice, Margaret E; Machold, Robert P

    2012-01-01

    Dopamine transmission is critical for exploratory motor behaviour. A key regulator is acetylcholine; forebrain acetylcholine regulates striatal dopamine release, whereas brainstem cholinergic inputs regulate the transition of dopamine neurons from tonic to burst firing modes. How these sources of cholinergic activity combine to control dopamine efflux and exploratory motor behaviour is unclear. Here we show that mice lacking total forebrain acetylcholine exhibit enhanced frequency-dependent striatal dopamine release and are hyperactive in a novel environment, whereas mice lacking rostral brainstem acetylcholine are hypoactive. Exploratory motor behaviour is normalized by the removal of both cholinergic sources. Involvement of dopamine in the exploratory motor phenotypes observed in these mutants is indicated by their altered sensitivity to the dopamine D2 receptor antagonist raclopride. These results support a model in which forebrain and brainstem cholinergic systems act in tandem to regulate striatal dopamine signalling for proper control of motor activity.

  19. Altering cAMP levels within a central pattern generator modifies or disrupts rhythmic motor output.

    PubMed

    Clemens, Stefan; Calin-Jageman, Robert; Sakurai, Akira; Katz, Paul S

    2007-12-01

    Cyclic AMP is a second messenger that has been implicated in the neuromodulation of rhythmically active motor patterns. Here, we tested whether manipulating cAMP affects swim motor pattern generation in the mollusc, Tritonia diomedea. Inhibiting adenylyl cyclase (AC) with 9-cyclopentyladenine (9-CPA) slowed or stopped the swim motor pattern. Inhibiting phosphodiesterase with 3-isobutyl-1-methylxanthine (IBMX) or applying dibutyryl-cAMP (dB-cAMP) disrupted the swim motor pattern, as did iontophoresing cAMP into the central pattern generator neuron C2. Additionally, during wash-in, IBMX sometimes temporarily produced extended or spontaneous swim motor patterns. Photolysis of caged cAMP in C2 after initiation of the swim motor pattern inhibited subsequent bursting. These results suggest that cAMP levels can dynamically modulate swim motor pattern generation, possibly shaping the output of the central pattern generator on a cycle-by-cycle basis.

  20. BDNF effects on functional recovery across motor behaviors after cervical spinal cord injury.

    PubMed

    Hernandez-Torres, Vivian; Gransee, Heather M; Mantilla, Carlos B; Wang, Yao; Zhan, Wen-Zhi; Sieck, Gary C

    2017-02-01

    Unilateral C2 cervical spinal cord hemisection (SH) disrupts descending excitatory drive to phrenic motor neurons, thereby paralyzing the ipsilateral diaphragm muscle (DIAm) during ventilatory behaviors. Recovery of rhythmic DIAm activity ipsilateral to injury occurs over time, consistent with neuroplasticity and strengthening of spared synaptic inputs to phrenic motor neurons. Localized intrathecal delivery of brain-derived neurotrophic factor (BDNF) to phrenic motor neurons after SH enhances recovery of eupneic DIAm activity. However, the impact of SH and BDNF treatment on the full range of DIAm motor behaviors has not been fully characterized. We hypothesized that all DIAm motor behaviors are affected by SH and that intrathecal BDNF enhances the recovery of both ventilatory and higher force, nonventilatory motor behaviors. An intrathecal catheter was placed in adult, male Sprague-Dawley rats at C4 to chronically infuse artificial cerebrospinal fluid (aCSF) or BDNF. DIAm electromyography (EMG) electrodes were implanted bilaterally to record activity across motor behaviors, i.e., eupnea, hypoxia-hypercapnia (10% O2 and 5% CO2), sighs, airway occlusion, and sneezing. After SH, ipsilateral DIAm EMG activity was evident in only 43% of aCSF-treated rats during eupnea, and activity was restored in all rats after BDNF treatment. The amplitude of DIAm EMG (root mean square, RMS) was reduced following SH during eupnea and hypoxia-hypercapnia in aCSF-treated rats, and BDNF treatment promoted recovery in both conditions. The amplitude of DIAm RMS EMG during sighs, airway occlusion, and sneezing was not affected by SH or BDNF treatment. We conclude that the effects of SH and BDNF treatment on DIAm activity depend on motor behavior.

  1. Locomotor training alters the behavior of flexor reflexes during walking in human spinal cord injury.

    PubMed

    Smith, Andrew C; Mummidisetty, Chaithanya K; Rymer, William Zev; Knikou, Maria

    2014-11-01

    In humans, a chronic spinal cord injury (SCI) impairs the excitability of pathways mediating early flexor reflexes and increases the excitability of late, long-lasting flexor reflexes. We hypothesized that in individuals with SCI, locomotor training will alter the behavior of these spinally mediated reflexes. Nine individuals who had either chronic clinically motor complete or incomplete SCI received an average of 44 locomotor training sessions. Flexor reflexes, elicited via sural nerve stimulation of the right or left leg, were recorded from the ipsilateral tibialis anterior (TA) muscle before and after body weight support (BWS)-assisted treadmill training. The modulation pattern of the ipsilateral TA responses following innocuous stimulation of the right foot was also recorded in 10 healthy subjects while they stepped at 25% BWS to investigate whether body unloading during walking affects the behavior of these responses. Healthy subjects did not receive treadmill training. We observed a phase-dependent modulation of early TA flexor reflexes in healthy subjects with reduced body weight during walking. The early TA flexor reflexes were increased at heel contact, progressively decreased during the stance phase, and then increased throughout the swing phase. In individuals with SCI, locomotor training induced the reappearance of early TA flexor reflexes and changed the amplitude of late TA flexor reflexes during walking. Both early and late TA flexor reflexes were modulated in a phase-dependent pattern after training. These new findings support the adaptive capability of the injured nervous system to return to a prelesion excitability and integration state.

  2. The Relationship between Motor Function and Behavioral Function in Infants with Low Birth Weight

    PubMed Central

    AMINI, Malek; ALIABADI, Faranak; ALIZADE, Mehdi; KALANI, Majid; QORBANI, Mostafa

    2016-01-01

    Objective Nowadays, the evaluation of all aspects of infant development is important. However, in practice, some of these assessments, especially those requiring more manipulation on high-risk infants, may impose additional stress on them. Therefore, sometimes it is essential to utilize the results of a developmental assessment for the prediction of some other aspects of development. This study evaluated the relationship between the scores of the behavioral tests and the motor function test. Materials & Methods This cross-sectional study and was undertaken in the Neonatal Intensive Care Center and Clinic of Shahid Akbar Abadi Hospital, Tehran, Iran. A group of 50 infants with low birth weights was selected based on the easy non-contingency method and the inclusion criteria, and served as the participants. In order to assess the motor function and the behavioral performance, the motor function test (a test of infant motor performance (TIMP)) and the neonatal behavioral assessment scale (neonatal behavioral assessment scale (NBAS)) were used respectively. TIMP has both stimulation and observation sections. The items include habituation, social interaction, motor system, state organization, state regulation, autonomic system, smile, supplementary items, and the reflex. Results No significant association was found between the items of the habituation of behavioral testing and the observation of the movement test. There was no statistically significant relationship between the habituation and stimulation sections as well as between the system autonomous of the behavioral test and the observation section of the motor test (P>0.05). The relationship between other variables was statistically significant (P<0.05). Conclusion The scores of some behavioral performance items could be a good predictor of the scores of the motor function items for low birth weight infants in the neonatal period. PMID:27843466

  3. Relationships between problematic behaviors and motor abilities of children with cerebral palsy

    PubMed Central

    Uesugi, Masayuki; Miyamoto, Akira; Nanba, Yosifumi; Otani, Yoshitaka; Takemasa, Seiichi; Hujii, Shun

    2015-01-01

    [Purpose] This study aimed to examine whether motor abilities of children with cerebral palsy are related to their problematic behaviors. [Subjects] The subjects were children with mental retardation who were undergoing physical therapy. [Methods] Twenty-one examiners, 13 physical therapists, and 8 occupational therapists treated and examined the subjects by using the Japanese version of the Aberrant Behavior Checklist. The Japanese version of the Aberrant Behavior Checklist scores were compared between the Gross Motor Function Classification System I to III (12 subjects) and Gross Motor Function Classification System IV and V groups (17 subjects). [Results] Lethargy and stereotypy scores significantly differed between the groups, proving that patients with Gross Motor Function Classification System levels IV and V have more severe problematic behaviors. [Conclusion] In this study, only five types of problematic behaviors, namely irritability, lethargy, stereotypy, hyperactivity, and inappropriate speech, were examined. Despite this limitation, the study clarifies that problematic behaviors of children with cerebral palsy, except lethargy and stereotypy, have little relationship with their motor abilities. PMID:26504335

  4. Post-impact behavior of composite solid rocket motor cases

    NASA Technical Reports Server (NTRS)

    Highsmith, Alton L.

    1992-01-01

    In recent years, composite materials have seen increasing use in advanced structural applications because of the significant weight savings they offer when compared to more traditional engineering materials. The higher cost of composites must be offset by the increased performance that results from reduced structural weight if these new materials are to be used effectively. At present, there is considerable interest in fabricating solid rocket motor cases out of composite materials, and capitalizing on the reduced structural weight to increase rocket performance. However, one of the difficulties that arises when composite materials are used is that composites can develop significant amounts of internal damage during low velocity impacts. Such low velocity impacts may be encountered in routine handling of a structural component like a rocket motor case. The ability to assess the reduction in structural integrity of composite motor cases that experience accidental impacts is essential if composite rocket motor cases are to be certified for manned flight. The study described herein was an initial investigation of damage development and reduction of tensile strength in an idealized composite subjected to low velocity impacts.

  5. Response-Specific Effects of Pain Observation on Motor Behavior

    ERIC Educational Resources Information Center

    Morrison, India; Poliakoff, Ellen; Gordon, Lucy; Downing, Paul

    2007-01-01

    How does seeing a painful event happening to someone else influence the observer's own motor system? To address this question, we measured simple reaction times following videos showing noxious or innocuous implements contacting corporeal or noncorporeal objects. Key releases in a go/nogo task were speeded, and key presses slowed, after subjects…

  6. Effects of Interventions Based in Behavior Analysis on Motor Skill Acquisition: A Meta-Analysis

    ERIC Educational Resources Information Center

    Alstot, Andrew E.; Kang, Minsoo; Alstot, Crystal D.

    2013-01-01

    Techniques based in applied behavior analysis (ABA) have been shown to be useful across a variety of settings to improve numerous behaviors. Specifically within physical activity settings, several studies have examined the effect of interventions based in ABA on a variety of motor skills, but the overall effects of these interventions are unknown.…

  7. The Development of Verbal Control over Motor Behavior: A Replication and Extension of Luria's Findings.

    ERIC Educational Resources Information Center

    Tinsley, Virginia S.; Waters, Harriet Salatas

    1982-01-01

    Two experiments replicate and extend Luria's (1959, 1961) findings on the development of verbal self-regulation during early childhood. Results support Luria's hypothesis that overt verbalizations facilitate control of motor behavior in young children and that language can play an active and integrative role in the development of behavioral and…

  8. Magnesium impacts myosin V motor activity by altering key conformational changes in the mechanochemical cycle.

    PubMed

    Trivedi, Darshan V; Muretta, Joseph M; Swenson, Anja M; Thomas, David D; Yengo, Christopher M

    2013-07-09

    We investigated how magnesium (Mg) impacts key conformational changes during the ADP binding/release steps in myosin V and how these alterations impact the actomyosin mechanochemical cycle. The conformation of the nucleotide binding pocket was examined with our established FRET system in which myosin V labeled with FlAsH in the upper 50 kDa domain participates in energy transfer with mant labeled nucleotides. We examined the maximum actin-activated ATPase activity of MV FlAsH at a range of free Mg concentrations (0.1-9 mM) and found that the highest activity occurs at low Mg (0.1-0.3 mM), while there is a 50-60% reduction in activity at high Mg (3-9 mM). The motor activity examined with the in vitro motility assay followed a similar Mg-dependence, and the trend was similar with dimeric myosin V. Transient kinetic FRET studies of mantdADP binding/release from actomyosin V FlAsH demonstrate that the transition between the weak and strong actomyosin.ADP states is coupled to movement of the upper 50 kDa domain and is dependent on Mg with the strong state stabilized by Mg. We find that the kinetics of the upper 50 kDa conformational change monitored by FRET correlates well with the ATPase and motility results over a wide range of Mg concentrations. Our results suggest the conformation of the upper 50 kDa domain is highly dynamic in the Mg free actomyosin.ADP state, which is in agreement with ADP binding being entropy driven in the absence of Mg. Overall, our results demonstrate that Mg is a key factor in coupling the nucleotide- and actin-binding regions. In addition, Mg concentrations in the physiological range can alter the structural transition that limits ADP dissociation from actomyosin V, which explains the impact of Mg on actin-activated ATPase activity and in vitro motility.

  9. Altered sensory-motor control of the head as an etiological factor in space-motion sickness

    NASA Technical Reports Server (NTRS)

    Lackner, J. R.; DiZio, P.

    1989-01-01

    Mechanical unloading during head movements in weightlessness may be an etiological factor in space-motion sickness. We simulated altered head loading on Earth without affecting vestibular stimulation by having subjects wear a weighted helmet. Eight subjects were exposed to constant velocity rotation about a vertical axis with direction reversals every 60 sec. for eight reversals with the head loaded and eight with the head unloaded. The severity of motion sickness elicited was significantly higher when the head was loaded. This suggests that altered sensory-motor control of the head is also an etiological factor in space-motion sickness.

  10. Applying Behavioral Principles to Motor Vehicle Occupant Protection.

    ERIC Educational Resources Information Center

    Sleet, David A.; And Others

    1986-01-01

    Successful programs designed to encourage protective behaviors (e.g., wearing safety belts and using child safety seats) have applied such behavioral principles as a combination of rewards, feedback, guidance, contingency management, and modeling. (Author/DB)

  11. Tio2-dopamine complex implanted unilaterally in the caudate nucleus improves motor activity and behavior function of rats with induced hemiparkinsonism.

    PubMed

    Vergara-Aragón, Patricia; Domínguez-Marrufo, Leonardo Eduardo; Ibarra-Guerrero, Patricia; Hernandez-Ramírez, Heidi; Hernández-Téllez, Beatriz; López-Martínez, Irma Elena; Sánchez-Cervantes, Ivonne; Santiago-Jacinto, Patricia; García-Macedo, Jorge Alberto; Valverde-Aguilar, Guadalupe; Santiago, Julio

    2011-01-01

    Parkinson's disease (PD) is characterized by malfunction of dopaminergic systems, and the current symptomatic treatment is to replace lost dopamine. For investigating mechanisms of pathogenesis and alternative treatments to compensate lack of dopamine (DA) activity in PD, the 6-hydroxydopamine (6-OHDA)-lesioned rat model of PD has been useful, these animals display apomorphine-induced contralateral rotational behavior, when they are examined after lesion. The purpose of this study was to assess Titania-dopamine (TiO2-DA) complexes implanted on the caudate nucleus for diminishing motor behavior alterations of the 6-OHDA rat model. Rats with 6-OHDA unilateral lesions received TiO2 alone or TiO2-DA implants, and were tested for open field (OF) gross motor crossing and rearing behaviors, and apomorphine-induced rotation (G) behavior. TiO2 complex have no effects on rearing OF and G behaviors, and a significant reducing effect on crossing motor behavior of normal rats compared to control non-treated rats throughout 56 days of observation. Interestingly, TiO2-DA treatment significant recovered motor crossing and rearing behaviors in 6-OHDA-lesioned rats, and diminished the G behaviors during 56 days of examination. Additionally, in the 6-OHDA-lesioned rats TiO2 treatment had a moderate recovering effect only on crossing behavior compared to lesioned non treated rats. Our results suggest that continuous release of dopamine in the caudate nucleus from TiO2-DA complex is capable of reversing gross motor deficits observed in the 6-OHDA-lesioned rat model of PD. Thistype of delivery system of DA represents a promising therapy for PD in humans.

  12. The relationship between the behavior problems and motor skills of students with intellectual disability

    PubMed Central

    Lee, Yangchool; Jeoung, Bogja

    2016-01-01

    The purpose of this study was to determine the relationship between the motor skills and the behavior problems of students with intellectual disabilities. The study participants were 117 students with intellectual disabilities who were between 7 and 25 years old (male, n=79; female, n=38) and attending special education schools in South Korea. Motor skill abilities were assessed by using the second version of the Bruininks-Oseretsky test of motor proficiency, which includes subtests in fine motor control, manual coordination, body coordination, strength, and agility. Data were analyzed with SPSS IBM 21 by using correlation and regression analyses, and the significance level was set at P<0.05. The results showed that fine motor precision and integration had a statistically significant influence on aggressive behavior. Manual dexterity showed a statistically significant influence on somatic complaint and anxiety/depression, and bilateral coordination had a statistically significant influence on social problems, attention problem, and aggressive behavior. Our results showed that balance had a statistically significant influence on social problems and aggressive behavior, and speed and agility had a statistically significant influence on social problems and aggressive behavior. Upper limb coordination and strength had a statistically significant influence on social problems. PMID:28119883

  13. Motor Alterations Induced by Chronic 4-Aminopyridine Infusion in the Spinal Cord In vivo: Role of Glutamate and GABA Receptors

    PubMed Central

    Lazo-Gómez, Rafael; Tapia, Ricardo

    2016-01-01

    Motor neuron (MN) degeneration is the pathological hallmark of MN diseases, a group of neurodegenerative disorders clinically manifested as muscle fasciculations and hyperreflexia, followed by paralysis, respiratory failure, and death. Ample evidence supports a role of glutamate-mediated excitotoxicity in motor death. In previous work we showed that stimulation of glutamate release from nerve endings by perfusion of the K+-channel blocker 4-aminopyridine (4-AP) in the rat hippocampus induces seizures and neurodegeneration, and that AMPA infusion in the spinal cord produces paralysis and MN death. On these bases, in this work we have tested the effect of the chronic infusion of 4-AP in the spinal cord, using implanted osmotic minipumps, on motor activity and on MN survival, and the mechanisms underlying this effect. 4-AP produced muscle fasciculations and motor deficits assessed in two motor tests, which start 2–3 h after the implant, which ameliorated spontaneously within 6–7 days, but no neurodegeneration. These effects were prevented by both AMPA and NMDA receptors blockers. The role of GABAA receptors was also explored, and we found that chronic infusion of bicuculline induced moderate MN degeneration and enhanced the hyperexcitation produced by 4-AP. Unexpectedly, the GABAAR agonist muscimol also induced motor deficits and failed to prevent the MN death induced by AMPA. We conclude that motor alterations induced by chronic 4-AP infusion in the spinal cord in vivo is due to ionotropic glutamate receptor overactivation and that blockade of GABAergic neurotransmission induces MN death under chronic conditions. These results shed light on the role of glutamatergic and GABAergic neurotransmission in the regulation of MN excitability in the spinal cord. PMID:27242406

  14. Sensorimotor Oscillations Prior to Speech Onset Reflect Altered Motor Networks in Adults Who Stutter

    PubMed Central

    Mersov, Anna-Maria; Jobst, Cecilia; Cheyne, Douglas O.; De Nil, Luc

    2016-01-01

    Adults who stutter (AWS) have demonstrated atypical coordination of motor and sensory regions during speech production. Yet little is known of the speech-motor network in AWS in the brief time window preceding audible speech onset. The purpose of the current study was to characterize neural oscillations in the speech-motor network during preparation for and execution of overt speech production in AWS using magnetoencephalography (MEG). Twelve AWS and 12 age-matched controls were presented with 220 words, each word embedded in a carrier phrase. Controls were presented with the same word list as their matched AWS participant. Neural oscillatory activity was localized using minimum-variance beamforming during two time periods of interest: speech preparation (prior to speech onset) and speech execution (following speech onset). Compared to controls, AWS showed stronger beta (15–25 Hz) suppression in the speech preparation stage, followed by stronger beta synchronization in the bilateral mouth motor cortex. AWS also recruited the right mouth motor cortex significantly earlier in the speech preparation stage compared to controls. Exaggerated motor preparation is discussed in the context of reduced coordination in the speech-motor network of AWS. It is further proposed that exaggerated beta synchronization may reflect a more strongly inhibited motor system that requires a stronger beta suppression to disengage prior to speech initiation. These novel findings highlight critical differences in the speech-motor network of AWS that occur prior to speech onset and emphasize the need to investigate further the speech-motor assembly in the stuttering population. PMID:27642279

  15. Manipulating the Behavior-Altering Effect of the Motivating Operation: Examination of the Influence on Challenging Behavior during Leisure Activities

    ERIC Educational Resources Information Center

    O'Reilly, Mark F.; Sigafoos, Jeff; Lancioni, Giulio; Rispoli, Mandy; Lang, Russell; Chan, Jeff; Machalicek, Wendy; Langthorne, Paul

    2008-01-01

    We examined the behavior-altering effect of the motivating operation on challenging behavior during leisure activities for three individuals with severe disabilities. Prior functional analyses indicated that challenging behavior was maintained by positive reinforcement in the form of attention or tangible items for all participants. During leisure…

  16. Development of oral motor behavior related to the skill assisted spoon feeding.

    PubMed

    van den Engel-Hoek, Lenie; van Hulst, Karen C M; van Gerven, Marjo H J C; van Haaften, Leenke; de Groot, Sandra A F

    2014-05-01

    Milestones in the typical development of eating skills are considered to be nippling (breast or bottle), eating from a spoon, drinking from a cup, biting and chewing. The purpose of this research was to study the development and consolidation of oral motor behavior related to the skill assisted spoon feeding in young infants. The present study longitudinally investigated the development of this skill in 39 healthy children from the start of spoon feeding until the skill was acquired. The Observation List Spoon Feeding with 7 observation items for oral motor behavior and 6 items for abnormal behavior was used. Results showed that infants between 4 and 8 months of age needed 5.7 weeks (SD 2.1), with a range of 8 weeks (from 2 to 10 weeks) to acquire this skill. No significant correlation (p=.109) between age at start spoon feeding and weeks needed to develop the skill was found. During this period oral motor behavior consolidated and abnormal behavior diminished. With this study it is shown that the period in weeks needed to acquire the oral motor behavior for the skill assisted spoon feeding is important in case of feeding problems.

  17. Sensory and motor behaviors of infant siblings of children with and without autism.

    PubMed

    Mulligan, Shelley; White, Barbara Prudhomme

    2012-01-01

    We compared the sensory and motor behaviors of typically developing infants with those of infant siblings of children with autism spectrum disorders (ASD), who are considered high risk for the disorder, to explore potential sensory and motor markers for use in early diagnosis of ASD. We compared frequencies of sensory and motor behaviors during 10-min, videotaped, infant-mother play sessions and during 5 min of spoon-feeding between groups of 12-mo-old infants. Data from standardized measures of development, sensory processing, and behaviors commonly associated with ASD were also analyzed descriptively for the high-risk group. The results indicated that high-risk infants demonstrated fewer movement transitions (t [23] = -2.4, p = .03) and less object manipulation (t [23] = -2.4, p = .03) than low-risk infants. The sensory and motor differences found between typical and high-risk infants suggest that early screenings for ASD should include the examination of sensory and motor behaviors.

  18. Evoked Potentials in Motor Cortical Local Field Potentials Reflect Task Timing and Behavioral Performance

    PubMed Central

    Confais, Joachim; Ponce-Alvarez, Adrián; Diesmann, Markus; Riehle, Alexa

    2010-01-01

    Evoked potentials (EPs) are observed in motor cortical local field potentials (LFPs) during movement execution (movement-related potentials [MRPs]) and in response to relevant visual cues (visual evoked potentials [VEPs]). Motor cortical EPs may be directionally selective, but little is known concerning their relation to other aspects of motor behavior, such as task timing and performance. We recorded LFPs in motor cortex of two monkeys during performance of a precued arm-reaching task. A time cue at the start of each trial signaled delay duration and thereby the pace of the task and the available time for movement preparation. VEPs and MRPs were strongly modulated by the delay duration, VEPs being systematically larger in short-delay trials and MRPs larger in long-delay trials. Despite these systematic modulations related to the task timing, directional selectivity was similar in short and long trials. The behavioral reaction time was positively correlated with MRP size and negatively correlated with VEP size, within sessions. In addition, the behavioral performance improved across sessions, in parallel with a slow decrease in the size of VEPs and MRPs. Our results clearly show the strong influence of the behavioral context and performance on motor cortical population activity during movement preparation and execution. PMID:20884766

  19. Walking in School-Aged Children in a Dual-Task Paradigm Is Related to Age But Not to Cognition, Motor Behavior, Injuries, or Psychosocial Functioning

    PubMed Central

    Hagmann-von Arx, Priska; Manicolo, Olivia; Lemola, Sakari; Grob, Alexander

    2016-01-01

    Age-dependent gait characteristics and associations with cognition, motor behavior, injuries, and psychosocial functioning were investigated in 138 typically developing children aged 6.7–13.2 years (M = 10.0 years). Gait velocity, normalized velocity, and variability were measured using the walkway system GAITRite without an additional task (single task) and while performing a motor or cognitive task (dual task). Assessment of children’s cognition included tests for intelligence and executive functions; parents reported on their child’s motor behavior, injuries, and psychosocial functioning. Gait variability (an index of gait regularity) decreased with increasing age in both single- and dual-task walking. Dual-task gait decrements were stronger when children walked in the motor compared to the cognitive dual-task condition and decreased with increasing age in both dual-task conditions. Gait alterations from single- to dual-task conditions were not related to children’s cognition, motor behavior, injuries, or psychosocial functioning. PMID:27014158

  20. Metabolic changes and DNA hypomethylation in cerebellum are associated with behavioral alterations in mice exposed to trichloroethylene postnatally

    SciTech Connect

    Blossom, Sarah J.; Cooney, Craig A.; Melnyk, Stepan B.; Rau, Jenny L.; Swearingen, Christopher J.; Wessinger, William D.

    2013-06-15

    Previous studies demonstrated that low-level postnatal and early life exposure to the environmental contaminant, trichloroethylene (TCE), in the drinking water of MRL +/+ mice altered glutathione redox homeostasis and increased biomarkers of oxidative stress indicating a more oxidized state. Plasma metabolites along the interrelated transmethylation pathway were also altered indicating impaired methylation capacity. Here we extend these findings to further characterize the impact of TCE exposure in mice exposed to water only or two doses of TCE in the drinking water (0, 2, and 28 mg/kg/day) postnatally from birth until 6 weeks of age on redox homeostasis and biomarkers of oxidative stress in the cerebellum. In addition, pathway intermediates involved in methyl metabolism and global DNA methylation patterns were examined in cerebellar tissue. Because the cerebellum is functionally important for coordinating motor activity, including exploratory and social approach behaviors, these parameters were evaluated in the present study. Mice exposed to 28 mg/kg/day TCE exhibited increased locomotor activity over time as compared with control mice. In the novel object exploration test, these mice were more likely to enter the zone with the novel object as compared to control mice. Similar results were obtained in a second test when an unfamiliar mouse was introduced into the testing arena. The results show for the first time that postnatal exposure to TCE causes key metabolic changes in the cerebellum that may contribute to global DNA methylation deficits and behavioral alterations in TCE-exposed mice. - Highlights: • We exposed male mice to low-level trichloroethylene from postnatal days 1 through 42. • This exposure altered redox potential and increased oxidative stress in cerebellum. • This exposure altered metabolites important in cellular methylation in cerebellum. • This exposure promoted DNA hypomethylation in cerebellum. • This exposure enhanced locomotor

  1. Sensory Plasticity in Human Motor Learning.

    PubMed

    Ostry, David J; Gribble, Paul L

    2016-02-01

    There is accumulating evidence from behavioral, neurophysiological, and neuroimaging studies that the acquisition of motor skills involves both perceptual and motor learning. Perceptual learning alters movements, motor learning, and motor networks of the brain. Motor learning changes perceptual function and the sensory circuits of the brain. Here, we review studies of both human limb movement and speech that indicate that plasticity in sensory and motor systems is reciprocally linked. Taken together, this points to an approach to motor learning in which perceptual learning and sensory plasticity have a fundamental role.

  2. Exercise-induced Alteration in Brain Activity during Motor Performance under Cognitive Stress

    DTIC Science & Technology

    2014-07-02

    stress . It is possible that the correlated activity between EEG and EMG is used for “fine-tuning” brain activity during the performance of fine motor...brain and muscle during simple fine motor performance under stress after high-intensity physical exertion. Healthy young adults were assigned to...leg resistance exercise. Oscillations in EEG and corticomuscular coherence in beta band both tended to decrease 1. REPORT DATE (DD-MM-YYYY) 4. TITLE

  3. Stochastic kinetics of ribosomes: Single motor properties and collective behavior

    NASA Astrophysics Data System (ADS)

    Garai, Ashok; Chowdhury, Debanjan; Chowdhury, Debashish; Ramakrishnan, T. V.

    2009-07-01

    Syntheses of protein molecules in a cell are carried out by ribosomes. A ribosome can be regarded as a molecular motor which utilizes the input chemical energy to move on a messenger RNA (mRNA) track that also serves as a template for the polymerization of the corresponding protein. The forward movement, however, is characterized by an alternating sequence of translocation and pause. Using a quantitative model, which captures the mechanochemical cycle of an individual ribosome, we derive an exact analytical expression for the distribution of its dwell times at the successive positions on the mRNA track. Inverse of the average dwell time satisfies a “Michaelis-Menten-type” equation and is consistent with the general formula for the average velocity of a molecular motor with an unbranched mechanochemical cycle. Extending this formula appropriately, we also derive the exact force-velocity relation for a ribosome. Often many ribosomes simultaneously move on the same mRNA track, while each synthesizes a copy of the same protein. We extend the model of a single ribosome by incorporating steric exclusion of different individuals on the same track. We draw the phase diagram of this model of ribosome traffic in three-dimensional spaces spanned by experimentally controllable parameters. We suggest new experimental tests of our theoretical predictions.

  4. Functional organization of motor cortex of adult macaque monkeys is altered by sensory loss in infancy.

    PubMed

    Qi, Hui-Xin; Jain, Neeraj; Collins, Christine E; Lyon, David C; Kaas, Jon H

    2010-02-16

    When somatosensory cortex (S1) is deprived of some of its inputs after section of ascending afferents in the dorsal columns of the spinal cord, it reorganizes to overrepresent the surviving inputs. As somatosensory cortex provides guiding sensory information to motor cortex, such sensory loss and representational reorganization could affect the development of the motor map in primary motor cortex (M1), especially if the sensory loss occurs early in development. To address this possibility, the dorsal columns of the spinal cord were sectioned between cervical levels (C3-5) 3-12 days after birth in five macaque monkeys. After 3-5 years of maturation (young adults), we determined how movements were represented in M1 contralateral to the lesion by using microelectrodes to electrically stimulate sites in M1 to evoke movements. Although the details of the motor maps in these five monkeys varied, the forelimb motor maps were abnormal. The representations of digit movements were reduced and abnormally arranged. Current levels for evoking movements from the forelimb region of M1 were in the normal range, but the lowest mean stimulation thresholds were for wrist or elbow instead of digit movements. Incomplete lesions and bilateral lesions produced fewer abnormalities. The results suggest that the development of normal motor cortex maps in M1 depends on sensory feedback from somatosensory maps.

  5. 3. Impact of altered gravity on CNS development and behavior in male and female rats

    NASA Astrophysics Data System (ADS)

    Sajdel-Sulkowska, E. M.; Nguon, K.; Ladd, B.; Sulkowski, V. A.; Sulkowski, Z. L.; Baxter, M. G.

    The present study examined the effect of altered gravity on CNS development. Specifically, we compared neurodevelopment, behavior, cerebellar structure and protein expression in rat neonates exposed perinatally to hypergravity. Pregnant Sprague-Dawley rats were exposed to 1.5G-1.75G hypergravity on a 24-ft centrifuge starting on gestational day (G) 10, through giving birth on G22/G23, and nursing their offspring through postnatal day (P) 21. Cerebellar mass on P6 was decreased in 1.75G-exposed male pups by 27.5 percent; in 1.75G-exposed female pups it was decreased by 22.5 percent. The observed cerebellar changes were associated with alterations in neurodevelopment and motor behavior. Exposure to hypergravity impaired performance on the following neurocognitive tests: (1) righting time on P3 was more than doubled in 1.75G-exposed rats and the effect appeared more pronounced in female pups, (2) startle response on P10 was delayed in both male and female HG pups; HG pups were one-fifth as likely to respond to a clapping noise as SC pups, and (3) performance on a rotorod on P21 was decreased in HG pups; the duration of the stay on rotorod recorded for HG pups of both sexes was one tenth of the SC pups. Furthermore, Western blot analysis of selected cerebellar proteins suggested gender-specific changes in glial and neuronal proteins. On P6, GFAP expression was decreased by 59.2 percent in HG males, while no significant decrease was observed in female cerebella. Synaptophysin expression was decreased in HG male neonates by 29.9 percent and in HG female neonates by 20.7 percent as compared to its expression in SC cerebella. The results of this experiment suggest that perinatal exposure to hypergravity affects cerebellar development and behavior differently in male and female neonates. If one accepts that hypergravity is a good paradigm to study the effect of microgravity on the CNS, and since males and females were shown to respond differently to hypergravity, it can be

  6. Electrophysiological correlates of the limbic-motor interactions in various behavioral states in rats.

    PubMed

    Korzeniewska, A; Kasicki, S; Zagrodzka, J

    1997-08-01

    Depth electroencephalographic (EEG) activity was recorded from basolateral amygdala (BLA), ventral subiculum (VSB), n. accumbens (ACC) and subpallidal area (SPL) in freely moving rats, during locomotor tasks with various types of reinforcement in order to compare the strength of limbic-motor interactions in selected behavioral situations. For all EEG signals multichannel coherences (ordinary, multiple and partial) were calculated using autoregression model. Partial coherences indicate the level of synchronization between two signals, thus they were assumed to indicate the strength of direct connection between the structures from which these signals have been recorded. The partial coherences were calculated for six selected frequency bands and the strength of connections within the BLA-VSB-ACC-SPL circuit was estimated for two different behavioral situations and compared. It was found that the strength of connections is sensitive to changes in both motor and emotional aspects of behavioral situation: the strength of BLA-VSB, VSB-ACC, and ACC-SPL depended on motor demands of behavioral task; these of BLA-VSB increased in the highest frequency bands in all emotionally engaging situations when compared with well trained locomotive; the strength of ACC-SPL increased in situations when automatic stereotyped motor behavior was induced by biologically important stimuli, while it decreased or did not change in the motor tasks demanding more precise and quickly adjustable movements. The results are discussed according to the motor-limbic integration model of proposed by Mogenson and show the dynamics of its connections in relation to the motivational-emotional context of the task.

  7. Functional Genetic Screen to Identify Interneurons Governing Behaviorally Distinct Aspects of Drosophila Larval Motor Programs

    PubMed Central

    Clark, Matt Q.; McCumsey, Stephanie J.; Lopez-Darwin, Sereno; Heckscher, Ellie S.; Doe, Chris Q.

    2016-01-01

    Drosophila larval crawling is an attractive system to study rhythmic motor output at the level of animal behavior. Larval crawling consists of waves of muscle contractions generating forward or reverse locomotion. In addition, larvae undergo additional behaviors, including head casts, turning, and feeding. It is likely that some neurons (e.g., motor neurons) are used in all these behaviors, but the identity (or even existence) of neurons dedicated to specific aspects of behavior is unclear. To identify neurons that regulate specific aspects of larval locomotion, we performed a genetic screen to identify neurons that, when activated, could elicit distinct motor programs. We used 165 Janelia CRM-Gal4 lines—chosen for sparse neuronal expression—to ectopically express the warmth-inducible neuronal activator TrpA1, and screened for locomotor defects. The primary screen measured forward locomotion velocity, and we identified 63 lines that had locomotion velocities significantly slower than controls following TrpA1 activation (28°). A secondary screen was performed on these lines, revealing multiple discrete behavioral phenotypes, including slow forward locomotion, excessive reverse locomotion, excessive turning, excessive feeding, immobile, rigid paralysis, and delayed paralysis. While many of the Gal4 lines had motor, sensory, or muscle expression that may account for some or all of the phenotype, some lines showed specific expression in a sparse pattern of interneurons. Our results show that distinct motor programs utilize distinct subsets of interneurons, and provide an entry point for characterizing interneurons governing different elements of the larval motor program. PMID:27172197

  8. Motor unit firing behavior during prolonged 50% MVC dorsiflexion contractions in young and older adults.

    PubMed

    Christie, Anita; Kamen, Gary

    2009-08-01

    The purpose of this study was to investigate changes in motor unit firing behavior during prolonged contractions in young and older adults. Motor unit activity was recorded from the tibialis anterior of 16 subjects (8 young and 8 older), while they performed isometric dorsiflexion at 50% MVC until task failure. Mean motor unit firing rate, the standard deviation (SD), and coefficient of variation (CV) of the interspike intervals, and number of doublet discharges were calculated for a total of 52 motor units, tracked for an average of 92.9+/-68.6s. There was no age-related difference in the time to task failure. A modest decline in firing rate was observed in 71% of the motor units, with no significant age-related difference. The SD and CV of the interspike interval had a positive slope in 65% and 69% of the motor units, respectively, with no significant age-related differences. The number of doublet discharges remained stable throughout the contraction. Both groups exhibited motor unit dropout (discharge cessation) during the contraction. Thus, a fatiguing task producing modest changes in firing rate in young and older adults is accompanied by an appreciable increase in firing rate variability. The incidence of doublet discharges is not increased during fatiguing contractions.

  9. Altered Resting-State Functional Connectivity in the Hand Motor Network in Glioma Patients.

    PubMed

    Mallela, Arka N; Peck, Kyung K; Petrovich-Brennan, Nicole M; Zhang, Zhigang; Lou, William; Holodny, Andrei I

    2016-08-22

    To examine the functional connectivity of the primary and supplementary motor areas (SMA) in glioma patients using resting-state functional MRI (rfMRI). To correlate rfMRI data with tumor characteristics and clinical information to characterize functional reorganization of resting-state networks (RSN) and the limitations of this method. This study was IRB approved and in compliance with Health Insurance Portability and Accountability Act. Informed consent was waived in this retrospective study. We analyzed rfMRI in 24 glioma patients and 12 age- and sex-matched controls. We compared global activation, interhemispheric connectivity, and functional connectivity in the hand motor RSNs using hemispheric voxel counts, pairwise Pearson correlation, and pairwise total spectral coherence. We explored the relationship between tumor grade, volume, location, and the patient's clinical status to functional connectivity. Global network activation and interhemispheric connectivity were reduced in gliomas (p < 0.05). Functional connectivity between the bilateral motor cortices and the SMA was reduced in gliomas (p < 0.01). High-grade gliomas had lower functional connectivity than low-grade gliomas (p < 0.05). Tumor volume and distance to ipsilateral motor cortex demonstrated no association with functional connectivity loss. Functional connectivity loss is associated with motor deficits in low-grade gliomas, but not in high-grade gliomas. Global reduction in resting-state connectivity in areas distal to tumor suggests that radiological tumor boundaries underestimate areas affected by glioma. Association between motor deficits and rfMRI suggests that rfMRI may accurately reflect functional changes in low-grade gliomas. Lack of association between rfMRI and clinical motor deficits implies decreased sensitivity of rfMRI in high-grade gliomas, possibly due to neurovascular uncoupling.

  10. Postnatal dietary choline supplementation alters behavior in a mouse model of Rett syndrome.

    PubMed

    Nag, Nupur; Berger-Sweeney, Joanne E

    2007-05-01

    Rett syndrome (RTT), a neurodevelopmental disorder primarily affecting females, is accompanied by behavioral and neuropathological abnormalities and decreases in brain cholinergic markers. Because the cholinergic system is associated with cognitive and motor functions, cholinergic deficits in RTT may underlie some of the behavioral abnormalities. In rodents, increased choline availability during development enhances transmission at cholinergic synapses and improves behavioral performance throughout life. We examined whether choline supplementation of nursing dams would attenuate deficits in Mecp2(1lox) offspring, a mouse model of RTT. Dams were given choline in drinking water, and pups nursed from birth to weaning. Offspring were assessed on development and behavior. In Mecp2(1lox) males, choline supplementation improved motor coordination and locomotor activity, whereas in females it enhanced grip strength. Choline supplementation did not improve response to fear conditioning. Postnatal choline supplementation attenuates some behavioral deficits in Mecp2(1lox) mice and should be explored further as a therapeutic agent in RTT.

  11. Metabolic changes and DNA hypomethylation in cerebellum are associated with behavioral alterations in mice exposed to trichloroethylene postnatally

    PubMed Central

    Blossom, Sarah J.; Cooney, Craig A.; Melnyk, Stepan B.; Rau, Jenny L.; Swearingen, Christopher J.; Wessinger, William D.

    2013-01-01

    Previous studies demonstrated that low-level postnatal and early life exposure to the environmental contaminant, trichloroethylene (TCE), in the drinking water of MRL+/+ mice altered glutathione redox homeostasis and increased biomarkers of oxidative stress indicating a more oxidized state. Plasma metabolites along the interrelated transmethylation pathway were also altered indicating impaired methylation capacity. Here we extend these findings to further characterize the impact of TCE exposure in mice exposed to water only or two doses of TCE in the drinking water (0, 2, and 28 mg/kg/day) postnatally from birth until 6 weeks of age on redox homeostasis and biomarkers of oxidative stress in the cerebellum. In addition, pathway intermediates involved in methyl metabolism and global DNA methylation patterns were examined in cerebellar tissue. Because the cerebellum is functionally important for coordinating motor activity, including exploratory and social approach behaviors, these parameters were evaluated in the present study. Mice exposed to 28 mg/kg/day TCE exhibited increased locomotor activity over time as compared with control mice. In the novel object exploration test, these mice were more likely to enter the zone with the novel object as compared to control mice Similar results were obtained in a second test when an unfamiliar mouse was introduced into the testing arena. The results show for the first time that postnatal exposure to TCE causes key metabolic changes in the cerebellum that may contribute to global DNA methylation deficits and behavioral alterations in TCE-exposed mice. PMID:23566951

  12. Altered motor activity of alternative splice variants of the mammalian kinesin-3 protein KIF1B.

    PubMed

    Matsushita, Masafumi; Yamamoto, Ruri; Mitsui, Keiji; Kanazawa, Hiroshi

    2009-11-01

    Several mammalian kinesin motor proteins exist as multiple isoforms that arise from alternative splicing of a single gene. However, the roles of many motor protein splice variants remain unclear. The kinesin-3 motor protein KIF1B has alternatively spliced isoforms distinguished by the presence or absence of insertion sequences in the conserved amino-terminal region of the protein. The insertions are located in the loop region containing the lysine-rich cluster, also known as the K-loop, and in the hinge region adjacent to the motor domain. To clarify the functions of these alternative splice variants of KIF1B, we examined the biochemical properties of recombinant KIF1B with and without insertion sequences. In a microtubule-dependent ATPase assay, KIF1B variants that contained both insertions had higher activity and affinity for microtubules than KIF1B variants that contained no insertions. Mutational analysis of the K-loop insertion revealed that variants with a longer insertion sequence at this site had higher activity. However, the velocity of movement in motility assays was similar between KIF1B with and without insertion sequences. Our results indicate that splicing isoforms of KIF1B that vary in their insertion sequences have different motor activities.

  13. Delta-9-tetrahydrocannabinol (THC) affects forelimb motor map expression but has little effect on skilled and unskilled behavior.

    PubMed

    Scullion, K; Guy, A R; Singleton, A; Spanswick, S C; Hill, M N; Teskey, G C

    2016-04-05

    It has previously been shown in rats that acute administration of delta-9-tetrahydrocannabinol (THC) exerts a dose-dependent effect on simple locomotor activity, with low doses of THC causing hyper-locomotion and high doses causing hypo-locomotion. However the effect of acute THC administration on cortical movement representations (motor maps) and skilled learned movements is completely unknown. It is important to determine the effects of THC on motor maps and skilled learned behaviors because behaviors like driving place people at a heightened risk. Three doses of THC were used in the current study: 0.2mg/kg, 1.0mg/kg and 2.5mg/kg representing the approximate range of the low to high levels of available THC one would consume from recreational use of cannabis. Acute peripheral administration of THC to drug naïve rats resulted in dose-dependent alterations in motor map expression using high resolution short duration intracortical microstimulation (SD-ICMS). THC at 0.2mg/kg decreased movement thresholds and increased motor map size, while 1.0mg/kg had the opposite effect, and 2.5mg/kg had an even more dramatic effect. Deriving complex movement maps using long duration (LD)-ICMS at 1.0mg/kg resulted in fewer complex movements. Dosages of 1.0mg/kg and 2.5mg/kg THC reduced the number of reach attempts but did not affect percentage of success or the kinetics of reaching on the single pellet skilled reaching task. Rats that received 2.5mg/kg THC did show an increase in latency of forelimb removal on the bar task, while dose-dependent effects of THC on unskilled locomotor activity using the rotorod and horizontal ladder tasks were not observed. Rats may be employing compensatory strategies after receiving THC, which may account for the robust changes in motor map expression but moderate effects on behavior.

  14. Altered Behavioral Performance and Live Imaging of Circuit-Specific Neural Deficiencies in a Zebrafish Model for Psychomotor Retardation

    PubMed Central

    Lerer-Goldshtein, Tali; Vatine, Gad David; Appelbaum, Lior

    2014-01-01

    The mechanisms and treatment of psychomotor retardation, which includes motor and cognitive impairment, are indefinite. The Allan-Herndon-Dudley syndrome (AHDS) is an X-linked psychomotor retardation characterized by delayed development, severe intellectual disability, muscle hypotonia, and spastic paraplegia, in combination with disturbed thyroid hormone (TH) parameters. AHDS has been associated with mutations in the monocarboxylate transporter 8 (mct8/slc16a2) gene, which is a TH transporter. In order to determine the pathophysiological mechanisms of AHDS, MCT8 knockout mice were intensively studied. Although these mice faithfully replicated the abnormal serum TH levels, they failed to exhibit the neurological and behavioral symptoms of AHDS patients. Here, we generated an mct8 mutant (mct8−/−) zebrafish using zinc-finger nuclease (ZFN)-mediated targeted gene editing system. The elimination of MCT8 decreased the expression levels of TH receptors; however, it did not affect the expression of other TH-related genes. Similar to human patients, mct8−/− larvae exhibited neurological and behavioral deficiencies. High-throughput behavioral assays demonstrated that mct8−/− larvae exhibited reduced locomotor activity, altered response to external light and dark transitions and an increase in sleep time. These deficiencies in behavioral performance were associated with altered expression of myelin-related genes and neuron-specific deficiencies in circuit formation. Time-lapse imaging of single-axon arbors and synapses in live mct8−/− larvae revealed a reduction in filopodia dynamics and axon branching in sensory neurons and decreased synaptic density in motor neurons. These phenotypes enable assessment of the therapeutic potential of three TH analogs that can enter the cells in the absence of MCT8. The TH analogs restored the myelin and axon outgrowth deficiencies in mct8−/− larvae. These findings suggest a mechanism by which MCT8 regulates neural

  15. Altered behavioral performance and live imaging of circuit-specific neural deficiencies in a zebrafish model for psychomotor retardation.

    PubMed

    Zada, David; Tovin, Adi; Lerer-Goldshtein, Tali; Vatine, Gad David; Appelbaum, Lior

    2014-09-01

    The mechanisms and treatment of psychomotor retardation, which includes motor and cognitive impairment, are indefinite. The Allan-Herndon-Dudley syndrome (AHDS) is an X-linked psychomotor retardation characterized by delayed development, severe intellectual disability, muscle hypotonia, and spastic paraplegia, in combination with disturbed thyroid hormone (TH) parameters. AHDS has been associated with mutations in the monocarboxylate transporter 8 (mct8/slc16a2) gene, which is a TH transporter. In order to determine the pathophysiological mechanisms of AHDS, MCT8 knockout mice were intensively studied. Although these mice faithfully replicated the abnormal serum TH levels, they failed to exhibit the neurological and behavioral symptoms of AHDS patients. Here, we generated an mct8 mutant (mct8-/-) zebrafish using zinc-finger nuclease (ZFN)-mediated targeted gene editing system. The elimination of MCT8 decreased the expression levels of TH receptors; however, it did not affect the expression of other TH-related genes. Similar to human patients, mct8-/- larvae exhibited neurological and behavioral deficiencies. High-throughput behavioral assays demonstrated that mct8-/- larvae exhibited reduced locomotor activity, altered response to external light and dark transitions and an increase in sleep time. These deficiencies in behavioral performance were associated with altered expression of myelin-related genes and neuron-specific deficiencies in circuit formation. Time-lapse imaging of single-axon arbors and synapses in live mct8-/- larvae revealed a reduction in filopodia dynamics and axon branching in sensory neurons and decreased synaptic density in motor neurons. These phenotypes enable assessment of the therapeutic potential of three TH analogs that can enter the cells in the absence of MCT8. The TH analogs restored the myelin and axon outgrowth deficiencies in mct8-/- larvae. These findings suggest a mechanism by which MCT8 regulates neural circuit assembly

  16. Relations of Preschoolers' Visual-Motor and Object Manipulation Skills with Executive Function and Social Behavior

    ERIC Educational Resources Information Center

    MacDonald, Megan; Lipscomb, Shannon; McClelland, Megan M.; Duncan, Rob; Becker, Derek; Anderson, Kim; Kile, Molly

    2016-01-01

    Purpose: The purpose of this article was to examine specific linkages between early visual-motor integration skills and executive function, as well as between early object manipulation skills and social behaviors in the classroom during the preschool year. Method: Ninety-two children aged 3 to 5 years old (M[subscript age] = 4.31 years) were…

  17. Reducing the Stress of Intensive Care: Effects on Motor and State Behavior. Conference Summary.

    ERIC Educational Resources Information Center

    Becker, Patricia T.

    This report presents outcome data on infant motor activity and behavioral state. Subjects were 45 infants who had birth weight of less than 1,501 grams, were appropriate for gestational age, and were free of major complications. A total of 21 infants were studied during a preintervention (control period), and 24 were studied in a posttraining…

  18. Functional alterations of the ubiquitin-proteasome system in motor neurons of a mouse model of familial amyotrophic lateral sclerosis†

    PubMed Central

    Cheroni, Cristina; Marino, Marianna; Tortarolo, Massimo; Veglianese, Pietro; De Biasi, Silvia; Fontana, Elena; Zuccarello, Laura Vitellaro; Maynard, Christa J.; Dantuma, Nico P.; Bendotti, Caterina

    2009-01-01

    In familial and sporadic amyotrophic lateral sclerosis (ALS) and in rodent models of the disease, alterations in the ubiquitin-proteasome system (UPS) may be responsible for the accumulation of potentially harmful ubiquitinated proteins, leading to motor neuron death. In the spinal cord of transgenic mice expressing the familial ALS superoxide dismutase 1 (SOD1) gene mutation G93A (SOD1G93A), we found a decrease in constitutive proteasome subunits during disease progression, as assessed by real-time PCR and immunohistochemistry. In parallel, an increased immunoproteasome expression was observed, which correlated with a local inflammatory response due to glial activation. These findings support the existence of proteasome modifications in ALS vulnerable tissues. To functionally investigate the UPS in ALS motor neurons in vivo, we crossed SOD1G93A mice with transgenic mice that express a fluorescently tagged reporter substrate of the UPS. In double-transgenic UbG76V-GFP /SOD1G93A mice an increase in UbG76V-GFP reporter, indicative of UPS impairment, was detectable in a few spinal motor neurons and not in reactive astrocytes or microglia, at symptomatic stage but not before symptoms onset. The levels of reporter transcript were unaltered, suggesting that the accumulation of UbG76V-GFP was due to deficient reporter degradation. In some motor neurons the increase of UbG76V-GFP was accompanied by the accumulation of ubiquitin and phosphorylated neurofilaments, both markers of ALS pathology. These data suggest that UPS impairment occurs in motor neurons of mutant SOD1-linked ALS mice and may play a role in the disease progression. PMID:18826962

  19. AN ENVIRONMENTAL ANTIANDROGEN, VINCLOZOLIN, ALTERS THE ORGANIZATION OF PLAY BEHAVIOR

    EPA Science Inventory

    ABSTRACT

    During mammalian sexual differentiation, the androgens, testosterone and dihydrotestosterone are critical for the organization of the male phenotype. In rats, play behavior is sexually dimorphic. Administration of exogenous androgens during the perinatal period r...

  20. [Cognitive, linguistic, motoric, and social deficits in schoolstarters with behavioral disorders].

    PubMed

    Korsch, Franziska; Petermann, Ulrike; Schmidt, Sören; Petermann, Franz

    2013-01-01

    Studies show that ADHD, conduct disorders, and anxiety disorders are clinical disorders mostly diagnosed in schoolstarters. The preschool medical examination in Bremen was therefore extended by behavioral screenings. Based on their screening results from the SEU (health examination for school entry) 2011 in Bremen, 67 preschoolers were tested for behavioral disorders. Subsequently, children with behavioral or emotional symptoms (N = 56) were compared to symptomfree controls (N = 52) for their cognitive, motoric, linguistic, and social-emotional development. Psychosocial health was obtained through external assessment by the parents and kindergarten teachers. Results of the WPPSI-III, M-ABC-2, and ET 6-6 were included in the analysis. 32 children met the criteria for behavioral disorders. Children with behavioral or emotional symptoms showed significant lower scores on tests measuring cognitive, motoric, linguistic and emotional development compared to controls. Results suggest that there is necessity to screen all preschoolers for behavioral disorders before entering school. Because children with clinical or subclinical behavioral disorders showed major developmental deficits compared to children without behavioral symptoms, it is essential to conduct a multiple assessment on children with suspected behavioral disorders to ensure early developmental support and adequate interventional programs.

  1. Paternal environmental enrichment transgenerationally alters affective behavioral and neuroendocrine phenotypes.

    PubMed

    Yeshurun, Shlomo; Short, Annabel K; Bredy, Timothy W; Pang, Terence Y; Hannan, Anthony J

    2017-03-01

    Recent studies have demonstrated that paternal stress in rodents can result in modification of offspring behavior. Environmental enrichment, which enhances cognitive stimulation and physical activity, modifies various behaviors and reduces stress responses in adult rodents. We investigated the transgenerational influence of paternal environmental enrichment on offspring behavior and physiological stress response. Adult C57BL/6J male mice (F0) were exposed to either environmental enrichment or standard housing for four weeks and then pair-mated with naïve females. The F2 generation was generated using F1 male offspring. Male and female F1 and F2 offspring were tested for anxiety using the elevated-plus maze and large open field at 8 weeks of age. Depression-related behavior was assessed using the forced-swim test. Hypothalamic-pituitary-adrenal (HPA) axis function was determined by quantification of serum corticosterone and adrenocorticotropic hormone (ACTH) levels at baseline and after forced-swim stress. Paternal environmental enrichment was associated with increased body weights of male F1 and F2 offspring. There was no significant effect on F1 offspring anxiety and depression-related behaviors. There were no changes in anxiety-related behaviors in the F2 offspring, however these mice displayed a reduced latency to immobility in the forced-swim test. Furthermore, F2 females had significantly higher serum corticosterone levels post-stress, but not ACTH. These results show that paternal environmental enrichment exerts a sex-specific transgenerational impact on the behavioral and physiological response to stress. Our findings have implications for the modelling of psychiatric disorders in rodents.

  2. Altered mRNA Splicing in SMN-Depleted Motor Neuron-Like Cells

    PubMed Central

    Todd, A. Gary; Astroski, Jacob W.; Lin, Hai; Liu, Yunlong

    2016-01-01

    Spinal muscular atrophy (SMA) is an intractable neurodegenerative disease afflicting 1 in 6–10,000 live births. One of the key functions of the SMN protein is regulation of spliceosome assembly. Reduced levels of the SMN protein that are observed in SMA have been shown to result in aberrant mRNA splicing. SMN-dependent mis-spliced transcripts in motor neurons may cause stresses that are particularly harmful and may serve as potential targets for the treatment of motor neuron disease or as biomarkers in the SMA patient population. We performed deep RNA sequencing using motor neuron-like NSC-34 cells to screen for SMN-dependent mRNA processing changes that occur following acute depletion of SMN. We identified SMN-dependent splicing changes, including an intron retention event that results in the production of a truncated Rit1 transcript. This intron-retained transcript is stable and is mis-spliced in spinal cord from symptomatic SMA mice. Constitutively active Rit1 ameliorated the neurite outgrowth defect in SMN depleted NSC-34 cells, while expression of the truncated protein product of the mis-spliced Rit1 transcript inhibited neurite extension. These results reveal new insights into the biological consequence of SMN-dependent splicing in motor neuron-like cells. PMID:27736905

  3. Altered Intracellular Milieu of ADAR2-Deficient Motor Neurons in Amyotrophic Lateral Sclerosis.

    PubMed

    Yamashita, Takenari; Akamatsu, Megumi; Kwak, Shin

    2017-02-08

    Transactive response DNA-binding protein (TDP-43) pathology, and failure of A-to-I conversion (RNA editing) at the glutamine/arginine (Q/R) site of α-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA) receptor subunit GluA2, are etiology-linked molecular abnormalities that concomitantly occur in the motor neurons of most patients with amyotrophic lateral sclerosis (ALS). Adenosine deaminase acting on RNA 2 (ADAR2) specifically catalyzes GluA2 Q/R site-RNA editing. Furthermore, conditional ADAR2 knockout mice (AR2) exhibit a progressive ALS phenotype with TDP-43 pathology in the motor neurons, which is the most reliable pathological marker of ALS. Therefore, the evidence indicates that ADAR2 downregulation is a causative factor in ALS, and AR2 mice exhibit causative molecular changes that occur in ALS. We discuss the contributors to ADAR2 downregulation and TDP-43 pathology in AR2 mouse motor neurons. We describe mechanisms of exaggerated Ca(2+) influx amelioration via AMPA receptors, which is neuroprotective in ADAR2-deficient motor neurons with normalization of TDP-43 pathology in AR2 mice. Development of drugs to treat diseases requires appropriate animal models and a sensitive method of evaluating efficacy. Therefore, normalization of disrupted intracellular environments resulting from ADAR2 downregulation may be a therapeutic target for ALS. We discuss the development of targeted therapy for ALS using the AR2 mouse model.

  4. Altered Intracellular Milieu of ADAR2-Deficient Motor Neurons in Amyotrophic Lateral Sclerosis

    PubMed Central

    Yamashita, Takenari; Akamatsu, Megumi; Kwak, Shin

    2017-01-01

    Transactive response DNA-binding protein (TDP-43) pathology, and failure of A-to-I conversion (RNA editing) at the glutamine/arginine (Q/R) site of α-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA) receptor subunit GluA2, are etiology-linked molecular abnormalities that concomitantly occur in the motor neurons of most patients with amyotrophic lateral sclerosis (ALS). Adenosine deaminase acting on RNA 2 (ADAR2) specifically catalyzes GluA2 Q/R site-RNA editing. Furthermore, conditional ADAR2 knockout mice (AR2) exhibit a progressive ALS phenotype with TDP-43 pathology in the motor neurons, which is the most reliable pathological marker of ALS. Therefore, the evidence indicates that ADAR2 downregulation is a causative factor in ALS, and AR2 mice exhibit causative molecular changes that occur in ALS. We discuss the contributors to ADAR2 downregulation and TDP-43 pathology in AR2 mouse motor neurons. We describe mechanisms of exaggerated Ca2+ influx amelioration via AMPA receptors, which is neuroprotective in ADAR2-deficient motor neurons with normalization of TDP-43 pathology in AR2 mice. Development of drugs to treat diseases requires appropriate animal models and a sensitive method of evaluating efficacy. Therefore, normalization of disrupted intracellular environments resulting from ADAR2 downregulation may be a therapeutic target for ALS. We discuss the development of targeted therapy for ALS using the AR2 mouse model. PMID:28208729

  5. Early Brain Damage and the Development of Motor Behavior in Children: Clues for Therapeutic Intervention?

    PubMed Central

    Hadders-Algra, Mijna

    2001-01-01

    The Neuronal Group Selection Theory (NGST) could offer new insights into the mechanisms directing motor disorders, such as cerebral palsy and developmental coordination disorder. According to NGST, normal motor development is characterized by two phases of variability. Variation is not at random but determined by criteria set by genetic information. Development starts with the phase of primary variability,during which variation in motor behavior is not geared to external conditions. At function-specific ages secondary variability starts, during which motor performance can be adapted to specific situations. In both forms, of variability, selection on the basis of afferent information plays a significant role. From the NGST point of view, children with pre- or perinatally acquired brain damage, such as children with cerebral palsy and part of the children with developmental coordination disorder, suffer from stereotyped motor behavior, produced by a limited repertoire or primary (sub)cortical neuronal networks. These children also have roblems in selecting the most efficient neuronal activity, due to deficits in the processing of sensory information. Therefore, NGST suggests that intervention in these children at early age should aim at an enlargement of the primary neuronal networks. With increasing age, the emphasis of intervention could shift to the provision of ample opportunities for active practice, which might form a compensation for the impaired selection. PMID:11530887

  6. Pre-reproductive maternal enrichment influences offspring developmental trajectories: motor behavior and neurotrophin expression

    PubMed Central

    Caporali, Paola; Cutuli, Debora; Gelfo, Francesca; Laricchiuta, Daniela; Foti, Francesca; De Bartolo, Paola; Mancini, Laura; Angelucci, Francesco; Petrosini, Laura

    2014-01-01

    Environmental enrichment is usually applied immediately after weaning or in adulthood, with strong effects on CNS anatomy and behavior. To examine the hypothesis that a pre-reproductive environmental enrichment of females could affect the motor development of their offspring, female rats were reared in an enriched environment from weaning to sexual maturity, while other female rats used as controls were reared under standard conditions. Following mating with standard-reared males, all females were housed individually. To evaluate the eventual transgenerational influence of positive pre-reproductive maternal experiences, postural and motor development of male pups was analyzed from birth to weaning. Moreover, expression of Brain Derived Neurotrophic Factor and Nerve Growth Factor in different brain regions was evaluated at birth and weaning. Pre-reproductive environmental enrichment of females affected the offspring motor development, as indicated by the earlier acquisition of complex motor abilities displayed by the pups of enriched females. The earlier acquisition of motor abilities was associated with enhanced neurotrophin levels in striatum and cerebellum. In conclusion, maternal positive experiences were transgenerationally transmitted, and influenced offspring phenotype at both behavioral and biochemical levels. PMID:24910599

  7. Electrophysiological Evidence for Alternative Motor Networks in REM Sleep Behavior Disorder.

    PubMed

    Hackius, Marc; Werth, Esther; Sürücü, Oguzkan; Baumann, Christian R; Imbach, Lukas L

    2016-11-16

    Patients with Parkinson's disease (PD) and REM sleep behavior disorder (RBD) show mostly unimpaired motor behavior during REM sleep, which contrasts strongly to coexistent nocturnal bradykinesia. The reason for this sudden amelioration of motor control in REM sleep is unknown, however. We set out to determine whether movements during REM sleep are processed by different motor networks than movements in the waking state. We recorded local field potentials in the subthalamic nucleus (STN) and scalp EEG (modified 10/20 montage) during sleep in humans with PD and RBD. Time-locked event-related β band oscillations were calculated during movements in REM sleep compared with movements in the waking state and during NREM sleep. Spectral analysis of STN local field potentials revealed elevated β power during REM sleep compared with NREM sleep and β power in REM sleep reached levels similar as in the waking state. Event-related analysis showed time-locked β desynchronization during WAKE movements. In contrast, we found significantly elevated β activity before and during movements in REM sleep and NREM sleep. Corticosubthalamic coherence was reduced during REM and NREM movements. We conclude that sleep-related movements are not processed by the same corticobasal ganglia network as movements in the waking state. Therefore, the well-known seemingly normal motor performance during RBD in PD patients might be generated by activating alternative motor networks for movement initiation. These findings support the hypothesis that pathological movement-inhibiting basal ganglia networks in PD patients are bypassed during sleep.

  8. Structural and functional connectivity in healthy aging: Associations for cognition and motor behavior.

    PubMed

    Hirsiger, Sarah; Koppelmans, Vincent; Mérillat, Susan; Liem, Franziskus; Erdeniz, Burak; Seidler, Rachael D; Jäncke, Lutz

    2016-03-01

    Age-related behavioral declines may be the result of deterioration of white matter tracts, affecting brain structural (SC) and functional connectivity (FC) during resting state. To date, it is not clear if the combination of SC and FC data could better predict cognitive/motor performance than each measure separately. We probed these relationships in the cingulum bundle, a major white matter pathway of the default mode network. We aimed to attain deeper knowledge about: (a) the relationship between age and the cingulum's SC and FC strength, (b) the association between SC and FC, and particularly (c) how the cingulum's SC and FC are related to cognitive/motor performance separately and combined. We examined these associations in a healthy and well-educated sample of 165 older participants (aged 64-85). SC and FC were acquired using probabilistic tractography to derive measures to capture white matter integrity within the cingulum bundle (fractional anisotropy, mean, axial and radial diffusivity) and a seed-based resting-state functional MRI correlation approach, respectively. Participants performed cognitive tests measuring processing speed, memory and executive functions, and motor tests measuring motor speed and grip force. Our data revealed that only SC but not resting state FC was significantly associated with age. Further, the cingulum's SC and FC showed no relation. Different relationships between cognitive/motor performance and SC/FC separately were found, but no additive effect of the combined analysis of cingulum's SC and FC for predicting cognitive/motor performance was apparent.

  9. Depressive-like behaviors alterations induced by intranigral MPTP, 6-OHDA, LPS and rotenone models of Parkinson's disease are predominantly associated with serotonin and dopamine.

    PubMed

    Santiago, Ronise M; Barbieiro, Janaína; Lima, Marcelo M S; Dombrowski, Patrícia A; Andreatini, Roberto; Vital, Maria A B F

    2010-08-16

    Depression is a frequently encountered non-motor feature of Parkinson's disease (PD) and it can have a significant impact on patient's quality of life. Considering the differential pathophysiology of depression in PD, it prompts the idea that a degenerated nigrostriatal system plays a role in depressive-like behaviors, whilst animal models of PD are employed. Therefore, we addressed the question of whether dopamine (DA) depletion, promoted by the neurotoxins 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), 6-hydroxydopamine (6-OHDA), lipopolysaccharide (LPS) and rotenone are able to induce depressive-like behaviors and neurotransmitters alterations similarly that encountered in PD. To test this rationale, we performed intranigral injections of each neurotoxin, followed by motor behavior, depressive-like behaviors, histological and neurochemical tests. After the motor recovery period, MPTP, 6-OHDA and rotenone were able to produce anhedonia and behavioral despair. These altered behavioral responses were accompanied by reductions of striatal DA, homovanillic acid (HVA) and 3,4-dihydroxyphenylacetic acid (DOPAC) restricted to the 6-OHDA group. Additionally, decreases on the hippocampal serotonin (5-HT) content were detected for the MPTP, 6-OHDA and rotenone groups. Notably, strong correlations were detected among the groups when 5-HT and DA were correlated with swimming (r=+0.97; P=0.001) and immobility (r=-0.90; P=0.012), respectively. Our data indicate that MPTP, 6-OHDA and rotenone, but not LPS were able to produce depressive-like behaviors accompanied primarily by hippocampal 5-HT reductions. Moreover, DA and 5-HT strongly correlated with "emotional" impairments suggesting an important participation of these neurotransmitters in anhedonia and behavioral despair after nigral lesions promoted by the neurotoxins.

  10. Vulnerability of conditional NCAM-deficient mice to develop stress-induced behavioral alterations.

    PubMed

    Bisaz, Reto; Sandi, Carmen

    2012-03-01

    Previous studies in rodents showed that chronic stress induces structural and functional alterations in several brain regions, including shrinkage of the hippocampus and the prefrontal cortex, which are accompanied by cognitive and emotional disturbances. Reduced expression of the neural cell adhesion molecule (NCAM) following chronic stress has been proposed to be crucially involved in neuronal retraction and behavioral alterations. Since NCAM gene polymorphisms and altered expression of alternatively spliced NCAM isoforms have been associated with bipolar depression and schizophrenia in humans, we hypothesized that reduced expression of NCAM renders individuals more vulnerable to the deleterious effects of stress on behavior. Here, we specifically questioned whether mice in which the NCAM gene is inactivated in the forebrain by cre-recombinase under the control of the calcium-calmodulin-dependent kinase II promoter (conditional NCAM-deficient mice), display increased vulnerability to stress. We assessed the evolving of depressive-like behaviors and spatial learning and memory impairments following a subchronic stress protocol (2 weeks) that does not result in behavioral dysfunction, nor in altered NCAM expression, in wild-type mice. Indeed, while no behavioral alterations were detected in wild-type littermates after subchronic stress, conditional NCAM-deficient mice showed increased immobility in the tail suspension test and deficits in reversal spatial learning in the water maze. These findings indicate that diminished NCAM expression might be a critical vulnerability factor for the development of behavioral alterations by stress and further support a functional involvement of NCAM in stress-induced cognitive and emotional disturbances.

  11. Motor behaviors in the sheep evoked by electrical stimulation of the subthalamic nucleus.

    PubMed

    Lentz, Linnea; Zhao, Yan; Kelly, Matthew T; Schindeldecker, William; Goetz, Steven; Nelson, Dwight E; Raike, Robert S

    2015-11-01

    Deep brain stimulation (DBS) of the subthalamic nucleus (STN) is used to treat movement disorders, including advanced Parkinson's disease (PD). The pathogenesis of PD and the therapeutic mechanisms of DBS are not well understood. Large animal models are essential for investigating the mechanisms of PD and DBS. The purpose of this study was to develop a novel sheep model of STN DBS and quantify the stimulation-evoked motor behaviors. To do so, a large sample of animals was chronically-implanted with commercial DBS systems. Neuroimaging and histology revealed that the DBS leads were implanted accurately relative to the neurosurgical plan and also precisely relative to the STN. It was also possible to repeatedly conduct controlled evaluations of stimulation-evoked motor behavior in the awake-state. The evoked motor responses depended on the neuroanatomical location of the electrode contact selected for stimulation, as contacts proximal to the STN evoked movements at significantly lower voltages. Tissue stimulation modeling demonstrated that selecting any of the contacts stimulated the STN, whereas selecting the relatively distal contacts often also stimulated thalamus but only the distal-most contact stimulated internal capsule. The types of evoked motor behaviors were specific to the stimulation frequency, as low but not high frequencies consistently evoked movements resembling human tremor or dyskinesia. Electromyography confirmed that the muscle activity underlying the tremor-like movements in the sheep was consistent with human tremor. Overall, this work establishes that the sheep is a viable a large-animal platform for controlled testing of STN DBS with objective motor outcomes. Moreover, the results support the hypothesis that exaggerated low-frequency activity within individual nodes of the motor network can drive symptoms of human movement disorders, including tremor and dyskinesia.

  12. Children with Autism and Attention Difficulties: A Pilot Study of the Association between Sensory, Motor, and Adaptive Behaviors

    PubMed Central

    Mattard-Labrecque, Carolanne; Ben Amor, Leila; Couture, Mélanie M.

    2013-01-01

    Objectives: This pilot study aimed to compare sensory processing, motor skills and adaptive behaviors in children with a double diagnosis of Autism Spectrum Disorder (ASD) and Attention Deficit Hyperactivity Disorder (ADHD) (ASD+ADHD) with children with ADHD alone and to examine the association of sensory processing and motor skills with adaptive behaviors (self-care). Method: Thirty children aged 5–14 years diagnosed with ASD+ADHD (n = 13) or ADHD (n = 17) were evaluated on their sensory processing and motor skills and adaptive behaviors. Analysis of covariance compared the groups on these dimensions. Correlation analyses examined the association between sensory processing and motor skills and adaptive behaviors. Results: Compared to children with ADHD alone, children with ASD+ADHD had poorer skills in sensory processing (p < 0.001), motor (p = 0.001) and adaptive behaviors (p < 0.001). For all children, increased autonomy in self-care was correlated with better sensory processing (p < 0.001) and motor skills (p = 0.002). Conclusion: Children with ASD+ADHD have poorer sensory processing, motor and adaptive skills than those with ADHD alone. Sensory processing and motor deficits were negatively associated with autonomy in self-care. Interventions aiming to improve sensory processing and motor skills and autonomy in self-care should become important targets for these children. PMID:23667360

  13. Perinatal thiamine restriction affects central GABA and glutamate concentrations and motor behavior of adult rat offspring.

    PubMed

    Ferreira-Vieira, Talita Hélen; de Freitas-Silva, Danielle Marra; Ribeiro, Andrea Frozino; Pereira, Sílvia Rejane Castanheira; Ribeiro, Ângela Maria

    2016-03-23

    The purposes of the present study were to investigate the effects of perinatal thiamine deficiency, from the 11th day of gestation until the 5th day of lactation, on motor behavior and neurochemical parameters in adult rat offspring, using 3-month-old, adult, male Wistar rats. All rats were submitted to motor tests, using the rotarod and paw print tasks. After behavioral tests, their thalamus, cerebellum and spinal cord were dissected for glutamate and GABA quantifications by high performance liquid chromatography. The thiamine-restricted mothers (RM) group showed a significant reduction of time spent on the rotarod at 25 rpm and an increase in hind-base width. A significant decrease of glutamate concentration in the cerebellum and an increase of GABA concentrations in the thalamus were also observed. For the offspring from control mothers (CM) group there were significant correlations between thalamic GABA concentrations and both rotarod performance and average hind-base width. In addition, for rats from the RM group a significant correlation between stride length and cerebellar GABA concentration was found. These results show that the deficiency of thiamine during an early developmental period affects certain motor behavior parameters and GABA and glutamate levels in specific brain areas. Hence, a thiamine deficiency episode during an early developmental period can induce motor impairments and excitatory and inhibitory neurotransmitter changes that are persistent and detectable in later periods of life.

  14. Harmony from Chaos? Perceptual-Motor Delays Enhance Behavioral Anticipation in Social Interaction

    PubMed Central

    Washburn, Auriel; Kallen, Rachel W.; Coey, Charles A.; Shockley, Kevin; Richardson, Michael J.

    2015-01-01

    Effective interpersonal coordination is fundamental to robust social interaction, and the ability to anticipate a co-actor's behavior is essential for achieving this coordination. However, coordination research has focused on the behavioral synchrony that occurs between the simple periodic movements of co-actors and, thus, little is known about the anticipation that occurs during complex, everyday interaction. Research on the dynamics of coupled neurons, human motor control, electrical circuits, and laser semiconductors universally demonstrates that small temporal feedback delays are necessary for the anticipation of chaotic events. We therefore investigated whether similar feedback delays would promote anticipatory behavior during social interaction. Results revealed that co-actors were not only able to anticipate others' chaotic movements when experiencing small perceptual-motor delays, but also exhibited movement patterns of equivalent complexity. This suggests that such delays, including those within the human nervous system, may enhance, rather than hinder, the anticipatory processes that underlie successful social interaction. PMID:26030437

  15. Housing conditions influence motor functions and exploratory behavior following focal damage of the rat brain.

    PubMed

    Gornicka-Pawlak, Elzbieta; Jabłońska, Anna; Chyliński, Andrzej; Domańska-Janik, Krystyna

    2009-01-01

    The present study investigated influence of housing conditions on motor functions recovery and exploratory behavior following ouabain focal brain lesion in the rat. During 30 days post-surgery period rats were housed individually in standard cages (IS) or in groups in enriched environment (EE) and behaviorally tested. The EE lesioned rats showed enhanced recovery from motor impairments in walking beam task, comparing with IS animals. Contrarily, in the open field IS rats (both lesioned and control) traveled a longer distance, showed less habituation and spent less time resting at the home base than the EE animals. Unlike the EE lesioned animals, the lesioned IS rats, presented a tendency to hyperactivity in postinjury period. Turning tendency was significantly affected by unilateral brain lesion only in the EE rats. We can conclude that housing conditions distinctly affected the rat's behavior in classical laboratory tests.

  16. Primary motor cortex of the parkinsonian monkey: altered encoding of active movement

    PubMed Central

    Pasquereau, Benjamin; DeLong, Mahlon R.

    2016-01-01

    Abnormalities in the movement-related activation of the primary motor cortex (M1) are thought to be a major contributor to the motor signs of Parkinson’s disease. The existing evidence, however, variably indicates that M1 is under-activated with movement, overactivated (due to a loss of functional specificity) or activated with abnormal timing. In addition, few models consider the possibility that distinct cortical neuron subtypes may be affected differently. Those gaps in knowledge were addressed by studying the extracellular activity of antidromically-identified lamina 5b pyramidal-tract type neurons (n = 153) and intratelencephalic-type corticostriatal neurons (n = 126) in the M1 of two monkeys as they performed a step-tracking arm movement task. We compared movement-related discharge before and after the induction of parkinsonism by administration of MPTP (1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine) and quantified the spike rate encoding of specific kinematic parameters of movement using a generalized linear model. The fraction of M1 neurons with movement-related activity declined following MPTP but only marginally. The strength of neuronal encoding of parameters of movement was reduced markedly (mean 29% reduction in the coefficients from the generalized linear model). This relative decoupling of M1 activity from kinematics was attributable to reductions in the coefficients that estimated the spike rate encoding of movement direction (−22%), speed (−40%), acceleration (−49%) and hand position (−33%). After controlling for MPTP-induced changes in motor performance, M1 activity related to movement itself was reduced markedly (mean 36% hypoactivation). This reduced activation was strong in pyramidal tract-type neurons (−50%) but essentially absent in corticostriatal neurons. The timing of M1 activation was also abnormal, with earlier onset times, prolonged response durations, and a 43% reduction in the prevalence of movement-related changes

  17. Constructs of human neuropathy target esterase catalytic domain containing mutations related to motor neuron disease have altered enzymatic properties.

    PubMed

    Hein, Nichole D; Stuckey, Jeanne A; Rainier, Shirley R; Fink, John K; Richardson, Rudy J

    2010-07-01

    Neuropathy target esterase (NTE) is a phospholipase/lysophospholipase associated with organophosphorus (OP) compound-induced delayed neurotoxicity (OPIDN). Distal degeneration of motor axons occurs in both OPIDN and the hereditary spastic paraplegias (HSPs). Recently, mutations within the esterase domain of NTE were identified in patients with a novel type of HSP (SPG39) designated NTE-related motor neuron disease (NTE-MND). Two of these mutations, arginine 890 to histidine (R890H) and methionine 1012 to valine (M1012V), were created in human recombinant NTE catalytic domain (NEST) to measure possible changes in catalytic properties. These mutated enzymes had decreased specific activities for hydrolysis of the artificial substrate, phenyl valerate. In addition, the M1012V mutant exhibited a reduced bimolecular rate constant of inhibition (k(i)) for all three inhibitors tested: mipafox, diisopropylphosphorofluoridate, and chlorpyrifos oxon. Finally, while both mutated enzymes inhibited by OP compounds exhibited altered time-dependent loss of their ability to be reactivated by nucleophiles (aging), more pronounced effects were seen with the M1012V mutant. Taken together, the results from specific activity, inhibition, and aging experiments suggest that the mutations found in association with NTE-MND have functional correlates in altered enzymological properties of NTE.

  18. On the Behavior of Phosphorus During the Aqueous Alteration of CM2 Carbonaceous Chondrites

    NASA Technical Reports Server (NTRS)

    Brearley, Adrian J.; Chizmadia, Lysa J.

    2005-01-01

    During the earliest period of solar system formation, water played an important role in the evolution of primitive dust, both after accretion of planetesimals and possible before accretion within the protoplanetary disk. Many chondrites show evidence of variable degrees of aqueous alteration, the CM2 chondrites being among the most studied [1]. This group of chondrites is characterized by mineral assemblages of both primary and secondary alteration phases. Hence, these meteorites retain a particularly important record of the reactions that occurred between primary high temperature nebular phases and water. Studies of these chondrites can provide information on the conditions and environments of aqueous alteration and the mobility of elements during alteration. This latter question is at the core of a debate concerning the location of aqueous alteration, i.e. whether alteration occurred predominantly within a closed system after accretion (parent body alteration) or whether some degree of alteration occurred within the solar nebula or on ephemeral protoplanetary bodies prior to accretion. At the core of the parent body alteration model is the hypothesis that elemental exchange between different components, principally chondrules and matrix, must have occurred. chondrules and matrix, must have occurred. In this study, we focus on the behavior of the minor element, phosphorus. This study was stimulated by observations of the behavior of P during the earliest stages of alteration in glassy mesostasis in type II chondrules in CR chondrites and extends the preliminary observations of on Y791198 to other CM chondrites.

  19. Natural descriptions of motor behavior: examples from E. coli and C. elegans.

    NASA Astrophysics Data System (ADS)

    Ryu, William

    2007-03-01

    E. coli has a natural behavioral variable - the direction of rotation of its flagellar rotorary motor. Monitoring this one-dimensional behavioral response in reaction to chemical perturbation has been instrumental in the understanding of how E. coli performs chemotaxis at the genetic, physiological, and computational level. Here we apply this experimental strategy to the study of bacterial thermotaxis - a sensory mode that is less well understood. We investigate bacterial thermosensation by studying the motor response of single cells subjected to impulses of heat produced by an IR laser. A simple temperature dependent modification to an existing chemotaxis model can explain the observed temperature response. Higher organisms may have a more complicated behavioral response due to the simple fact that their motions have more degrees of freedom. Here we provide a principled analysis of motor behavior of such an organism -- the roundworm C. elegans. Using tracking video-microscopy we capture a worm's image and extract the skeleton of the shape as a head-to-tail ordered collection of tangent angles sampled along the curve. Applying principal components analysis we show that the space of shapes is remarkably low dimensional, with four dimensions accounting for > 95% of the shape variance. We also show that these dimensions align with behaviorally relevant states. As an application of this analysis we study the thermal response of worms stimulated by laser heating. Our quantitative description of C. elegans movement should prove useful in a wide variety of contexts, from the linking of motor output with neural circuitry to the genetic basis of adaptive behavior.

  20. Improvement in motor and exploratory behavior in Rett syndrome mice with restricted ketogenic and standard diets.

    PubMed

    Mantis, John G; Fritz, Christie L; Marsh, Jeremy; Heinrichs, Stephen C; Seyfried, Thomas N

    2009-06-01

    Rett syndrome (RTT) is a rare X-linked autistic-spectrum neurological disorder associated with impaired energy metabolism, seizure susceptibility, progressive social behavioral regression, and motor impairment primarily in young girls. The objective of this study was to examine the influence of restricted diets, including a ketogenic diet (KD) and a standard rodent chow diet (SD), on behavior in male Mecp2(308/y) mice, a model of RTT. The KD is a high-fat, low-carbohydrate diet that has anticonvulsant efficacy in children with intractable epilepsy and may be therapeutic in children with RTT. Following an 11-day pretrial period, adult wild-type and mutant Rett mice were separated into groups that were fed either an SD in unrestricted or restricted amounts or a ketogenic diet (KetoCal) in restricted amounts for a total of 30 days. The restricted diets were administered to reduce mouse body weight by 20-23% compared to the body weight of each mouse before the initiation of the diet. All mice were subjected to a battery of behavioral tests to determine the influence of the diet on the RTT phenotype. We found that performance in tests of motor behavior and anxiety was significantly worse in male RTT mice compared to wild-type mice and that restriction of either the KD or the SD improved motor behavior and reduced anxiety. We conclude that although both restricted diets increased the tendency of Rett mice to explore a novel environment, the beneficial effects of the KD were due more to calorie restriction than to the composition of the diet. Our findings suggest that calorically restricted diets could be effective in reducing the anxiety and in improving motor behavior in girls with RTT.

  1. Motor learning in individuals with autism spectrum disorder: activation in superior parietal lobule related to learning and repetitive behaviors.

    PubMed

    Travers, Brittany G; Kana, Rajesh K; Klinger, Laura G; Klein, Christopher L; Klinger, Mark R

    2015-02-01

    Motor-linked implicit learning is the learning of a sequence of movements without conscious awareness. Although motor symptoms are frequently reported in individuals with autism spectrum disorder (ASD), recent behavioral studies have suggested that motor-linked implicit learning may be intact in ASD. The serial reaction time (SRT) task is one of the most common measures of motor-linked implicit learning. The present study used a 3T functional magnetic resonance imaging scanner to examine the behavioral and neural correlates of real-time motor sequence learning in adolescents and adults with ASD (n = 15) compared with age- and intelligence quotient-matched individuals with typical development (n = 15) during an SRT task. Behavioral results suggested less robust motor sequence learning in individuals with ASD. Group differences in brain activation suggested that individuals with ASD, relative to individuals with typical development, showed decreased activation in the right superior parietal lobule (SPL) and right precuneus (Brodmann areas 5 and 7, and extending into the intraparietal sulcus) during learning. Activation in these areas (and in areas such as the right putamen and right supramarginal gyrus) was found to be significantly related to behavioral learning in this task. Additionally, individuals with ASD who had more severe repetitive behavior/restricted interest symptoms demonstrated greater decreased activation in these regions during motor learning. In conjunction, these results suggest that the SPL may play an important role in motor learning and repetitive behavior in individuals with ASD.

  2. Altered cortical beta‐band oscillations reflect motor system degeneration in amyotrophic lateral sclerosis

    PubMed Central

    Proudfoot, Malcolm; Rohenkohl, Gustavo; Quinn, Andrew; Colclough, Giles L.; Wuu, Joanne; Talbot, Kevin; Woolrich, Mark W.; Benatar, Michael

    2016-01-01

    Abstract Continuous rhythmic neuronal oscillations underpin local and regional cortical communication. The impact of the motor system neurodegenerative syndrome amyotrophic lateral sclerosis (ALS) on the neuronal oscillations subserving movement might therefore serve as a sensitive marker of disease activity. Movement preparation and execution are consistently associated with modulations to neuronal oscillation beta (15–30 Hz) power. Cortical beta‐band oscillations were measured using magnetoencephalography (MEG) during preparation for, execution, and completion of a visually cued, lateralized motor task that included movement inhibition trials. Eleven “classical” ALS patients, 9 with the primary lateral sclerosis (PLS) phenotype, and 12 asymptomatic carriers of ALS‐associated gene mutations were compared with age‐similar healthy control groups. Augmented beta desynchronization was observed in both contra‐ and ipsilateral motor cortices of ALS patients during motor preparation. Movement execution coincided with excess beta desynchronization in asymptomatic mutation carriers. Movement completion was followed by a slowed rebound of beta power in all symptomatic patients, further reflected in delayed hemispheric lateralization for beta rebound in the PLS group. This may correspond to the particular involvement of interhemispheric fibers of the corpus callosum previously demonstrated in diffusion tensor imaging studies. We conclude that the ALS spectrum is characterized by intensified cortical beta desynchronization followed by delayed rebound, concordant with a broader concept of cortical hyperexcitability, possibly through loss of inhibitory interneuronal influences. MEG may potentially detect cortical dysfunction prior to the development of overt symptoms, and thus be able to contribute to the assessment of future neuroprotective strategies. Hum Brain Mapp 38:237–254, 2017. © 2016 Wiley Periodicals, Inc. PMID:27623516

  3. The Association of Intelligence, Visual-Motor Functioning, and Personality Characteristics With Adaptive Behavior in Individuals With Williams Syndrome.

    PubMed

    Fu, Trista J; Lincoln, Alan J; Bellugi, Ursula; Searcy, Yvonne M

    2015-07-01

    Williams syndrome (WS) is associated with deficits in adaptive behavior and an uneven adaptive profile. This study investigated the association of intelligence, visual-motor functioning, and personality characteristics with the adaptive behavior in individuals with WS. One hundred individuals with WS and 25 individuals with developmental disabilities of other etiologies were included in this study. This study found that IQ and visual-motor functioning significantly predicted adaptive behavior in individuals of WS. Visual-motor functioning especially predicted the most amount of unique variance in overall adaptive behavior and contributed to the variance above and beyond that of IQ. Present study highlights the need for interventions that address visual-motor and motor functioning in individuals with WS.

  4. Temporal Lobe Epilepsy Alters Auditory-motor Integration For Voice Control

    PubMed Central

    Li, Weifeng; Chen, Ziyi; Yan, Nan; Jones, Jeffery A.; Guo, Zhiqiang; Huang, Xiyan; Chen, Shaozhen; Liu, Peng; Liu, Hanjun

    2016-01-01

    Temporal lobe epilepsy (TLE) is the most common drug-refractory focal epilepsy in adults. Previous research has shown that patients with TLE exhibit decreased performance in listening to speech sounds and deficits in the cortical processing of auditory information. Whether TLE compromises auditory-motor integration for voice control, however, remains largely unknown. To address this question, event-related potentials (ERPs) and vocal responses to vocal pitch errors (1/2 or 2 semitones upward) heard in auditory feedback were compared across 28 patients with TLE and 28 healthy controls. Patients with TLE produced significantly larger vocal responses but smaller P2 responses than healthy controls. Moreover, patients with TLE exhibited a positive correlation between vocal response magnitude and baseline voice variability and a negative correlation between P2 amplitude and disease duration. Graphical network analyses revealed a disrupted neuronal network for patients with TLE with a significant increase of clustering coefficients and path lengths as compared to healthy controls. These findings provide strong evidence that TLE is associated with an atypical integration of the auditory and motor systems for vocal pitch regulation, and that the functional networks that support the auditory-motor processing of pitch feedback errors differ between patients with TLE and healthy controls. PMID:27356768

  5. Constraining movement alters the recruitment of motor processes in mental rotation.

    PubMed

    Moreau, David

    2013-02-01

    Does mental rotation depend on the readiness to act? Recent evidence indicates that the involvement of motor processes in mental rotation is experience-dependent, suggesting that different levels of expertise in sensorimotor interactions lead to different strategies to solve mental rotation problems. Specifically, experts in motor activities perceive spatial material as objects that can be acted upon, triggering covert simulation of rotations. Because action simulation depends on the readiness to act, movement restriction should therefore disrupt mental rotation performance in individuals favoring motor processes. In this experiment, wrestlers and non-athletes judged whether pairs of three-dimensional stimuli were identical or different, with their hands either constrained or unconstrained. Wrestlers showed higher performance than controls in the rotation of geometric stimuli, but this difference disappeared when their hands were constrained. However, movement restriction had similar consequences for both groups in the rotation of hands. These findings suggest that expert's advantage in mental rotation of abstract objects is based on the readiness to act, even when physical manipulation is impossible.

  6. Alterations in multidimensional motor unit number index of hand muscles after incomplete cervical spinal cord injury

    PubMed Central

    Li, Le; Li, Xiaoyan; Liu, Jie; Zhou, Ping

    2015-01-01

    The objective of this study was to apply a novel multidimensional motor unit number index (MD-MUNIX) technique to examine hand muscles in patients with incomplete cervical spinal cord injury (SCI). The MD-MUNIX was estimated from the compound muscle action potential (CMAP) and different levels of surface interference pattern electromyogram (EMG) at multiple directions of voluntary isometric muscle contraction. The MD-MUNIX was applied in the first dorsal interosseous (FDI), thenar and hypothenar muscles of SCI (n = 12) and healthy control (n = 12) subjects. The results showed that the SCI subjects had significantly smaller CMAP and MD-MUNIX in all the three examined muscles, compared to those derived from the healthy control subjects. The multidimensional motor unit size index (MD-MUSIX) demonstrated significantly larger values for the FDI and hypothenar muscles in SCI subjects than those from healthy control subjects, whereas the MD-MUSIX enlargement was marginally significant for the thenar muscles. The findings from the MD-MUNIX analyses provide an evidence of motor unit loss in hand muscles of cervical SCI patients, contributing to hand function deterioration. PMID:26005410

  7. Nicotine-Cadmium Interaction Alters Exploratory Motor Function and Increased Anxiety in Adult Male Mice

    PubMed Central

    Chris Ajonijebu, Duyilemi; Adeyemi Adeniyi, Philip; Oloruntoba Adekeye, Adeshina; Peter Olatunji, Babawale; Olakunle Ishola, Azeez; Michael Ogundele, Olalekan

    2014-01-01

    In this study we evaluated the time dependence in cadmium-nicotine interaction and its effect on motor function, anxiety linked behavioural changes, serum electrolytes, and weight after acute and chronic treatment in adult male mice. Animals were separated randomly into four groups of n = 6 animals each. Treatment was done with nicotine, cadmium, or nicotine-cadmium for 21 days. A fourth group received normal saline for the same duration (control). Average weight was determined at 7-day interval for the acute (D1-D7) and chronic (D7-D21) treatment phases. Similarly, the behavioural tests for exploratory motor function (open field test) and anxiety were evaluated. Serum electrolytes were measured after the chronic phase. Nicotine, cadmium, and nicotine-cadmium treatments caused no significant change in body weight after the acute phase while cadmium-nicotine and cadmium caused a decline in weight after the chronic phase. This suggests the role of cadmium in the weight loss observed in tobacco smoke users. Both nicotine and cadmium raised serum Ca2+ concentration and had no significant effect on K+ ion when compared with the control. In addition, nicotine-cadmium treatment increased bioaccumulation of Cd2+ in the serum which corresponded to a decrease in body weight, motor function, and an increase in anxiety. PMID:26317007

  8. Fish Chromatophores--From Molecular Motors to Animal Behavior.

    PubMed

    Sköld, Helen Nilsson; Aspengren, Sara; Cheney, Karen L; Wallin, Margareta

    2016-01-01

    Chromatophores are pigment-bearing cells of lower vertebrates, including fish that cater for the ability of individual animals to shift body coloration and pattern. Color change provides dynamic camouflage and various kinds of communication. It is also a spectacular example of phenotypic plasticity, and of significant importance for adaptation and survival in novel environments. Through different cellular mechanisms, color change can occur within minutes or more slowly over weeks. Chromatophores have different pigment types and are located not only in the skin, but also in the eyes and internally. While morphological color change, including seasonal color change, has received a lot of interest from evolutionary biologists and behavioral ecologists, the more rapid physiological color change has been largely a research subject for cell physiologists. In this cross-disciplinary review, we have highlighted emerging trends in pigment cell research and identified unsolved problems for future research.

  9. Effect of prenatal haloperidol exposure on behavioral alterations in rats.

    PubMed

    Singh, K P; Singh, Mandavi

    2002-01-01

    Pregnant Charles-Foster rats were exposed to haloperidol (HAL), a neuroleptic drug that binds to and blocks dopamine (DA) receptor subtypes at a dose of 2.5 mg/kg body weight (intraperitoneally) from Gestation Day (GD) 12 to 20. The animals from both treated as well as vehicle control groups were allowed to deliver on GD 21. The offspring culled at birth on the basis of sex and weight were subjected to behavioral tests at the age of 8 weeks. The HAL-treated rat offspring showed a significant increase in anxiogenic behavior on the open field, elevated plus-maze and elevated zero-maze tests when compared with the vehicle-treated (control) rat offspring of the same age group. These findings suggest that prenatal exposure to HAL during a critical period of brain development leaves a lasting imprint on the brain, resulting in abnormal anxiety states, possibly through dopaminergic neurotransmission mechanisms.

  10. Altering Leadership Thinking and Organizational Behavior Through Web Services

    DTIC Science & Technology

    2010-04-01

    result. The proliferation of Web 2.0 services is enabling information sharing among employees and leaders. Regrettably, this level of information...investigates the relationship between Web services, commonly called Web 2.0 , and the influence these services wield on organizational behavior. To support the...infrastructure for those who can use Web 2.0 and other IT services. The data were sorted by officer, noncommissioned officer, and enlisted ranks for the

  11. Peripheral injury alters schooling behavior in squid, Doryteuthis pealeii.

    PubMed

    Oshima, Megumi; di Pauli von Treuheim, Theodor; Carroll, Julia; Hanlon, Roger T; Walters, Edgar T; Crook, Robyn J

    2016-07-01

    Animals with detectable injuries are at escalated threat of predation. The anti-predation tactic of schooling reduces individual predation risk overall, but it is not known how schooling behavior affects injured animals, or whether risks are reduced equally for injured animals versus other school members. In this laboratory study we examined the effects of minor fin injury on schooling decisions made by squid. Schooling behavior of groups of squid, in which one member was injured, was monitored over 24h. Injured squid were more likely to be members of a school shortly after injury (0.5-2h), but there were no differences compared with sham-injured squid at longer time points (6-24h). Overall, the presence of an injured conspecific increased the probability that a school would form, irrespective of whether the injured squid was a member of the school. When groups containing one injured squid were exposed to a predator cue, injured squid were more likely to join the school, but their position depended on whether the threat was a proximate visual cue or olfactory cue. We found no evidence that injured squid oriented themselves to conceal their injury from salient threats. Overall we conclude that nociceptive sensitization after injury changes grouping behaviors in ways that are likely to be adaptive.

  12. Chronic Creatine Supplementation Alters Depression-like Behavior in Rodents in a Sex-Dependent Manner

    PubMed Central

    Allen, Patricia J; D'Anci, Kristen E; Kanarek, Robin B; Renshaw, Perry F

    2010-01-01

    Impairments in bioenergetic function, cellular resiliency, and structural plasticity are associated with the pathogenesis of mood disorders. Preliminary evidence suggests that creatine, an ergogenic compound known to promote cell survival and influence the production and usage of energy in the brain, can improve mood in treatment-resistant patients. This study examined the effects of chronic creatine supplementation using the forced swim test (FST), an animal model selectively sensitive to antidepressants with clinical efficacy in human beings. Thirty male (experiment 1) and 36 female (experiment 2) Sprague–Dawley rats were maintained on either chow alone or chow blended with either 2% w/w creatine monohydrate or 4% w/w creatine monohydrate for 5 weeks before the FST. Open field exploration and wire suspension tests were used to rule out general psychostimulant effects. Male rats maintained on 4% creatine displayed increased immobility in the FST as compared with controls with no differences by diet in the open field test, whereas female rats maintained on 4% creatine displayed decreased immobility in the FST and less anxiety in the open field test compared with controls. Open field and wire suspension tests confirmed that creatine supplementation did not produce differences in physical ability or motor function. The present findings suggest that creatine supplementation alters depression-like behavior in the FST in a sex-dependent manner in rodents, with female rats displaying an antidepressant-like response. Although the mechanisms of action are unclear, sex differences in creatine metabolism and the hormonal milieu are likely involved. PMID:19829292

  13. Manipulating the behavior-altering effect of the motivating operation: examination of the influence on challenging behavior during leisure activities.

    PubMed

    O'Reilly, Mark F; Sigafoos, Jeff; Lancioni, Giulio; Rispoli, Mandy; Lang, Russell; Chan, Jeff; Machalicek, Wendy; Langthorne, Paul

    2008-01-01

    We examined the behavior-altering effect of the motivating operation on challenging behavior during leisure activities for three individuals with severe disabilities. Prior functional analyses indicated that challenging behavior was maintained by positive reinforcement in the form of attention or tangible items for all participants. During leisure sessions, each participant played preferred games (cards, jigsaws) with two individuals without disabilities. The discriminative stimuli for challenging behavior were present during leisure sessions but challenging behavior was never reinforced. Immediately prior to leisure sessions, the participants received either access to the reinforcers that maintained challenging behavior or no access. Access versus no access to reinforcers for challenging behavior prior to leisure sessions was alternated in a multi-element design. Results demonstrated higher levels of challenging behavior during leisure sessions when the participants did not have access to the reinforcers prior to the sessions. Little challenging behavior occurred during leisure sessions when the participants had prior access to the reinforcers. Arguments for further examining the behavior-altering effects of the motivating operation in future applied research are presented.

  14. The time course for kinetic versus kinematic planning of goal-directed human motor behavior.

    PubMed

    Vesia, Michael; Vander, Helena; Yan, Xiaogang; Sergio, Lauren E

    2005-01-01

    The present psychophysical study compares motor planning during goal-directed reaching movements and isometric spatial force generation. Our objective is to characterize the extent to which the motor system accounts for the biomechanical details of an impending reach. One issue that the nervous system must take into account when transforming a spatial sensory signal into an intrinsic pattern of joint torques is that of limb dynamics, including intersegmental dynamics and inertial anisotropy of the arm. These will act to displace the hand away from a straight path to an object. In theory, if the nervous system accounts for movement-related limb dynamics prior to its initial motor output, early force direction for a movement will differ from an isometric force to the same spatial target. Alternatively, biomechanical details of motor behavior may be implemented into the motor act following its initiation. Limb position and force output at the wrist were recorded while subjects displaced a cursor to targets viewed on a computer monitor. To generate isometric forces, a magnetic brake held a mechanical linkage supporting the arm in place. Subjects were cued to displace the cursor by using either isometric force or limb movement. On random trials, a movement was cued but an isometric force was unexpectedly required. Results show that there is not a significant directional difference in the initial force trajectory when planning a movement versus planning an isometric force. These findings suggest that the motor system may initially use a coarse approximation of movement-related limb dynamics, allowing for the refinement of the motor plan as the movement unfolds.

  15. Biographic and behavioral factors are associated with music-related motor skills in children pianists.

    PubMed

    Spector, June T; Yong, Raymond; Altenmüller, Eckart; Jabusch, Hans-Christian

    2014-10-01

    This study aimed to identify biographical and behavioral factors associated with children pianists' motor skills using an objective assessment of a music-relevant motor task. Motor skills at the piano were assessed in 30 children pianists by measuring temporal unevenness in standardized scale playing using musical instrument digital interface (MIDI)-based scale analysis. Questionnaires were used to collect detailed information about the amount of time playing the piano, practice characteristics, attitudes toward music and practice, and the environment of music and practice. Associations between performance values and variables from the questionnaire were investigated using multivariable linear regression. A higher number of years playing the piano, more frequent parental involvement in the child's practice, more frequent practice of technical exercises, and greater enjoyment of practice and of the visual arts were associated with better motor performance. In addition to cumulative experience and aspects of practice, extrinsic motivational factors (e.g., parental interest) and intrinsic motivational factors (e.g., an artistic disposition) were associated with better performance on a musically-relevant motor task in children pianists.

  16. Diet-induced obesity progressively alters cognition, anxiety-like behavior and lipopolysaccharide-induced depressive-like behavior: focus on brain indoleamine 2,3-dioxygenase activation.

    PubMed

    André, Caroline; Dinel, Anne-Laure; Ferreira, Guillaume; Layé, Sophie; Castanon, Nathalie

    2014-10-01

    Obesity is associated with a high prevalence of mood symptoms and cognitive dysfunctions that emerges as significant risk factors for important health complications such as cardiovascular diseases and type 2 diabetes. It is therefore important to identify the dynamic of development and the pathophysiological mechanisms underlying these neuropsychiatric symptoms. Obesity is also associated with peripheral low-grade inflammation and increased susceptibility to immune-mediated diseases. Excessive production of proinflammatory cytokines and the resulting activation of the brain tryptophan catabolizing enzyme indoleamine 2,3-dioxygenase (IDO) have been shown to promote neurobehavioral complications, particularly depression. In that context, questions arise about the impact of diet-induced obesity on the onset of neuropsychiatric alterations and the increased susceptibility to immune-mediated diseases displayed by obese patients, particularly through brain IDO activation. To answer these questions, we used C57Bl/6 mice exposed to standard diet or western diet (WD; consisting of palatable energy-dense food) since weaning and for 20 weeks. We then measured inflammatory and behavioral responses to a systemic immune challenge with lipopolysaccharide (LPS) in experimental conditions known to alter cognitive and emotional behaviors independently of any motor impairment. We first showed that in absence of LPS, 9 weeks of WD is sufficient to impair spatial recognition memory (in the Y-maze). On the other hand, 18 weeks of WD increased anxiety-like behavior (in the elevated plus-maze), but did not affect depressive-like behavior (in the tail-suspension and forced-swim tests). However, 20 weeks of WD altered LPS-induced depressive-like behavior compared to LPS-treated lean mice and exacerbated hippocampal and hypothalamic proinflammatory cytokine expression and brain IDO activation. Taken together, these results show that WD exposure alters cognition and anxiety in unstimulated

  17. Long-term treatment with L-DOPA or pramipexole affects adult neurogenesis and corresponding non-motor behavior in a mouse model of Parkinson's disease.

    PubMed

    Chiu, W-H; Depboylu, C; Hermanns, G; Maurer, L; Windolph, A; Oertel, W H; Ries, V; Höglinger, G U

    2015-08-01

    Non-motor symptoms such as hyposmia and depression are often observed in Parkinson's disease (PD) and can precede the onset of motor symptoms for years. The underlying pathological alterations in the brain are not fully understood so far. Dysregulation of adult neurogenesis in the dentate gyrus of the hippocampus and the olfactory bulb has been recently suggested to be implicated in non-motor symptoms of PD. However, there is so far no direct evidence to support the relationship of non-motor symptoms and the modulation of adult neurogenesis following dopamine depletion and/or dopamine replacement. In this study, we investigated the long-term effects of l-DOPA and pramipexole, a dopamine agonist, in a mouse model of bilateral intranigral 6-OHDA lesion, in order to assess the impact of adult neurogenesis on non-motor behavior. We found that l-DOPA and pramipexole can normalize decreased neurogenesis in the hippocampal dentate gyrus and the periglomerular layer of the olfactory bulb caused by a 6-OHDA lesion. Interestingly, pramipexole showed an antidepressant and anxiolytic effect in the forced swim test and social interaction test. However, there was no significant change in learning and memory function after dopamine depletion and dopamine replacement, respectively.

  18. Deprivation and Recovery of Sleep in Succession Enhances Reflexive Motor Behavior

    PubMed Central

    Sprenger, Andreas; Weber, Frederik D.; Machner, Bjoern; Talamo, Silke; Scheffelmeier, Sabine; Bethke, Judith; Helmchen, Christoph; Gais, Steffen; Kimmig, Hubert; Born, Jan

    2015-01-01

    Sleep deprivation impairs inhibitory control over reflexive behavior, and this impairment is commonly assumed to dissipate after recovery sleep. Contrary to this belief, here we show that fast reflexive behaviors, when practiced during sleep deprivation, is consolidated across recovery sleep and, thereby, becomes preserved. As a model for the study of sleep effects on prefrontal cortex-mediated inhibitory control in humans, we examined reflexive saccadic eye movements (express saccades), as well as speeded 2-choice finger motor responses. Different groups of subjects were trained on a standard prosaccade gap paradigm before periods of nocturnal sleep and sleep deprivation. Saccade performance was retested in the next morning and again 24 h later. The rate of express saccades was not affected by sleep after training, but slightly increased after sleep deprivation. Surprisingly, this increase augmented even further after recovery sleep and was still present 4 weeks later. Additional experiments revealed that the short testing after sleep deprivation was sufficient to increase express saccades across recovery sleep. An increase in speeded responses across recovery sleep was likewise found for finger motor responses. Our findings indicate that recovery sleep can consolidate motor disinhibition for behaviors practiced during prior sleep deprivation, thereby persistently enhancing response automatization. PMID:26048955

  19. Cellular Mechanisms Underlying Behavioral State-Dependent Bidirectional Modulation of Motor Cortex Output

    PubMed Central

    Schiemann, Julia; Puggioni, Paolo; Dacre, Joshua; Pelko, Miha; Domanski, Aleksander; van Rossum, Mark C.W.; Duguid, Ian

    2015-01-01

    Summary Neuronal activity in primary motor cortex (M1) correlates with behavioral state, but the cellular mechanisms underpinning behavioral state-dependent modulation of M1 output remain largely unresolved. Here, we performed in vivo patch-clamp recordings from layer 5B (L5B) pyramidal neurons in awake mice during quiet wakefulness and self-paced, voluntary movement. We show that L5B output neurons display bidirectional (i.e., enhanced or suppressed) firing rate changes during movement, mediated via two opposing subthreshold mechanisms: (1) a global decrease in membrane potential variability that reduced L5B firing rates (L5Bsuppressed neurons), and (2) a coincident noradrenaline-mediated increase in excitatory drive to a subpopulation of L5B neurons (L5Benhanced neurons) that elevated firing rates. Blocking noradrenergic receptors in forelimb M1 abolished the bidirectional modulation of M1 output during movement and selectively impaired contralateral forelimb motor coordination. Together, our results provide a mechanism for how noradrenergic neuromodulation and network-driven input changes bidirectionally modulate M1 output during motor behavior. PMID:25981037

  20. Deprivation and Recovery of Sleep in Succession Enhances Reflexive Motor Behavior.

    PubMed

    Sprenger, Andreas; Weber, Frederik D; Machner, Bjoern; Talamo, Silke; Scheffelmeier, Sabine; Bethke, Judith; Helmchen, Christoph; Gais, Steffen; Kimmig, Hubert; Born, Jan

    2015-11-01

    Sleep deprivation impairs inhibitory control over reflexive behavior, and this impairment is commonly assumed to dissipate after recovery sleep. Contrary to this belief, here we show that fast reflexive behaviors, when practiced during sleep deprivation, is consolidated across recovery sleep and, thereby, becomes preserved. As a model for the study of sleep effects on prefrontal cortex-mediated inhibitory control in humans, we examined reflexive saccadic eye movements (express saccades), as well as speeded 2-choice finger motor responses. Different groups of subjects were trained on a standard prosaccade gap paradigm before periods of nocturnal sleep and sleep deprivation. Saccade performance was retested in the next morning and again 24 h later. The rate of express saccades was not affected by sleep after training, but slightly increased after sleep deprivation. Surprisingly, this increase augmented even further after recovery sleep and was still present 4 weeks later. Additional experiments revealed that the short testing after sleep deprivation was sufficient to increase express saccades across recovery sleep. An increase in speeded responses across recovery sleep was likewise found for finger motor responses. Our findings indicate that recovery sleep can consolidate motor disinhibition for behaviors practiced during prior sleep deprivation, thereby persistently enhancing response automatization.

  1. Norepinephrine transporter heterozygous knockout mice exhibit altered transport and behavior.

    PubMed

    Fentress, H M; Klar, R; Krueger, J J; Sabb, T; Redmon, S N; Wallace, N M; Shirey-Rice, J K; Hahn, M K

    2013-11-01

    The norepinephrine (NE) transporter (NET) regulates synaptic NE availability for noradrenergic signaling in the brain and sympathetic nervous system. Although genetic variation leading to a loss of NET expression has been implicated in psychiatric and cardiovascular disorders, complete NET deficiency has not been found in people, limiting the utility of NET knockout mice as a model for genetically driven NET dysfunction. Here, we investigate NET expression in NET heterozygous knockout male mice (NET(+/-) ), demonstrating that they display an approximately 50% reduction in NET protein levels. Surprisingly, these mice display no significant deficit in NET activity assessed in hippocampal and cortical synaptosomes. We found that this compensation in NET activity was due to enhanced activity of surface-resident transporters, as opposed to surface recruitment of NET protein or compensation through other transport mechanisms, including serotonin, dopamine or organic cation transporters. We hypothesize that loss of NET protein in the NET(+/-) mouse establishes an activated state of existing surface NET proteins. The NET(+/-) mice exhibit increased anxiety in the open field and light-dark box and display deficits in reversal learning in the Morris water maze. These data suggest that recovery of near basal activity in NET(+/-) mice appears to be insufficient to limit anxiety responses or support cognitive performance that might involve noradrenergic neurotransmission. The NET(+/-) mice represent a unique model to study the loss and resultant compensatory changes in NET that may be relevant to behavior and physiology in human NET deficiency disorders.

  2. Norepinephrine Transporter Heterozygous Knockout Mice Exhibit Altered Transport and Behavior

    PubMed Central

    Fentress, HM; Klar, R; Krueger, JK; Sabb, T; Redmon, SN; Wallace, NM; Shirey-Rice, JK; Hahn, MK

    2013-01-01

    The norepinephrine (NE) transporter (NET) regulates synaptic NE availability for noradrenergic signaling in the brain and sympathetic nervous system. Although genetic variation leading to a loss of NET expression has been implicated in psychiatric and cardiovascular disorders, complete NET deficiency has not been found in people, limiting the utility of NET knockout mice as a model for genetically-driven NET dysfunction. Here, we investigate NET expression in NET heterozygous knockout male mice (NET+/−), demonstrating that they display an ~50% reduction in NET protein levels. Surprisingly, these mice display no significant deficit in NET activity, assessed in hippocampal and cortical synaptosomes. We found that this compensation in NET activity was due to enhanced activity of surface-resident transporters, as opposed to surface recruitment of NET protein or compensation through other transport mechanisms, including serotonin, dopamine or organic cation transporters. We hypothesize that loss of NET protein in the NET+/− mouse establishes an activated state of existing, surface NET proteins. NET+/− mice exhibit increased anxiety in the open field and light-dark box and display deficits in reversal learning in the Morris Water Maze. These data suggest recovery of near basal activity in NET+/− mice appears to be insufficient to limit anxiety responses or support cognitive performance that might involve noradrenergic neurotransmission. The NET+/− mice represent a unique model to study the loss and resultant compensatory changes in NET that may be relevant to behavior and physiology in human NET deficiency disorders. PMID:24102798

  3. The Effects of a Motor Training Package on Minimally Assisted Standing Behavior in a Three-Month-Old Infant

    ERIC Educational Resources Information Center

    Dziewolska, Halina; Cautilli, Joseph

    2006-01-01

    Behavior analysts have spent relatively little time in designing interventions to enhance motor development in typically developing infants and children. This study examines the effect of a motor training package consisting of opportunity to respond and practice (standing the infant and letting her hold the fingers of the experimenter),…

  4. Altered behavioral and metabolic circadian rhythms in mice with disrupted NAD+ oscillation

    PubMed Central

    Sahar, Saurabh; Nin, Veronica; Barbosa, Maria Thereza; Chini, Eduardo Nunes; Sassone-Corsi, Paolo

    2011-01-01

    The Intracellular levels of nicotinamide adenine dinucleotide (NAD+) are rhythmic and controlled by the circadian clock. However, whether NAD+ oscillation in turn contributes to circadian physiology is not fully understood. To address this question we analyzed mice mutated for the NAD+ hydrolase CD38. We found that rhythmicity of NAD+ was altered in the CD38-deficient mice. The high, chronic levels of NAD+ results in several anomalies in circadian behavior and metabolism. CD38-null mice display a shortened period length of locomotor activity and alteration in the rest-activity rhythm. Several clock genes and, interestingly, genes involved in amino acid metabolism were deregulated in CD38-null livers. Metabolomic analysis identified alterations in the circadian levels of several amino acids, specifically tryptophan levels were reduced in the CD38-null mice at a circadian time paralleling with elevated NAD+ levels. Thus, CD38 contributes to behavioral and metabolic circadian rhythms and altered NAD+ levels influence the circadian clock. PMID:21937766

  5. Congenital nystagmus: hypotheses for its genesis and complex waveforms within a behavioral ocular motor system model.

    PubMed

    Jacobs, Jonathan B; Dell'Osso, Louis F

    2004-07-27

    Attempts to simulate dysfunction within ocular motor system (OMS) models capable of exhibiting known ocular motor behavior have provided valuable insight into the structure of the OMS required for normal visual function. The pendular waveforms of congenital nystagmus (CN) appear to be quite complex, composed of a sustained sinusoidal oscillation punctuated by braking saccades and foveating saccades followed by periods of extended foveation. Previously, we verified that these quick phases are generated by the same mechanism as voluntary saccades. We propose a computer model of the ocular motor system that simulates the responses of individuals with pendular CN (including its variable waveforms) based on the instability exhibited by the normal pursuit subsystem and its interaction with other components of the normal ocular motor control system. Fixation data from subjects with CN using both infrared and magnetic search coil oculography were used as templates for our simulations. Our OMS model simulates data from individuals with CN during fixation and in response to complex stimuli. The use of position and velocity efference copy to suppress oscillopsia is the key element in allowing for normal ocular motor behavior. The model's responses to target steps, pulse-steps, ramps, and step-ramps support the hypothetical explanation for the conditions that result in sustained pendular oscillation and the rules for the corrective saccadic responses that shape this underlying oscillation into the well-known family of pendular CN waveforms: pendular (P), pseudopendular (PP), pendular with foveating saccades (Pfs), and pseudopendular with foveating saccades (PPfs). Position error determined the saccadic amplitudes of foveating saccades, whereas stereotypical braking saccades were not dependent on visual information. Additionally, we propose a structure and method of operation for the fixation subsystem, and use it to prolong the low-velocity intervals immediately following

  6. Caffeine triggers behavioral and neurochemical alterations in adolescent rats.

    PubMed

    Ardais, A P; Borges, M F; Rocha, A S; Sallaberry, C; Cunha, R A; Porciúncula, L O

    2014-06-13

    Caffeine is the psychostimulant most consumed worldwide but concerns arise about the growing intake of caffeine-containing drinks by adolescents since the effects of caffeine on cognitive functions and neurochemical aspects of late brain maturation during adolescence are poorly known. We now studied the behavioral impact in adolescent male rats of regular caffeine intake at low (0.1mg/mL), moderate (0.3mg/mL) and moderate/high (1.0mg/mL) doses only during their active period (from 7:00 P.M. to 7:00 A.M.). All tested doses of caffeine were devoid of effects on locomotor activity, but triggered anxiogenic effects. Caffeine (0.3 and 1mg/mL) improved the performance in the object recognition task, but the higher dose of caffeine (1.0mg/mL) decreased the habituation to an open-field arena, suggesting impaired non-associative memory. All tested doses of caffeine decreased the density of glial fibrillary acidic protein and synaptosomal-associated protein-25, but failed to modify neuron-specific nuclear protein immunoreactivity in the hippocampus and cerebral cortex. Caffeine (0.3-1mg/mL) increased the density of brain-derived neurotrophic factor (BDNF) and proBDNF density as well as adenosine A1 receptor density in the hippocampus, whereas the higher dose of caffeine (1mg/mL) increased the density of proBDNF and BDNF and decreased A1 receptor density in the cerebral cortex. These findings document an impact of caffeine consumption in adolescent rats with a dual impact on anxiety and recognition memory, associated with changes in BDNF levels and decreases of astrocytic and nerve terminal markers without overt neuronal damage in hippocampal and cortical regions.

  7. Prenatal chlorpyrifos exposure in rats causes persistent behavioral alterations.

    PubMed

    Levin, Edward D; Addy, Nii; Baruah, Avanti; Elias, Alana; Christopher, N Channelle; Seidler, Frederic J; Slotkin, Theodore A

    2002-01-01

    Use of chlorpyrifos (CPF) has been curtailed due to its developmental neurotoxicity. In rats, postnatal CPF administration produces lasting changes in cognitive performance, but less information is available about the effects of prenatal exposure. We administered CPF to pregnant rats on gestational days (GD) 17-20, a peak period of neurogenesis, using doses (1 or 5 mg/kg/day) below the threshold for fetal growth impairment. We then evaluated performance in the T-maze, Figure-8 apparatus and 16-arm radial maze, beginning in adolescence and continuing into adulthood. CPF elicited initial locomotor hyperactivity in the T-maze. Females showed slower habituation in the Fig. 8 maze; no effects were seen in males. In the radial-arm maze, females showed impaired choice accuracy for both working and reference memory and again, males were unaffected. Despite the deficits, all animals eventually learned the maze with continued training. At that point, we challenged them with the muscarinic antagonist, scopolamine, to determine the dependence of behavioral performance on cholinergic function. Whereas control females showed impairment with scopolamine, CPF-exposed females did not, implying that the delayed acquisition of the task had been accomplished through alternative mechanisms. The differences were specific to muscarinic circuits, as control and CPF groups responded similarly to the nicotinic antagonist, mecamylamine. Surprisingly, adverse effects of CPF were greater in the group receiving 1 mg/kg as compared to 5 mg/kg. Promotional effects of acetylcholine (ACh) on cell differentiation may thus help to offset CPF-induced developmental damage that occurs through other noncholinergic mechanisms. Our results indicate that late prenatal exposure to CPF induces long-term changes in cognitive performance that are distinctly gender-selective. Additional defects may be revealed by similar strategies that subject the animals to acute challenges, thus, uncovering the adaptive

  8. Alterations in primary motor cortex neurotransmission and gene expression in hemi-Parkinsonian rats with drug-induced dyskinesia

    PubMed Central

    Lindenbach, David; Conti, Melissa M.; Ostock, Corinne Y.; Dupre, Kristin B.; Bishop, Christopher

    2015-01-01

    Treatment of Parkinson’s disease (PD) with dopamine replacement relieves symptoms of poverty of movement, but often causes drug-induced dyskinesias. Accumulating clinical and pre-clinical evidence suggests that the primary motor cortex (M1) is involved in the pathophysiology of PD and that modulating cortical activity may be a therapeutic target in PD and dyskinesia. However, surprisingly little is known about how M1 neurotransmitter tone or gene expression are altered in PD, dyskinesia or associated animal models. The present study utilized the rat unilateral 6-hydroxydopamine (6-OHDA) model of PD / dyskinesia to characterize structural and functional changes taking place in M1 monoamine innervation and gene expression. 6-OHDA caused dopamine pathology in M1, although the lesion was less severe than in the striatum. Rats with 6-OHDA lesions showed a PD motor impairment and developed dyskinesia when given L-DOPA or the D1 receptor agonist, SKF81297. M1 expression of two immediate-early genes (c-Fos and ARC) was strongly enhanced by either L-DOPA or SKF81297. At the same time, expression of genes specifically involved in glutamate and GABA signaling were either modestly affected or unchanged by lesion and/or treatment. We conclude that M1 neurotransmission and signal transduction in the rat 6-OHDA model of PD / dyskinesia mirror features of human PD, supporting the utility of the model to study M1 dysfunction in PD and the elucidation of novel pathophysiological mechanisms and therapeutic targets. PMID:26363150

  9. Alterations in primary motor cortex neurotransmission and gene expression in hemi-parkinsonian rats with drug-induced dyskinesia.

    PubMed

    Lindenbach, D; Conti, M M; Ostock, C Y; Dupre, K B; Bishop, C

    2015-12-03

    Treatment of Parkinson's disease (PD) with dopamine replacement relieves symptoms of poverty of movement, but often causes drug-induced dyskinesias. Accumulating clinical and pre-clinical evidence suggests that the primary motor cortex (M1) is involved in the pathophysiology of PD and that modulating cortical activity may be a therapeutic target in PD and dyskinesia. However, surprisingly little is known about how M1 neurotransmitter tone or gene expression is altered in PD, dyskinesia or associated animal models. The present study utilized the rat unilateral 6-hydroxydopamine (6-OHDA) model of PD/dyskinesia to characterize structural and functional changes taking place in M1 monoamine innervation and gene expression. 6-OHDA caused dopamine pathology in M1, although the lesion was less severe than in the striatum. Rats with 6-OHDA lesions showed a PD motor impairment and developed dyskinesia when given L-DOPA or the D1 receptor agonist, SKF81297. M1 expression of two immediate-early genes (c-Fos and ARC) was strongly enhanced by either L-DOPA or SKF81297. At the same time, expression of genes specifically involved in glutamate and GABA signaling were either modestly affected or unchanged by lesion and/or treatment. We conclude that M1 neurotransmission and signal transduction in the rat 6-OHDA model of PD/dyskinesia mirror features of human PD, supporting the utility of the model to study M1 dysfunction in PD and the elucidation of novel pathophysiological mechanisms and therapeutic targets.

  10. Theta-burst Transcranial Magnetic Stimulation Alters the Functional Topography of the Cortical Motor Network

    PubMed Central

    NOH, Nor Azila; FUGGETTA, Giorgio; MANGANOTTI, Paolo

    2015-01-01

    Background: Transcranial magnetic stimulation (TMS) is a non-invasive tool that is able to modulate the electrical activity of the brain depending upon its protocol of stimulation. Theta burst stimulation (TBS) is a high-frequency TMS protocol that is able to induce prolonged plasticity changes in the brain. The induction of plasticity-like effects by TBS is useful in both experimental and therapeutic settings; however, the underlying neural mechanisms of this modulation remain unclear. The aim of this study was to investigate the effects of continuous TBS (cTBS) on the intrahemispheric and interhemispheric functional connectivity of the resting and active brain. Methods: A total of 26 healthy humans were randomly divided into two groups that received either real cTBS or sham (control) over the left primary motor cortex. Surface electroencephalogram (EEG) was used to quantify the changes of neural oscillations after cTBS at rest and after a choice reaction time test. The cTBS-induced EEG oscillations were computed using spectral analysis of event-related coherence (ERCoh) of theta (4–7.5 Hz), low alpha (8–9.5 Hz), high alpha (10–12.5 Hz), low beta (13–19.5 Hz), and high beta (20–30 Hz) brain rhythms. Results: We observed a global decrease in functional connectivity of the brain in the cTBS group when compared to sham in the low beta brain rhythm at rest and high beta brain rhythm during the active state. In particular, EEG spectral analysis revealed that high-frequency beta, a cortically generated brain rhythm, was the most sensitive band that was modulated by cTBS. Conclusion: Overall, our findings suggest that cTBS, a TMS protocol that mimics the mechanism of long-term depression of synaptic plasticity, modulates motor network oscillations primarily at the cortical level and might interfere with cortical information coding. PMID:27006636

  11. Interaction of morphine and haloperidol on agonistic and motor behaviors of male mice.

    PubMed

    Rodríguez-Arias, M; Miñarro, J; Simón, V M

    1997-09-01

    To further clarify the interaction between opioid and dopaminergic systems, the effects of simultaneous administration of morphine hydrochloride (1.25 or 2.5 mg/kg) and haloperidol (0.1 mg/kg) on aggressive behavior of male mice were explored. Isolated male mice (experimental animals) were confronted in a neutral area with anosmic, group-housed consepecifics (standard opponents) 30 min after injection of both compounds, and aggression was evaluated by estimation of times allocated to 11 different behavioral categories. In the first experiment (which functioned as a pilot study), the two doses of morphine were explored. In the second one, incorporating a more complete experimental design, only the lowest morphine dose was used and the animals were preselected by a previous aggression test. In attack behavior, morphine added to haloperidol counteracted, at least partially, the antiaggressive effect of the neuroleptic. In contrast, the impairing effects of haloperidol on motor activity were increased by the addition of morphine. These results show that the behavioral effects of dopaminergic antagonists are modulated by opioid influences and that opiates and dopaminergic agents interact in a different manner on motor and on aggressive behaviors.

  12. Effects of Dechlorane Plus exposure on axonal growth, musculature and motor behavior in embryo-larval zebrafish.

    PubMed

    Chen, Xiangping; Dong, Qiaoxiang; Chen, Yuanhong; Zhang, Zhenxuan; Huang, Changjiang; Zhu, Yaxian; Zhang, Yong

    2017-03-10

    Developmental neurobehavioral toxicity of Dechlorane Plus (DP) was investigated using the embryo-larval stages of zebrafish (Danio rerio). Normal fertilized embryos were waterborne exposed to DP at 15, 30, 60 μg/L beginning from 6 h post-fertilization (hpf). Larval teratology, motor activity, motoneuron axonal growth and muscle morphology were assessed at different developmental stages. Results showed that DP exposure significantly altered embryonic spontaneous movement, reduced touch-induced movement and free-swimming speed and decreased swimming speed of larvae in response to dark stimulation. These changes occurred at DP doses that resulted no significant teratogenesis in zebrafish. Interestingly, in accord with these behavioral anomalies, DP exposure significantly inhibited axonal growth of primary motoneuron and induced apoptotic cell death and lesions in the muscle fibers of zebrafish. Furthermore, DP exposure at 30 μg/L and 60 μg/L significantly increased reactive oxygen species (ROS) and malondialdehyde (MDA) formation, as well as the mRNA transcript levels of apoptosis-related genes bax and caspase-3. Together, our data indicate that DP induced neurobehavioral deficits may result from combined effects of altered neuronal connectivity and muscle injuries.

  13. Alteration of eating behaviors in patients with Parkinson's disease: possibly overlooked?

    PubMed

    Miwa, Hideto; Kondo, Tomoyoshi

    2008-01-01

    Patients with Parkinson's disease (PD) occasionally show food cravings and/or compulsive eating that result in significant, undesired weight gain. Dopamine replacement therapy may be the cause of this type of eating disorder. We evaluated 60 consecutive patients to see if they had any alteration of eating patterns after starting levodopa. Among them, five (8.3%) patients exhibited characteristic alterations of food preference following the start of dopamine replacement therapy. One patient showed an undesirable weight gain. Of the five patients exhibiting food preference alterations, all showed increased preference to consume sweet snacks, although this alteration was not always associated with hyperphagia (eating too much). This type of dietary alteration was not related to a specific antiparkinsonian drug, and could be observed in patients undergoing dopamine agonist monotherapy. Alteration of eating behavior may not be uncommon in PD patients, and is possibly overlooked. Since dopamine is closely involved in acquisition of food preferences, dietary changes with/without compulsive eating may be a manifestation of an alteration of appetitive behaviors due to excessive dopaminergic neurotransmission.

  14. Regression rate behaviors of HTPB-based propellant combinations for hybrid rocket motor

    NASA Astrophysics Data System (ADS)

    Sun, Xingliang; Tian, Hui; Li, Yuelong; Yu, Nanjia; Cai, Guobiao

    2016-02-01

    The purpose of this paper is to characterize the regression rate behavior of hybrid rocket motor propellant combinations, using hydrogen peroxide (HP), gaseous oxygen (GOX), nitrous oxide (N2O) as the oxidizer and hydroxyl-terminated poly-butadiene (HTPB) as the based fuel. In order to complete this research by experiment and simulation, a hybrid rocket motor test system and a numerical simulation model are established. Series of hybrid rocket motor firing tests are conducted burning different propellant combinations, and several of those are used as references for numerical simulations. The numerical simulation model is developed by combining the Navies-Stokes equations with the turbulence model, one-step global reaction model, and solid-gas coupling model. The distribution of regression rate along the axis is determined by applying simulation mode to predict the combustion process and heat transfer inside the hybrid rocket motor. The time-space averaged regression rate has a good agreement between the numerical value and experimental data. The results indicate that the N2O/HTPB and GOX/HTPB propellant combinations have a higher regression rate, since the enhancement effect of latter is significant due to its higher flame temperature. Furthermore, the containing of aluminum (Al) and/or ammonium perchlorate(AP) in the grain does enhance the regression rate, mainly due to the more energy released inside the chamber and heat feedback to the grain surface by the aluminum combustion.

  15. Toll-like receptor 9 deficiency impacts sensory and motor behaviors.

    PubMed

    Khariv, Veronika; Pang, Kevin; Servatius, Richard J; David, Brian T; Goodus, Matthew T; Beck, Kevin D; Heary, Robert F; Elkabes, Stella

    2013-08-01

    Toll-like receptors (TLRs) mediate the induction of the innate immune system in response to pathogens, injury and disease. However, they also play non-immune roles and are expressed in the central nervous system (CNS) during prenatal and postnatal stages including adulthood. Little is known about their roles in the CNS in the absence of pathology. Several members of the TLR family have been implicated in the development of neural and cognitive function although the contribution of TLR9 to these processes has not been well defined. The current studies were undertaken to determine whether developmental TLR9 deficiency affects motor, sensory or cognitive functions. We report that TLR9 deficient (TLR9(-/-)) mice show a hyper-responsive sensory and motor phenotype compared to wild type (TLR9(+/+)) controls. This is indicated by hypersensitivity to thermal stimuli in the hot plate paw withdrawal test, enhanced motor-responsivity under anxious conditions in the open field test and greater sensorimotor reactivity in the acoustic startle response. Prepulse inhibition (PPI) of the acoustic startle response was also enhanced, which indicates abnormal sensorimotor gating. In addition, subtle, but significant, gait abnormalities were noted in the TLR9(-/-) mice on the horizontal balance beam test with higher foot slip numbers than TLR9(+/+) controls. In contrast, spatial learning and memory, assessed by the Morris water maze, was similar in the TLR9(-/-) and TLR9(+/+) mice. These findings support the notion that TLR9 is important for the appropriate development of sensory and motor behaviors.

  16. Transition to superdiffusive behavior in intracellular actin-based transport mediated by molecular motors

    NASA Astrophysics Data System (ADS)

    Bruno, L.; Levi, V.; Brunstein, M.; Despósito, M. A.

    2009-07-01

    Intracellular transport of large cargoes, such as organelles, vesicles, or large proteins, is a complex dynamical process that involves the interplay of adenosine triphosphate-consuming molecular motors, cytoskeleton filaments, and the viscoelastic cytoplasm. In this work we investigate the motion of pigment organelles (melanosomes) driven by myosin-V motors in Xenopus laevis melanocytes using a high-spatio-temporal resolution tracking technique. By analyzing the obtained trajectories, we show that the melanosomes mean-square displacement undergoes a transition from a subdiffusive to a superdiffusive behavior. A stochastic theoretical model, which explicitly considers the collective action of the molecular motors, is introduced to generalize the interpretation of our data. Starting from a generalized Langevin equation, we derive an analytical expression for the mean square displacement, which also takes into account the experimental noise. By fitting theoretical expressions to experimental data we were able to discriminate the exponents that characterize the passive and active contributions to the dynamics and to estimate the “global” motor forces correctly. Then, our model gives a quantitative description of active transport in living cells with a reduced number of parameters.

  17. Post-Stroke Longitudinal Alterations of Inter-Hemispheric Correlation and Hemispheric Dominance in Mouse Pre-Motor Cortex

    PubMed Central

    Panarese, Alessandro; Alia, Claudia; Micera, Silvestro; Caleo, Matteo; Di Garbo, Angelo

    2016-01-01

    Purpose Limited restoration of function is known to occur spontaneously after an ischemic injury to the primary motor cortex. Evidence suggests that Pre-Motor Areas (PMAs) may “take over” control of the disrupted functions. However, little is known about functional reorganizations in PMAs. Forelimb movements in mice can be driven by two cortical regions, Caudal and Rostral Forelimb Areas (CFA and RFA), generally accepted as primary motor and pre-motor cortex, respectively. Here, we examined longitudinal changes in functional coupling between the two RFAs following unilateral photothrombotic stroke in CFA (mm from Bregma: +0.5 anterior, +1.25 lateral). Methods Local field potentials (LFPs) were recorded from the RFAs of both hemispheres in freely moving injured and naïve mice. Neural signals were acquired at 9, 16 and 23 days after surgery (sub-acute period in stroke animals) through one bipolar electrode per hemisphere placed in the center of RFA, with a ground screw over the occipital bone. LFPs were pre-processed through an efficient method of artifact removal and analysed through: spectral,cross-correlation, mutual information and Granger causality analysis. Results Spectral analysis demonstrated an early decrease (day 9) in the alpha band power in both the RFAs. In the late sub-acute period (days 16 and 23), inter-hemispheric functional coupling was reduced in ischemic animals, as shown by a decrease in the cross-correlation and mutual information measures. Within the gamma and delta bands, correlation measures were already reduced at day 9. Granger analysis, used as a measure of the symmetry of the inter-hemispheric causal connectivity, showed a less balanced activity in the two RFAs after stroke, with more frequent oscillations of hemispheric dominance. Conclusions These results indicate robust electrophysiological changes in PMAs after stroke. Specifically, we found alterations in transcallosal connectivity, with reduced inter-hemispheric functional

  18. Protective effect of alprazolam against sleep deprivation-induced behavior alterations and oxidative damage in mice.

    PubMed

    Singh, Anant; Kumar, Anil

    2008-04-01

    Sleep deprivation is considered as a risk factor for various diseases. Sleep deprivation leads to behavioral, hormonal, neurochemical and biochemical alterations in the animals. The present study was designed to explore the possible involvement of GABAergic mechanism in protective effect of alprazolam against 72h sleep deprivation-induced behavior alterations and oxidative damage in mice. In the present study, sleep deprivation caused anxiety-like behavior, weight loss, impaired ambulatory movements and oxidative damage as indicated by increase in lipid peroxidation, nitrite level and depletion of reduced glutathione and catalase activity in sleep-deprived mice brain. Treatment with alprazolam (0.25 and 0.5 mg/kg, ip) significantly improved behavioral alterations. Biochemically, alprazolam treatment significantly restored depleted reduced glutathione, catalase activity, reversed raised lipid peroxidation and nitrite level. Combination of flumazenil (0.5 mg/kg) and picrotoxin (0.5 mg/kg) with lower dose of alprazolam (0.25mg/kg) significantly antagonized protective effect of alprazolam. However, combination of muscimol (0.05 mg/kg) with alprazolam (0.25 mg/kg, ip) potentiated protective effect of alprazolam. On the basis of these results, it might be suggested that alprazolam might produce protective effect by involving GABAergic system against sleep deprivation-induced behavior alterations and related oxidative damage.

  19. Maternal treatment with picrotoxin in late pregnancy improved female sexual behavior but did not alter male sexual behavior of offspring.

    PubMed

    Bernardi, Maria M; Scanzerla, Kayne K; Chamlian, Mayra; Teodorov, Elizabeth; Felicio, Luciano F

    2013-08-01

    Previous studies from our laboratory investigated the effects of picrotoxin (PT), a γ-aminobutyric acid receptor antagonist administered during several perinatal periods, on the sexual behavior of male and female rats. We observed that the time of perinatal exposure to PT is critical to determine either facilitation or impairment of sexual behavior. The present study evaluated the effects of prenatal administration of a single dose of PT on gestation day 18 of dams (the first critical period of male brain sexual differentiation) on sexual behavior of male and female offspring. Thus, female Wistar rats were mated with males and, on gestation day 18, received 0.6 mg/kg of PT or 0.9% saline solution subcutaneously. On postnatal day 1, the offspring were weighed and several measures of sexual development were assessed. The sexual behaviors and the general activity in the open field of adult male and ovariectomized, hormone-treated female rats were observed. On comparison with the control group, maternal PT treatment: (i) did not alter the maternal weight, pup weight, anogenital distance, or male and female general activity; (ii) increased female sexual behavior, that is, decreased the latencies to first mount, first lordosis, and tenth lordosis, and the percentage of females presenting lordosis; and (iii) did not alter male sexual behavior. It is suggested that prenatal PT exposure interfered with epigenetic mechanisms related to the development of sex differences in the brain, leading to the observed sexually dimorphic effects on sexual behavior.

  20. Modular laboratory exercises to analyze the development of zebrafish motor behavior.

    PubMed

    McKeown, Kelly Anne; Downes, Gerald B; Hutson, Lara D

    2009-06-01

    The embryonic zebrafish is an excellent research model to examine the neural networks that coordinate locomotive behavior. It demonstrates robust locomotive behavior early in development, its nervous system is relatively simple and accessible compared to mammalian systems, and there are mutants available with specific molecular and motor deficits. We have developed a series of four exercises that provide students with a basic understanding of locomotive behavior development, nervous system organization, development of neurotransmitter responsiveness, and genetics. The first two exercises can be performed in one 3-h laboratory period, and the third and fourth exercises, which build on the first two, can be completed in one or two subsequent periods. In the first exercise, students observe and quantify two distinct behaviors that characterize different developmental stages, spontaneous movement, and touch-evoked tail coiling. In the second, the students use a pharmacological approach to determine if the neurotransmitter glycine is required for the embryo to perform each behavior. In the third, they use simple lesions to assess whether the brain is required for each type of behavior. In the fourth, the students examine bandoneon, a zebrafish motility mutant that has a glycine receptor defect, by observing its behavior during spontaneous movement and touch-evoked tail coiling, performing lesions, and applying pharmacological drugs. These exercises are readily adaptable, such that portions can be omitted or expanded to examine other neurotransmitter systems or later stages of locomotive behavior development.

  1. Explicit Agency in Patients with Cervical Dystonia: Altered Recognition of Temporal Discrepancies between Motor Actions and Their Feedback

    PubMed Central

    Delorme, Cécile; Roze, Emmanuel; Grabli, David; Mayer, Jean-Michel; Degos, Bertrand; Vidailhet, Marie; Worbe, Yulia

    2016-01-01

    Background Abnormalities in the cognitive processing of movement have been demonstrated in patients with dystonia. The sense of agency, which is the experience of initiating and controlling one’s own actions, has never before been studied in these patients. Objectives We investigated whether the sense of agency is altered in patients with cervical dystonia. Methods We used an explicit metacognitive agency task in which participants had to catch targets with a cursor by moving a computer’s mouse. The task included several conditions in which the control over the cursor could be disrupted by adding a spatial or a temporal discrepancy between the mouse and the cursor’s movements. Participants had to acknowledge these discrepancies and reflect them in metacognitive judgements of agency. Results Twenty cervical dystonia patients and 20 matched controls were included in the study. Despite performing equally well as the matched controls, cervical dystonia patients did not fully recognize alterations of agency when a temporal lag was added between their movement and the visual feedback. Moreover, they relied predominantly on their perceived performance to provide judgements of agency and less on their objective degree of controls. There was no correlation between agency scores and clinical severity of dystonia measured by the Toronto Western Spasmodic Torticollis Rating Scale. Conclusion We demonstrated an abnormal processing of agency in cervical dystonia patients, even for motor actions not affected by dystonia. The exact contribution of abnormal agency to dystonia pathophysiology remains to be clarified. PMID:27575487

  2. Assessing altered motor unit recruitment patterns in paretic muscles of stroke survivors using surface electromyography

    NASA Astrophysics Data System (ADS)

    Hu, Xiaogang; Suresh, Aneesha K.; Rymer, William Z.; Suresh, Nina L.

    2015-12-01

    Objective. The advancement of surface electromyogram (sEMG) recording and signal processing techniques has allowed us to characterize the recruitment properties of a substantial population of motor units (MUs) non-invasively. Here we seek to determine whether MU recruitment properties are modified in paretic muscles of hemispheric stroke survivors. Approach. Using an advanced EMG sensor array, we recorded sEMG during isometric contractions of the first dorsal interosseous muscle over a range of contraction levels, from 20% to 60% of maximum, in both paretic and contralateral muscles of stroke survivors. Using MU decomposition techniques, MU action potential amplitudes and recruitment thresholds were derived for simultaneously activated MUs in each isometric contraction. Main results. Our results show a significant disruption of recruitment organization in paretic muscles, in that the size principle describing recruitment rank order was materially distorted. MUs were recruited over a very narrow force range with increasing force output, generating a strong clustering effect, when referenced to recruitment force magnitude. Such disturbances in MU properties also correlated well with the impairment of voluntary force generation. Significance. Our findings provide direct evidence regarding MU recruitment modifications in paretic muscles of stroke survivors, and suggest that these modifications may contribute to weakness for voluntary contractions.

  3. Alterations to functional analysis methodology to clarify the functions of low rate, high intensity problem behavior.

    PubMed

    Davis, Barbara J; Kahng, Sungwoo; Schmidt, Jonathan; Bowman, Lynn G; Boelter, Eric W

    2012-01-01

    Current research provides few suggestions for modifications to functional analysis procedures to accommodate low rate, high intensity problem behavior. This study examined the results of the extended duration functional analysis procedures of Kahng, Abt, and Schonbachler (2001) with six children admitted to an inpatient hospital for the treatment of severe problem behavior. Results of initial functional analyses (Iwata, Dorsey, Slifer, Bauman, & Richman, 1982/1994) were inconclusive for all children because of low levels of responding. The altered functional analyses, which changed multiple variables including the duration of the functional analysis (i.e., 6 or 7 hrs), yielded clear behavioral functions for all six participants. These results add additional support for the utility of an altered analysis of low rate, high intensity problem behavior when standard functional analyses do not yield differentiated results.

  4. Alterations to Functional Analysis Methodology to Clarify the Functions of Low Rate, High Intensity Problem Behavior

    PubMed Central

    Davis, Barbara J; Kahng, SungWoo; Schmidt, Jonathan; Bowman, Lynn G; Boelter, Eric W

    2012-01-01

    Current research provides few suggestions for modifications to functional analysis procedures to accommodate low rate, high intensity problem behavior. This study examined the results of the extended duration functional analysis procedures of Kahng, Abt, and Schonbachler (2001) with six children admitted to an inpatient hospital for the treatment of severe problem behavior. Results of initial functional analyses (Iwata, Dorsey, Slifer, Bauman, & Richman, 1982/1994) were inconclusive for all children because of low levels of responding. The altered functional analyses, which changed multiple variables including the duration of the functional analysis (i.e., 6 or 7 hrs), yielded clear behavioral functions for all six participants. These results add additional support for the utility of an altered analysis of low rate, high intensity problem behavior when standard functional analyses do not yield differentiated results. PMID:23326628

  5. Odor-identity dependent motor programs underlie behavioral responses to odors

    PubMed Central

    Jung, Seung-Hye; Hueston, Catherine; Bhandawat, Vikas

    2015-01-01

    All animals use olfactory information to perform tasks essential to their survival. Odors typically activate multiple olfactory receptor neuron (ORN) classes and are therefore represented by the patterns of active ORNs. How the patterns of active ORN classes are decoded to drive behavior is under intense investigation. In this study, using Drosophila as a model system, we investigate the logic by which odors modulate locomotion. We designed a novel behavioral arena in which we could examine a fly’s locomotion under precisely controlled stimulus condition. In this arena, in response to similarly attractive odors, flies modulate their locomotion differently implying that odors have a more diverse effect on locomotion than was anticipated. Three features underlie odor-guided locomotion: First, in response to odors, flies modulate a surprisingly large number of motor parameters. Second, similarly attractive odors elicit changes in different motor programs. Third, different ORN classes modulate different subset of motor parameters. DOI: http://dx.doi.org/10.7554/eLife.11092.001 PMID:26439011

  6. The effects of yoga practice in school physical education on children's motor abilities and social behavior

    PubMed Central

    Folleto, Júlia C; Pereira, Keila RG; Valentini, Nadia Cristina

    2016-01-01

    Background: In recent years, yoga programs in childhood have been implemented in schools, to promote the development for children. Aim: To investigate the effects of yoga program in physical education classes on the motor abilities and social behavior parameters of 6–8-year-old children. Methods: The study included 16 children from the 1st grade of a public elementary school in the South of Brazil. The children participated in a 12-week intervention, twice weekly, with 45 min each session. To assess children's performance, we used the Bruininks-Oseretsky Test of Motor Proficiency - Second Edition, the flexibility test (sit and reach – Eurofit, 1988), the Pictorial Scale of Perceived Competence and Social Acceptance for Young Children and semi-structured interviews with children, parents, and classroom’ teacher. Data were analyzed with Wilcoxon test and level of significance was 5%. Results: The yoga program was well accepted by children, children also demonstrated significant and positive changes in overall motor abilities scores (balance, strength, and flexibility). In addition, the interviews reported changing in social behavior and the use of the knowledge learned in the program in contexts outside of school. Conclusion: These findings suggest that the implementation of yoga practice in physical education lessons contributed to children's development. PMID:27512323

  7. Parasites alter freshwater communities in mesocosms by modifying invasive crayfish behavior.

    PubMed

    Reisinger, Lindsey S; Lodge, David M

    2016-06-01

    Parasites can alter communities by reducing densities of keystone hosts, but few studies have examined how trait-mediated indirect effects of parasites can alter ecological communities. We test how trematode parasites (Microphallus spp.) that affect invasive crayfish (Orconectes rusticus) behavior alter how crayfish impact lake littoral communities. O. rusticus drive community composition in north temperate lakes, and predatory fish can reduce crayfish activity and feeding. In laboratory studies, Microphallus parasites also alter O. rusticus behavior: infected O. rusticus eat fewer macroinvertebrates and are bolder near predatory fish than uninfected individuals. We used a 2 x 2 factorial experiment to test how predatory fish and parasites affect O. rusticus impacts in large mesocosms over 4 weeks. We predicted (1) that when predators were absent, infected crayfish would have lower impacts than uninfected crayfish on macrophytes and macroinvertebrates (as well as reduced growth and higher mortality). However, (2) when predators were present but unable to consume crayfish, infected crayfish would have greater impacts (as well as greater growth and lower mortality) than uninfected crayfish because of increased boldness. Because of its effect on crayfish feeding behavior, we also predicted (3) that infection would alter macrophyte and macroinvertebrate community composition. In contrast to our first hypothesis, we found that infected and uninfected crayfish had similar impacts on lower trophic levels when predators were absent. Across all treatments, infected crayfish were more likely to be outside shelters and had greater growth than uninfected crayfish, suggesting that the reduced feeding observed in short-term experiments does not occur over longer timescales. However, in support of the second hypothesis, when predatory fish were present, infected crayfish ate more macroinvertebrates than did uninfected crayfish, likely due to increased boldness. We also observed a

  8. COMMUNICATION: On variability and use of rat primary motor cortex responses in behavioral task discrimination

    NASA Astrophysics Data System (ADS)

    Jensen, Winnie; Rousche, Patrick J.

    2006-03-01

    The success of a cortical motor neuroprosthetic system will rely on the system's ability to effectively execute complex motor tasks in a changing environment. Invasive, intra-cortical electrodes have been successfully used to predict joint movement and grip force of a robotic arm/hand with a non-human primate (Chapin J K, Moxon K A, Markowitz R S and Nicolelis M A L 1999 Real-time control of a robotic arm using simultaneously recorded neurons in the motor cortex Nat. Neurosci. 2 664-70). It is well known that cortical encoding occurs with a high degree of cortical plasticity and depends on both the functional and behavioral context. Questions on the expected robustness of future motor prosthesis systems therefore still remain. The objective of the present work was to study the effect of minor changes in functional movement strategies on the M1 encoding. We compared the M1 encoding in freely moving, non-constrained animals that performed two similar behavioral tasks with the same end-goal, and investigated if these behavioral tasks could be discriminated based on the M1 recordings. The rats depressed a response paddle either with a set of restrictive bars ('WB') or without the bars ('WOB') placed in front of the paddle. The WB task required changes in the motor strategy to complete the paddle press and resulted in highly stereotyped movements, whereas in the WOB task the movement strategy was not restricted. Neural population activity was recorded from 16-channel micro-wire arrays and data up to 200 ms before a paddle hit were analyzed off-line. The analysis showed a significant neural firing difference between the two similar WB and WOB tasks, and using principal component analysis it was possible to distinguish between the two tasks with a best classification at 76.6%. While the results are dependent upon a small, randomly sampled neural population, they indicate that information about similar behavioral tasks may be extracted from M1 based on relatively few

  9. Motor dysfunction and altered synaptic transmission at the parallel fiber-Purkinje cell synapse in mice lacking potassium channels Kv3.1 and Kv3.3.

    PubMed

    Matsukawa, Hiroshi; Wolf, Alexander M; Matsushita, Shinichi; Joho, Rolf H; Knöpfel, Thomas

    2003-08-20

    Micelacking both Kv3.1 and both Kv3.3 K+ channel alleles display severe motor deficits such as tremor, myoclonus, and ataxic gait. Micelacking one to three alleles at the Kv3.1 and Kv3.3 loci exhibit in an allele dose-dependent manner a modest degree of ataxia. Cerebellar granule cells coexpress Kv3.1 and Kv3.3 K+ channels and are therefore candidate neurons that might be involved in these behavioral deficits. Hence, we investigated the synaptic mechanisms of transmission in the parallel fiber-Purkinje cell system. Action potentials of parallel fibers were broader in mice lacking both Kv3.1 and both Kv3.3 alleles and in mice lacking both Kv3.1 and a single Kv3.3 allele compared with those of wild-type mice. The transmission of high-frequency trains of action potentials was only impaired at 200 Hz but not at 100 Hz in mice lacking both Kv3.1 and Kv3.3 genes. However, paired-pulse facilitation (PPF) at parallel fiber-Purkinje cell synapses was dramatically reduced in a gene dose-dependent manner in mice lacking Kv3.1 or Kv3.3 alleles. Normal PPF could be restored by reducing the extracellular Ca2+ concentration indicating that increased activity-dependent presynaptic Ca2+ influx, at least in part caused the altered PPF in mutant mice. Induction of metabotropic glutamate receptor-mediated EPSCs was facilitated, whereas longterm depression was not impaired but rather facilitated in Kv3.1/Kv3.3 double-knockout mice. These results demonstrate the importance of Kv3 potassium channels in regulating the dynamics of synaptic transmission at the parallel fiber-Purkinje cell synapse and suggest a correlation between short-term plasticity at the parallel fiber-Purkinje cell synapse and motor performance.

  10. Understory avifauna exhibits altered mobbing behavior in tropical forest degraded by selective logging.

    PubMed

    Hua, Fangyuan; Sieving, Kathryn E

    2016-11-01

    In understanding the impacts of selective logging on biodiversity, relatively little is known about the critical behavioral link between altered forest conditions and population persistence. Predator-mobbing is a widespread anti-predator behavior in birds that expresses a well-known trade-off influencing prey survival under predation risk. Here, we ask whether the predator-mobbing behavior of understory forest birds is altered by selective logging and associated forest structural changes in the highly endangered lowland rainforest of Sumatra. At four study sites spanning a gradient of logging-induced forest degradation, we used standardized mobbing and owl call playbacks with predator model presentation to elicit the predator-mobbing behavior of understory prey birds, compared birds' mobbing intensity across sites, and related variation in this intensity to forest vegetation structure. We found that selective logging altered birds' predator-mobbing intensity (measured by behavioral conspicuousness and propensity to approach the predator) as well as forest structure, and that vegetative changes to canopy and understory were correlated with contrasting responses by the two major bird foraging guilds, gleaning versus flycatching birds. We additionally discuss the implications of our findings for further hypothesis testing pertaining to the impacts of selective logging on the ecological processes underlying prey mobbing behavior, particularly with regards to predator-prey interactions and prey accruement of energy reserves.

  11. Multiplexing of Motor Information in the Discharge of a Collision Detecting Neuron during Escape Behaviors

    PubMed Central

    Fotowat, Haleh; Harrison, Reid R; Gabbiani, Fabrizio

    2010-01-01

    Locusts possess an identified neuron, the descending contralateral movement detector (DCMD), conveying visual information about impending collision from the brain to thoracic motor centers. We built a telemetry system to simultaneously record, in freely behaving animals, the activity of the DCMD and of motoneurons involved in jump execution. Co-contraction of antagonistic leg muscles, a required preparatory phase, was triggered after the DCMD firing rate crossed a threshold. Thereafter, the number of DCMD spikes predicted precisely motoneuron activity and jump occurrence. Additionally, the time of DCMD peak firing rate predicted that of jump. Ablation experiments suggest that the DCMD, together with a nearly identical ipsilateral descending neuron, is responsible for the timely execution of the escape. Thus, three distinct features that are multiplexed in a single neuron’s sensory response to impending collision – firing rate threshold, peak firing time, and spike count – likely control three distinct motor aspects of escape behaviors. PMID:21220105

  12. Muscle cramp in Machado-Joseph disease: altered motor axonal excitability properties and mexiletine treatment.

    PubMed

    Kanai, Kazuaki; Kuwabara, Satoshi; Arai, Kimihito; Sung, Jia-Ying; Ogawara, Kazue; Hattori, Takamichi

    2003-04-01

    Machado-Joseph disease is one of the most common hereditary spinocerebellar degenerative disorders with a wide range of clinical manifestations. Pathology studies have shown mild to moderate loss of anterior horn cells and, in terms of spinal pathology, Machado-Joseph disease is regarded as a type of lower motoneuron disease. Muscle cramps are often associated with lower motoneuron disorders, but features of cramps in Machado-Joseph disease patients have never been studied. We investigated the incidence and nature of muscle cramps in Machado-Joseph disease patients, the excitability properties of motor axons [strength-duration time constant (tau(SD)), threshold electrotonus, refractoriness and supernormality] using threshold tracking and the effects of mexiletine hydrochloride on those cramps. Of 20 consecutive patients, 16 (80%) had frequent, severe muscle cramps in the legs, trunk or arms that disturbed their daily activities. The frequency of pathological muscle cramps was similar to that for patients with amyotrophic lateral sclerosis (68%) and higher than those for patients with spinal muscular atrophy (33%) or peripheral axonal neuropathy (24%). Threshold-tracking studies showed that tau(SD), which in part reflects Na(+) conductance at the resting membrane potential, was significantly greater in the Machado-Joseph disease patients than in normal subjects; severe muscle cramps were associated with a longer tau(SD). Threshold electrotonus, refractoriness and supernormality were not significantly different between Machado-Joseph disease patients and normal subjects. Eight Machado-Joseph disease patients with severe cramps, who received mexiletine treatment, experienced nearly complete relief with a partial normalization of tau(SD) (P = 0.08). Muscle cramps are a very frequent and disabling factor in Machado-Joseph disease. Pathological muscle cramps responded well to mexiletine treatment, and this is consistent with the hypothesis that they are caused by an

  13. Alterations in the functional neural circuitry supporting flexible choice behavior in autism spectrum disorders

    PubMed Central

    D'Cruz, A-M; Mosconi, M W; Ragozzino, M E; Cook, E H; Sweeney, J A

    2016-01-01

    Restricted and repetitive behaviors, and a pronounced preference for behavioral and environmental consistency, are distinctive characteristics of autism spectrum disorder (ASD). Alterations in frontostriatal circuitry that supports flexible behavior might underlie this behavioral impairment. In an functional magnetic resonance imaging study of 17 individuals with ASD, and 23 age-, gender- and IQ-matched typically developing control participants, reversal learning tasks were used to assess behavioral flexibility as participants switched from one learned response choice to a different response choice when task contingencies changed. When choice outcome after reversal was uncertain, the ASD group demonstrated reduced activation in both frontal cortex and ventral striatum, in the absence of task performance differences. When the outcomes of novel responses were certain, there was no difference in brain activation between groups. Reduced activation in frontal cortex and ventral striatum suggest problems in decision-making and response planning, and in processing reinforcement cues, respectively. These processes, and their integration, are essential for flexible behavior. Alterations in these systems may therefore contribute to a rigid adherence to preferred behavioral patterns in individuals with an ASD. These findings provide an additional impetus for the use of reversal learning paradigms as a translational model for treatment development targeting the domain of restricted and repetitive behaviors in ASD. PMID:27727243

  14. Parallel evolution of serotonergic neuromodulation underlies independent evolution of rhythmic motor behavior.

    PubMed

    Lillvis, Joshua L; Katz, Paul S

    2013-02-06

    Neuromodulation can dynamically alter neuronal and synaptic properties, thereby changing the behavioral output of a neural circuit. It is therefore conceivable that natural selection might act upon neuromodulation as a mechanism for sculpting the behavioral repertoire of a species. Here we report that the presence of neuromodulation is correlated with the production of a behavior that most likely evolved independently in two species: Tritonia diomedea and Pleurobranchaea californica (Mollusca, Gastropoda, Opisthobranchia, Nudipleura). Individuals of both species exhibit escape swimming behaviors consisting of repeated dorsal-ventral whole-body flexions. The central pattern generator (CPG) circuits underlying these behaviors contain homologous identified neurons: DSI and C2 in Tritonia and As and A1 in Pleurobranchaea. Homologs of these neurons also can be found in Hermissenda crassicornis where they are named CPT and C2, respectively. However, members of this species do not exhibit an analogous swimming behavior. In Tritonia and Pleurobranchaea, but not in Hermissenda, the serotonergic DSI homologs modulated the strength of synapses made by C2 homologs. Furthermore, the serotonin receptor antagonist methysergide blocked this neuromodulation and the swimming behavior. Additionally, in Pleurobranchaea, the robustness of swimming correlated with the extent of the synaptic modulation. Finally, injection of serotonin induced the swimming behavior in Tritonia and Pleurobranchaea, but not in Hermissenda. This suggests that the analogous swimming behaviors of Tritonia and Pleurobranchaea share a common dependence on serotonergic neuromodulation. Thus, neuromodulation may provide a mechanism that enables species to acquire analogous behaviors independently using homologous neural circuit components.

  15. Adaptive Responses to Prochloraz Exposure That Alter Dose-Response and Time-Course Behaviors

    EPA Science Inventory

    Dose response and time-course (DRTC) are, along with exposure, the major determinants of health risk. Adaptive changes within exposed organisms in response to environmental stress are common, and alter DRTC behaviors to minimize the effects caused by stressors. In this project, ...

  16. Neonatal handling alters the structure of maternal behavior and affects mother-pup bonding.

    PubMed

    Reis, A R; de Azevedo, M S; de Souza, M A; Lutz, M L; Alves, M B; Izquierdo, I; Cammarota, M; Silveira, P P; Lucion, A B

    2014-05-15

    During early life, a mother and her pups establish a very close relationship, and the olfactory learning of the nest odor is very important for the bond formation. The olfactory bulb (OB) is a structure that plays a fundamental role in the olfactory learning (OL) mechanism that also involves maternal behavior (licking and contact). We hypothesized that handling the pups would alter the structure of the maternal behavior, affect OL, and alter mother-pup relationships. Moreover, changes in the cyclic AMP-response element binding protein phosphorylation (CREB) and neurotrophic factors could be a part of the mechanism of these changes. This study aimed to analyze the effects of neonatal handling, 1 min per day from postpartum day 1 to 10 (PPD 1 to PPD 10), on the maternal behavior and pups' preference for the nest odor in a Y maze (PPD 11). We also tested CREB's phosphorylation and BDNF signaling in the OB of the pups (PPD 7) by Western blot analysis. The results showed that handling alters mother-pups interaction by decreasing mother-pups contact and changing the temporal pattern of all components of the maternal behavior especially the daily licking and nest-building. We found sex-dependent changes in the nest odor preference, CREB and BDNF levels in pups OB. Male pups were more affected by alterations in the licking pattern, and female pups were more affected by changes in the mother-pup contact (the time spent outside the nest and nursing).

  17. Mutations alter the sodium versus proton use of a Bacillus clausii flagellar motor and confer dual ion use on Bacillus subtilis motors.

    PubMed

    Terahara, Naoya; Krulwich, Terry A; Ito, Masahiro

    2008-09-23

    Bacterial flagella contain membrane-embedded stators, Mot complexes, that harness the energy of either transmembrane proton or sodium ion gradients to power motility. Use of sodium ion gradients is associated with elevated pH and sodium concentrations. The Mot complexes studied to date contain channels that use either protons or sodium ions, with some bacteria having only one type and others having two distinct Mot types with different ion-coupling. Here, alkaliphilic Bacillus clausii KSM-K16 was shown to be motile in a pH range from 7 to 11 although its genome encodes only one Mot (BCl-MotAB). Assays of swimming as a function of pH, sodium concentration, and ion-selective motility inhibitors showed that BCl-MotAB couples motility to sodium at the high end of its pH range but uses protons at lower pH. This pattern was confirmed in swimming assays of a statorless Bacillus subtilis mutant expressing either BCl-MotAB or one of the two B. subtilis stators, sodium-coupled Bs-MotPS or proton-coupled Bs-MotAB. Pairs of mutations in BCl-MotB were identified that converted the naturally bifunctional BCl-MotAB to stators that preferentially use either protons or sodium ions across the full pH range. We then identified trios of mutations that added a capacity for dual-ion coupling on the distinct B. subtilis Bs-MotAB and Bs-MotPS motors. Determinants that alter the specificity of bifunctional and single-coupled flagellar stators add to insights from studies of other ion-translocating transporters that use both protons and sodium ions.

  18. Descending influences on escape behavior and motor pattern in the cockroach.

    PubMed

    Schaefer, P L; Ritzmann, R E

    2001-10-01

    The escape behavior of the cockroach is a ballistic behavior with well characterized kinematics. The circuitry known to control the behavior lies in the thoracic ganglia, abdominal ganglia, and abdominal nerve cord. Some evidence suggests inputs may occur from the brain or suboesophageal ganglion. We tested this notion by decapitating cockroaches, removing all descending inputs, and evoking escape responses. The decapitated cockroaches exhibited directionally appropriate escape turns. However, there was a front-to-back gradient of change: the front legs moved little if at all, the middle legs moved in the proper direction but with reduced excursion, and the rear legs moved normally. The same pattern was seen when only inputs from the brain were removed, the suboesophageal ganglion remaining intact and connected to the thoracic ganglia. Electromyogram (EMG) analysis showed that the loss of or reduction in excursion was accompanied by a loss of or reduction in fast motor neuron activity. The loss of fast motor neuron activity was also observed in a reduced preparation in which descending neural signals were reversibly blocked via an isotonic sucrose solution superfusing the neck connectives, indicating that the changes seen were not due to trauma. Our data demonstrate that while the thoracic circuitry is sufficient to produce directional escape, lesion or blockage of the connective affects the excitability of components of the escape circuitry. Because of the rapidity of the escape response, such effects are likely due to the elimination of tonic descending inputs.

  19. Different neural systems adjust motor behavior in response to reward and punishment.

    PubMed

    Wrase, Jana; Kahnt, Thorsten; Schlagenhauf, Florian; Beck, Anne; Cohen, Michael X; Knutson, Brian; Heinz, Andreas

    2007-07-15

    Individuals use the outcomes of their actions to adjust future behavior. However, it remains unclear whether the same neural circuits are used to adjust behavior due to rewarding and punishing outcomes. Here we used functional magnetic resonance imaging (fMRI) and a reward-providing reaction time task to investigate the adaptation of a simple motor response following four different outcomes (delivery versus omission and monetary gain versus loss). We found that activation in the thalamus and insula predicted adjustments of motor responses due to outcomes that were cued and delivered, whereas activation in the ventral striatum predicted such adjustments when outcomes were cued but omitted. Further, activation of OFC predicted improvement after all punishing outcomes, independent of whether they were omitted rewards or delivered punishments. Finally, we found that activity in anterior cingulate predicted adjustment after delivered punishments and activity in dorsal striatum predicted adaptation after delivered rewards. Our results provide evidence that different but somewhat overlapping circuits mediate the same behavioral adaptation when it is driven by different incentive outcomes.

  20. Optical imaging in galagos reveals parietal-frontal circuits underlying motor behavior.

    PubMed

    Stepniewska, Iwona; Friedman, Robert M; Gharbawie, Omar A; Cerkevich, Christina M; Roe, Anna W; Kaas, Jon H

    2011-09-13

    The posterior parietal cortex (PPC) of monkeys and prosimian galagos contains a number of subregions where complex, behaviorally meaningful movements, such as reaching, grasping, and body defense, can be evoked by electrical stimulation with long trains of electrical pulses through microelectrodes. Shorter trains of pulses evoke no or simple movements. One possibility for the difference in effectiveness of intracortical microstimulation is that long trains activate much larger regions of the brain. Here, we show that long-train stimulation of PPC does not activate widespread regions of frontal motor and premotor cortex but instead, produces focal, somatotopically appropriate activations of frontal motor and premotor cortex. Shorter stimulation trains activate the same frontal foci but less strongly, showing that longer stimulus trains do not produce less specification. Because the activated sites in frontal cortex correspond to the locations of direct parietal-frontal anatomical connections from the stimulated PPC subregions, the results show the usefulness of optical imaging in conjunction with electrical stimulation in showing functional pathways between nodes in behavior-specific cortical networks. Thus, long-train stimulation is effective in evoking ethologically relevant sequences of movements by activating nodes in a cortical network for a behaviorally relevant period rather than spreading activation in a nonspecific manner.

  1. Relationship between dopamine deficit and the expression of depressive behavior resulted from alteration of serotonin system.

    PubMed

    Lee, Minkyung; Ryu, Young Hoon; Cho, Won Gil; Kang, Yeo Wool; Lee, Soo Jin; Jeon, Tae Joo; Lyoo, Chul Hyoung; Kim, Chul Hoon; Kim, Dong Goo; Lee, Kyochul; Choi, Tae Hyun; Choi, Jae Yong

    2015-09-01

    Depression frequently accompanies in Parkinson's disease (PD). Previous research suggested that dopamine (DA) and serotonin systems are closely linked with depression in PD. However, comprehensive studies about the relationship between these two neurotransmitter systems are limited. Therefore, the purpose of this study is to evaluate the effect of dopaminergic destruction on the serotonin system. The interconnection between motor and depression was also examined. Two PET scans were performed in the 6-hydroxydopamine (6-OHDA) lesioned and sham operated rats: [(18) F]FP-CIT for DA transporters and [(18) F]Mefway for serotonin 1A (5-HT(1A)) receptors. Here, 6-OHDA is a neurotoxin for dopaminergic neurons. Behavioral tests were used to evaluate the severity of symptoms: rotational number for motor impairment and immobility time, acquired from the forced swim test for depression. Region-of-interests were drawn in the striatum and cerebellum for the DA system and hippocampus and cerebellum for the 5-HT system. The cerebellum was chosen as a reference region. Nondisplaceable binding potential in the striatum and hippocampus were compared between 6-OHDA and sham groups. As a result, the degree of DA depletion was negatively correlated with rotational behavior (R(2)  = 0.79, P = 0.003). In 6-OHDA lesioned rats, binding values for 5-HT(1A) receptors was 22% lower than the sham operated group. This decrement of 5-HT(1A) receptor binding was also correlated with the severity of depression (R(2)  = 0.81, P = 0.006). Taken together, this research demonstrated that the destruction of dopaminergic system causes the reduction of the serotonergic system resulting in the expression of depressive behavior. The degree of dopaminergic dysfunction was positively correlated with the impairment of the serotonin system. Severity of motor symptoms was also closely related to depressive behavior.

  2. Puberty and gonadal hormones: role in adolescent-typical behavioral alterations.

    PubMed

    Varlinskaya, Elena I; Vetter-O'Hagen, Courtney S; Spear, Linda P

    2013-07-01

    This article is part of a Special Issue "Puberty and Adolescence". Adolescence is characterized by a variety of behavioral alterations, including elevations in novelty-seeking and experimentation with alcohol and other drugs of abuse. Some adolescent-typical neurobehavioral alterations may depend upon pubertal rises in gonadal hormones, whereas others may be unrelated to puberty. Using a variety of approaches, studies in laboratory animals have not revealed clear relationships between pubertal-related changes and adolescent- or adult-typical behaviors that are not strongly sexually dimorphic. Data reviewed suggest surprisingly modest influences of gonadal hormones on alcohol intake, alcohol preference and novelty-directed behaviors. Gonadectomy in males (but not females) increased ethanol intake in adulthood following surgery either pre-pubertally or in adulthood, with these increases in intake largely reversed by testosterone replacement in adulthood, supporting an activational role of androgens in moderating ethanol intake in males. In contrast, neither pre-pubertal nor adult gonadectomy influenced sensitivity to the social inhibitory or aversive effects of ethanol when indexed via conditioned taste aversions, although gonadectomy at either age altered the microstructure of social behavior of both males and females. Unexpectedly, the pre-pubertal surgical manipulation process itself was found to increase later ethanol intake, decrease sensitivity to ethanol's social inhibitory effects, attenuate novelty-directed behavior and lower social motivation, with gonadal hormones being necessary for these long-lasting effects of early surgical perturbations.

  3. Chronic social instability in adult female rats alters social behavior, maternal aggression and offspring development.

    PubMed

    Pittet, Florent; Babb, Jessica A; Carini, Lindsay; Nephew, Benjamin C

    2017-04-01

    We investigated the consequences of chronic social instability (CSI) during adulthood on social and maternal behavior in females and social behavior of their offspring in a rat model. CSI consisted of changing the social partners of adult females every 2-3 days for 28 days, 2 weeks prior to mating. Females exposed to CSI behaved less aggressively and more pro-socially towards unfamiliar female intruders. Maternal care was not affected by CSI in a standard testing environment, but maternal behavior of CSI females was less disrupted by a male intruder. CSI females were quicker to attack prey and did not differ from control females in their saccharin consumption indicating, respectively, no stress-induced sensory-motor or reward system impairments. Offspring of CSI females exhibited slower growth and expressed more anxiety in social encounters. This study demonstrates continued adult vulnerability to social challenges with an impact specific to social situations for mothers and offspring.

  4. Mutagenesis and behavioral screening for altered circadian activity identifies the mouse mutant, Wheels.

    PubMed

    Pickard, G E; Sollars, P J; Rinchik, E M; Nolan, P M; Bucan, M

    1995-12-24

    The molecular processes underlying the generation of circadian behavior in mammals are virtually unknown. To identify genes that regulate or alter circadian activity rhythms, a mouse mutagenesis program was initiated in conjunction with behavioral screening for alterations in circadian period (tau), a fundamental property of the biological clock. Male mice of the inbred BALB/c strain, treated with the potent mutagen N-ethyl-N-nitrosourea were mated with wild-type hybrids. Wheel-running activity of approximately 300 male progeny was monitored for 6-10 weeks under constant dark (DD) conditions. The tau DD of a single mouse (#187) was longer than the population mean by more than three standard deviations (24.20 vs. 23.32 +/- 0.02 h; mean +/- S.E.M.; n = 277). In addition, mouse #187 exhibited other abnormal phenotypes, including hyperactive bi-directional circling/spinning activity and an abnormal response to light. Heterozygous progeny of the founder mouse, generated from outcrossings with wild-type C57BL/6J mice, displayed lengthened tau DD although approximately 20% of the animals showed no wheel-running activity despite being quite active. Under light:dark conditions, all animals displaying circling behavior that ran in the activity wheels exhibited robust wheel-running activity at lights-ON and these animals also showed enhanced wheel-running activity in constant light conditions. The genetic dissection of the complex behavior associated with this mutation was facilitated by the previously described genetic mapping of the mutant locus causing circling behavior, designated Wheels (Whl), to the subcentromeric portion of mouse chromosome 4. In this report, the same locus is shown to be responsible for the abnormal responses to light and presumably for the altered circadian behavior. Characterization of the gene altered in the novel Whl mutation will contribute to understanding the molecular elements involved in mammalian circadian regulation.

  5. Altering the function of commands presented to boys with oppositional and hyperactive behavior

    PubMed Central

    Danforth, Jeffrey S.

    2002-01-01

    Mentalistic and behavioral analyses of noncompliance among children with hyperactive behavior are contrasted. Then, a behavioral training program for 3 boys with behavior characteristic of attention deficit hyperactivity disorder and oppositional defiant disorder is described. The child-focused training was conducted in conjunction with parent training. In an effort to increase the rate of compliance, the child-training program was designed to alter the function of parent commands by teaching the boys to verbalize rules about parent commands and consequences in the context of observing parent—child role-plays. Training was conducted within a multiple baseline design across children. Direct observation of mother—child interactions, telephone interviews, and standardized rating scales showed that training resulted in clinically significant reductions in noncompliance and improved parenting behavior. A 6-month follow-up revealed stable outcomes. PMID:22477227

  6. Motor control of jaw movements: An fMRI study of parafunctional clench and grind behavior.

    PubMed

    Wong, Donald; Dzemidzic, Mario; Talavage, Thomas M; Romito, Laura M; Byrd, Kenneth E

    2011-04-06

    Jaw-clenching and tooth-grinding associated with bruxism can contribute to abnormal tooth wear and pain in the masticatory system. Clench and tooth-grinding jaw-movement tasks were evaluated in a block-design fMRI study comparing a dental-control (DC) group with a tooth-grinding (TG) group. Group classification was made prior to imaging based upon self-reported parafunctional clench and grind behavior and clinical evidence of abnormal tooth wear. Group differences in brain activation patterns were found for each task compared to the resting baseline. The DC group showed a more widely distributed pattern; more extensive activity in the supplementary motor area (SMA) proper that extended into the pre-SMA; and, for clench, activity in the left inferior parietal lobule (IPL). The DC group activated more than the TG subjects the left IPL for clench, and pre-SMA for grind. Neither task elicited more activity in the TG than DC subjects. Our group findings suggest that jaw-movement tasks executed by the TG group elicited (1) more efficient brain activation pattern consistent with other studies that found less extensive activity with executing "over-learned" tasks; (2) "underactive" SMA activity that underlies reduced motor planning; (3) decreased inferior parietal activity that is associated with lesser motor-attentional demands. Thus orofacial parafunctional habits may influence brain circuits recruited for jaw movements, providing a possible basis for understanding involuntary jaw movements in bruxism and oral movement disorders in general.

  7. Behavioral Problems in Children with Motor and Intellectual Disabilities: Prevalence and Associations with Maladaptive Personality and Marital Relationship

    ERIC Educational Resources Information Center

    Vrijmoeth, Cis; Monbaliu, Elegast; Lagast, Emmy; Prinzie, Peter

    2012-01-01

    Prevalence rates of behavioral problems in children with motor disabilities are commonly based on questionnaires developed for a general population (e.g., Child Behavior CheckList). These questionnaires do not take into account lower levels of intellectual functioning. The first aim of this study was to examine the prevalence of parent-reported…

  8. The Cinderella of Psychology: The Neglect of Motor Control in the Science of Mental Life and Behavior

    ERIC Educational Resources Information Center

    Rosenbaum, David A.

    2005-01-01

    One would expect psychology--the science of mental life and behavior--to place great emphasis on the means by which mental life is behaviorally expressed. Surprisingly, however, the study of how decisions are enacted--the focus of motor control research--has received little attention in psychology. This article documents the neglect and considers…

  9. Antibiotic-induced dysbiosis alters host-bacterial interactions and leads to colonic sensory and motor changes in mice.

    PubMed

    Aguilera, M; Cerdà-Cuéllar, M; Martínez, V

    2015-01-01

    Alterations in the composition of the commensal microbiota (dysbiosis) seem to be a pathogenic component of functional gastrointestinal disorders, mainly irritable bowel syndrome (IBS), and might participate in the secretomotor and sensory alterations observed in these patients.We determined if a state antibiotics-induced intestinal dysbiosis is able to modify colonic pain-related and motor responses and characterized the neuro-immune mechanisms implicated in mice. A 2-week antibiotics treatment induced a colonic dysbiosis (increments in Bacteroides spp, Clostridium coccoides and Lactobacillus spp and reduction in Bifidobacterium spp). Bacterial adherence was not affected. Dysbiosis was associated with increased levels of secretory-IgA, up-regulation of the antimicrobial lectin RegIIIγ, and toll-like receptors (TLR) 4 and 7 and down-regulation of the antimicrobial-peptide Resistin-Like Molecule-β and TLR5. Dysbiotic mice showed less goblet cells, without changes in the thickness of the mucus layer. Neither macroscopical nor microscopical signs of inflammation were observed. In dysbiotic mice, expression of the cannabinoid receptor 2 was up-regulated, while the cannabinoid 1 and the mu-opioid receptors were down-regulated. In antibiotic-treated mice, visceral pain-related responses elicited by intraperitoneal acetic acid or intracolonic capsaicin were significantly attenuated. Colonic contractility was enhanced during dysbiosis. Intestinal dysbiosis induce changes in the innate intestinal immune system and modulate the expression of pain-related sensory systems, an effect associated with a reduction in visceral pain-related responses. Commensal microbiota modulates gut neuro-immune sensory systems, leading to functional changes, at least as it relates to viscerosensitivity. Similar mechanisms might explain the beneficial effects of antibiotics or certain probiotics in the treatment of IBS.

  10. Antibiotic-induced dysbiosis alters host-bacterial interactions and leads to colonic sensory and motor changes in mice

    PubMed Central

    Aguilera, M; Cerdà-Cuéllar, M; Martínez, V

    2015-01-01

    Alterations in the composition of the commensal microbiota (dysbiosis) seem to be a pathogenic component of functional gastrointestinal disorders, mainly irritable bowel syndrome (IBS), and might participate in the secretomotor and sensory alterations observed in these patients.We determined if a state antibiotics-induced intestinal dysbiosis is able to modify colonic pain-related and motor responses and characterized the neuro-immune mechanisms implicated in mice. A 2-week antibiotics treatment induced a colonic dysbiosis (increments in Bacteroides spp, Clostridium coccoides and Lactobacillus spp and reduction in Bifidobacterium spp). Bacterial adherence was not affected. Dysbiosis was associated with increased levels of secretory-IgA, up-regulation of the antimicrobial lectin RegIIIγ, and toll-like receptors (TLR) 4 and 7 and down-regulation of the antimicrobial-peptide Resistin-Like Molecule-β and TLR5. Dysbiotic mice showed less goblet cells, without changes in the thickness of the mucus layer. Neither macroscopical nor microscopical signs of inflammation were observed. In dysbiotic mice, expression of the cannabinoid receptor 2 was up-regulated, while the cannabinoid 1 and the mu-opioid receptors were down-regulated. In antibiotic-treated mice, visceral pain-related responses elicited by intraperitoneal acetic acid or intracolonic capsaicin were significantly attenuated. Colonic contractility was enhanced during dysbiosis. Intestinal dysbiosis induce changes in the innate intestinal immune system and modulate the expression of pain-related sensory systems, an effect associated with a reduction in visceral pain-related responses. Commensal microbiota modulates gut neuro-immune sensory systems, leading to functional changes, at least as it relates to viscerosensitivity. Similar mechanisms might explain the beneficial effects of antibiotics or certain probiotics in the treatment of IBS. PMID:25531553

  11. Dissociation of Structural and Functional Integrities of the Motor System in Amyotrophic Lateral Sclerosis and Behavioral-Variant Frontotemporal Dementia

    PubMed Central

    Bae, Jong Seok; Ferguson, Michele; Tan, Rachel; Mioshi, Eneida; Simon, Neil; Burrell, James; Vucic, Steve; Hodges, John R.; Kiernan, Matthew C

    2016-01-01

    Background and Purpose This study investigated the structural and functional changes in the motor system in amyotrophic lateral sclerosis (ALS; n=25) and behavioral-variant fronto-temporal dementia (bvFTD; n=17) relative to healthy controls (n=37). Methods Structural changes were examined using a region-of-interest approach, applying voxel-based morphometry for gray-matter changes and diffusion tensor imaging for white-matter changes. Functional changes in the motor system were elucidated using threshold-tracking transcranial magnetic stimulation (TMS) measurements of upper motor-neuron excitability. Results The structural analyses showed that in ALS there were more white-matter changes in the corticospinal and motor-cortex regions and more gray-matter changes in the cerebellum in comparison to controls. bvFTD showed substantial gray- and white-matter changes across virtually all motor-system regions compared to controls, although the brainstem was affected less than the other regions. Direct comparisons across patient groups showed that the gray- and white-matter motor-system changes inclusive of the motor cortex were greater in bvFTD than in ALS. By contrast, the functional integrity of the motor system was more adversely affected in ALS than in bvFTD, with both patient groups showing increased excitability of upper motor neurons compared to controls. Conclusions Cross-correlation of structural and functional data further revealed a neural dissociation of different motor-system regions and tracts covarying with the TMS excitability across both patient groups. The structural and functional motor-system integrities appear to be dissociated between ALS and bvFTD, which represents useful information for the diagnosis of motor-system changes in these two disorders. PMID:26932257

  12. Hypnagogic behavior disorder: complex motor behaviors during wake-sleep transitions in 2 young children.

    PubMed

    Pareja, Juan A; Cuadrado, María Luz; García-Morales, Irene; Gil-Nagel, Antonio; Franch, Oriol

    2008-08-01

    A nondescribed behavioral disorder was observed during wake-sleep transitions in 2 young children. Two boys had episodes of abnormal behavior in hypnagogic-and occasionally hypnopompic-periods for 1 year from the time they were 1 year and several months old. The episodes consisted of irregular body movements, which could be either gentle or violent but never made the children get out of bed. They lasted from a few seconds to 2 hours and were associated with poor reactivity and amnesia of the events. Electroencephalography (EEG) recordings showed wake-state features, with brief bursts of hypnagogic hypersynchrony, and did not display seizure activity. A distinctive behavior disorder occurring during wake-sleep transitions with a wake EEG pattern has been identified in very early childhood. The clinical profile does not fit any of the known parasomnias and might belong to a new category of parasomnia.

  13. Altered structural and functional connectivity between the bilateral primary motor cortex in unilateral subcortical stroke: A multimodal magnetic resonance imaging study.

    PubMed

    Zhang, Yong; Li, Kuang-Shi; Ning, Yan-Zhe; Fu, Cai-Hong; Liu, Hong-Wei; Han, Xiao; Cui, Fang-Yuan; Ren, Yi; Zou, Yi-Huai

    2016-08-01

    A large number of functional imaging studies have focused on the understanding of motor-related neural activities after ischemic stroke. However, the knowledge is still limited in the structural and functional changes of the interhemispheric connections of the bilateral primary motor cortices (M1s) and their potential influence on motor function recovery following stroke.Twenty-four stroke patients with right hemispheric subcortical infarcts and 25 control subjects were recruited to undergo multimodal magnetic resonance imaging examinations. Structural impairments between the bilateral M1s were measured by fractional anisotropy. Functional changes of the bilateral M1s were assessed via M1-M1 resting-state functional connectivity. Task-evoked activation analysis was applied to identify the roles of the bilateral hemispheres in motor function recovery. Compared with control subjects, unilateral subcortical stroke patients revealed significantly decreased fractional anisotropy and functional connectivity between the bilateral M1s. Stroke patients also revealed higher activations in multiple brain regions in both hemispheres and that more regions were located in the contralesional hemisphere.This study increased our understanding of the structural and functional alterations between the bilateral M1s that occur in unilateral subcortical stroke and provided further evidence for the compensatory role played by the contralesional hemisphere for these alterations during motor function recovery.

  14. Motor Behavior Mediated by Continuously Generated Dopaminergic Neurons in the Zebrafish Hypothalamus Recovers After Cell Ablation

    PubMed Central

    McPherson, Adam D.; Barrios, Joshua P.; Luks-Morgan, Sasha J.; Manfredi, John P.; Bonkowsky, Joshua L.; Douglass, Adam D.; Dorsky, Richard I.

    2015-01-01

    Summary Postembryonic neurogenesis has been observed in several regions of the vertebrate brain, including the dentate gyrus and rostral migratory stream in mammals, and is required for normal behavior [1–3]. Recently the hypothalamus has also been shown to undergo continuous neurogenesis as a way to mediate energy balance [4–10]. As the hypothalamus regulates multiple functional outputs, it is likely that additional behaviors may be affected by postembryonic neurogenesis in this brain structure. Here, we have identified a progenitor population in the zebrafish hypothalamus that continuously generates neurons that express tyrosine hydroxylase 2 (th2). We develop and use novel transgenic tools to characterize the lineage of th2+ cells and demonstrate that they are dopaminergic. Through genetic ablation and optogenetic activation we then show that th2+ neurons modulate the initiation of swimming behavior in zebrafish larvae. Finally we find that the generation of new th2+ neurons following ablation correlates with restoration of normal behavior. This work thus identifies for the first time a population of dopaminergic neurons that regulates motor behavior capable of functional recovery. PMID:26774784

  15. Visual cues influence motor coordination: behavioral results and potential neural mechanisms mediating perception-action coupling and response selection.

    PubMed

    Wenderoth, Nicole; Weigelt, Matthias

    2009-01-01

    Here we review behavioral and brain imaging results on stimulus-response selection in the context of bimanual movements, which is a prototypical paradigm frequently used to investigate the coordination of complex motor behavior. We propose that stimulus-response selection is constrained at the motor, perceptual, and cognitive levels, with the relative importance of each dependent on the task context. Motor constraints seem to dominate when response selection requirements are low, whereas perceptual and cognitive constraints become increasingly important when the appropriate movement has to be associated with a visual cue. We argue that certain cue features determine how task goals are conceptualized, which influences how a particular motor response is selected and implemented by the nervous system.

  16. A Perceptual Motor Intervention Improves Play Behavior in Children with Moderate to Severe Cerebral Palsy

    PubMed Central

    Ryalls, Brigette O.; Harbourne, Regina; Kelly-Vance, Lisa; Wickstrom, Jordan; Stergiou, Nick; Kyvelidou, Anastasia

    2016-01-01

    For children with moderate or severe cerebral palsy (CP), a foundational early goal is independent sitting. Sitting offers additional opportunities for object exploration, play and social engagement. The achievement of sitting coincides with important milestones in other developmental areas, such as social engagement with others, understanding of spatial relationships, and the use of both hands to explore objects. These milestones are essential skills necessary for play behavior. However, little is known about how sitting and play behavior might be affected by a physical therapy intervention in children with moderate or severe CP. Therefore, our overall purpose in this study was to determine if sitting skill could be advanced in children with moderate to severe CP using a perceptual motor intervention, and if play skills would change significantly as sitting advanced. Thirty children between the ages of 18 months and 6 years who were able to hold prop sitting for at least 10 s were recruited for this study. Outcome measures were the sitting subsection of the Gross Motor Function Measure (GMFM), and the Play Assessment of Children with Motor Impairment play assessment scale, which is a modified version of the Play in Early Childhood Evaluation System. Significant improvements in GMFM sitting scores (p < 0.001) and marginally significant improvement in play assessment scores (p = 0.067) were found from pre- to post-intervention. Sitting change explained a significant portion of the variance in play change for children over the age of 3 years, who were more severely affected by CP. The results of this study indicate that advances in sitting skill may be a factor in supporting improvements in functional play, along with age and severity of physical impairment. PMID:27199868

  17. Time-varying motor control of autotomized leopard gecko tails: multiple inputs and behavioral modulation.

    PubMed

    Higham, Timothy E; Russell, Anthony P

    2012-02-01

    Autotomy (voluntary loss of an appendage) is common among diverse groups of vertebrates and invertebrates, and much attention has been given to ecological and developmental aspects of tail autotomy in lizards. Although most studies have focused on the ramifications for the lizard (behavior, biomechanics, energetics, etc.), the tail itself can exhibit interesting behaviors once segregated from the body. For example, recent work highlighted the ability of leopard gecko tails to jump and flip, in addition to being able to swing back and forth. Little is known, however, about the control mechanisms underlying these movements. Using electromyography, we examined the time-varying in vivo motor patterns at four sites (two proximal and two distal) in the tail of the leopard gecko, Eublepharis macularius, following autotomy. Using these data we tested the hypothesis that the disparity in movements results simply from overlapping pattern generators within the tail. We found that burst duration, but not cycle duration, of the rhythmic swings reached a plateau at approximately 150 s following autotomy. This is likely because of physiological changes related to muscle fatigue and ischemia. For flips and jumps, burst and cycle duration exhibited no regular pattern. The coefficient of variation in motor patterns was significantly greater for jumps and flips than for rhythmic swings. This supports the conclusion that the different tail behaviors do not stem from overlapping pattern generators, but that they rely upon independent neural circuits. The signal controlling jumps and flips may be modified by sensory information from the environment. Finally, we found that jumps and flips are initiated using relatively synchronous activity between the two sides of the tail. In contrast, alternating activation of the right and left sides of the tail result in rhythmic swings. The mechanism underlying this change in tail behavior is comparable to locomotor gait changes in vertebrates.

  18. Chronic behavioral stress exaggerates motor deficit and neuroinflammation in the MPTP mouse model of Parkinson's disease

    PubMed Central

    Lauretti, E; Di Meco, A; Merali, S; Praticò, D

    2016-01-01

    Environmental stressor exposure is associated with a variety of age-related diseases including neurodegeneration. Although the initial events of sporadic Parkinson's disease (PD) are not known, consistent evidence supports the hypothesis that the disease results from the combined effect of genetic and environmental risk factors. Among them, behavioral stress has been shown to cause damage and neuronal loss in different areas of the brain, however, its effect on the dopaminergic system and PD pathogenesis remains to be characterized. The C57BL/6 mice underwent chronic restraint/isolation (RI) stress and were then treated with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), whereas the control mice were treated only with MPTP and the effect on the PD-like phenotype was evaluated. The mice that underwent RI before the administration of MPTP manifested an exaggerated motor deficit and impairment in the acquisition of motor skills, which were associated with a greater loss of neuronal tyrosine hydroxylase and astrocytes activation. By showing that RI influences the onset and progression of the PD-like phenotype, our study underlines the novel pathogenetic role that chronic behavioral stressor has in the disease process by triggering neuroinflammation and degeneration of the nigral dopaminergic system. PMID:26859816

  19. Chronic behavioral stress exaggerates motor deficit and neuroinflammation in the MPTP mouse model of Parkinson's disease.

    PubMed

    Lauretti, E; Di Meco, A; Merali, S; Praticò, D

    2016-02-09

    Environmental stressor exposure is associated with a variety of age-related diseases including neurodegeneration. Although the initial events of sporadic Parkinson's disease (PD) are not known, consistent evidence supports the hypothesis that the disease results from the combined effect of genetic and environmental risk factors. Among them, behavioral stress has been shown to cause damage and neuronal loss in different areas of the brain, however, its effect on the dopaminergic system and PD pathogenesis remains to be characterized. The C57BL/6 mice underwent chronic restraint/isolation (RI) stress and were then treated with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), whereas the control mice were treated only with MPTP and the effect on the PD-like phenotype was evaluated. The mice that underwent RI before the administration of MPTP manifested an exaggerated motor deficit and impairment in the acquisition of motor skills, which were associated with a greater loss of neuronal tyrosine hydroxylase and astrocytes activation. By showing that RI influences the onset and progression of the PD-like phenotype, our study underlines the novel pathogenetic role that chronic behavioral stressor has in the disease process by triggering neuroinflammation and degeneration of the nigral dopaminergic system.

  20. New insights into sucking, swallowing and breathing central generators: A complexity analysis of rhythmic motor behaviors.

    PubMed

    Samson, Nathalie; Praud, Jean-Paul; Quenet, Brigitte; Similowski, Thomas; Straus, Christian

    2017-01-18

    Sucking, swallowing and breathing are dynamic motor behaviors. Breathing displays features of chaos-like dynamics, in particular nonlinearity and complexity, which take their source in the automatic command of breathing. In contrast, buccal/gill ventilation in amphibians is one of the rare motor behaviors that do not display nonlinear complexity. This study aimed at assessing whether sucking and swallowing would also follow nonlinear complex dynamics in the newborn lamb. Breathing movements were recorded before, during and after bottle-feeding. Sucking pressure and the integrated EMG of the thyroartenoid muscle, as an index of swallowing, were recorded during bottle-feeding. Nonlinear complexity of the whole signals was assessed through the calculation of the noise limit value (NL). Breathing and swallowing always exhibited chaos-like dynamics. The NL of breathing did not change significantly before, during or after bottle-feeding. On the other hand, sucking inconsistently and significantly less frequently than breathing exhibited a chaos-like dynamics. Therefore, the central pattern generator (CPG) that drives sucking may be functionally different from the breathing CPG. Furthermore, the analogy between buccal/gill ventilation and sucking suggests that the latter may take its phylogenetic origin in the gill ventilation CPG of the common ancestor of extant amphibians and mammals.

  1. The effect of altering self-descriptive behavior on self-concept and classroom behavior.

    PubMed

    Lane, J; Muller, D

    1977-09-01

    This research examined the impact of operant reinforcement of positive self-descriptive behavior on the self-concepts and classroom behavior of 60 fifth-grade students. Three groups of 10 male and 10 female low self-concept students wrote a series of eight essays describing their school performance. The first group (P) received written reinforcement for positive self-descriptions of their school performance. The second group (G) received an equal number of reinforcements for general statements. The third group (C) received no reinforcement for written statements. Three areas of self-concept were measured with the Primary Self-Concept Inventory: personal-self, social-self, and intellectual-self. A frequency count was also made of nine classroom behaviors thought to be influenced by self-concept. The P group displayed increases in the frequency of positive self-descriptive statement and in intellectual self-concept but no changes in personal self-concept, social self-concept, or the nine classroom behaviors. The G and C groups showed no change in self-description, self-concept, or the nine classroom behaviors.

  2. Microbiota alteration is associated with the development of stress-induced despair behavior

    PubMed Central

    Marin, Ioana A.; Goertz, Jennifer E.; Ren, Tiantian; Rich, Stephen S.; Onengut-Gumuscu, Suna; Farber, Emily; Wu, Martin; Overall, Christopher C.; Kipnis, Jonathan; Gaultier, Alban

    2017-01-01

    Depressive disorders often run in families, which, in addition to the genetic component, may point to the microbiome as a causative agent. Here, we employed a combination of behavioral, molecular and computational techniques to test the role of the microbiota in mediating despair behavior. In chronically stressed mice displaying despair behavior, we found that the microbiota composition and the metabolic signature dramatically change. Specifically, we observed reduced Lactobacillus and increased circulating kynurenine levels as the most prominent changes in stressed mice. Restoring intestinal Lactobacillus levels was sufficient to improve the metabolic alterations and behavioral abnormalities. Mechanistically, we identified that Lactobacillus-derived reactive oxygen species may suppress host kynurenine metabolism, by inhibiting the expression of the metabolizing enzyme, IDO1, in the intestine. Moreover, maintaining elevated kynurenine levels during Lactobacillus supplementation diminished the treatment benefits. Collectively, our data provide a mechanistic scenario for how a microbiota player (Lactobacillus) may contribute to regulating metabolism and resilience during stress. PMID:28266612

  3. Microbiota alteration is associated with the development of stress-induced despair behavior.

    PubMed

    Marin, Ioana A; Goertz, Jennifer E; Ren, Tiantian; Rich, Stephen S; Onengut-Gumuscu, Suna; Farber, Emily; Wu, Martin; Overall, Christopher C; Kipnis, Jonathan; Gaultier, Alban

    2017-03-07

    Depressive disorders often run in families, which, in addition to the genetic component, may point to the microbiome as a causative agent. Here, we employed a combination of behavioral, molecular and computational techniques to test the role of the microbiota in mediating despair behavior. In chronically stressed mice displaying despair behavior, we found that the microbiota composition and the metabolic signature dramatically change. Specifically, we observed reduced Lactobacillus and increased circulating kynurenine levels as the most prominent changes in stressed mice. Restoring intestinal Lactobacillus levels was sufficient to improve the metabolic alterations and behavioral abnormalities. Mechanistically, we identified that Lactobacillus-derived reactive oxygen species may suppress host kynurenine metabolism, by inhibiting the expression of the metabolizing enzyme, IDO1, in the intestine. Moreover, maintaining elevated kynurenine levels during Lactobacillus supplementation diminished the treatment benefits. Collectively, our data provide a mechanistic scenario for how a microbiota player (Lactobacillus) may contribute to regulating metabolism and resilience during stress.

  4. Altered negative priming in older subjects: first evidence from behavioral and neural level

    PubMed Central

    Bauer, Eva; Gebhardt, Helge; Gruppe, Harald; Gallhofer, Bernd; Sammer, Gebhard

    2012-01-01

    The impact of aging on the negative priming (NP) effect has been subject of many studies using behavioral measures. Results are inconsistent and corresponding neural data do not exist. We were interested in, whether or not processing of NP is altered in older in comparison to young adults (YA) on behavioral and neural level. Eighteen young and eighteen older healthy adults performed a location-based NP paradigm during fMRI. YA behaviorally showed a NP effect and NP associated fronto-striatal activation, which is in accordance with the inhibitory model of NP. In older subjects no significant behavioral NP effect and no NP-related activation in predefined brain regions could be found. This is discussed in context of the “loss of efficiency” hypothesis. One possible source for the lack of NP-related activation is a reduction of gray matter (GM) volume in older subjects as shown using voxel based morphometry (VBM). PMID:23060774

  5. A hybrid electrical/chemical circuit in the spinal cord generates a transient embryonic motor behavior.

    PubMed

    Knogler, Laura D; Ryan, Joel; Saint-Amant, Louis; Drapeau, Pierre

    2014-07-16

    Spontaneous network activity is a highly stereotyped early feature of developing circuits throughout the nervous system, including in the spinal cord. Spinal locomotor circuits produce a series of behaviors during development before locomotion that reflect the continual integration of spinal neurons into a functional network, but how the circuitry is reconfigured is not understood. The first behavior of the zebrafish embryo (spontaneous coiling) is mediated by an electrical circuit that subsequently generates mature locomotion (swimming) as chemical neurotransmission develops. We describe here a new spontaneous behavior, double coiling, that consists of two alternating contractions of the tail in rapid succession. Double coiling was glutamate-dependent and required descending hindbrain excitation, similar to but preceding swimming, making it a discrete intermediary developmental behavior. At the cellular level, motoneurons had a distinctive glutamate-dependent activity pattern that correlated with double coiling. Two glutamatergic interneurons, CoPAs and CiDs, had different activity profiles during this novel behavior. CoPA neurons failed to show changes in activity patterns during the period in which double coiling appears, whereas CiD neurons developed a glutamate-dependent activity pattern that correlated with double coiling and they innervated motoneurons at that time. Additionally, double coils were modified after pharmacological reduction of glycinergic neurotransmission such that embryos produced three or more rapidly alternating coils. We propose that double coiling behavior represents an important transition of the motor network from an electrically coupled spinal cord circuit that produces simple periodic coils to a spinal network driven by descending chemical neurotransmission, which generates more complex behaviors.

  6. Effects of fentanyl on pain and motor behaviors following a collagenase-induced intracerebral hemorrhage in rats

    PubMed Central

    Saine, Laurence; Hélie, Pierre; Vachon, Pascal

    2016-01-01

    Purpose Intracerebral hemorrhage (IH) and cephalalgia are common consequences of traumatic brain injury. One of the primary obstacles for patient recovery is the paucity of treatments to support an appropriate analgesic protocol. The present study aimed to assess pain and motor behaviors following different doses of fentanyl on a rat model of IH. Methods Twenty-one male Sprague Dawley rats underwent a stereotaxic surgery to produce a collagenase-induced IH in the right caudoputamen nucleus. The control group (n=6) received saline subcutaneously (SC), and experimental groups received either 5 (n=6), 10 (n=6), or 20 (n=3) µg/kg of fentanyl SC, 2 hours following surgery and on 2 subsequent days. Only 3 animals received 20 µg/kg because this dose caused catalepsy for 15–20 minutes following the injection. The rat grimace scale, a neurological examination, balance beam test, and rotarod test were performed for 5 consecutive days postoperatively to evaluate pain and motor performance. At the end of the experimentation, the brains were evaluated to determine hematoma volume, and the number of reactive astrocytes and necrotic neurons. Results When compared to controls, the grimace scale showed that 5 µg/kg fentanyl significantly alleviated pain on day 2 only (P<0.01) and that 10 µg/kg alleviated pain on days 1 (P<0.01), 2 (P<0.001), and 3 (P<0.01). For the rotarod test, only the 10 µg/kg group showed significant decreases in performance on days 5 (P<0.05) and 6 (P<0.02). The neurological examination was not significantly different between the groups, but only the hopping test showed poor recuperation for the 5 and 10 µg/kg fentanyl group when compared to saline (P<0.01). No differences were found between the groups for the balance beam test, the histopathological results. Conclusion Fentanyl, at a dose of 10 µg/kg SC, provides substantial analgesia following a collagenase-induced IH in rats; however, it can alter motor performance following analgesic treatments

  7. Presynaptic G protein-coupled receptors dynamically modify vesicle fusion, synaptic cleft glutamate concentrations and motor behavior

    PubMed Central

    Gerachshenko, Tatyana; Schwartz, Eric; Bleckert, Adam; Photowala, Huzefa; Seymour, Andrew; Alford, Simon

    2009-01-01

    Understanding how neuromodulators regulate behavior requires investigating their effects on functional neural systems, but also their underlying cellular mechanisms. Utilizing extensively characterized lamprey motor circuits, and the unique access to reticulospinal presynaptic terminals in the intact spinal cord that initiate these behaviours, we have investigated effects of presynaptic G protein-coupled receptors on locomotion from the systems level, to the molecular control of vesicle fusion. 5-HT inhibits neurotransmitter release via a Gβγ interaction with the SNARE complex that promotes kiss-and-run vesicle fusion. In the lamprey spinal cord we demonstrate that while presynaptic 5-HT receptors inhibit evoked neurotransmitter release from reticulospinal command neurons, their activation does not abolish locomotion, but rather modulates locomotor rhythms. Liberation of presynaptic Gβγ causes substantial inhibition of AMPA receptor-mediated synaptic responses, but leaves NMDA receptor-mediated components of neurotransmission largely intact. Because Gβγ binding to the SNARE complex is displaced by Ca2+-synaptotagmin binding, 5-HT-mediated inhibition displays Ca2+ sensitivity. We show that as Ca2+ accumulates presynaptically during physiological bouts of activity, 5-HT/Gβγ-mediated presynaptic inhibition is relieved leading to a frequency-dependent increase in synaptic concentrations of glutamate. This frequency dependent phenomenon mirrors a shift in the vesicle fusion mode and a recovery of AMPA receptor-mediated EPSCs from inhibition without a modification of NMDA receptor EPSCs. We conclude that activation of presynaptic 5-HT GPCRs state-dependently alters vesicle fusion properties to shift the weight of NMDA vs AMPA receptor-mediated responses at excitatory synapses. We have therefore identified a novel mechanism in which modification of vesicle fusion modes may profoundly alter locomotor behaviour. PMID:19692597

  8. Cortical Structure Alterations and Social Behavior Impairment in p50-Deficient Mice

    PubMed Central

    Bonini, Sara Anna; Mastinu, Andrea; Maccarinelli, Giuseppina; Mitola, Stefania; Premoli, Marika; La Rosa, Luca Rosario; Ferrari-Toninelli, Giulia; Grilli, Mariagrazia; Memo, Maurizio

    2016-01-01

    Alterations in genes that regulate neurodevelopment can lead to cortical malformations, resulting in malfunction during postnatal life. The NF-κB pathway has a key role during neurodevelopment by regulating the maintenance of the neural progenitor cell pool and inhibiting neuronal differentiation. In this study, we evaluated whether mice lacking the NF-κB p50 subunit (KO) present alterations in cortical structure and associated behavioral impairment. We found that, compared with wild type (WT), KO mice at postnatal day 2 present an increase in radial glial cells, an increase in Reelin protein expression levels, in addition to an increase of specific layer thickness. Moreover, adult KO mice display abnormal columnar organization in the somatosensory cortex, a specific decrease in somatostatin- and parvalbumin-expressing interneurons, altered neurite orientation, and a decrease in Synapsin I protein levels. Concerning behavior, KO mice, in addition to an increase in locomotor and exploratory activity, display impairment in social behaviors, with a reduction in social interaction. Finally, we found that risperidone treatment decreased hyperactivity of KO mice, but had no effect on defective social interaction. Altogether, these data add complexity to a growing body of data, suggesting a link between dysregulation of the NF-κB pathway and neurodevelopmental disorders pathogenesis. PMID:26946128

  9. Cortical Structure Alterations and Social Behavior Impairment in p50-Deficient Mice.

    PubMed

    Bonini, Sara Anna; Mastinu, Andrea; Maccarinelli, Giuseppina; Mitola, Stefania; Premoli, Marika; La Rosa, Luca Rosario; Ferrari-Toninelli, Giulia; Grilli, Mariagrazia; Memo, Maurizio

    2016-06-01

    Alterations in genes that regulate neurodevelopment can lead to cortical malformations, resulting in malfunction during postnatal life. The NF-κB pathway has a key role during neurodevelopment by regulating the maintenance of the neural progenitor cell pool and inhibiting neuronal differentiation. In this study, we evaluated whether mice lacking the NF-κB p50 subunit (KO) present alterations in cortical structure and associated behavioral impairment. We found that, compared with wild type (WT), KO mice at postnatal day 2 present an increase in radial glial cells, an increase in Reelin protein expression levels, in addition to an increase of specific layer thickness. Moreover, adult KO mice display abnormal columnar organization in the somatosensory cortex, a specific decrease in somatostatin- and parvalbumin-expressing interneurons, altered neurite orientation, and a decrease in Synapsin I protein levels. Concerning behavior, KO mice, in addition to an increase in locomotor and exploratory activity, display impairment in social behaviors, with a reduction in social interaction. Finally, we found that risperidone treatment decreased hyperactivity of KO mice, but had no effect on defective social interaction. Altogether, these data add complexity to a growing body of data, suggesting a link between dysregulation of the NF-κB pathway and neurodevelopmental disorders pathogenesis.

  10. Interferon-gamma deficiency modifies the motor and co-morbid behavioral pathology and neurochemical changes provoked by the pesticide paraquat.

    PubMed

    Litteljohn, D; Mangano, E; Shukla, N; Hayley, S

    2009-12-29

    In addition to nigrostriatal pathology and corresponding motor disturbances, Parkinson's disease (PD) is often characterized by co-morbid neuropsychiatric symptoms, most notably anxiety and depression. Separate lines of evidence indicate that inflammatory processes associated with microglial activation and cytokine release may be fundamental to the progression of both PD and its co-morbid psychiatric pathology. Accordingly, we assessed the contribution of the pro-inflammatory cytokine, interferon-gamma (IFN-gamma), to a range of PD-like pathology provoked by the ecologically relevant herbicide and dopamine (DA) toxin, paraquat. To this end, paraquat provoked overt motor impairment (reduced home-cage activity and impaired vertical climbing) and signs of anxiety-like behavior (reduced open field exploration) in wild-type but not IFN-gamma-deficient mice. Correspondingly, paraquat promoted somewhat divergent variations in neurochemical activity among wild-type and IFN-gamma null mice at brain sites important for both motor (striatum) and co-morbid affective pathologies (dorsal hippocampus, medial prefrontal cortex, and locus coeruleus). Specifically, the herbicide provoked a dosing regimen-dependent reduction in striatal DA levels that was prevented by IFN-gamma deficiency. In addition, the herbicide influenced serotonergic and noradrenergic activity within the dorsal hippocampus and medial prefrontal cortex; and elevated noradrenergic activity within the locus coeruleus. Although genetic ablation of IFN-gamma had relatively few effects on monoamine variations within the locus coeruleus and prefrontal cortex, loss of the pro-inflammatory cytokine did normalize the paraquat-induced noradrenergic alterations within the hippocampus. These findings further elucidate the functional implications of paraquat intoxication and suggest an important role for IFN-gamma in the striatal and motor pathology, as well as the co-morbid behavioral and hippocampal changes induced by

  11. A high performance sensorimotor beta rhythm-based brain computer interface associated with human natural motor behavior

    NASA Astrophysics Data System (ADS)

    Bai, Ou; Lin, Peter; Vorbach, Sherry; Floeter, Mary Kay; Hattori, Noriaki; Hallett, Mark

    2008-03-01

    To explore the reliability of a high performance brain-computer interface (BCI) using non-invasive EEG signals associated with human natural motor behavior does not require extensive training. We propose a new BCI method, where users perform either sustaining or stopping a motor task with time locking to a predefined time window. Nine healthy volunteers, one stroke survivor with right-sided hemiparesis and one patient with amyotrophic lateral sclerosis (ALS) participated in this study. Subjects did not receive BCI training before participating in this study. We investigated tasks of both physical movement and motor imagery. The surface Laplacian derivation was used for enhancing EEG spatial resolution. A model-free threshold setting method was used for the classification of motor intentions. The performance of the proposed BCI was validated by an online sequential binary-cursor-control game for two-dimensional cursor movement. Event-related desynchronization and synchronization were observed when subjects sustained or stopped either motor execution or motor imagery. Feature analysis showed that EEG beta band activity over sensorimotor area provided the largest discrimination. With simple model-free classification of beta band EEG activity from a single electrode (with surface Laplacian derivation), the online classifications of the EEG activity with motor execution/motor imagery were: >90%/~80% for six healthy volunteers, >80%/~80% for the stroke patient and ~90%/~80% for the ALS patient. The EEG activities of the other three healthy volunteers were not classifiable. The sensorimotor beta rhythm of EEG associated with human natural motor behavior can be used for a reliable and high performance BCI for both healthy subjects and patients with neurological disorders. Significance: The proposed new non-invasive BCI method highlights a practical BCI for clinical applications, where the user does not require extensive training.

  12. NLRP3 INFLAMMASOME ACTIVATION CONTRIBUTES TO LONG-TERM BEHAVIORAL ALTERATIONS IN MICE INJECTED WITH LIPOPOLYSACCHARIDE

    PubMed Central

    ZHU, WEI; CAO, FENG-SHENG; FENG, JUN; CHEN, HUA-WENG; WAN, JIE-RU; LU, QING; WANG, JIAN

    2017-01-01

    Lipopolysaccharide (LPS) might affect the central nervous system by causing neuroinflammation, which subsequently leads to brain damage and dysfunction. In this study, we evaluated the role of nod-like receptor pyrin domain-containing protein 3 (NLRP3) inflammasome activation in long-term behavioral alterations of 8-week-old male C57BL/6 mice injected intraperitoneally with LPS (5 mg/kg). At different time points after injection, we assessed locomotor function with a 24-point neurologic deficit scoring system and the rotarod test; assessed recognition memory with the novel object recognition test; and assessed emotional abnormality (anhedonia and behavioral despair) with the tail suspension test, forced swim test, and sucrose preference test. We also assessed protein expression of NLRP3, apoptosis-associated speck-like protein (ASC), and caspase-1 p10 in hippocampus by Western blotting; measured levels of interleukin (IL)-1β, IL-18, tumor necrosis factor α (TNFα), and IL-10 in hippocampus; measured TNFα and IL-1β in serum by ELISA; and evaluated microglial activity in hippocampus by Iba1 immunofluorescence. We found that LPS-injected mice displayed long-term depression-like behaviors and recognition memory deficit; elevated expression of NLRP3, ASC, and caspase-1 p10; increased levels of IL-1β, IL-18, and TNFα; decreased levels of IL-10; and increased microglial activation. These effects were blocked by the NLRP3 inflammasome inhibitor Ac-Tyr-Val-Ala-Asp-chloromethylketone. The results demonstrate proof of concept that NLRP3 inflammasome activation contributes to long-term behavioral alterations in LPS-exposed mice, probably through enhanced inflammation, and that NLRP3 inflammasome inhibition might alleviate peripheral and brain inflammation and thereby ameliorate long-term behavioral alterations in LPS-exposed mice. PMID:27923741

  13. Modulation of motor cortex neuronal activity and motor behavior during subthalamic nucleus stimulation in the normal primate.

    PubMed

    Johnson, Luke A; Xu, Weidong; Baker, Kenneth B; Zhang, Jianyu; Vitek, Jerrold L

    2015-04-01

    Deep brain stimulation (DBS) of the subthalamic nucleus (STN) is a well-established surgical therapy for advanced Parkinson's disease (PD). An emerging hypothesis is that the therapeutic benefit of DBS is derived from direct modulation of primary motor cortex (M1), yet little is known about the influence of STN DBS on individual neurons in M1. We investigated the effect of STN DBS, delivered at discrete interval intensities (20, 40, 60, 80, and 100%) of corticospinal tract threshold (CSTT), on motor performance and M1 neuronal activity in a naive nonhuman primate. Motor performance during a food reach and retrieval task improved during low-intensity stimulation (20% CSTT) but worsened as intensity approached the threshold for activation of corticospinal fibers (80% and 100% CSTT). To assess cortical effects of STN DBS, spontaneous, extracellular neuronal activity was collected from M1 neurons before, during, and after DBS at the same CSTT stimulus intensities. STN DBS significantly modulated the firing of a majority of M1 neurons; however, the direction of effect varied with stimulus intensity such that, at 20% CSTT, most neurons were suppressed, whereas at the highest stimulus intensities the majority of neurons were activated. At a population level, firing rates increased as stimulus intensity increased. These results show that STN DBS influences both motor performance and M1 neuronal activity systematically according to stimulus intensity. In addition, the unanticipated reduction in reach times suggests that STN DBS, at stimulus intensities lower than typically used for treatment of PD motor signs, can enhance normal motor performance.

  14. Altered Sensory Code Drives Juvenile-to-Adult Behavioral Maturation in Caenorhabditis elegans

    PubMed Central

    Pantazis, Alexandros K.

    2016-01-01

    Abstract Adults perform better than juveniles in food-seeking tasks. Using the nematode Caenorhabditis elegans to probe the neural mechanisms underlying behavioral maturation, we found that adults and juveniles require different combinations of sensory neurons to generate age-specific food-seeking behavior. We first show that adults and juveniles differ in their response to and preference for food-associated odors, and we analyze genetic mutants to map the neuronal circuits required for those behavioral responses. We developed a novel device to trap juveniles and record their neuronal activity. Activity measurements revealed that adult and juvenile AWA sensory neurons respond to the addition of diacetyl stimulus, whereas AWB, ASK, and AWC sensory neurons encode its removal specifically in adults. Further, we show that reducing neurotransmission from the additional AWB, ASK, and AWC sensory neurons transforms odor preferences from an adult to a juvenile-like state. We also show that AWB and ASK neurons drive behavioral changes exclusively in adults, providing more evidence that age-specific circuits drive age-specific behavior. Collectively, our results show that an odor-evoked sensory code is modified during the juvenile-to-adult transition in animal development to drive age-appropriate behavior. We suggest that this altered sensory code specifically enables adults to extract additional stimulus features and generate robust behavior. PMID:28083560

  15. Raclopride or high-frequency stimulation of the subthalamic nucleus stops cocaine-induced motor stereotypy and restores related alterations in prefrontal basal ganglia circuits.

    PubMed

    Aliane, Verena; Pérez, Sylvie; Deniau, Jean-Michel; Kemel, Marie-Louise

    2012-11-01

    Motor stereotypy is a key symptom of various neurological or neuropsychiatric disorders. Neuroleptics or the promising treatment using deep brain stimulation stops stereotypies but the mechanisms underlying their actions are unclear. In rat, motor stereotypies are linked to an imbalance between prefrontal and sensorimotor cortico-basal ganglia circuits. Indeed, cortico-nigral transmission was reduced in the prefrontal but not sensorimotor basal ganglia circuits and dopamine and acetylcholine release was altered in the prefrontal but not sensorimotor territory of the dorsal striatum. Furthermore, cholinergic transmission in the prefrontal territory of the dorsal striatum plays a crucial role in the arrest of motor stereotypy. Here we found that, as previously observed for raclopride, high-frequency stimulation of the subthalamic nucleus (HFS STN) rapidly stopped cocaine-induced motor stereotypies in rat. Importantly, raclopride and HFS STN exerted a strong effect on cocaine-induced alterations in prefrontal basal ganglia circuits. Raclopride restored the cholinergic transmission in the prefrontal territory of the dorsal striatum and the cortico-nigral information transmissions in the prefrontal basal ganglia circuits. HFS STN also restored the N-methyl-d-aspartic-acid-evoked release of acetylcholine and dopamine in the prefrontal territory of the dorsal striatum. However, in contrast to raclopride, HFS STN did not restore the cortico-substantia nigra pars reticulata transmissions but exerted strong inhibitory and excitatory effects on neuronal activity in the prefrontal subdivision of the substantia nigra pars reticulata. Thus, both raclopride and HFS STN stop cocaine-induced motor stereotypy, but exert different effects on the related alterations in the prefrontal basal ganglia circuits.

  16. Postpartum Behavioral Profiles in Wistar Rats Following Maternal Separation - Altered Exploration and Risk-Assessment Behavior in MS15 Dams.

    PubMed

    Daoura, Loudin; Hjalmarsson, My; Oreland, Sadia; Nylander, Ingrid; Roman, Erika

    2010-01-01

    The rodent maternal separation (MS) model is frequently used to investigate the impact of early environmental factors on adult neurobiology and behavior. The majority of MS studies assess effects in the offspring and few address the consequences of repeated pup removal in the dam. Such studies are of interest since alterations detected in offspring subjected to MS may, at least in part, be mediated by variations in maternal behavior and the amount of maternal care provided by the dam. The aim of this study was to investigate how daily short (15 min; MS15) and prolonged (360 min; MS360) periods of MS affects the dam by examining postpartum behavioral profiles using the multivariate concentric square field (MCSF) test. The dams were tested on postpartum days 24-25, i.e., just after the end of the separation period and weaning. The results reveal a lower exploratory drive and lower risk-assessment behavior in MS15 dams relative to MS360 or animal facility reared dams. The present results contrast some of the previously reported findings and provide new information about early post-weaning behavioral characteristics in a multivariate setting. Plausible explanations for the results are provided including a discussion how the present results fit into the maternal mediation hypothesis.

  17. Visual-motor deficits relate to altered gray and white matter in young adults born preterm with very low birth weight.

    PubMed

    Sripada, Kam; Løhaugen, Gro C; Eikenes, Live; Bjørlykke, Kjerstin M; Håberg, Asta K; Skranes, Jon; Rimol, Lars M

    2015-04-01

    , inferior fronto-occipital fasciculus bilaterally, and anterior thalamic radiation bilaterally, driven primarily by an increase in radial diffusivity. VMI scores did not demonstrate a significant relationship to cortical surface area, cortical thickness, or diffusion measures in the control group. Our results indicate that visual-motor integration problems persist into adulthood for very low birth weight individuals, which may be due to structural alterations in several specific gray-white matter networks. Visual-motor deficits appear related to reduced surface area of motor and visual cortices and disturbed connectivity in long association tracts containing visual and motor information. We conjecture that these outcomes may be due to perinatal brain injury or aberrant cortical development secondary to injury or due to very preterm birth.

  18. The Sensorimotor System Can Sculpt Behaviorally Relevant Representations for Motor Learning

    PubMed Central

    2016-01-01

    Abstract The coordinate system in which humans learn novel motor skills is controversial. The representation of sensorimotor skills has been extensively studied by examining generalization after learning perturbations specifically designed to be ambiguous as to their coordinate system. Recent studies have found that learning is not represented in any simple coordinate system and can potentially be accounted for by a mixed representation. Here, instead of probing generalization, which has led to conflicting results, we examine whether novel dynamics can be learned when explicitly and unambiguously presented in particular coordinate systems. Subjects performed center–out reaches to targets in the presence of a force field, while varying the orientation of their hand (i.e., the wrist angle) across trials. Different groups of subjects experienced force fields that were explicitly presented either in Cartesian coordinates (field independent of hand orientation), in object coordinates (field rotated with hand orientation), or in anti-object coordinates (field rotated counter to hand orientation). Subjects learned to represent the dynamics when presented in either Cartesian or object coordinates, learning these as well as an ambiguous force field. However, learning was slower for the object-based dynamics and substantially impaired for the anti-object presentation. Our results show that the motor system is able to tune its representation to at least two natural coordinate systems but is impaired when the representation of the task does not correspond to a behaviorally relevant coordinate system. Our results show that the motor system can sculpt its representation through experience to match those of natural tasks. PMID:27588304

  19. The Sensorimotor System Can Sculpt Behaviorally Relevant Representations for Motor Learning.

    PubMed

    Franklin, David W; Batchelor, Alexandra V; Wolpert, Daniel M

    2016-01-01

    The coordinate system in which humans learn novel motor skills is controversial. The representation of sensorimotor skills has been extensively studied by examining generalization after learning perturbations specifically designed to be ambiguous as to their coordinate system. Recent studies have found that learning is not represented in any simple coordinate system and can potentially be accounted for by a mixed representation. Here, instead of probing generalization, which has led to conflicting results, we examine whether novel dynamics can be learned when explicitly and unambiguously presented in particular coordinate systems. Subjects performed center-out reaches to targets in the presence of a force field, while varying the orientation of their hand (i.e., the wrist angle) across trials. Different groups of subjects experienced force fields that were explicitly presented either in Cartesian coordinates (field independent of hand orientation), in object coordinates (field rotated with hand orientation), or in anti-object coordinates (field rotated counter to hand orientation). Subjects learned to represent the dynamics when presented in either Cartesian or object coordinates, learning these as well as an ambiguous force field. However, learning was slower for the object-based dynamics and substantially impaired for the anti-object presentation. Our results show that the motor system is able to tune its representation to at least two natural coordinate systems but is impaired when the representation of the task does not correspond to a behaviorally relevant coordinate system. Our results show that the motor system can sculpt its representation through experience to match those of natural tasks.

  20. Thermal and motor behavior in experimental autoimmune encephalitis in Lewis rats.

    PubMed

    Wrotek, Sylwia; Rosochowicz, Tomasz; Nowakowska, Anna; Kozak, Wiesław

    2014-08-01

    Thermoregulation in patients, who suffer from multiple sclerosis (MS) is impaired and may result in either increases or decreases in body temperature. Disturbances in body temperature correlate with acute relapses, and for this reason, it is an important issue in everyday life of those who suffer from MS. Although rat experimental autoimmune encephalitis (EAE) appeared useful for the examination of current therapies against MS, it has not been thoroughly investigated in terms of body temperature. The purpose of this study was to examine the effect of EAE induction on thermal and motor behavior in the rats. Subcutaneous injection of encephalitogenic emulsion into both pads of hind feet of the Lewis rats provoked symptoms of EAE. Body temperature (T(b)) and motor activity of rats were measured using biotelemetry system. We report a significant increase in body temperature within 24 h prior to the EAE manifestation (12 h average of T(b) for EAE induced animals was higher by 1.07 ± 0.06 °C during day-time and by 0.5 ± 0.05 °C during night time in comparison to the control rats). On the other hand, the onset of EAE symptoms was associated with gradual decrease of body temperature, and during the first night-time T(b) was lower by 1.03 ± 0.08 °C in comparison to the control rats. The inhibition of the motor activity started from the night time, 2 days before EAE onset. On the basis of our data, we concluded that the pattern of body temperature changes after EAE induction may be considered as useful symptom (prodrom) to predict precisely the time of EAE onset. Furthermore, we suggest that EAE in rats may be a suitable model to study mechanism of body temperature alternations observed in MS patients.

  1. Rat hippocampal alterations could underlie behavioral abnormalities induced by exposure to moderate noise levels.

    PubMed

    Uran, S L; Aon-Bertolino, M L; Caceres, L G; Capani, F; Guelman, L R

    2012-08-30

    Noise exposure is known to affect auditory structures in living organisms. However, it should not be ignored that many of the effects of noise are extra-auditory. Previous findings of our laboratory demonstrated that noise was able to induce behavioral alterations that are mainly related to the cerebellum (CE) and the hippocampus (HC). Therefore, the aim of this work was to reveal new data about the vulnerability of developing rat HC to moderate noise levels through the assessment of potential histological changes and hippocampal-related behavioral alterations. Male Wistar rats were exposed to noise (95-97 dB SPL, 2h daily) either for 1 day (acute noise exposure, ANE) or between postnatal days 15 and 30 (sub-acute noise exposure, SANE). Hippocampal histological evaluation as well as short (ST) and long term (LT) habituation and recognition memory assessments were performed. Results showed a mild disruption in the different hippocampal regions after ANE and SANE schemes, along with significant behavioral abnormalities. These data suggest that exposure of developing rats to noise levels of moderate intensity is able to trigger changes in the HC, an extra-auditory structure of the Central Nervous System (CNS), that could underlie the observed behavioral effects.

  2. Individual prediction of chronic motor outcome in the acute post-stroke stage: Behavioral parameters versus functional imaging.

    PubMed

    Rehme, Anne K; Volz, Lukas J; Feis, Delia-Lisa; Eickhoff, Simon B; Fink, Gereon R; Grefkes, Christian

    2015-11-01

    Several neurobiological factors have been found to correlate with functional recovery after brain lesions. However, predicting the individual potential of recovery remains difficult. Here we used multivariate support vector machine (SVM) classification to explore the prognostic value of functional magnetic resonance imaging (fMRI) to predict individual motor outcome at 4-6 months post-stroke. To this end, 21 first-ever stroke patients with hand motor deficits participated in an fMRI hand motor task in the first few days post-stroke. Motor impairment was quantified assessing grip force and the Action Research Arm Test. Linear SVM classifiers were trained to predict good versus poor motor outcome of unseen new patients. We found that fMRI activity acquired in the first week post-stroke correctly predicted the outcome for 86% of all patients. In contrast, the concurrent assessment of motor function provided 76% accuracy with low sensitivity (<60%). Furthermore, the outcome of patients with initially moderate impairment and high outcome variability could not be predicted based on motor tests. In contrast, fMRI provided 87.5% prediction accuracy in these patients. Classifications were driven by activity in ipsilesional motor areas and contralesional cerebellum. The accuracy of subacute fMRI data (two weeks post-stroke), age, time post-stroke, lesion volume, and location were at 50%-chance-level. In conclusion, multivariate decoding of fMRI data with SVM early after stroke enables a robust prediction of motor recovery. The potential for recovery is influenced by the initial dysfunction of the active motor system, particularly in those patients whose outcome cannot be predicted by behavioral tests.

  3. Waterborne manganese exposure alters plasma, brain, and liver metabolites accompanied by changes in stereotypic behaviors

    PubMed Central

    Fordahl, Steve; Cooney, Paula; Qiu, Yunping; Xie, Guoxiang; Jia, Wei; Erikson, Keith M.

    2011-01-01

    Overexposure to waterborne manganese (Mn) is linked with cognitive impairment in children and neurochemical abnormalities in other experimental models. In order to characterize the threshold between Mn-exposure and altered neurochemistry, it is important to identify biomarkers that positively correspond with brain Mn-accumulation. The objective of this study was to identify Mn-induced alterations in plasma, liver, and brain metabolites using liquid/gas chromatography-time of flight-mass spectrometry metabolomic analyses; and to monitor corresponding Mn-induced behavior changes. Weanling Sprague-Dawley rats had access to deionized drinking water either Mn-free or containing 1g Mn/L for six weeks. Behaviors were monitored during the sixth week for a continuous 24h period while in a home cage environment using video surveillance. Mn-exposure significantly increased liver, plasma, and brain Mn concentrations compared to control, specifically targeting the globus pallidus (GP). Mn significantly altered 98 metabolites in the brain, liver, and plasma; notably shifting cholesterol and fatty acid metabolism in the brain (increased oleic and palmitic acid; 12.57 and 15.48 fold change (FC), respectively), and liver (increased oleic acid, 14.51 FC; decreased hydroxybutyric acid, −14.29 FC). Additionally, Mn-altered plasma metabolites homogentisic acid, chenodeoxycholic acid, and aspartic acid correlated significantly with GP and striatal Mn. Total distance traveled was significantly increased and positively correlated with Mn-exposure, while nocturnal stereotypic and exploratory behaviors were reduced with Mn-exposure and performed largely during the light cycle compared to unexposed rats. These data provide putative biomarkers for Mn-neurotoxicity and suggest that Mn disrupts the circadian cycle in rats. PMID:22056924

  4. Waterborne manganese exposure alters plasma, brain, and liver metabolites accompanied by changes in stereotypic behaviors.

    PubMed

    Fordahl, Steve; Cooney, Paula; Qiu, Yunping; Xie, Guoxiang; Jia, Wei; Erikson, Keith M

    2012-01-01

    Overexposure to waterborne manganese (Mn) is linked with cognitive impairment in children and neurochemical abnormalities in other experimental models. In order to characterize the threshold between Mn-exposure and altered neurochemistry, it is important to identify biomarkers that positively correspond with brain Mn-accumulation. The objective of this study was to identify Mn-induced alterations in plasma, liver, and brain metabolites using liquid/gas chromatography-time of flight-mass spectrometry metabolomic analyses; and to monitor corresponding Mn-induced behavior changes. Weanling Sprague-Dawley rats had access to deionized drinking water either Mn-free or containing 1g Mn/L for 6 weeks. Behaviors were monitored during the sixth week for a continuous 24h period while in a home cage environment using video surveillance. Mn-exposure significantly increased liver, plasma, and brain Mn concentrations compared to control, specifically targeting the globus pallidus (GP). Mn significantly altered 98 metabolites in the brain, liver, and plasma; notably shifting cholesterol and fatty acid metabolism in the brain (increased oleic and palmitic acid; 12.57 and 15.48 fold change (FC), respectively), and liver (increased oleic acid, 14.51 FC; decreased hydroxybutyric acid, -14.29 FC). Additionally, Mn-altered plasma metabolites homogentisic acid, chenodeoxycholic acid, and aspartic acid correlated significantly with GP and striatal Mn. Total distance traveled was significantly increased and positively correlated with Mn-exposure, while nocturnal stereotypic and exploratory behaviors were reduced with Mn-exposure and performed largely during the light cycle compared to unexposed rats. These data provide putative biomarkers for Mn-neurotoxicity and suggest that Mn disrupts the circadian cycle in rats.

  5. Motor learning with augmented feedback: modality-dependent behavioral and neural consequences.

    PubMed

    Ronsse, Renaud; Puttemans, Veerle; Coxon, James P; Goble, Daniel J; Wagemans, Johan; Wenderoth, Nicole; Swinnen, Stephan P

    2011-06-01

    Sensory information is critical to correct performance errors online during the execution of complex tasks and can be complemented by augmented feedback (FB). Here, 2 groups of participants acquired a new bimanual coordination pattern under different augmented FB conditions: 1) visual input reflecting coordination between the 2 hands and 2) auditory pacing integrating the timing of both hands into a single temporal structure. Behavioral findings revealed that the visual group became dependent on this augmented FB for performance, whereas the auditory group performed equally well with or without augmented FB by the end of practice. Functional magnetic resonance imaging (fMRI) results corroborated these behavioral findings: the visual group showed neural activity increases in sensory-specific areas during practice, supporting increased reliance on augmented FB. Conversely, the auditory group showed a neural activity decrease, specifically in areas associated with cognitive/sensory monitoring of motor task performance, supporting the development of a control mode that was less reliant on augmented FB sources. Finally, some remnants of brain activity in sensory-specific areas in the absence of augmented FB were found for the visual group only, illustrating ongoing reliance on these areas. These findings provide the first neural account for the "guidance hypothesis of information FB," extensively supported by behavioral research.

  6. Effects of multisensory and motor stimulation on the behavior of people with dementia.

    PubMed

    Sposito, Giovana; Barbosa, Ana; Figueiredo, Daniela; Yassuda, Mônica Sanches; Marques, Alda

    2015-06-25

    A quasi-experimental study using a pre-posttest design was conducted in four aged care facilities to assess the effects of a person-centred care (PCC) multisensory stimulation (MSS) and motor stimulation (MS) program, implemented by direct care workers, on the behaviors of residents with dementia. Data were collected at baseline and after the intervention through video recordings of morning care routines. Forty-five residents with moderate and severe dementia participated in the study. A total of 266 morning care routines were recorded. The frequency and duration of a list of behaviors were analyzed. The frequency of engagement in task decreased significantly (p = .002) however, its duration increased (p = .039). The duration of gaze directed at direct care workers improved significantly (p = .014) and the frequency of closed eyes decreased (p = .046). There was a significant decrease in the frequency of the expression of sadness. These results support the implementation of PCC-MSS and MS programs as they may stimulate residents' behaviors.

  7. IL-4 Inhibits IL-1β-Induced Depressive-Like Behavior and Central Neurotransmitter Alterations.

    PubMed

    Park, Hyun-Jung; Shim, Hyun-Soo; An, Kyungeh; Starkweather, Angela; Kim, Kyung Soo; Shim, Insop

    2015-01-01

    It has been known that activation of the central innate immune system or exposure to stress can disrupt balance of anti-/proinflammatory cytokines. The aim of the present study was to investigate the role of pro- and anti-inflammatory cytokines in the modulation of depressive-like behaviors, the hormonal and neurotransmitter systems in rats. We investigated whether centrally administered IL-1β is associated with activation of CNS inflammatory pathways and behavioral changes and whether treatment with IL-4 could modulate IL-1β-induced depressive-like behaviors and central neurotransmitter systems. Infusion of IL-4 significantly decreased IL-1β-induced anhedonic responses and increased social exploration and total activity. Treatment with IL-4 markedly blocked IL-1β-induced increase in PGE2 and CORT levels. Also, IL-4 reduced IL-1β-induced 5-HT levels by inhibiting tryptophan hydroxylase (TPH) mRNA and activating serotonin transporter (SERT) in the hippocampus, and levels of NE were increased by activating tyrosine hydroxylase (TH) mRNA expression. These results demonstrate that IL-4 may locally contribute to the regulation of noradrenergic and serotonergic neurotransmission and may inhibit IL-1β-induced behavioral and immunological changes. The present results suggest that IL-4 modulates IL-1β-induced depressive behavior by inhibiting IL-1β-induced central glial activation and neurotransmitter alterations. IL-4 reduced central and systemic mediatory inflammatory activation, as well as reversing the IL-1β-induced alterations in neurotransmitter levels. The present findings contribute a biochemical pathway regulated by IL-4 that may have therapeutic utility for treatment of IL-1β-induced depressive behavior and neuroinflammation which warrants further study.

  8. IL-4 Inhibits IL-1β-Induced Depressive-Like Behavior and Central Neurotransmitter Alterations

    PubMed Central

    Park, Hyun-Jung; Shim, Hyun-Soo; An, Kyungeh; Starkweather, Angela; Kim, Kyung Soo; Shim, Insop

    2015-01-01

    It has been known that activation of the central innate immune system or exposure to stress can disrupt balance of anti-/proinflammatory cytokines. The aim of the present study was to investigate the role of pro- and anti-inflammatory cytokines in the modulation of depressive-like behaviors, the hormonal and neurotransmitter systems in rats. We investigated whether centrally administered IL-1β is associated with activation of CNS inflammatory pathways and behavioral changes and whether treatment with IL-4 could modulate IL-1β-induced depressive-like behaviors and central neurotransmitter systems. Infusion of IL-4 significantly decreased IL-1β-induced anhedonic responses and increased social exploration and total activity. Treatment with IL-4 markedly blocked IL-1β-induced increase in PGE2 and CORT levels. Also, IL-4 reduced IL-1β-induced 5-HT levels by inhibiting tryptophan hydroxylase (TPH) mRNA and activating serotonin transporter (SERT) in the hippocampus, and levels of NE were increased by activating tyrosine hydroxylase (TH) mRNA expression. These results demonstrate that IL-4 may locally contribute to the regulation of noradrenergic and serotonergic neurotransmission and may inhibit IL-1β-induced behavioral and immunological changes. The present results suggest that IL-4 modulates IL-1β-induced depressive behavior by inhibiting IL-1β-induced central glial activation and neurotransmitter alterations. IL-4 reduced central and systemic mediatory inflammatory activation, as well as reversing the IL-1β-induced alterations in neurotransmitter levels. The present findings contribute a biochemical pathway regulated by IL-4 that may have therapeutic utility for treatment of IL-1β-induced depressive behavior and neuroinflammation which warrants further study. PMID:26417153

  9. Altered anxiety-related and abnormal social behaviors in rats exposed to early life seizures

    PubMed Central

    Castelhano, Adelisandra Silva Santos; Cassane, Gustavo dos Santos Teada; Scorza, Fulvio Alexandre; Cysneiros, Roberta Monterazzo

    2013-01-01

    Neonatal seizures are the most common manifestation of neurological dysfunction in the neonate. The prognosis of neonatal seizures is highly variable, and the controversy remains whether the severity, duration, or frequency of seizures may contribute to brain damage independently of its etiology. Animal data indicates that seizures during development are associated with a high probability of long-term adverse effects such as learning and memory impairment, behavioral changes and even epilepsy, which is strongly age dependent, as well as the severity, duration, and frequency of seizures. In preliminary studies, we demonstrated that adolescent male rats exposed to one-single neonatal status epilepticus (SE) episode showed social behavior impairment, and we proposed the model as relevant for studies of developmental disorders. Based on these facts, the goal of this study was to verify the existence of a persistent deficit and if the anxiety-related behavior could be associated with that impairment. To do so, male Wistar rats at 9 days postnatal were submitted to a single episode of SE by pilocarpine injection (380 mg/kg, i.p.) and control animals received saline (0.9%, 0.1 mL/10 g). It was possible to demonstrate that in adulthood, animals exposed to neonatal SE displayed low preference for social novelty, anxiety-related behavior, and increased stereotyped behavior in anxiogenic environment with no locomotor activity changes. On the balance, these data suggests that neonatal SE in rodents leads to altered anxiety-related and abnormal social behaviors. PMID:23675329

  10. Chronic social stress in puberty alters appetitive male sexual behavior and neural metabolic activity.

    PubMed

    Bastida, Christel C; Puga, Frank; Gonzalez-Lima, Francisco; Jennings, Kimberly J; Wommack, Joel C; Delville, Yvon

    2014-07-01

    Repeated social subjugation in early puberty lowers testosterone levels. We used hamsters to investigate the effects of social subjugation on male sexual behavior and metabolic activity within neural systems controlling social and motivational behaviors. Subjugated animals were exposed daily to aggressive adult males in early puberty for postnatal days 28 to 42, while control animals were placed in empty clean cages. On postnatal day 45, they were tested for male sexual behavior in the presence of receptive female. Alternatively, they were tested for mate choice after placement at the base of a Y-maze containing a sexually receptive female in one tip of the maze and an ovariectomized one on the other. Social subjugation did not affect the capacity to mate with receptive females. Although control animals were fast to approach females and preferred ovariectomized individuals, subjugated animals stayed away from them and showed no preference. Cytochrome oxidase activity was reduced within the preoptic area and ventral tegmental area in subjugated hamsters. In addition, the correlation of metabolic activity of these areas with the bed nucleus of the stria terminalis and anterior parietal cortex changed significantly from positive in controls to negative in subjugated animals. These data show that at mid-puberty, while male hamsters are capable of mating, their appetitive sexual behavior is not fully mature and this aspect of male sexual behavior is responsive to social subjugation. Furthermore, metabolic activity and coordination of activity in brain areas related to sexual behavior and motivation were altered by social subjugation.

  11. Neonatal isolation alters the estrous cycle interactions on the acute behavioral effects of cocaine.

    PubMed

    Kosten, Therese A; Sanchez, Hayde; Jatlow, Peter I; Kehoe, Priscilla

    2005-09-01

    We demonstrated that neonatal isolation (ISO) increases acquisition of cocaine self-administration and alters psychostimulant-induced ventral striatal dopamine and serotonin levels in female rats. Both dopamine and serotonin modulate the behavioral effects of cocaine and these effects can vary across estrous stages. We now test whether ISO modifies the manner in which estrous stage affects the acute behavioral responses to cocaine. Litters were assigned to ISO (1 h/day isolation; post-natal days 2-9) or non-handled (NH) conditions. In Experiment 1, the ability of cocaine (0.3-30 mg/kg; IP) to disrupt schedule-controlled responding for food was assessed in proestrus, estrus, and diestrus stages. Diestrus and proestrus NH females showed increased response rates at low cocaine doses and decreased rates at higher doses relative to baseline. In contrast, estrus NH females showed decreased responding across all doses. ISO eliminated this estrous stage distinction; only decreased responding to high cocaine doses were seen. Yet, estrous cyclicity during food restriction (Experiment 2) did not differ by group. To confirm this ISO effect, proestrus or estrus rats were administered cocaine (0, 5, 10 mg/kg; IP) and activity monitored in Experiment 3. Locomotor activity differed by estrous stage in NH but not ISO rats. Cocaine plasma levels (Experiment 4) at the time of peak behavioral activity did not differ by group or estrous stage. Results extend prior studies to show estrous stage alters the behavioral effects of cocaine. Neonatal isolation eliminates these effects perhaps reflecting alterations in accumbens monoamine levels or the effects of estrogen on this system.

  12. Invasive plant species alters consumer behavior by providing refuge from predation.

    PubMed

    Dutra, Humberto P; Barnett, Kirk; Reinhardt, Jason R; Marquis, Robert J; Orrock, John L

    2011-07-01

    Understanding the effects of invasive plants on native consumers is important because consumer-mediated indirect effects have the potential to alter the dynamics of coexistence in native communities. Invasive plants may promote changes in consumer pressure due to changes in protective cover (i.e., the architectural complexity of the invaded habitat) and in food availability (i.e., subsidies of fruits and seeds). No experimental studies have evaluated the relative interplay of these two effects. In a factorial experiment, we manipulated cover and food provided by the invasive shrub Amur honeysuckle (Lonicera maackii) to evaluate whether this plant alters the foraging activity of native mammals. Using tracking plates to quantify mammalian foraging activity, we found that removal of honeysuckle cover, rather than changes in the fruit resources it provides, reduced the activity of important seed consumers, mice in the genus Peromyscus. Two mesopredators, Procyon lotor and Didelphis virginiana, were also affected. Moreover, we found rodents used L. maackii for cover only on cloudless nights, indicating that the effect of honeysuckle was weather-dependent. Our work provides experimental evidence that this invasive plant species changes habitat characteristics, and in so doing alters the behavior of small- and medium-sized mammals. Changes in seed predator behavior may lead to cascading effects on the seeds that mice consume.

  13. Dominance of the Unaffected Hemisphere Motor Network and Its Role in the Behavior of Chronic Stroke Survivors

    PubMed Central

    Bajaj, Sahil; Housley, Stephen N.; Wu, David; Dhamala, Mukesh; James, G. A.; Butler, Andrew J.

    2016-01-01

    Balance of motor network activity between the two brain hemispheres after stroke is crucial for functional recovery. Several studies have extensively studied the role of the affected brain hemisphere to better understand changes in motor network activity following stroke. Very few studies have examined the role of the unaffected brain hemisphere and confirmed the test–retest reliability of connectivity measures on unaffected hemisphere. We recorded blood oxygenation level dependent functional magnetic resonance imaging (fMRI) signals from nine stroke survivors with hemiparesis of the left or right hand. Participants performed a motor execution task with affected hand, unaffected hand, and both hands simultaneously. Participants returned for a repeat fMRI scan 1 week later. Using dynamic causal modeling (DCM), we evaluated effective connectivity among three motor areas: the primary motor area (M1), the premotor cortex (PMC) and the supplementary motor area for the affected and unaffected hemispheres separately. Five participants’ manual motor ability was assessed by Fugl-Meyer Motor Assessment scores and root-mean square error of participants’ tracking ability during a robot-assisted game. We found (i) that the task performance with the affected hand resulted in strengthening of the connectivity pattern for unaffected hemisphere, (ii) an identical network of the unaffected hemisphere when participants performed the task with their unaffected hand, and (iii) the pattern of directional connectivity observed in the affected hemisphere was identical for tasks using the affected hand only or both hands. Furthermore, paired t-test comparison found no significant differences in connectivity strength for any path when compared with one-week follow-up. Brain-behavior linear correlation analysis showed that the connectivity patterns in the unaffected hemisphere more accurately reflected the behavioral conditions than the connectivity patterns in the affected hemisphere

  14. Dominance of the Unaffected Hemisphere Motor Network and Its Role in the Behavior of Chronic Stroke Survivors.

    PubMed

    Bajaj, Sahil; Housley, Stephen N; Wu, David; Dhamala, Mukesh; James, G A; Butler, Andrew J

    2016-01-01

    Balance of motor network activity between the two brain hemispheres after stroke is crucial for functional recovery. Several studies have extensively studied the role of the affected brain hemisphere to better understand changes in motor network activity following stroke. Very few studies have examined the role of the unaffected brain hemisphere and confirmed the test-retest reliability of connectivity measures on unaffected hemisphere. We recorded blood oxygenation level dependent functional magnetic resonance imaging (fMRI) signals from nine stroke survivors with hemiparesis of the left or right hand. Participants performed a motor execution task with affected hand, unaffected hand, and both hands simultaneously. Participants returned for a repeat fMRI scan 1 week later. Using dynamic causal modeling (DCM), we evaluated effective connectivity among three motor areas: the primary motor area (M1), the premotor cortex (PMC) and the supplementary motor area for the affected and unaffected hemispheres separately. Five participants' manual motor ability was assessed by Fugl-Meyer Motor Assessment scores and root-mean square error of participants' tracking ability during a robot-assisted game. We found (i) that the task performance with the affected hand resulted in strengthening of the connectivity pattern for unaffected hemisphere, (ii) an identical network of the unaffected hemisphere when participants performed the task with their unaffected hand, and (iii) the pattern of directional connectivity observed in the affected hemisphere was identical for tasks using the affected hand only or both hands. Furthermore, paired t-test comparison found no significant differences in connectivity strength for any path when compared with one-week follow-up. Brain-behavior linear correlation analysis showed that the connectivity patterns in the unaffected hemisphere more accurately reflected the behavioral conditions than the connectivity patterns in the affected hemisphere. Above

  15. Antioxidant-Rich Fraction of Urtica dioica Mediated Rescue of Striatal Mito-Oxidative Damage in MPTP-Induced Behavioral, Cellular, and Neurochemical Alterations in Rats.

    PubMed

    Bisht, Rohit; Joshi, Bhuwan Chandra; Kalia, Ajudhiya Nath; Prakash, Atish

    2016-09-13

    Parkinson's disease (PD) having a complex and multi-factorial neuropathology includes mainly the degeneration of the dopaminergic nigrostriatal pathway, which is a cumulative effect of depleted endogenous antioxidant enzymes, increased oxidative DNA damage, mitochondrial dysfunction, excitotoxicity, and neuroinflammation. The present study was designed to investigate the neuroprotective effect of a potent antioxidant from Urtica dioica in a 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) model of parkinsonism. MPTP was administered intranigrally for the induction of PD in male Wistar rats. Behavioral alterations were assessed in between the study period. Animals were sacrificed immediately after behavioral session, and different biochemical, cellular, and neurochemical parameters were measured. Intranigrally repeated administration of MPTP showed significant impairment of motor co-ordination and marked increase of mito-oxidative damage and neuroinflammation in rats. Intranigral MPTP significantly decreases the dopamine and its metabolites with impairment of dopaminergic cell density in rat brain. However, post-treatment with the potent antioxidant fraction of Urtica dioica Linn. (UD) (20, 40, 80 mg/kg) improved the motor function, mito-oxidative defense alteration significantly and dose dependently in MPTP-treated rats. In addition, the potent antioxidant fraction of UD attenuated the pro-inflammatory cytokines (TNF-α and IL-β) and restored the level of dopamine and its metabolites in MPTP-induced PD in rats. Moreover, minocycline (30 mg/kg) with lower dose of UD (20 mg/kg) had significantly potentiated the protective effect of minocycline as compared to its effect with other individual drug-treated groups. In conclusion, Urtica dioica protected the dopaminergic neurons probably by reducing mito-oxidative damage, neuroinflammation, and cellular alteration along with enhanced neurotrophic potential. The above results revealed that the antioxidant rich

  16. Fluconazole alters the polysaccharide capsule of Cryptococcus gattii and leads to distinct behaviors in murine Cryptococcosis.

    PubMed

    Santos, Julliana Ribeiro Alves; Holanda, Rodrigo Assunção; Frases, Susana; Bravim, Mayara; Araujo, Glauber de S; Santos, Patrícia Campi; Costa, Marliete Carvalho; Ribeiro, Maira Juliana Andrade; Ferreira, Gabriella Freitas; Baltazar, Ludmila Matos; Miranda, Aline Silva; Oliveira, Danilo Bretas; Santos, Carolina Maria Araújo; Fontes, Alide Caroline Lima; Gouveia, Ludmila Ferreira; Resende-Stoianoff, Maria Aparecida; Abrahão, Jonatas Santos; Teixeira, Antônio Lúcio; Paixão, Tatiane Alves; Souza, Danielle G; Santos, Daniel Assis

    2014-01-01

    Cryptococcus gattii is an emergent human pathogen. Fluconazole is commonly used for treatment of cryptococcosis, but the emergence of less susceptible strains to this azole is a global problem and also the data regarding fluconazole-resistant cryptococcosis are scarce. We evaluate the influence of fluconazole on murine cryptococcosis and whether this azole alters the polysaccharide (PS) from cryptococcal cells. L27/01 strain of C. gattii was cultivated in high fluconazole concentrations and developed decreased drug susceptibility. This phenotype was named L27/01F, that was less virulent than L27/01 in mice. The physical, structural and electrophoretic properties of the PS capsule of L27/01F were altered by fluconazole. L27/01F presented lower antiphagocytic properties and reduced survival inside macrophages. The L27/01F did not affect the central nervous system, while the effect in brain caused by L27/01 strain began after only 12 hours. Mice infected with L27/01F presented lower production of the pro-inflammatory cytokines, with increased cellular recruitment in the lungs and severe pulmonary disease. The behavioral alterations were affected by L27/01, but no effects were detected after infection with L27/01F. Our results suggest that stress to fluconazole alters the capsule of C. gattii and influences the clinical manifestations of cryptococcosis.

  17. Fluconazole Alters the Polysaccharide Capsule of Cryptococcus gattii and Leads to Distinct Behaviors in Murine Cryptococcosis

    PubMed Central

    Santos, Julliana Ribeiro Alves; Holanda, Rodrigo Assunção; Frases, Susana; Bravim, Mayara; Araujo, Glauber de S.; Santos, Patrícia Campi; Costa, Marliete Carvalho; Ribeiro, Maira Juliana Andrade; Ferreira, Gabriella Freitas; Baltazar, Ludmila Matos; Miranda, Aline Silva; Oliveira, Danilo Bretas; Santos, Carolina Maria Araújo; Fontes, Alide Caroline Lima; Gouveia, Ludmila Ferreira; Resende-Stoianoff, Maria Aparecida; Abrahão, Jonatas Santos; Teixeira, Antônio Lúcio; Paixão, Tatiane Alves; Souza, Danielle G.; Santos, Daniel Assis

    2014-01-01

    Cryptococcus gattii is an emergent human pathogen. Fluconazole is commonly used for treatment of cryptococcosis, but the emergence of less susceptible strains to this azole is a global problem and also the data regarding fluconazole-resistant cryptococcosis are scarce. We evaluate the influence of fluconazole on murine cryptococcosis and whether this azole alters the polysaccharide (PS) from cryptococcal cells. L27/01 strain of C. gattii was cultivated in high fluconazole concentrations and developed decreased drug susceptibility. This phenotype was named L27/01F, that was less virulent than L27/01 in mice. The physical, structural and electrophoretic properties of the PS capsule of L27/01F were altered by fluconazole. L27/01F presented lower antiphagocytic properties and reduced survival inside macrophages. The L27/01F did not affect the central nervous system, while the effect in brain caused by L27/01 strain began after only 12 hours. Mice infected with L27/01F presented lower production of the pro-inflammatory cytokines, with increased cellular recruitment in the lungs and severe pulmonary disease. The behavioral alterations were affected by L27/01, but no effects were detected after infection with L27/01F. Our results suggest that stress to fluconazole alters the capsule of C. gattii and influences the clinical manifestations of cryptococcosis. PMID:25392951

  18. The effects of gestational and chronic atrazine exposure on motor behaviors and striatal dopamine in male Sprague-Dawley rats

    PubMed Central

    Walters, Jennifer L.; Lansdell, Theresa A.; Lookingland, Keith J.; Baker, Lisa E.

    2016-01-01

    This study sought to investigate the effects of environmentally relevant gestational followed by continued chronic exposure to the herbicide, atrazine, on motor function, cognition, and neurochemical indices of nigrostriatal dopamine (DA) activity in male rats. Dams were treated with 100 µg/kg atrazine, 10 mg/kg atrazine, or vehicle on gestational day 1 through postnatal day 21. Upon weaning, male offspring continued daily vehicle or atrazine gavage treatments for an additional six months. Subjects were tested in a series of behavioral assays, and 24 h after the last treatment, tissue samples from the striatum were analyzed for DA and 3,4-dihydroxyphenylacetic acid (DOPAC). At 10 mg/kg, this herbicide was found to produce modest disruptions in motor functioning, and at both dose levels it significantly lowered striatal DA and DOPAC concentrations. These results suggest exposures to atrazine have the potential to disrupt nigrostriatal DA neurons and behaviors associated with motor functioning. PMID:26440580

  19. The effects of gestational and chronic atrazine exposure on motor behaviors and striatal dopamine in male Sprague-Dawley rats.

    PubMed

    Walters, Jennifer L; Lansdell, Theresa A; Lookingland, Keith J; Baker, Lisa E

    2015-12-01

    This study sought to investigate the effects of environmentally relevant gestational followed by continued chronic exposure to the herbicide, atrazine, on motor function, cognition, and neurochemical indices of nigrostriatal dopamine (DA) activity in male rats. Dams were treated with 100 μg/kg atrazine, 10mg/kg atrazine, or vehicle on gestational day 1 through postnatal day 21. Upon weaning, male offspring continued daily vehicle or atrazine gavage treatments for an additional six months. Subjects were tested in a series of behavioral assays, and 24h after the last treatment, tissue samples from the striatum were analyzed for DA and 3,4-dihydroxyphenylacetic acid (DOPAC). At 10mg/kg, this herbicide was found to produce modest disruptions in motor functioning, and at both dose levels it significantly lowered striatal DA and DOPAC concentrations. These results suggest that exposures to atrazine have the potential to disrupt nigrostriatal DA neurons and behaviors associated with motor functioning.

  20. Invader danger: lizards faced with novel predators exhibit an altered behavioral response to stress.

    PubMed

    Trompeter, Whitney P; Langkilde, Tracy

    2011-07-01

    Animals respond to stressors by producing glucocorticoid stress hormones, such as corticosterone (CORT). CORT acts too slowly to trigger immediate behavioral responses to a threat, but can change longer-term behavior, facilitating an individual's survival to subsequent threats. To be adaptive, the nature of an animal's behavior following elevated CORT levels should be matched to the predominant threats that they face. Seeking refuge following a stressful encounter could be beneficial if the predominant predator is a visual hunter, but may prove detrimental when the predominant predator is able to enter these refuge sites. As a result, an individual's behavior when their CORT levels are high may differ among populations of a single species. Invasive species impose novel pressures on native populations, which may select for a shift in their behavior when CORT levels are high. We tested whether the presence of predatory invasive fire ants (Solenopsis invicta) at a site affects the behavioral response of native eastern fence lizards (Sceloporus undulatus) to elevated CORT levels. Lizards from an uninvaded site were more likely to hide when their CORT levels were experimentally elevated; a response that likely provides a survival advantage for lizards faced with native predatory threats (e.g. birds and snakes). Lizards from a fire ant invaded site showed the opposite response; spending more time moving and up on the basking log when their CORT levels were elevated. Use of the basking log likely reflects a refuge-seeking behavior, rather than thermoregulatory activity, as selected body temperatures were not affected by CORT. Fleeing off the ground may prove more effective than hiding for lizards that regularly encounter small, terrestrially-foraging fire ant predators. This study suggests that invasive species may alter the relationship between the physiological and behavioral stress response of native species.

  1. Behavioral, Cognitive, and Motor Preparation Deficits in a Visual Cued Spatial Attention Task in Autism Spectrum Disorder

    PubMed Central

    Sokhadze, Estate M.; Tasman, Allan; Sokhadze, Guela E.; El-Baz, Ayman S.; Casanova, Manuel F.

    2015-01-01

    Abnormalities in motor skills have been regarded as part of the symptomatology characterizing autism spectrum disorder (ASD). It has been estimated that 80% of subjects with autism display “motor dyspraxia” or clumsiness that are not readily identified in a routine neurological examination. In this study we used behavioral measures, event-related potentials (ERP), and lateralized readiness potential (LRP) to study cognitive and motor preparation deficits contributing to the dyspraxia of autism. A modified Posner cueing task was used to analyze motor preparation abnormalities in children with autism and in typically developing children (N=30/per group). In this task, subjects engage in preparing motor response based on a visual cue, and then execute a motor movement based on the subsequent imperative stimulus. The experimental conditions, such as the validity of the cue and the spatial location of the target stimuli were manipulated to influence motor response selection, preparation, and execution. Reaction time and accuracy benefited from validly cued targets in both groups, while main effects of target spatial position were more obvious in the autism group. The main ERP findings were prolonged and more negative early frontal potentials in the ASD in incongruent trials in both types of spatial location. The LRP amplitude was larger in incongruent trials and had stronger effect in the children with ASD. These effects were better expressed at the earlier stages of LRP, specifically those related to response selection, and showed difficulties at the cognitive phase of stimulus processing rather that at the motor execution stage. The LRP measures at different stages reflect the chronology of cognitive aspects of movement preparation and are sensitive to manipulations of cue correctness, thus representing very useful biomarker in autism dyspraxia research. Future studies may use more advance and diverse manipulations of movement preparation demands in testing more

  2. Behavioral, Cognitive, and Motor Preparation Deficits in a Visual Cued Spatial Attention Task in Autism Spectrum Disorder.

    PubMed

    Sokhadze, Estate M; Tasman, Allan; Sokhadze, Guela E; El-Baz, Ayman S; Casanova, Manuel F

    2016-03-01

    Abnormalities in motor skills have been regarded as part of the symptomatology characterizing autism spectrum disorder (ASD). It has been estimated that 80 % of subjects with autism display "motor dyspraxia" or clumsiness that are not readily identified in a routine neurological examination. In this study we used behavioral measures, event-related potentials (ERP), and lateralized readiness potential (LRP) to study cognitive and motor preparation deficits contributing to the dyspraxia of autism. A modified Posner cueing task was used to analyze motor preparation abnormalities in children with autism and in typically developing children (N = 30/per group). In this task, subjects engage in preparing motor response based on a visual cue, and then execute a motor movement based on the subsequent imperative stimulus. The experimental conditions, such as the validity of the cue and the spatial location of the target stimuli were manipulated to influence motor response selection, preparation, and execution. Reaction time and accuracy benefited from validly cued targets in both groups, while main effects of target spatial position were more obvious in the autism group. The main ERP findings were prolonged and more negative early frontal potentials in the ASD in incongruent trials in both types of spatial location. The LRP amplitude was larger in incongruent trials and had stronger effect in the children with ASD. These effects were better expressed at the earlier stages of LRP, specifically those related to response selection, and showed difficulties at the cognitive phase of stimulus processing rather that at the motor execution stage. The LRP measures at different stages reflect the chronology of cognitive aspects of movement preparation and are sensitive to manipulations of cue correctness, thus representing very useful biomarker in autism dyspraxia research. Future studies may use more advance and diverse manipulations of movement preparation demands in testing more

  3. Environmental prenatal stress alters sexual dimorphism of maternal behavior in rats.

    PubMed

    Pérez-Laso, Carmen; Segovia, Santiago; Martín, José Luis R; Ortega, Esperanza; Gómez, Francisco; Del Cerro, M Cruz R

    2008-03-05

    The prenatal external environment can affect fetuses, altering the maternal behavior that they express when mature. In the present study, environmental prenatal stress (EPS) was applied to pregnant rats in their final week of gestation, and when their female offspring reached maturity, the long latency effect of the stress on those offspring was ascertained on their induced maternal behavior (MB), accessory olfactory bulb (AOB) morphology and plasma levels of ACTH and corticosterone (Cpd B). EPS reduced: the percentage of these virgins that showed induced MB, their retrieval of foster pups, the time spent crouching, and the quality of nest building; it also increased the incidence of their cannibalism of foster pups. The EPS-treated females presented a male-like pattern of induced MB. They showed increased plasma levels of ACTH and Cpd B and increased numbers of mitral cells in the AOB. These findings provide evidence that stress applied to the pregnant rat produces long-lasting behavioral, neuroanatomical and hormonal alterations in the female offspring that can be observed when they reach maturity.

  4. Moderate prenatal alcohol exposure alters behavior and neuroglial parameters in adolescent rats.

    PubMed

    Brolese, Giovana; Lunardi, Paula; Broetto, Núbia; Engelke, Douglas S; Lírio, Franciane; Batassini, Cristiane; Tramontina, Ana Carolina; Gonçalves, Carlos-Alberto

    2014-08-01

    Alcohol consumption by women during gestation has become increasingly common. Although it is widely accepted that exposure to high doses of ethanol has long-lasting detrimental effects on brain development, the case for moderate doses is underappreciated, and benchmark studies have demonstrated structural and behavioral defects associated with moderate prenatal alcohol exposure in humans and animal models. This study aimed to investigate the influence of in utero exposure to moderate levels of ethanol throughout pregnancy on learning/memory, anxiety parameters and neuroglial parameters in adolescent offspring. Female rats were exposed to an experimental protocol throughout gestation up to weaning. After mating, the dams were divided into three groups and treated with only water (control), non-alcoholic beer (vehicle) or 10% (vv) beer solution (moderate prenatal alcohol exposure - MPAE). Adolescent male offspring were subjected to the plus-maze discriminative avoidance task to evaluate learning/memory and anxiety-like behavior. Hippocampi were dissected and slices were obtained for immunoquantification of GFAP, NeuN, S100B and the NMDA receptor. The MPAE group clearly presented anxiolytic-like behavior, even though they had learned how to avoid the aversive arm. S100B protein was increased in the cerebrospinal fluid (CSF) in the group treated with alcohol, and alterations in GFAP expression were also shown. This study indicates that moderate ethanol doses administered during pregnancy could induce anxiolytic-like effects, suggesting an increase in risk-taking behavior in adolescent male offspring. Furthermore, the data show the possibility that glial cells are involved in the altered behavior present after prenatal ethanol treatment.

  5. Does changing from a first generation antipsychotic (perphenazin) to a second generation antipsychotic (risperidone) alter brain activation and motor activity? A case report

    PubMed Central

    2013-01-01

    Background In patients with schizophrenia, altered brain activation and motor activity levels are central features, reflecting cognitive impairments and negative symptoms, respectively. Newer studies using nonlinear methods have addressed the severe disturbances in neurocognitive functioning that is regarded as one of the core features of schizophrenia. Our aim was to compare brain activation and motor activity in a patient during pharmacological treatment that was switched from a first- to a second-generation antipsychotic drug. We hypothesised that this change of medication would increase level of responding in both measures. Case presentation We present the case of a 53-year-old male with onset of severe mental illness in adolescence, ICD-10 diagnosed as schizophrenia of paranoid type, chronic form. We compared brain activation and motor activity in this patient during pharmacological treatment with a first-generation (perphenazin), and later switched to a second-generation (risperidone) antipsychotic drug. We used functional magnetic resonance imaging (fMRI) to measure brain activation and wrist worn actigraphy to measure motor activity. Conclusion Our study showed that brain activation decreased in areas critical for cognitive functioning in this patient, when changing from a first to a second generation antipsychotic drug. However the mean motor activity level was unchanged, although risperidone reduced variability, particularly short-term variability from minute to minute. Compared to the results from previous studies, the present findings indicate that changing to a second-generation antipsychotic alters variability measures towards that seen in a control group, but with reduced brain activation, which was an unexpected finding. PMID:23648137

  6. Attenuation of the Type IV Pilus Retraction Motor Influences Neisseria gonorrhoeae Social and Infection Behavior.

    PubMed

    Hockenberry, Alyson M; Hutchens, Danielle M; Agellon, Al; So, Magdalene

    2016-12-06

    Retraction of the type IV pilus (Tfp) mediates DNA uptake, motility, and social and infection behavior in a wide variety of prokaryotes. To date, investigations into Tfp retraction-dependent activities have used a mutant deleted of PilT, the ATPase motor protein that causes the pilus fiber to retract. ΔpilT cells are nontransformable, nonmotile, and cannot aggregate into microcolonies. We tested the hypothesis that these retraction-dependent activities are sensitive to the strength of PilT enzymatic activity by using the pathogen Neisseria gonorrhoeae as a model. We constructed an N. gonorrhoeae mutant with an amino acid substitution in the PilT Walker B box (a substitution of cysteine for leucine at position 201, encoded by pilTL201C). Purified PilTL201C forms a native hexamer, but mutant hexamers hydrolyze ATP at half the maximal rate. N. gonorrhoeae pilTL201C cells produce Tfp fibers, crawl at the same speed as the wild-type (wt) parent, and are equally transformable. However, the social behavior of pilTL201C cells is intermediate between the behaviors of wt and ΔpilT cells. The infection behavior of pilTL201C is also defective, due to its failure to activate the epidermal growth factor receptor (EGFR)-heparin-binding EGF-like growth factor (HB-EGF) pathway. Our study indicates that pilus retraction, per se, is not sufficient for N. gonorrhoeae microcolony formation or infectivity; rather, these activities are sensitive to the strength of PilT enzymatic activity. We discuss the implications of these findings for Neisseria pathogenesis in the context of mechanobiology.

  7. Attenuation of the Type IV Pilus Retraction Motor Influences Neisseria gonorrhoeae Social and Infection Behavior

    PubMed Central

    Hutchens, Danielle M.; Agellon, Al

    2016-01-01

    ABSTRACT Retraction of the type IV pilus (Tfp) mediates DNA uptake, motility, and social and infection behavior in a wide variety of prokaryotes. To date, investigations into Tfp retraction-dependent activities have used a mutant deleted of PilT, the ATPase motor protein that causes the pilus fiber to retract. ΔpilT cells are nontransformable, nonmotile, and cannot aggregate into microcolonies. We tested the hypothesis that these retraction-dependent activities are sensitive to the strength of PilT enzymatic activity by using the pathogen Neisseria gonorrhoeae as a model. We constructed an N. gonorrhoeae mutant with an amino acid substitution in the PilT Walker B box (a substitution of cysteine for leucine at position 201, encoded by pilTL201C). Purified PilTL201C forms a native hexamer, but mutant hexamers hydrolyze ATP at half the maximal rate. N. gonorrhoeae pilTL201C cells produce Tfp fibers, crawl at the same speed as the wild-type (wt) parent, and are equally transformable. However, the social behavior of pilTL201C cells is intermediate between the behaviors of wt and ΔpilT cells. The infection behavior of pilTL201C is also defective, due to its failure to activate the epidermal growth factor receptor (EGFR)-heparin-binding EGF-like growth factor (HB-EGF) pathway. Our study indicates that pilus retraction, per se, is not sufficient for N. gonorrhoeae microcolony formation or infectivity; rather, these activities are sensitive to the strength of PilT enzymatic activity. We discuss the implications of these findings for Neisseria pathogenesis in the context of mechanobiology. PMID:27923924

  8. Altered Neural and Behavioral Dynamics in Huntington's Disease: An Entropy Conservation Approach

    PubMed Central

    Hong, S. Lee; Barton, Scott J.; Rebec, George V.

    2012-01-01

    Background Huntington's disease (HD) is an inherited condition that results in neurodegeneration of the striatum, the forebrain structure that processes cortical information for behavioral output. In the R6/2 transgenic mouse model of HD, striatal neurons exhibit aberrant firing patterns that are coupled with reduced flexibility in the motor system. The aim of this study was to test the patterns of unpredictability in brain and behavior in wild-type (WT) and R6/2 mice. Methodology/Principal Findings Striatal local field potentials (LFP) were recorded from 18 WT and 17 R6/2 mice (aged 8–11 weeks) while the mice were exploring a plus-shaped maze. We targeted LFP activity for up to 2 s before and 2 s after each choice-point entry. Approximate Entropy (ApEn) was calculated for LFPs and Shannon Entropy was used to measure the probability of arm choice, as well as the likelihood of making consecutive 90-degree turns in the maze. We found that although the total number of choice-point crossings and entropy of arm-choice probability was similar in both groups, R6/2 mice had more predictable behavioral responses (i.e., were less likely to make 90-degree turns and perform them in alternation with running straight down the same arm), while exhibiting more unpredictable striatal activity, as indicated by higher ApEn values. In both WT and R6/2 mice, however, behavioral unpredictability was negatively correlated with LFP ApEn. Conclusions/Significance HD results in a perseverative exploration of the environment, occurring in concert with more unpredictable brain activity. Our results support the entropy conservation hypothesis in which unpredictable behavioral patterns are coupled with more predictable brain activation patterns, suggesting that this may be a fundamental process unaffected by HD. PMID:22292068

  9. Stereotyped Motor Behaviors Associated with Autism in High-Risk Infants: A Pilot Videotape Analysis of a Sibling Sample

    ERIC Educational Resources Information Center

    Loh, Alvin; Soman, Teesta; Brian, Jessica; Bryson, Susan E.; Roberts, Wendy; Szatmari, Peter; Smith, Isabel M.; Zwaigenbaum, Lonnie

    2007-01-01

    This study examined motor behaviors in a longitudinal cohort of infant siblings of children with autism. Stereotypic movements and postures occurring during standardized observational assessments at 12 and 18 months were coded from videotapes. Participants included eight infant siblings later diagnosed with autism spectrum disorder (ASD), a random…

  10. Children with Multiple Disabilities and Minimal Motor Behavior Using Chin Movements to Operate Microswitches to Obtain Environmental Stimulation

    ERIC Educational Resources Information Center

    Lancioni, Giulio E.; O'Reilly, Mark F.; Singh, Nirbhay N.; Sigafoos, Jeff; Tota, Alessia; Antonucci, Massimo; Oliva, Doretta

    2006-01-01

    In these two studies, two children with multiple disabilities and minimal motor behavior were assessed to see if they could use chin movements to operate microswitches to obtain environmental stimulation. In Study I, we applied an adapted version of a recently introduced electronic microswitch [Lancioni, G. E., O'Reilly, M. F., Singh, N. N.,…

  11. Assisting People with Multiple Disabilities and Minimal Motor Behavior to Control Environmental Stimulation through a Mouse Wheel

    ERIC Educational Resources Information Center

    Shih, Ching-Hsiang; Shih, Ching-Tien; Lin, Kun-Tsan; Chiang, Ming-Shan

    2009-01-01

    This study assessed whether two people with profound multiple disabilities and minimal motor behavior would be able to control environmental stimulation using thumb poke ability with a mouse wheel and a newly developed mouse driver (i.e., a new mouse driver replacing standard mouse driver, and turning a mouse into a precise thumb poke detector).…

  12. Assisting People with Multiple Disabilities and Minimal Motor Behavior to Improve Computer Pointing Efficiency through a Mouse Wheel

    ERIC Educational Resources Information Center

    Shih, Ching-Hsiang; Chang, Man-Ling; Shih, Ching-Tien

    2009-01-01

    This study evaluated whether two people with multiple disabilities and minimal motor behavior would be able to improve their pointing performance using finger poke ability with a mouse wheel through a Dynamic Pointing Assistive Program (DPAP) and a newly developed mouse driver (i.e., a new mouse driver replaces standard mouse driver, changes a…

  13. Fluoxetine alters behavioral consistency of aggression and courtship in male Siamese fighting fish, Betta splendens.

    PubMed

    Dzieweczynski, Teresa L; Hebert, Olivia L

    2012-08-20

    The detrimental effects of steroid-mimics are well known but investigations on non-steroid pharmaceuticals are less common. In addition, most behavioral studies do not examine the effects at multiple time points. This study examined the effects of fluoxetine, a selective serotonin reuptake inhibitor, on behavior when male Siamese fighting fish encounter female and male dummy conspecifics simultaneously. Thus, how chemical exposure impacts behavioral consistency and whether individuals differ in their sensitivity to exposure was assessed. Overall aggression was reduced after fluoxetine administration while courtship was unaffected. Fluoxetine affected behavioral consistency towards both the male and female, with individuals behaving less consistently to the male and more consistently to the female. In addition, males appeared to differ in their sensitivity to fluoxetine exposure as not all males reduced their aggression after administration. This has important implications for studying the effects of unintended pharmaceutical exposure. Exposure may have evolutionary implications as it may influence both territorial defense and mating success. In sum, these findings demonstrate that pharmaceutical exposure may alter more than just overall level of behavior and stress the importance of examining the effects of exposure on an individual level.

  14. Altered Modulation of Silent Period in Tongue Motor Cortex of Persistent Developmental Stuttering in Relation to Stuttering Severity

    PubMed Central

    Busan, Pierpaolo; Del Ben, Giovanni; Bernardini, Simona; Natarelli, Giulia; Bencich, Marco; Monti, Fabrizio; Manganotti, Paolo; Battaglini, Piero Paolo

    2016-01-01

    Motor balance in developmental stuttering (DS) was investigated with Transcranial Magnetic Stimulation (TMS), with the aim to define novel neural markers of persistent DS in adulthood. Eleven DS adult males were evaluated with TMS on tongue primary motor cortex, compared to 15 matched fluent speakers, in a “state” condition (i.e. stutterers vs. fluent speakers, no overt stuttering). Motor and silent period thresholds (SPT), recruitment curves, and silent period durations were acquired by recording tongue motor evoked potentials. Tongue silent period duration was increased in DS, especially in the left hemisphere (P<0.05; Hedge’s g or Cohen’s dunbiased = 1.054, i.e. large effect size), suggesting a “state” condition of higher intracortical inhibition in left motor cortex networks. Differences in motor thresholds (different excitatory/inhibitory ratios in DS) were evident, as well as significant differences in SPT. In fluent speakers, the left hemisphere may be marginally more excitable than the right one in motor thresholds at lower muscular activation, while active motor thresholds and SPT were higher in the left hemisphere of DS with respect to the right one, resulting also in a positive correlation with stuttering severity. Pre-TMS electromyography data gave overlapping evidence. Findings suggest the existence of a complex intracortical balance in DS tongue primary motor cortex, with a particular interplay between excitatory and inhibitory mechanisms, also in neural substrates related to silent periods. Findings are discussed with respect to functional and structural impairments in stuttering, and are also proposed as novel neural markers of a stuttering “state” in persistent DS, helping to define more focused treatments (e.g. neuro-modulation). PMID:27711148

  15. Altered serotonin receptor expression is associated with depression-related behavior in the R6/1 transgenic mouse model of Huntington's disease.

    PubMed

    Pang, Terence Y C; Du, Xin; Zajac, Michelle S; Howard, Monique L; Hannan, Anthony J

    2009-02-15

    Dysregulation of the serotonergic signaling system has been implicated in the pathology of mood disorders including depression, and various rodent models of disrupted serotonergic signaling display depression-related behavioral phenotypes. Depression is a common neuropsychiatric feature of preclinical Huntington's disease (HD) but the underlying changes in the HD brain contributing to the development of depression are unknown. Using the R6/1 transgenic mouse model of HD, we show that pre-motor symptomatic HD mice display sex-specific depressive-related behaviors on the forced-swim (FST), tail-suspension (TST) and novelty-suppressed feeding (NSFT) tests while having muted responses to acute anti-depressant administration. The baseline behaviors of HD mice were similar to the behavioral phenotypes of serotonin (5-HT) receptor and transporter null mutants, and gene expression of specific serotonin receptors were subsequently found to be reduced in the hippocampus and cortex of HD mice. Female HD mice had an additional deficit in cortical expression of serotonin transporter (SerT). Environmental enrichment normalized the FST behavioral response of female HD mice corresponding with increased gene expression of specific 5-HT receptors in the hippocampus and cortex. Our findings implicate altered serotonergic signaling as the basis for the development of depression during the preclinical stages of HD.

  16. Intranasal administration of testosterone increased immobile-sniffing, exploratory behavior, motor behavior and grooming behavior in rats.

    PubMed

    Zhang, Guoliang; Shi, Geming; Tan, Huibing; Kang, Yunxiao; Cui, Huixian

    2011-04-01

    Currently, testosterone (T) replacement therapy is typically provided by oral medication, injectable T esters, surgically implanted T pellets, transdermal patches and gels. However, most of these methods of administration are still not ideal for targeting the central nervous system. Recently, therapeutic intranasal T administration (InT) has been considered as another option for delivering T to the brain. In the present study, the effects of 21-day InT treatment were assessed on open field behavior in gonadectomized (GDX) rats and intact rats. Subcutaneous injections of T at same dose were also tested in GDX rats. A total of 12 behavioral events were examined in GDX groups with or without T and in intact groups with or without InT. Significant decreases in open field activity were observed in rats after GDX without InT compared to sham-operated rats. The open field activity scores for most tests significantly increased with InT treatment in GDX rats and in intact rats compared with the corresponding GDX rats and intact rats. Intranasal administration of T improved the reduced behaviors resulted from T deficiency better than subcutaneous injection of T, demonstrating that T can be delivered to the brain by intranasal administration. Our results suggest that intranasal T delivery is an effective option for targeting the central nervous system.

  17. Properties of the Driving Behavior Survey among individuals with motor vehicle accident-related posttraumatic stress disorder.

    PubMed

    Clapp, Joshua D; Baker, Aaron S; Litwack, Scott D; Sloan, Denise M; Beck, J Gayle

    2014-01-01

    Data suggest anxious drivers may engage in problematic behaviors that place themselves and others at increased risk of negative traffic events. Three domains of problematic behavior--exaggerated safety/caution, performance deficits, and hostile/aggressive behaviors--previously were identified during development of the Driving Behavior Survey (DBS), a novel measure of anxiety-related behavior. Extending this research, the current study examined the psychometric properties of DBS scores among individuals with posttraumatic stress disorder (PTSD) subsequent to motor vehicle trauma (N=40). Internal consistencies and 12-week test-retest reliabilities for DBS scales ranged from good to excellent. Comparison of scores to normative student data indicated dose-response relationships for safety/caution and performance deficit subscales, with increased frequency of anxious behavior occurring within the PTSD sample. Associations with standard clinical measures provide additional evidence for anxiety-related driving behavior as a unique marker of functional impairment, distinct from both avoidance and disorder-specific symptoms.

  18. Normal and Abnormal Development of Motor Behavior: Lessons From Experiments in Rats

    PubMed Central

    Gramsbergen, Albert

    2001-01-01

    In this essay a few relevant aspects of the neural and behavioral development of the brain in the human and in the rat are reviewed and related to the consequences of lesions in the central and peripheral nervous system at early and later age. Movements initially are generated by local circuits in the spinal cord and without the involvement of descending projections. After birth, both in humans and in rats it seems that the devlopment of postural control is the limiting factor for several motor behaviors to mature. Strong indications exist that the cerebellum is significantly involved in this control. Lesions in the CNS at early stages interfere with fundamental processes of neural development, such as the establishment of fiber connections and cell death patterns. Consequently, the functional effects are strongly dependent on the stage of development. The young and undisturbed CNS, on the other hand, has a much greater capacity than the adult nervous system for compensating abnormal reinnervation in the peripheral nervous system. Animal experiments indicated that the cerebellar cortex might play an important part in this compensation. This possibility should be investigated further as it might offer important perspectives for treatment in the human. PMID:11530886

  19. Nonlinear dynamic behaviors of permanent magnet synchronous motors in electric vehicles caused by unbalanced magnetic pull

    NASA Astrophysics Data System (ADS)

    Xiang, Changle; Liu, Feng; Liu, Hui; Han, Lijin; Zhang, Xun

    2016-06-01

    Unbalanced magnetic pull (UMP) plays a key role in nonlinear dynamic behaviors of permanent magnet synchronous motors (PMSM) in electric vehicles. Based on Jeffcott rotor model, the stiffness characteristics of the rotor system of the PMSM are analyzed and the nonlinear dynamic behaviors influenced by UMP are investigated. In free vibration study, eigenvalue-based stability analysis for multiple equilibrium points is performed which offers an insight in system stiffness. Amplitude modulation effects are discovered of which the mechanism is explained and the period of modulating signal is carried out by phase analysis and averaging method. The analysis indicates that the effects are caused by the interaction of the initial phases of forward and backward whirling motions. In forced vibration study, considering dynamic eccentricity, frequency characteristics revealing softening type are obtained by harmonic balance method, and the stability of periodic solution is investigated by Routh-Hurwitz criterion. The frequency characteristics analysis indicates that the response amplitude is limited in the range between the amplitudes of the two kinds of equilibrium points. In the vicinity of the continuum of equilibrium points, the system hardly provides resistance to bending, and hence external disturbances easily cause loss of stability. It is useful for the design of the PMSM with high stability and low vibration and acoustic noise.

  20. Relative contribution of TARPs γ-2 and γ-7 to cerebellar excitatory synaptic transmission and motor behavior.

    PubMed

    Yamazaki, Maya; Le Pichon, Claire E; Jackson, Alexander C; Cerpas, Manuel; Sakimura, Kenji; Scearce-Levie, Kimberly; Nicoll, Roger A

    2015-01-27

    Transmembrane AMPA receptor regulatory proteins (TARPs) play an essential role in excitatory synaptic transmission throughout the central nervous system (CNS) and exhibit subtype-specific effects on AMPA receptor (AMPAR) trafficking, gating, and pharmacology. The function of TARPs has largely been determined through work on canonical type I TARPs such as stargazin (TARP γ-2), absent in the ataxic stargazer mouse. Little is known about the function of atypical type II TARPs, such as TARP γ-7, which exhibits variable effects on AMPAR function. Because γ-2 and γ-7 are both strongly expressed in multiple cell types in the cerebellum, we examined the relative contribution of γ-2 and γ-7 to both synaptic transmission in the cerebellum and motor behavior by using both the stargazer mouse and a γ-7 knockout (KO) mouse. We found that the loss of γ-7 alone had little effect on climbing fiber (cf) responses in Purkinje neurons (PCs), yet the additional loss of γ-2 all but abolished cf responses. In contrast, γ-7 failed to make a significant contribution to excitatory transmission in stellate cells and granule cells. In addition, we generated a PC-specific deletion of γ-2, with and without γ-7 KO background, to examine the relative contribution of γ-2 and γ-7 to PC-dependent motor behavior. Selective deletion of γ-2 in PCs had little effect on motor behavior, yet the additional loss of γ-7 resulted in a severe disruption in motor behavior. Thus, γ-7 is capable of supporting a component of excitatory transmission in PCs, sufficient to maintain essentially normal motor behavior, in the absence of γ-2.

  1. Deficiency in Na,K-ATPase alpha isoform genes alters spatial learning, motor activity, and anxiety in mice.

    PubMed

    Moseley, Amy E; Williams, Michael T; Schaefer, Tori L; Bohanan, Cynthia S; Neumann, Jon C; Behbehani, Michael M; Vorhees, Charles V; Lingrel, Jerry B

    2007-01-17

    Several disorders have been associated with mutations in Na,K-ATPase alpha isoforms (rapid-onset dystonia parkinsonism, familial hemiplegic migraine type-2), as well as reduction in Na,K-ATPase content (depression and Alzheimer's disease), thereby raising the issue of whether haploinsufficiency or altered enzymatic function contribute to disease etiology. Three isoforms are expressed in the brain: the alpha1 isoform is found in many cell types, the alpha2 isoform is predominantly expressed in astrocytes, and the alpha3 isoform is exclusively expressed in neurons. Here we show that mice heterozygous for the alpha2 isoform display increased anxiety-related behavior, reduced locomotor activity, and impaired spatial learning in the Morris water maze. Mice heterozygous for the alpha3 isoform displayed spatial learning and memory deficits unrelated to differences in cued learning in the Morris maze, increased locomotor activity, an increased locomotor response to methamphetamine, and a 40% reduction in hippocampal NMDA receptor expression. In contrast, heterozygous alpha1 isoform mice showed increased locomotor response to methamphetamine and increased basal and stimulated corticosterone in plasma. The learning and memory deficits observed in the alpha2 and alpha3 heterozygous mice reveal the Na,K-ATPase to be an important factor in the functioning of pathways associated with spatial learning. The neurobehavioral changes seen in heterozygous mice suggest that these mouse models may be useful in future investigations of the associated human CNS disorders.

  2. Dynamical and phase behavior of a phospholipid membrane altered by an antimicrobial peptide at low concentration

    SciTech Connect

    Mamontov, Eugene; Tyagi, M.; Qian, Shuo; Rai, Durgesh K.; Urban, Volker S.; Sharma, V. K.

    2016-05-27

    Here we discuss that the mechanism of action of antimicrobial peptides is traditionally attributed to the formation of pores in the lipid cell membranes of pathogens, which requires a substantial peptide to lipid ratio. However, using incoherent neutron scattering, we show that even at a concentration too low for pore formation, an archetypal antimicrobial peptide, melittin, disrupts the regular phase behavior of the microscopic dynamics in a phospholipid membrane, dimyristoylphosphatidylcholine (DMPC). At the same time, another antimicrobial peptide, alamethicin, does not exert a similar effect on the DMPC microscopic dynamics. The melittin-altered lateral motion of DMPC at physiological temperature no longer resembles the fluid-phase behavior characteristic of functional membranes of the living cells. The disruptive effect demonstrated by melittin even at low concentrations reveals a new mechanism of antimicrobial action relevant in more realistic scenarios, when peptide concentration is not as high as would be required for pore formation, which may facilitate treatment with antimicrobial peptides.

  3. Investigation of the Association Between Motor Stereotypy Behavior With Fundamental Movement Skills, Adaptive Functioning, and Autistic Spectrum Disorder Symptomology in Children With Intellectual Disabilities.

    PubMed

    Powell, Joanne L; Pringle, Lydia; Greig, Matt

    2017-02-01

    Motor stereotypy behaviors are patterned, coordinated, repetitive behaviors that are particularly evident in those with an autistic spectrum disorder and intellectual disabilities. The extent to which motor stereotypy behavior severity is associated with motor skills and maladaptive behavior, measures of adaptive functioning, along with fundamental movement skills and degree of autistic spectrum disorder symptomology is assessed in this preliminary report. Twelve participants, aged 7 to 16 years, with a reported motor stereotypy behavior and either mild or severe intellectual disability comprising developmental or global delay took part in the study. Spearman rho correlational analysis showed that severity of motor stereotypy behavior was significantly positively correlated with autistic spectrum disorder symptomology ( P = .008) and maladaptive behavior ( P = .008) but not fundamental movement skills ( P > .05). An increase in fundamental movement skills score was associated with a decrease in autistic spectrum disorder symptomology ( P = .01) and an increase in motor skills ( P = .002). This study provides evidence showing a significant relationship between motor stereotypy behavior severity with degree of autistic spectrum disorder symptomology and maladaptive behavior.

  4. Resistant Starch Alters the Microbiota-Gut Brain Axis: Implications for Dietary Modulation of Behavior.

    PubMed

    Lyte, Mark; Chapel, Ashley; Lyte, Joshua M; Ai, Yongfeng; Proctor, Alexandra; Jane, Jay-Lin; Phillips, Gregory J

    2016-01-01

    The increasing recognition that the gut microbiota plays a central role in behavior and cognition suggests that the manipulation of microbial taxa through diet may provide a means by which behavior may be altered in a reproducible and consistent manner in order to achieve a beneficial outcome for the host. Resistant starch continues to receive attention as a dietary intervention that can benefit the host through mechanisms that include altering the intestinal microbiota. Given the interest in dietary approaches to improve health, the aim of this study was to investigate whether the use of dietary resistant starch in mice to alter the gut microbiota also results in a change in behavior. Forty-eight 6 week-old male Swiss-Webster mice were randomly assigned to 3 treatment groups (n = 16 per group) and fed either a normal corn starch diet (NCS) or diets rich in resistant starches HA7 diet (HA7) or octenyl-succinate HA7 diet (OS-HA7) for 6 week and monitored for weight, behavior and fecal microbiota composition. Animals fed an HA7 diet displayed comparable weight gain over the feeding period to that recorded for NCS-fed animals while OS-HA7 displayed a lower weight gain as compared to either NCS or HA7 animals (ANOVA p = 0.0001; NCS:HA7 p = 0.244; HA7:OS-HA7 p<0.0001; NCS:OS-HA7 p<0.0001). Analysis of fecal microbiota using 16s rRNA gene taxonomic profiling revealed that each diet corresponded with a unique gut microbiota. The distribution of taxonomic classes was dynamic over the 6 week feeding period for each of the diets. At the end of the feeding periods, the distribution of taxa included statistically significant increases in members of the phylum Proteobacteria in OS-HA7 fed mice, while the Verrucomicrobia increased in HA7 fed mice over that of mice fed OS-HA7. At the class level, members of the class Bacilli decreased in the OS-HA7 fed group, and Actinobacteria, which includes the genus Bifidobacteria, was enriched in the HA7 fed group compared to the control

  5. Resistant Starch Alters the Microbiota-Gut Brain Axis: Implications for Dietary Modulation of Behavior

    PubMed Central

    Lyte, Mark; Chapel, Ashley; Lyte, Joshua M.; Ai, Yongfeng; Proctor, Alexandra; Jane, Jay-Lin; Phillips, Gregory J.

    2016-01-01

    The increasing recognition that the gut microbiota plays a central role in behavior and cognition suggests that the manipulation of microbial taxa through diet may provide a means by which behavior may be altered in a reproducible and consistent manner in order to achieve a beneficial outcome for the host. Resistant starch continues to receive attention as a dietary intervention that can benefit the host through mechanisms that include altering the intestinal microbiota. Given the interest in dietary approaches to improve health, the aim of this study was to investigate whether the use of dietary resistant starch in mice to alter the gut microbiota also results in a change in behavior. Forty-eight 6 week-old male Swiss-Webster mice were randomly assigned to 3 treatment groups (n = 16 per group) and fed either a normal corn starch diet (NCS) or diets rich in resistant starches HA7 diet (HA7) or octenyl-succinate HA7 diet (OS-HA7) for 6 week and monitored for weight, behavior and fecal microbiota composition. Animals fed an HA7 diet displayed comparable weight gain over the feeding period to that recorded for NCS-fed animals while OS-HA7 displayed a lower weight gain as compared to either NCS or HA7 animals (ANOVA p = 0.0001; NCS:HA7 p = 0.244; HA7:OS-HA7 p<0.0001; NCS:OS-HA7 p<0.0001). Analysis of fecal microbiota using 16s rRNA gene taxonomic profiling revealed that each diet corresponded with a unique gut microbiota. The distribution of taxonomic classes was dynamic over the 6 week feeding period for each of the diets. At the end of the feeding periods, the distribution of taxa included statistically significant increases in members of the phylum Proteobacteria in OS-HA7 fed mice, while the Verrucomicrobia increased in HA7 fed mice over that of mice fed OS-HA7. At the class level, members of the class Bacilli decreased in the OS-HA7 fed group, and Actinobacteria, which includes the genus Bifidobacteria, was enriched in the HA7 fed group compared to the control

  6. The dynamic behavior of a cantilever beam coupled to a non-ideal unbalanced motor through numerical and experimental analysis

    NASA Astrophysics Data System (ADS)

    Gonçalves, P. J. P.; Silveira, M.; Pontes Junior, B. R.; Balthazar, J. M.

    2014-09-01

    An excitation force that is not influenced by the system state is said to be an ideal energy source. In real situations, a direct and feedback coupling between the excitation source and the system must always exist at a certain level. This manifestation of the law of conservation of energy is known as the Sommerfeld effect. In the case of obtaining a mathematical model for such a system, additional equations are usually necessary to describe the vibration sources with limited power and its coupling with the mechanical system. In this work, a cantilever beam and a non-ideal DC motor fixed to its free end are analyzed. The motor has an unbalanced mass that provides excitation to the system which is proportional to the current applied to the motor. During the coast up operation of the motor, if the drive power is increased slowly, making the excitation frequency pass through the first natural frequency of the beam, the DC motor speed will remain the same until it suddenly jumps to a much higher value (simultaneously its amplitude jumps to a much lower value) upon exceeding a critical input power. It was found that the Sommerfeld effect depends on some system parameters and the motor operational procedures. These parameters are explored to avoid the resonance capture in the Sommerfeld effect. Numerical simulations and experimental tests are used to help gather insight of this dynamic behavior.

  7. Alterations of molecular and behavioral responses to cocaine by selective inhibition of Elk-1 phosphorylation.

    PubMed

    Besnard, Antoine; Bouveyron, Nicolas; Kappes, Vincent; Pascoli, Vincent; Pagès, Christiane; Heck, Nicolas; Vanhoutte, Peter; Caboche, Jocelyne

    2011-10-05

    Activation of the extracellular signal-regulated kinase (ERK) signaling pathway in the striatum is crucial for molecular adaptations and long-term behavioral alterations induced by cocaine. In response to cocaine, ERK controls the phosphorylation levels of both mitogen and stress-activated protein kinase 1 (MSK-1), a nuclear kinase involved in histone H3 (Ser10) and cAMP response element binding protein phosphorylation, and Elk-1, a transcription factor involved in serum response element (SRE)-driven gene regulations. We recently characterized the phenotype of msk-1 knock-out mice in response to cocaine. Herein, we wanted to address the role of Elk-1 phosphorylation in cocaine-induced molecular, morphological, and behavioral responses. We used a cell-penetrating peptide, named TAT-DEF-Elk-1 (TDE), which corresponds to the DEF docking domain of Elk-1 toward ERK and inhibits Elk-1 phosphorylation induced by ERKs without modifying ERK or MSK-1 in vitro. The peptide was injected in vivo before cocaine administration in mice. Immunocytochemical, molecular, morphological, and behavioral studies were performed. The TDE inhibited Elk-1 and H3 (Ser10) phosphorylation induced by cocaine, sparing ERK and MSK-1 activation. Consequently, TDE altered cocaine-induced regulation of genes bearing SRE site(s) in their promoters, including c-fos, zif268, ΔFosB, and arc/arg3.1 (activity-regulated cytoskeleton-associated protein). In a chronic cocaine administration paradigm, TDE reversed cocaine-induced increase in dendritic spine density. Finally, the TDE delayed the establishment of cocaine-induced psychomotor sensitization and conditioned-place preference. We conclude that Elk-1 phosphorylation downstream from ERK is a key molecular event involved in long-term neuronal and behavioral adaptations to cocaine.

  8. Calretinin and Neuropeptide Y interneurons are differentially altered in the motor cortex of the SOD1G93A mouse model of ALS

    PubMed Central

    Clark, Rosemary M.; Blizzard, Catherine A.; Young, Kaylene M.; King, Anna E.; Dickson, Tracey C.

    2017-01-01

    Increasing evidence indicates an excitatory/inhibitory imbalance may have a critical role in the pathogenesis of amyotrophic lateral sclerosis (ALS). Impaired inhibitory circuitry is consistently reported in the motor cortex of both familial and sporadic patients, closely associated with cortical hyperexcitability and ALS onset. Inhibitory network dysfunction is presumably mediated by intra-cortical inhibitory interneurons, however, the exact cell types responsible are yet to be identified. In this study we demonstrate dynamic changes in the number of calretinin- (CR) and neuropeptide Y-expressing (NPY) interneurons in the motor cortex of the familial hSOD1G93A ALS mouse model, suggesting their potential involvement in motor neuron circuitry defects. We show that the density of NPY-populations is significantly decreased by ~17% at symptom onset (8 weeks), and by end-stage disease (20 weeks) is significantly increased by ~30%. Conversely, the density of CR-populations is progressively reduced during later symptomatic stages (~31%) to end-stage (~36%), while CR-expressing interneurons also show alteration of neurite branching patterns at symptom onset. We conclude that a differential capacity for interneurons exists in the ALS motor cortex, which may not be a static phenomenon, but involves early dynamic changes throughout disease, implicating specific inhibitory circuitry. PMID:28294153

  9. Impaired motor learning attributed to altered AMPA receptor function in the cerebellum of rats with temporal lobe epilepsy: ameliorating effects of Withania somnifera and withanolide A.

    PubMed

    Soman, Smijin; Anju, T R; Jayanarayanan, S; Antony, Sherin; Paulose, C S

    2013-06-01

    The aim of this study was to investigate the effect of Withania somnifera (WS) extract, withanolide A (WA), and carbamazepine (CBZ) on cerebellar AMPA receptor function in pilocarpine-induced temporal lobe epilepsy (TLE). In the present study, motor learning deficit was studied by rotarod test, grid walk test, and narrow beam test. Motor learning was significantly impaired in rats with epilepsy. The treatment with WS and WA significantly reversed the motor learning deficit in rats with epilepsy when compared with control rats. There was an increase in glutamate content and IP3 content observed in rats with epilepsy which was reversed in WS- and WA-treated rats with epilepsy. alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid (AMPA) receptor dysfunction was analyzed using radiolabeled AMPA receptor binding assay, AMPA receptor mRNA expression, and immunohistochemistry using anti-AMPA receptor antibody. Our results suggest that there was a decrease in Bmax, mRNA expression, and AMPA receptor expression indicating AMPA receptor dysfunction, which is suggested to have contributed to the motor learning deficit observed in rats with epilepsy. Moreover, treatment with WS and WA resulted in physiological expression of AMPA receptors. There was also alteration in GAD and GLAST expression which supplemented the increase in extracellular glutamate. The treatment with WS and WA reversed the GAD and GLAST expression. These findings suggest that WS and WA regulate AMPA receptor function in the cerebellum of rats with TLE, which has therapeutic application in epilepsy.

  10. Chicoric acid regulates behavioral and biochemical alterations induced by chronic stress in experimental Swiss albino mice.

    PubMed

    Kour, Kiranjeet; Bani, Sarang

    2011-09-01

    The present study was taken up to see the effect of chicoric acid (CA) on behavioral and biochemical alterations induced by chronic restraint stress in experimental Swiss albino mice. CA at 1mg/kg dose level exhibited considerable antidepressant activity as shown by significant decrease in immobility period in the Porsolt's swim stress-induced behavioral despair test and escape failures in Learned "helplessness test". The antidepressant activity shown by CA can be attributed to its modulating effect on nor-adrenaline (NA), dopamine (DA) and 5- hydroxy tryptamine (5-HT) as shown by their quantification in CA treated chronically stressed mice. Further, a significant antioxidant effect was exhibited by CA as shown by estimation of lipid peroxidation, glutathione (GSH) and glycogen in liver of chronically stressed mice. It also normalized altered values of serum glucose, triglycerides, aspartate aminotransferase (AST) alanine aminotransferase (ALT) and alkaline phosphatase (ALP) in a dose dependent manner. The stress busting potential of CA was further confirmed by its regulating effect on raised plasma corticosterone levels and significant attenuation of the depleted ascorbic acid, cholesterol and corticosterone levels in adrenal glands. Thus, our results suggest that CA possesses considerable stress busting potential, and that anti-oxidation may be one of the mechanisms underlying its antistress action.

  11. Inducible Nitric Oxide Inhibitors Block NMDA Antagonist-Stimulated Motoric Behaviors and Medial Prefrontal Cortical Glutamate Efflux

    PubMed Central

    Bergstrom, Hadley C.; Darvesh, Altaf S.; Berger, S. P.

    2015-01-01

    Nitric oxide (NO) plays a critical role in the motoric and glutamate releasing action of N-methyl-D-aspartate (NMDA)-antagonist stimulants. Earlier studies utilized neuronal nitric oxide synthase inhibitors (nNOS) for studying the neurobehavioral effects of non-competitive NMDA-antagonist stimulants such as dizocilpine (MK-801) and phencyclidine (PCP). This study explores the role of the inducible nitric oxide synthase inhibitors (iNOS) aminoguanidine (AG) and (-)-epigallocatechin-3-gallate (EGCG) in NMDA-antagonist induced motoric behavior and prefrontal cortical glutamate efflux. Adult male rats were administered a dose range of AG, EGCG, or vehicle prior to receiving NMDA antagonists MK-801, PCP, or a conventional psychostimulant (cocaine) and tested for motoric behavior in an open arena. Glutamate in the medial prefrontal cortex (mPFC) was measured using in vivo microdialysis after a combination of AG or EGCG prior to MK-801. Acute administration of AG or EGCG dose-dependently attenuated the locomotor and ataxic properties of MK-801 and PCP. Both AG and EGCG were unable to block the motoric effects of cocaine, indicating the acute pharmacologic action of AG and EGCG is specific to NMDA antagonism and not generalizable to all stimulant class drugs. AG and EGCG normalized MK-801-stimulated mPFC glutamate efflux. These data demonstrate that AG and EGCG attenuates NMDA antagonist-stimulated motoric behavior and cortical glutamate efflux. Our results suggest that EGCG-like polyphenol nutraceuticals (contained in “green tea” and chocolate) may be clinically useful in protecting against the adverse behavioral dissociative and cortical glutamate stimulating effects of NMDA antagonists. Medications that interfere with NMDA antagonists such as MK-801 and PCP have been proposed as treatments for schizophrenia. PMID:26696891

  12. Vortex core deformation and stepper-motor ratchet behavior in a superconducting aluminum film containing an array of holes.

    PubMed

    Van de Vondel, J; Gladilin, V N; Silhanek, A V; Gillijns, W; Tempere, J; Devreese, J T; Moshchalkov, V V

    2011-04-01

    We investigated experimentally the frequency dependence of a superconducting vortex ratchet effect by means of electrical transport measurements and modeled it theoretically using the time-dependent Ginzburg-Landau formalism. We demonstrate that the high frequency vortex behavior can be described as a discrete motion of a particle in a periodic potential, i.e., the so-called stepper-motor behavior. Strikingly, in the more conventional low frequency response a transition takes place from an Abrikosov vortex rectifier to a phase slip line rectifier. This transition is characterized by a strong increase in the rectified voltage and the appearance of a pronounced hysteretic behavior.

  13. Chronic uranium contamination alters spinal motor neuron integrity via modulation of SMN1 expression and microglia recruitment.

    PubMed

    Saint-Marc, Brice; Elie, Christelle; Manens, Line; Tack, Karine; Benderitter, Marc; Gueguen, Yann; Ibanez, Chrystelle

    2016-07-08

    Consequences of uranium contamination have been extensively studied in brain as cognitive function impairments were observed in rodents. Locomotor disturbances have also been described in contaminated animals. Epidemiological studies have revealed increased risk of motor neuron diseases in veterans potentially exposed to uranium during their military duties. To our knowledge, biological response of spinal cord to uranium contamination has not been studied even though it has a crucial role in locomotion. Four groups of rats were contaminated with increasing concentrations of uranium in their drinking water compared to a control group to study cellular mechanisms involved in locomotor disorders. Nissl staining of spinal cord sections revealed the presence of chromatolytic neurons in the ventral horn. This observation was correlated with a decreased number of motor neurons in the highly contaminated group and a decrease of SMN1 protein expression (Survival of Motor Neuron 1). While contamination impairs motor neuron integrity, an increasing number of microglial cells indicates the trigger of a neuroinflammation process. Potential overexpression of a microglial recruitment chemokine, MCP-1 (Monocyte Chimioattractant Protein 1), by motor neurons themselves could mediate this process. Studies on spinal cord appear to be relevant for risk assessment of population exposed via contaminated food and water.

  14. ApoE2 Exaggerates PTSD-Related Behavioral, Cognitive, and Neuroendocrine Alterations

    PubMed Central

    Johnson, Lance A; Zuloaga, Damian G; Bidiman, Erin; Marzulla, Tessa; Weber, Sydney; Wahbeh, Helane; Raber, Jacob

    2015-01-01

    Apolipoprotein E (apoE) is an essential component of lipoprotein particles in both the brain and periphery, and exists in three isoforms in the human population: E2, E3, and E4. ApoE has numerous, well-established roles in neurobiology. Most notably, E4 is associated with earlier onset and increased risk of Alzheimer's disease (AD). Although possession of E2 is protective in the context of AD, E2 appears to confer an increased incidence and severity of posttraumatic stress disorder (PTSD). However, the biological processes underlying this link remain unclear. In this study, we began to elucidate these associations by examining the effects of apoE on PTSD severity in combat veterans, and on PTSD-like behavior in mice with human apoE. In a group of 92 veterans with PTSD, we observed significantly higher Clinician-Administered PTSD Scale and PTSD Checklist scores in E2+ individuals, as well as alterations in salivary cortisol levels. Furthermore, we measured behavioral and biological outcomes in mice expressing human apoE after a single stressful event as well as following a period of chronic variable stress, a model of combat-related trauma. Mice with E2 showed impairments in fear extinction, and behavioral, cognitive, and neuroendocrine alterations following trauma. To the best of our knowledge, these data constitute the first translational demonstration of PTSD severity in men and PTSD-like symptoms in mice with E2, and point to apoE as a novel biomarker of susceptibility, and potential therapeutic target, for PTSD. PMID:25857685

  15. Limited Nesting Stress Alters Maternal Behavior and In Vivo Intestinal Permeability in Male Wistar Pup Rats

    PubMed Central

    Moussaoui, Nabila; Larauche, Muriel; Biraud, Mandy; Molet, Jenny; Million, Mulugeta; Mayer, Emeran; Taché, Yvette

    2016-01-01

    A few studies indicate that limited nesting stress (LNS) alters maternal behavior and the hypothalamic pituitary adrenal (HPA) axis of dams and offspring in male Sprague Dawley rats. In the present study, we evaluated the impact of LNS on maternal behavior in Wistar rats, and on the HPA axis, glycemia and in vivo intestinal permeability of male and female offspring. Intestinal permeability is known to be elevated during the first week postnatally and influenced by glucocorticoids. Dams and neonatal litters were subjected to LNS or normal nesting conditions (control) from days 2 to 10 postnatally. At day 10, blood was collected from pups for determination of glucose and plasma corticosterone by enzyme immunoassay and in vivo intestinal permeability by oral gavage of fluorescein isothiocyanate–dextran 4kDa. Dams exposed to LNS compared to control showed an increase in the percentage of time spent building a nest (118%), self-grooming (69%), and putting the pups back to the nest (167%). LNS male and female pups exhibited a reduction of body weight by 5% and 4%, adrenal weights/100g body weight by 17% and 18%, corticosterone plasma levels by 64% and 62% and blood glucose by 11% and 12% respectively compared to same sex control pups. In male LNS pups, intestinal permeability was increased by 2.7-fold while no change was observed in females compared to same sex control. There was no sex difference in any of the parameters in control pups except the body weight. These data indicate that Wistar dams subjected to LNS during the first postnatal week have an altered repertoire of maternal behaviors which affects the development of the HPA axis in both sexes and intestinal barrier function in male offspring. PMID:27149676

  16. Altered Effective Connectivity of the Primary Motor Cortex in Stroke: A Resting-State fMRI Study with Granger Causality Analysis

    PubMed Central

    Fan, Mingxia; Yin, Dazhi; Sun, Limin; Jia, Jie; Tang, Chaozheng; Zheng, Xiaohui; Jiang, Yuwei; Wu, Jie; Gong, Jiayu

    2016-01-01

    The primary motor cortex (M1) is often abnormally recruited in stroke patients with motor disabilities. However, little is known about the alterations in the causal connectivity of M1 following stroke. The purpose of the present study was to investigate whether the effective connectivity of the ipsilesional M1 is disturbed in stroke patients who show different outcomes in hand motor function. 23 patients with left-hemisphere subcortical stroke were selected and divided into two subgroups: partially paralyzed hands (PPH) and completely paralyzed hands (CPH). Further, 24 matched healthy controls (HCs) were recruited. A voxel-wise Granger causality analysis (GCA) on the resting-state fMRI data between the ipsilesional M1 and the whole brain was performed to explore differences between the three groups. Our results showed that the influence from the frontoparietal cortices to ipsilesional M1 was diminished in both stroke subgroups and the influence from ipsilesional M1 to the sensorimotor cortices decreased greater in the CPH group than in the PPH group. Moreover, compared with the PPH group, the decreased influence from ipsilesional M1 to the contralesional cerebellum and from the contralesional superior parietal lobe to ipsilesional M1 were observed in the CPH group, and their GCA values were positively correlated with the FMA scores; Conversely, the increased influence from ipsilesional M1 to the ipsilesional middle frontal gyrus and middle temporal gyrus were observed, whose GCA values were negatively correlated with the FMA scores. This study suggests that the abnormalities of casual flow in the ipsilesional M1 are related to the severity of stroke-hand dysfunction, providing valuable information to understand the deficits in resting-state effective connectivity of motor execution and the frontoparietal motor control network during brain plasticity following stroke. PMID:27846290

  17. Extensive early motor and non-motor behavioral deficits are followed by striatal neuronal loss in Knock-in Huntington’s disease mice

    PubMed Central

    Hickey, Miriam A.; Kosmalska, Agata; Enayati, Joseph; Cohen, Rachel; Zeitlin, Scott; Levine, Michael S.; Chesselet, Marie-Françoise

    2008-01-01

    Huntington’s disease is a neurodegenerative disorder, caused by an elongation of CAG repeats in the huntingtin gene. Mice with an insertion of an expanded polyglutamine repeat in the mouse huntingtin gene (knock-in mice) most closely model the disease because the mutation is expressed in the proper genomic and protein context. However, few knock-in mouse lines have been extensively characterized and available data suggest marked differences in the extent and time course of their behavioral and pathological phenotype. We have previously described behavioral anomalies in the open field as early as 1 month of age, followed by the appearance at 2 months of progressive huntingtin neuropathology, in a mouse carrying a portion of human exon 1 with approximately 140 CAG repeats inserted into the mouse huntingtin gene. Here we extend these observations by showing that early behavioral anomalies exist in a wide range of motor (climbing, vertical pole, rotarod, and running wheel performance) and non-motor functions (fear conditioning and anxiety) starting at 1–4 months of age, and are followed by progressive gliosis and decrease in DARPP32 (12 months) and a loss of striatal neurons at 2 years. At this age, mice also present striking spontaneous behavioral deficits in their home cage. The data show that this line of knock-in mice reproduces canonical characteristics of Huntington’s disease, preceded by deficits which may correspond to the protracted pre-manifest phase of the disease in humans. Accordingly, they provide a useful model to elucidate early mechanisms of pathophysiology and the progression to overt neurodegeneration. PMID:18805465

  18. Effect of an altered rest-activity or feeding schedule on the shift of motor activity rhythm of mice.

    PubMed

    Murakami, H; Murakami, Y

    1980-04-01

    Preflight acclimatization to the rhythm of destination and postflight daytime activity are assumed to be effective countermeasures against the jet lag syndrome. Regarding this idea, resynchronization of motor activity rhythm was investigated in mice subjected to daytime exercises on a driven belt before or after the reversal of lighting regimen. In addition, the effect of prior daytime feeding was studied. No evidence was manifested that the forced exercises or feeding schedule would hasten synchronization. This result indicates that the central control system of motor activity rhythm could not be manipulated favorably by such method in mice. On the basis of the result obtained, the applicability of countermeasures to human beings was discussed.

  19. An automated system for quantitative analysis of newborns' oral-motor behavior and coordination during bottle feeding.

    PubMed

    Tamilia, Eleonora; Formica, Domenico; Visco, Anna Maria; Scaini, Alberto; Taffoni, Fabrizio

    2015-01-01

    In this work a novel unobtrusive technology-aided system is presented and tested for the assessment of newborns' oral-motor behavior and coordination during bottle feeding. A low-cost monitoring device was designed and developed in order to record Suction (S) and Expression (E) pressures from a typical feeding bottle. A software system was developed to automatically treat the data and analyze them. A set of measures of motor control and coordination has been implemented for the specific application to the analysis of sucking behavior. Experimental data were collected with the developed system on two groups of newborns (Healthy vs. Low Birth Weight) in a clinical setting. We identified the most sensitive S features to group differences, and analyzed their correlation with S/E coordination measures. Then, Principal Component Analysis (PCA) was used to explore the system suitability to automatically identify peculiar oral behaviors. Results suggest the suitability of the proposed system to perform an objective technology-aided assessment of the newborn's oral-motor behavior and coordination during the first days of life.

  20. Premixed ignition behavior of C{sub 9} fatty acid esters: A motored engine study

    SciTech Connect

    Zhang, Yu.; Yang, Yi; Boehman, Andre L.

    2009-06-15

    An experimental study on the premixed ignition behavior of C{sub 9} fatty acid esters has been conducted in a motored CFR engine. For each test fuel, the engine compression ratio was gradually increased from the lowest point (4.43) to the point where significant high temperature heat release (HTHR) was observed. The engine exhaust was sampled and analyzed through GC-FID/TCD and GC-MS. Combustion analysis showed that the four C{sub 9} fatty acid esters tested in this study exhibited evidently different ignition behavior. The magnitude of low temperature heat release (LTHR) follows the order, ethyl nonanoate > methyl nonanoate >> methyl 2-nonenoate > methyl 3-nonenoate. The lower oxidation reactivity for the unsaturated fatty acid esters in the low temperature regime can be explained by the reduced amount of six- or seven-membered transition state rings formed during the oxidation of the unsaturated esters due to the presence of a double bond in the aliphatic chain of the esters. The inhibition effect of the double bond on the low temperature oxidation reactivity of fatty acid esters becomes more pronounced as the double bond moves toward the central position of the aliphatic chain. GC-MS analysis of exhaust condensate collected under the engine conditions where only LTHR occurred showed that the alkyl chain of the saturated fatty acid esters participated in typical paraffin-like low temperature oxidation sequences. In contrast, for unsaturated fatty acid esters, the autoignition can undergo olefin ignition pathways. For all test compounds, the ester functional group remains largely intact during the early stage of oxidation. (author)

  1. Intercostal muscle motor behavior during tracheal occlusion conditioning in conscious rats

    PubMed Central

    Jaiswal, Poonam B.

    2016-01-01

    A respiratory load compensation response is characterized by increases in activation of primary respiratory muscles and/or recruitment of accessory respiratory muscles. The contribution of the external intercostal (EI) muscles, which are a primary respiratory muscle group, during normal and loaded breathing remains poorly understood in conscious animals. Consciousness has a significant role on modulation of respiratory activity, as it is required for the integration of behavioral respiratory responses and voluntary control of breathing. Studies of respiratory load compensation have been predominantly focused in anesthetized animals, which make their comparison to conscious load compensation responses challenging. Using our established model of intrinsic transient tracheal occlusions (ITTO), our aim was to evaluate the motor behavior of EI muscles during normal and loaded breathing in conscious rats. We hypothesized that 1) conscious rats exposed to ITTO will recruit the EI muscles with an increased electromyogram (EMG) activation and 2) repeated ITTO for 10 days would potentiate the baseline EMG activity of this muscle in conscious rats. Our results demonstrate that conscious rats exposed to ITTO respond by recruiting the EI muscle with a significantly increased EMG activation. This response to occlusion remained consistent over the 10-day experimental period with little or no effect of repeated ITTO exposure on the baseline ∫EI EMG amplitude activity. The pattern of activation of the EI muscle in response to an ITTO is discussed in detail. The results from the present study demonstrate the importance of EI muscles during unloaded breathing and respiratory load compensation in conscious rats. PMID:26823339

  2. Influence of flow velocity on motor behavior of sea cucumber Apostichopus japonicus.

    PubMed

    Pan, Yang; Zhang, Libin; Lin, Chenggang; Sun, Jiamin; Kan, Rentao; Yang, Hongsheng

    2015-05-15

    The influence of flow velocity on the motor behavior of the sea cucumber, Apostichopus japonicus was investigated in the laboratory. Cameras were used to record sea cucumber movements and behavior analysis software was used to measure the distance traveled, time spent, upstream or downstream of the start position and the speed of movements. In general, the mean velocity of A. japonicus was below 0.7mms(-1). The maximum velocity recorded for all the sea cucumbers tested was for a large individual (89.25±17.11g), at a flow rate of 4.6±0.5cms(-1). Medium sized (19.68±5.53g) and large individuals moved significantly faster than small individuals (2.65±1.24g) at the same flow rate. A. japonicus moved significantly faster when there was a moderate current (4.6±0.5cms(-1) and 14.7±0.3cms(-1)), compared with the fast flow rate (29.3±3.7cms(-1)) and when there was no flow (0cms(-1)). Sea cucumbers did not show positive rheotaxis in general, but did move in a downstream direction at faster current speeds. Large, medium and small sized individuals moved downstream at the fastest current speed tested, 29.3±3.7cms(-1). When there was no water flow, sea cucumbers tended to move in an irregular pattern. The movement patterns show that the sea cucumber, A. japonicus can move across the direction of flow, and can move both upstream and downstream along the direction of flow.

  3. An electrostatic mechanism closely reproducing observed behavior in the bacterial flagellar motor.

    PubMed Central

    Walz, D; Caplan, S R

    2000-01-01

    A mechanism coupling the transmembrane flow of protons to the rotation of the bacterial flagellum is studied. The coupling is accomplished by means of an array of tilted rows of positive and negative charges around the circumference of the rotor, which interacts with a linear array of proton binding sites in channels. We present a rigorous treatment of the electrostatic interactions using minimal assumptions. Interactions with the transition states are included, as well as proton-proton interactions in and between channels. In assigning values to the parameters of the model, experimentally determined structural characteristics of the motor have been used. According to the model, switching and pausing occur as a consequence of modest conformational changes in the rotor. In contrast to similar approaches developed earlier, this model closely reproduces a large number of experimental findings from different laboratories, including the nonlinear behavior of the torque-frequency relation in Escherichia coli, the stoichiometry of the system in Streptococcus, and the pH-dependence of swimming speed in Bacillus subtilis. PMID:10653777

  4. Rotating bouncing disks, tossing pizza dough, and the behavior of ultrasonic motors

    NASA Astrophysics Data System (ADS)

    Liu, Kuang-Chen; Friend, James; Yeo, Leslie

    2009-10-01

    Pizza tossing and certain forms of standing-wave ultrasonic motors (SWUMs) share a similar process for converting reciprocating input into continuous rotary motion. We show that the key features of this motion conversion process such as collision, separation and friction coupling are captured by the dynamics of a disk bouncing on a vibrating platform. The model shows that the linear or helical hand motions commonly used by pizza chefs and dough-toss performers for single tosses maximize energy efficiency and the dough’s airborne rotational speed; on the other hand, the semielliptical hand motions used for multiple tosses make it easier to maintain dough rotation at the maximum speed. The system’s bifurcation diagram and basins of attraction also provide a physical basis for understanding the peculiar behavior of SWUMs and provide a means to design them. The model is able to explain the apparently chaotic oscillations that occur in SWUMs and predict the observed trends in steady-state speed and stall torque as preload is increased.

  5. Crickets in space: morphological, physiological and behavioral alterations induced by space flight and hypergravity

    NASA Astrophysics Data System (ADS)

    Horn, E.; Agricola, H.; Böser, S.; Förster, S.; Kämper, G.; Riewe, P.; Sebastian, C.

    "Crickets in Space" was a Neurolab experiment by which the balance between genetic programs and the gravitational environment for the development of a gravity sensitive neuronal system was studied. The model character of crickets was justified by their external gravity receptors, identified position-sensitive interneurons (PSI) and gravity-related compensatory head response, and by the specific relation of this behavior to neuronal arousal systems activated by locomotion. These advantages allowed to study the impact of modified gravity on cellular processes in a complex organism. Eggs, 1st, 4th and 6th stage larvae of Acheta domesticus were used. Post-flight experiments revealed a low susceptibility of the behavior to micro- and hypergravity while the physiology of the PSI was significantly affected. Immunocytological investigations revealed a stage-dependent sensitivity of thoracic GABAergic motoneurons to 3g-conditions concerning their soma sizes but not their topographical arrangement. The morphology of neuromuscular junctions was not affected by 3g-hypergravity. Peptidergic neurons from cerebral sensorimotor centers revealed no significant modifications by microgravity (μg). The contrary physiological and behavioral results indicate a facilitation of 1g-readaptation originating from accessory gravity, proprioceptive and visual sense organs. Absence of anatomical modifications point to an effective time window of μg- or 3g-expo-sure related to the period of neuronal proliferation. The analysis of basic mechanisms of how animals and man adapt to altered gravitational conditions will profit from a continuation of the project "Crickets in Space".

  6. Exposition to tannery wastewater did not alter behavioral and biochemical parameters in Wistar rats.

    PubMed

    Moysés, Felipe dos Santos; Bertoldi, Karine; Spindler, Christiano; Sanches, Eduardo Farias; Elsner, Viviane Rostirola; Rodrigues, Marco Antonio Siqueira; Siqueira, Ionara Rodrigues

    2014-04-22

    There are scarce data on the neurotoxicity in mammalian induced by tannery wastewaters. Previously, the anxiogenic effect of tannery wastewater was demonstrated in mice, while wastewater submitted to photoelectrooxidation (PEO) process treatment did not affect the anxiety state. Considering that species may response differently to xenobiotics, the aim of the present work was to study the effects of exposure to tannery wastewaters (non-PEO or PEO-treated) on behavioral and neurochemical markers in another species of laboratory animals, specifically Wistar rats. Male Wistar rats were given free access to water bottles containing non-PEO or PEO-treated tannery wastewaters (0.1, 1 and 5% in drinking water). During the exposure, behavioral tests of anxiety (elevated plus-maze, neophobia, open field and light-dark box), depression (forced swimming) and memory (inhibitory avoidance, novel object and discriminative avoidance) were performed. On the 30th day, brain structures were dissected out to evaluate cellular oxidative state (hippocampus, cerebellum and striatum) and acetylcholinesterase activity (hippocampus and striatum). Exposure to tannery effluent with or without photoelectrochemical treatment did not alter any behavioral and neurochemical parameters evaluated. Our data indicate that Wistar rats may not be an adequate species for ecotoxicological studies involving tannery effluents and that POE treatment did not generate other toxic compounds.

  7. Chemosensory cues affect amygdaloid neurogenesis and alter behaviors in the socially monogamous prairie vole.

    PubMed

    Liu, Y; Lieberwirth, C; Jia, X; Curtis, J T; Meredith, M; Wang, Z X

    2014-05-01

    The current study examined the effects of pheromonal exposure on adult neurogenesis and revealed the role of the olfactory pathways on adult neurogenesis and behavior in the socially monogamous prairie vole (Microtus ochrogaster). Subjects were injected with a cell proliferation marker [5-bromo-2'-deoxyuridine (BrdU)] and then exposed to their own soiled bedding or bedding soiled by a same- or opposite-sex conspecific. Exposure to opposite-sex bedding increased BrdU labeling in the amygdala (AMY), but not the dentate gyrus (DG), of female, but not male, voles, indicating a sex-, stimulus-, and brain region-specific effect. The removal of the main olfactory bulbs or lesioning of the vomeronasal organ (VNOX) in females reduced BrdU labeling in the AMY and DG, and inhibited the male bedding-induced BrdU labeling in the AMY, revealing the importance of an intact olfactory pathway for amygdaloid neurogenesis. VNOX increased anxiety-like behavior and altered social preference, but it did not affect social recognition memory in female voles. VNOX also reduced the percentage of BrdU-labeled cells that co-expressed the neuronal marker TuJ1 in the AMY, but not the DG. Together, our data indicate the importance of the olfactory pathway in mediating brain plasticity in the limbic system as well as its role in behavior.

  8. Insulin resistance in brain alters dopamine turnover and causes behavioral disorders

    PubMed Central

    Kleinridders, Andre; Cai, Weikang; Cappellucci, Laura; Ghazarian, Armen; Collins, William R.; Vienberg, Sara G.; Pothos, Emmanuel N.; Kahn, C. Ronald

    2015-01-01

    Diabetes and insulin resistance are associated with altered brain imaging, depression, and increased rates of age-related cognitive impairment. Here we demonstrate that mice with a brain-specific knockout of the insulin receptor (NIRKO mice) exhibit brain mitochondrial dysfunction with reduced mitochondrial oxidative activity, increased levels of reactive oxygen species, and increased levels of lipid and protein oxidation in the striatum and nucleus accumbens. NIRKO mice also exhibit increased levels of monoamine oxidase A and B (MAO A and B) leading to increased dopamine turnover in these areas. Studies in cultured neurons and glia cells indicate that these changes in MAO A and B are a direct consequence of loss of insulin signaling. As a result, NIRKO mice develop age-related anxiety and depressive-like behaviors that can be reversed by treatment with MAO inhibitors, as well as the tricyclic antidepressant imipramine, which inhibits MAO activity and reduces oxidative stress. Thus, insulin resistance in brain induces mitochondrial and dopaminergic dysfunction leading to anxiety and depressive-like behaviors, demonstrating a potential molecular link between central insulin resistance and behavioral disorders. PMID:25733901

  9. Evaluation of potential gender-related differences in behavioral and cognitive alterations following pilocarpine-induced status epilepticus in C57BL/6 mice.

    PubMed

    Oliveira, Clarissa Vasconcelos de; Grigoletto, Jéssica; Funck, Vinícius Rafael; Ribeiro, Leandro Rodrigo; Royes, Luiz Fernando Freire; Fighera, Michele Rechia; Furian, Ana Flávia; Oliveira, Mauro Schneider

    2015-05-01

    Together with pharmacoresistant seizures, the quality of life of temporal lobe epilepsy (TLE) patients is negatively impacted by behavioral comorbidities including but not limited to depression, anxiety and cognitive deficits. The pilocarpine model of TLE has been widely used to study characteristics of human TLE, including behavioral comorbidities. Since the outcomes of pilocarpine-induced TLE might vary depending on several experimental factors, we sought to investigate potential gender-related differences regarding selected behavioral alterations in C57BL6 mice. We found that epileptic mice, independent of gender, displayed increased anxiety-like behavior in the open-field test. In the object recognition test, epileptic mice, regardless of gender, showed a decreased recognition index at 24 (but not at 4) hours after training. On the other hand, no significant differences were found regarding mice learning and memory performance in the Barnes maze paradigm. Motor coordination and balance as assessed by the beam walk and rotarod tests were not impaired in epileptic mice of both genders. However, female mice, independent of epilepsy, performed the beam walk and rotarod tasks better than their male counterparts. We also found that only male epileptic mice displayed disturbed behavior in the forced swim test, but the mice of both genders displayed anhedonia-like behavior in the taste preference test. Lastly, we found that the extent of hilar cell loss is similar in both genders. In summary, both genders can be successfully employed to study behavioral comorbidities of TLE; however, taking the potential gender differences into account may help choose the more appropriated gender for a given task, which may be of value for the minimization of the number of animals used during the experiments.

  10. Murine Motor and Behavior Functional Evaluations for Acute 1-Methyl-4-Phenyl-1,2,3,6-Tetrahydropyridine (MPTP) Intoxication

    PubMed Central

    Hutter-Saunders, Jessica A. L.; Mosley, R. Lee

    2011-01-01

    Acute intoxication with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) induces nigrostriatal neurodegeneration that reflects Parkinson’s disease (PD) pathobiology. The model is commonly used for rodent studies of PD pathogenesis and diagnostics and for developmental therapeutics. However, tests of motor function in MPTP-intoxicated mice have yielded mixed results. This unmet need reflects, in part, lesion severity, animal variability, and the overall test sensitivity and specificity. In attempts to standardize rodent motor function and behavioral tests, mice were trained on the rotarod or habituated in an open field test chamber, and baseline performance measurements were collected prior to MPTP intoxication. One week following MPTP intoxication, motor function and behavior were assessed and baseline measurements applied to post-MPTP measurements with normalization to PBS controls. Rotarod and open field tests assessed in this manner demonstrated significant differences between MPTP- and saline-treated mice, while tests of neuromuscular strength and endurance did not. We conclude that the rotarod and open field tests provide reliable measures of motor function for MPTP-intoxicated mice. PMID:21431472

  11. Functional near-infrared spectroscopy maps cortical plasticity underlying altered motor performance induced by transcranial direct current stimulation

    PubMed Central

    Hodics, Timea; Hervey, Nathan; Kondraske, George; Stowe, Ann M.; Alexandrakis, George

    2013-01-01

    Abstract. Transcranial direct current stimulation (tDCS) of the human sensorimotor cortex during physical rehabilitation induces plasticity in the injured brain that improves motor performance. Bi-hemispheric tDCS is a noninvasive technique that modulates cortical activation by delivering weak current through a pair of anodal–cathodal (excitation–suppression) electrodes, placed on the scalp and centered over the primary motor cortex of each hemisphere. To quantify tDCS-induced plasticity during motor performance, sensorimotor cortical activity was mapped during an event-related, wrist flexion task by functional near-infrared spectroscopy (fNIRS) before, during, and after applying both possible bi-hemispheric tDCS montages in eight healthy adults. Additionally, torque applied to a lever device during isometric wrist flexion and surface electromyography measurements of major muscle group activity in both arms were acquired concurrently with fNIRS. This multiparameter approach found that hemispheric suppression contralateral to wrist flexion changed resting-state connectivity from intra-hemispheric to inter-hemispheric and increased flexion speed (p<0.05). Conversely, exciting this hemisphere increased opposing muscle output resulting in a decrease in speed but an increase in accuracy (p<0.05 for both). The findings of this work suggest that tDCS with fNIRS and concurrent multimotor measurements can provide insights into how neuroplasticity changes muscle output, which could find future use in guiding motor rehabilitation. PMID:24193947

  12. Reduction of GABAergic transmission and alterations in behavior after 6-OHDA treatment of rats.

    PubMed

    Podkletnova, I; Raevsky, V; Alho, H

    1996-07-20

    We studied the effects of neonatal administration of 6-hydroxydopamine (6-OHDA) upon gamma-aminobutyric acid (GABA) and noradrenergic neurotransmission in the developing rat brain. After 6-OHDA administration tyrosine hydroxylase (TH) immunolabelling revealed more than 70% loss of catecholaminergic terminals in cortex. Glutamic acid decarboxylase (GAD) immunolabelling showed that the intensity of staining and the density of labelled terminals were decreased by approximately 50% in the prefrontal cortex of 6-OHDA treated animals, but in visual and somatosensory zones there was no difference between lesioned and control cortex. The open field test revealed an altered development of the searching activity after neonatal 6-OHDA injections. A significant difference was found between 6-OHDA treated and control rats in searching, orienting and skills performance. Our results indicate that the behavioral changes observed in young rats after 6-OHDA treatment may be reflections not only of reduced catecholaminergic transmission but also of GABAergic disturbance, occurring in the frontal cortex.

  13. Diet, age, and prior injury status differentially alter behavioral outcomes following concussion in rats.

    PubMed

    Mychasiuk, Richelle; Hehar, Harleen; van Waes, Linda; Esser, Michael J

    2015-01-01

    Mild traumatic brain injury (mTBI) or concussion affects a large portion of the population and although many of these individuals recover completely, a small subset of people experience lingering symptomology and poor outcomes. Little is known about the factors that affect individual susceptibility or resilience to poor outcomes after mTBI and there are currently no biomarkers to delineate mTBI diagnosis or prognosis. Based upon the growing literature associated with caloric intake and altered neurological aging and the ambiguous link between repetitive mTBI and progressive neurodegeneration, the current study was designed to examine the effect of a high fat diet (HFD), developmental age, and repetitive mTBI on behavioral outcomes following a mTBI. In addition, telomere length was examined before and after experimental mTBI. Sprague Dawley rats were maintained on a HFD or standard rat chow throughout life (including the prenatal period) and then experienced an mTBI/concussion at P30, P30 and P60, or only at P60. Behavioral outcomes were examined using a test battery that was administered between P61-P80 and included; beam-walking, open field, elevated plus maze, novel context mismatch, Morris water task, and forced swim task. Animals with a P30 mTBI often demonstrated lingering symptomology that was still present during testing at P80. Injuries at P30 and P60 rarely produced cumulative effects, and in some tests (i.e., beam walking), the first injury may have protected the brain from the second injury. Exposure to the high fat diet exacerbated many of the behavioral deficits associated with concussion. Finally, telomere length was shortened following mTBI and was influenced by the animal's dietary intake. Diet, age at the time of injury, and the number of prior concussion incidents differentially contribute to behavioral deficits and may help explain individual variations in susceptibility and resilience to poor outcomes following an mTBI.

  14. Metabolic and feeding behavior alterations provoked by prenatal exposure to aspartame.

    PubMed

    von Poser Toigo, E; Huffell, A P; Mota, C S; Bertolini, D; Pettenuzzo, L F; Dalmaz, C

    2015-04-01

    The use of artificial sweeteners has increased together with the epidemic growth of obesity. In addition to their widespread use in sodas, artificial sweeteners are added to nearly 6000 other products sold in the US, including baby foods, frozen dinners and even yogurts. It has been suggested that the use of nonnutritive sweeteners can lead to body weight gain and an altered metabolic profile. However, very few studies have evaluated the effects of maternal consumption of artificial non-caloric sweeteners on body weight, feeding behavior or the metabolism of offspring in adult life. In this study, we found that animals exposed to aspartame during the prenatal period presented a higher consumption of sweet foods during adulthood and a greater susceptibility to alterations in metabolic parameters, such as increased glucose, LDL and triglycerides. These effects were observed in both males and females, although they were more pronounced in males. Despite the preliminary nature of this study, and the need for further confirmation of these effects, our data suggest that the consumption of sweeteners during gestation may have deleterious long-term effects and should be used with caution.

  15. Human papillomavirus causes an angiogenic switch in keratinocytes which is sufficient to alter endothelial cell behavior

    SciTech Connect

    Chen, W.; Li, F.; Mead, L.; White, H.; Walker, J.; Ingram, D.A.; Roman, A.

    2007-10-10

    One of the requirements for tumor growth is the ability to recruit a blood supply, a process known as angiogenesis. Angiogenesis begins early in the progression of cervical disease from mild to severe dysplasia and on to invasive cancer. We have previously reported that expression of human papillomavirus type 16 E6 and E7 (HPV16 E6E7) proteins in primary foreskin keratinocytes (HFKs) decreases expression of two inhibitors and increases expression of two angiogenic inducers [Toussaint-Smith, E., Donner, D.B., Roman, A., 2004. Expression of human papillomavirus type 16 E6 and E7 oncoproteins in primary foreskin keratinocytes is sufficient to alter the expression of angiogenic factors. Oncogene 23, 2988-2995]. Here we report that HPV-induced early changes in the keratinocyte phenotype are sufficient to alter endothelial cell behavior both in vitro and in vivo. Conditioned media from HPV16 E6E7 expressing HFKs as well as from human cervical keratinocytes containing the intact HPV16 were able to stimulate proliferation and migration of human microvascular endothelial cells. In addition, introduction of the conditioned media into immunocompetent mice using a Matrigel plug model resulted in a clear angiogenic response. These novel data support the hypothesis that HPV proteins contribute not only to the uncontrolled keratinocyte growth seen following HPV infection but also to the angiogenic response needed for tumor formation.

  16. Brain–Computer Interface Training after Stroke Affects Patterns of Brain–Behavior Relationships in Corticospinal Motor Fibers

    PubMed Central

    Young, Brittany M.; Stamm, Julie M.; Song, Jie; Remsik, Alexander B.; Nair, Veena A.; Tyler, Mitchell E.; Edwards, Dorothy F.; Caldera, Kristin; Sattin, Justin A.; Williams, Justin C.; Prabhakaran, Vivek

    2016-01-01

    Background: Brain–computer interface (BCI) devices are being investigated for their application in stroke rehabilitation, but little is known about how structural changes in the motor system relate to behavioral measures with the use of these systems. Objective: This study examined relationships among diffusion tensor imaging (DTI)-derived metrics and with behavioral changes in stroke patients with and without BCI training. Methods: Stroke patients (n = 19) with upper extremity motor impairment were assessed using Stroke Impact Scale (SIS), Action Research Arm Test (ARAT), Nine-Hole Peg Test (9-HPT), and DTI scans. Ten subjects completed four assessments over a control period during which no training was administered. Seventeen subjects, including eight who completed the control period, completed four assessments over an experimental period during which subjects received interventional BCI training. Fractional anisotropy (FA) values were extracted from each corticospinal tract (CST) and transcallosal motor fibers for each scan. Results: No significant group by time interactions were identified at the group level in DTI or behavioral measures. During the control period, increases in contralesional CST FA and in asymmetric FA (aFA) correlated with poorer scores on SIS and 9-HPT. During the experimental period (with BCI training), increases in contralesional CST FA were correlated with improvements in 9-HPT while increases in aFA correlated with improvements in ARAT but with worsening 9-HPT performance; changes in transcallosal motor fibers positively correlated with those in the contralesional CST. All correlations p < 0.05 corrected. Conclusion: These findings suggest that the integrity of the contralesional CST may be used to track individual behavioral changes observed with BCI training after stroke. PMID:27695404

  17. Brain-Computer Interface Training after Stroke Affects Patterns of Brain-Behavior Relationships in Corticospinal Motor Fibers.

    PubMed

    Young, Brittany M; Stamm, Julie M; Song, Jie; Remsik, Alexander B; Nair, Veena A; Tyler, Mitchell E; Edwards, Dorothy F; Caldera, Kristin; Sattin, Justin A; Williams, Justin C; Prabhakaran, Vivek

    2016-01-01

    Background: Brain-computer interface (BCI) devices are being investigated for their application in stroke rehabilitation, but little is known about how structural changes in the motor system relate to behavioral measures with the use of these systems. Objective: This study examined relationships among diffusion tensor imaging (DTI)-derived metrics and with behavioral changes in stroke patients with and without BCI training. Methods: Stroke patients (n = 19) with upper extremity motor impairment were assessed using Stroke Impact Scale (SIS), Action Research Arm Test (ARAT), Nine-Hole Peg Test (9-HPT), and DTI scans. Ten subjects completed four assessments over a control period during which no training was administered. Seventeen subjects, including eight who completed the control period, completed four assessments over an experimental period during which subjects received interventional BCI training. Fractional anisotropy (FA) values were extracted from each corticospinal tract (CST) and transcallosal motor fibers for each scan. Results: No significant group by time interactions were identified at the group level in DTI or behavioral measures. During the control period, increases in contralesional CST FA and in asymmetric FA (aFA) correlated with poorer scores on SIS and 9-HPT. During the experimental period (with BCI training), increases in contralesional CST FA were correlated with improvements in 9-HPT while increases in aFA correlated with improvements in ARAT but with worsening 9-HPT performance; changes in transcallosal motor fibers positively correlated with those in the contralesional CST. All correlations p < 0.05 corrected. Conclusion: These findings suggest that the integrity of the contralesional CST may be used to track individual behavioral changes observed with BCI training after stroke.

  18. Prediction of Later Cognitive Behavior from Early School Perceptual-Motor, Perceptual, and Cognitive Performances.

    ERIC Educational Resources Information Center

    Belka, David E.; Williams, Harriet G.

    1979-01-01

    The battery of perceptual and perceptual-motor tests (including one fine and two gross perceptual-motor tasks, and one visual and two auditory perceptual tasks) were useful for prediction of cognitive performance one year later at kindergarten age. However, cognitive achievement in first grade, and even more so in second grade, was best predicted…

  19. GABAergic modulation with classical benzodiazepines prevent stress-induced neuro-immune dysregulation and behavioral alterations

    PubMed Central

    Ramirez, Karol; Niraula, Anzela; Sheridan, John F.

    2015-01-01

    Objective Psychosocial stress is associated with altered immunity, anxiety, and depression. Repeated social defeat (RSD), a model of social stress, triggers egress of inflammatory myeloid progenitor cells (MPCs; CD11b+ /Ly6Chi) that traffic to the brain, promoting anxiety-like behavior. In parallel, RSD enhances neuroinflammatory signaling and long-lasting social avoidant behavior. Lorazepam and clonazepam are routinely prescribed anxiolytics that act by enhancing GABAergic activity in the brain. Besides binding to the central benzodiazepine binding site (CBBS) in the central nervous system (CNS), lorazepam binds to the translocator protein (TSPO) with high affinity causing immunomodulation. Clonazepam targets the CBBS and has low affinity for the TSPO. Here the aims were to determine if lorazepam and clonazepam would: 1) prevent stress-induced peripheral and central inflammatory responses, and 2) block anxiety and social avoidance behavior in mice subjected to RSD. Methods C57/BL6 mice were divided into experimental groups, and treated with either lorazepam (0.10mg/kg), clonazepam (0.25 mg/kg) or vehicle (0.9%NaCl). Behavioral data and tissues were collected the morning after the last cycle of RSD. Results Lorazepam and clonazepam were effective in attenuating mRNA expression of CRH in the hypothalamus and corticosterone in plasma in mice subjected to RSD. Both drugs blocked stress-induced levels of IL-6 in plasma. Lorazepam and clonazepam had different effects on stress-induced enhancement of myelopoiesis and inhibited trafficking of monocytes and granulocytes in circulation. Furthermore, lorazepam, but not clonazepam, inhibited splenomegaly and the production of pro-inflammatory cytokines in the spleen following RSD. Additionally, lorazepam and clonazepam, blocked stress-induced accumulation of macrophages (CD11b+/CD45high) in the CNS. In a similar manner, both lorazepam and clonazepam prevented neuroinflammatory signaling and reversed anxiety-like and

  20. Repeated corticosterone injections in adult mice alter stress hormonal receptor expression in the cerebellum and motor coordination without affecting spatial learning.

    PubMed

    Harlé, Guillaume; Lalonde, Robert; Fonte, Coralie; Ropars, Armelle; Frippiat, Jean-Pol; Strazielle, Catherine

    2017-03-02

    Receptors for glucocorticoid (GR) and corticotropin-releasing hormone (CRH) are largely found in brain sensorimotor structures, particularly in cerebellum, underlining a potential role of stress hormones in the regulation of motor function. Since CRH is involved in neuroplasticity, known for its trophic effect on synapses, we investigated how manipulations in corticosterone serum levels can modulate the CRH system in the cerebellum and affect motor coordination. Corticosterone at doses of either 15 or 30mg/kg was injected in mice and the status of hormonal expression evaluated in cerebellum, hippocampus, and hypothalamus in undisturbed housing conditions or after different behavioral tests. Under both conditions, metabolic activity in numerous brain regions involved in motor functions and emotion was measured by means of cytochrome oxidase (COX) activity labeling. After six consecutive days of corticosterone administration, CRH-R1 transcription was downregulated in hypothalamic and cerebellar regions and hypometabolic changes were observed in mice treated with the higher dose for several limbic and sensorimotor circuitries, notably basal ganglia, deep cerebellar nuclei, and red nucleus. Corticosterone did not modify motor activity, anxiety, and spatial orientation, but decreased latencies before falling from the rotorod and prevented mice from reaching targets in the coat-hanger test. In addition, COX activities were similar to control mice except in ventromedial thalamus and dorsal neostriatum, possibly indicating that physical activity protected brain energy metabolism against the stress hormone. The present findings showed that the CRH/CRH-R1 system might play a role in mediating the effects of stress on cerebellar function, affecting especially motor learning tasks.

  1. Behavioral and Neural Plasticity of Ocular Motor Control: Changes in Performance and fMRI Activity Following Antisaccade Training

    PubMed Central

    Jamadar, Sharna D.; Johnson, Beth P.; Clough, Meaghan; Egan, Gary F.; Fielding, Joanne

    2015-01-01

    The antisaccade task provides a model paradigm that sets the inhibition of a reflexively driven behavior against the volitional control of a goal-directed behavior. The stability and adaptability of antisaccade performance was investigated in 23 neurologically healthy individuals. Behavior and brain function were measured using functional magnetic resonance imaging (fMRI) prior to and immediately following 2 weeks of daily antisaccade training. Participants performed antisaccade trials faster with no change in directional error rate following 2 weeks of training; however this increased speed came at the cost of the spatial accuracy of the saccade (gain) which became more hypometric following training. Training on the antisaccade task resulted in increases in fMRI activity in the fronto-basal ganglia-parietal-cerebellar ocular motor network. Following training, antisaccade latency was positively associated with fMRI activity in the frontal and supplementary eye fields, anterior cingulate and intraparietal sulcus; antisaccade gain was negatively associated with fMRI activity in supplementary eye fields, anterior cingulate, intraparietal sulcus, and cerebellar vermis. In sum, the results suggest that following training, larger antisaccade latency is associated with larger activity in fronto-parietal-cerebellar ocular motor regions, and smaller antisaccade gain is associated with larger activity in fronto-parietal ocular motor regions. PMID:26733841

  2. PFOS Induces Behavioral Alterations, Including Spontaneous Hyperactivity That Is Corrected by Dexamfetamine in Zebrafish Larvae

    PubMed Central

    Spulber, Stefan; Kilian, Pascal; Wan Ibrahim, Wan Norhamidah; Onishchenko, Natalia; Ulhaq, Mazhar; Norrgren, Leif; Negri, Sara; Di Tuccio, Marcello; Ceccatelli, Sandra

    2014-01-01

    Perfluorooctane sulfonate (PFOS) is a widely spread environmental contaminant. It accumulates in the brain and has potential neurotoxic effects. The exposure to PFOS has been associated with higher impulsivity and increased ADHD prevalence. We investigated the effects of developmental exposure to PFOS in zebrafish larvae, focusing on the modulation of activity by the dopaminergic system. We exposed zebrafish embryos to 0.1 or 1 mg/L PFOS (0.186 or 1.858 µM, respectively) and assessed swimming activity at 6 dpf. We analyzed the structure of spontaneous activity, the hyperactivity and the habituation during a brief dark period (visual motor response), and the vibrational startle response. The findings in zebrafish larvae were compared with historical data from 3 months old male mice exposed to 0.3 or 3 mg/kg/day PFOS throughout gestation. Finally, we investigated the effects of dexamfetamine on the alterations in spontaneous activity and startle response in zebrafish larvae. We found that zebrafish larvae exposed to 0.1 mg/L PFOS habituate faster than controls during a dark pulse, while the larvae exposed to 1 mg/L PFOS display a disorganized pattern of spontaneous activity and persistent hyperactivity. Similarly, mice exposed to 0.3 mg/kg/day PFOS habituated faster than controls to a new environment, while mice exposed to 3 mg/kg/day PFOS displayed more intense and disorganized spontaneous activity. Dexamfetamine partly corrected the hyperactive phenotype in zebrafish larvae. In conclusion, developmental exposure to PFOS in zebrafish induces spontaneous hyperactivity mediated by a dopaminergic deficit, which can be partially reversed by dexamfetamine in zebrafish larvae. PMID:24740186

  3. Moderate injury in motor-sensory cortex causes behavioral deficits accompanied by electrophysiological changes in mice adulthood.

    PubMed

    Ouyang, Wei; Yan, Qichao; Zhang, Yu; Fan, Zhiheng

    2017-01-01

    Moderate traumatic brain injury (TBI) in children often happen when there's a sudden blow to the frontal bone, end with long unconscious which can last for hours and progressive cognitive deficits. However, with regard to the influences of moderate TBI during children adulthood, injury-induced alterations of locomotive ability, long-term memory performance, and hippocampal electrophysiological firing changes have not yet been fully identified. In this study, lateral fluid percussion (LFP) method was used to fabricate moderate TBI in motor and somatosensory cortex of the 6-weeks-old mice. The motor function, learning and memory function, extracellular CA1 neural spikes were assessed during acute and subacute phase. Moreover, histopathology was performed on day post injury (DPI) 16 to evaluate the effect of TBI on tissue and cell morphological changes in cortical and hippocampal CA1 subregions. After moderate LFP injury, the 6-weeks-old mice showed severe motor deficits at the early stage in acute phase but gradually recovered later during adulthood. At the time points in acute and subacute phase after TBI, novel object recognition (NOR) ability and spatial memory functions were consistently impaired in TBI mice; hippocampal firing frequency and burst probability were hampered. Analysis of the altered burst firing shows a clear hippocampal theta rhythm drop. These electrophysiological impacts were associated with substantially lowered NOR preference as compared to the sham group during adulthood. These results suggest that moderate TBI introduced at motorsenory cortex in 6-weeks-old mice causes obvious motor and cognitive deficits during their adulthood. While the locomotive ability progressively recovers, the cognitive deficits persisted while the mice mature as adult mice. The cognitive deficits may be attributed to the general suppressing of whole neural network, which could be labeled by marked reduction of excitability in hippocampal CA1 subregion.

  4. Moderate injury in motor-sensory cortex causes behavioral deficits accompanied by electrophysiological changes in mice adulthood

    PubMed Central

    Yan, Qichao; Zhang, Yu; Fan, Zhiheng

    2017-01-01

    Moderate traumatic brain injury (TBI) in children often happen when there’s a sudden blow to the frontal bone, end with long unconscious which can last for hours and progressive cognitive deficits. However, with regard to the influences of moderate TBI during children adulthood, injury-induced alterations of locomotive ability, long-term memory performance, and hippocampal electrophysiological firing changes have not yet been fully identified. In this study, lateral fluid percussion (LFP) method was used to fabricate moderate TBI in motor and somatosensory cortex of the 6-weeks-old mice. The motor function, learning and memory function, extracellular CA1 neural spikes were assessed during acute and subacute phase. Moreover, histopathology was performed on day post injury (DPI) 16 to evaluate the effect of TBI on tissue and cell morphological changes in cortical and hippocampal CA1 subregions. After moderate LFP injury, the 6-weeks-old mice showed severe motor deficits at the early stage in acute phase but gradually recovered later during adulthood. At the time points in acute and subacute phase after TBI, novel object recognition (NOR) ability and spatial memory functions were consistently impaired in TBI mice; hippocampal firing frequency and burst probability were hampered. Analysis of the altered burst firing shows a clear hippocampal theta rhythm drop. These electrophysiological impacts were associated with substantially lowered NOR preference as compared to the sham group during adulthood. These results suggest that moderate TBI introduced at motorsenory cortex in 6-weeks-old mice causes obvious motor and cognitive deficits during their adulthood. While the locomotive ability progressively recovers, the cognitive deficits persisted while the mice mature as adult mice. The cognitive deficits may be attributed to the general suppressing of whole neural network, which could be labeled by marked reduction of excitability in hippocampal CA1 subregion. PMID

  5. Alterations in cognitive performance and affect-arousal state during fluctuations in motor function in Parkinson's disease.

    PubMed Central

    Brown, R G; Marsden, C D; Quinn, N; Wyke, M A

    1984-01-01

    Sixteen patients with idiopathic Parkinson's disease were selected who were all showing severe fluctuations in motor function ("on-off" phenomenon). Measures of cognitive function and of subjective affect/arousal state were taken on two occasions, once when "on" and once when "off". Twenty-five matched normal controls were also assessed on the same measures. Results revealed, on the average, a drop in cognitive function plus an adverse swing in affect/arousal state, in the patient group in the "off" condition, compared to the levels when "on". Analysis of the data suggested that the main factor associated with cognitive function when "off" was not the severity of disability but the level of affect/arousal. The fluctuations in cognitive function found tended to be mild relative to the severe changes in motor ability, and were present in only a proportion of patients. PMID:6736975

  6. Altered functional Connectivity in Lesional Peduncular Hallucinosis with REM Sleep Behavior Disorder

    PubMed Central

    Geddes, Maiya R.; Tie, Yanmei; Gabrieli, John D. E.; McGinnis, Scott M.; Golby, Alexandra J.; Whitfield-Gabrieli, Susan

    2016-01-01

    Brainstem lesions causing peduncular hallucinosis (PH) produce vivid visual hallucinations occasionally accompanied by sleep disorders. Overlapping brainstem regions modulate visual pathways and REM sleep functions via gating of thalamocortical networks. A 66-year-old man with paroxysmal atrial fibrillation developed abrupt-onset complex visual hallucinations with preserved insight and violent dream enactment behavior. Brain MRI showed restricted diffusion in the left rostrodorsal pons suggestive of an acute ischemic infarct. REM sleep behavior disorder (RBD) was diagnosed on polysomnography. We investigated the integrity of ponto-geniculate-occipital circuits with seed-based resting-state functional connectivity MRI (rs-fcMRI) in this patient compared to 46 controls. Rs-fcMRI revealed significantly reduced functional connectivity between the lesion and lateral geniculate nuclei (LGN), and between LGN and visual association cortex compared to controls. Conversely, functional connectivity between brainstem and visual association cortex, and between visual association cortex and PFC was significantly increased in the patient. Focal damage to the left rostrodorsal pons is sufficient to cause RBD and PH in humans, suggesting an overlapping mechanism in both syndromes. This lesion produced a pattern of altered functional connectivity consistent with disrupted visual cortex connectivity via de-afferentation of thalamocortical pathways. PMID:26656284

  7. Can a tablet device alter undergraduate science students' study behavior and use of technology?

    PubMed

    Morris, Neil P; Ramsay, Luke; Chauhan, Vikesh

    2012-06-01

    This article reports findings from a study investigating undergraduate biological sciences students' use of technology and computer devices for learning and the effect of providing students with a tablet device. A controlled study was conducted to collect quantitative and qualitative data on the impact of a tablet device on students' use of devices and technology for learning. Overall, we found that students made extensive use of the tablet device for learning, using it in preference to laptop computers to retrieve information, record lectures, and access learning resources. In line with other studies, we found that undergraduate students only use familiar Web 2.0 technologies and that the tablet device did not alter this behavior for the majority of tools. We conclude that undergraduate science students can make extensive use of a tablet device to enhance their learning opportunities without institutions changing their teaching methods or computer systems, but that institutional intervention may be needed to drive changes in student behavior toward the use of novel Web 2.0 technologies.

  8. Dynamical and phase behavior of a phospholipid membrane altered by an antimicrobial peptide at low concentration

    DOE PAGES

    Mamontov, Eugene; Tyagi, M.; Qian, Shuo; ...

    2016-05-27

    Here we discuss that the mechanism of action of antimicrobial peptides is traditionally attributed to the formation of pores in the lipid cell membranes of pathogens, which requires a substantial peptide to lipid ratio. However, using incoherent neutron scattering, we show that even at a concentration too low for pore formation, an archetypal antimicrobial peptide, melittin, disrupts the regular phase behavior of the microscopic dynamics in a phospholipid membrane, dimyristoylphosphatidylcholine (DMPC). At the same time, another antimicrobial peptide, alamethicin, does not exert a similar effect on the DMPC microscopic dynamics. The melittin-altered lateral motion of DMPC at physiological temperature nomore » longer resembles the fluid-phase behavior characteristic of functional membranes of the living cells. The disruptive effect demonstrated by melittin even at low concentrations reveals a new mechanism of antimicrobial action relevant in more realistic scenarios, when peptide concentration is not as high as would be required for pore formation, which may facilitate treatment with antimicrobial peptides.« less

  9. Adolescent binge ethanol treatment alters adult brain regional volumes, cortical extracellular matrix protein and behavioral flexibility.

    PubMed

    Coleman, Leon Garland; Liu, Wen; Oguz, Ipek; Styner, Martin; Crews, Fulton T

    2014-01-01

    Adolescents binge drink more than any other age group, increasing risk of disrupting the development of the frontal cortex. We hypothesized that adolescent binge drinking would lead to persistent alterations in adulthood. In this study, we modeled adolescent weekend underage binge-drinking, using adolescent mice (post-natal days [P] 28-37). The adolescent intermittent binge ethanol (AIE) treatment includes 6 binge intragastric doses of ethanol in an intermittent pattern across adolescence. Assessments were conducted in adulthood following extended abstinence to determine if there were persistent changes in adults. Reversal learning, open field and other behavioral assessments as well as brain structure using magnetic imaging and immunohistochemistry were determined. We found that AIE did not impact adult Barnes Maze learning. However, AIE did cause reversal learning deficits in adults. AIE also caused structural changes in the adult brain. AIE was associated with adulthood volume enlargements in specific brain regions without changes in total brain volume. Enlarged regions included the orbitofrontal cortex (OFC, 4%), cerebellum (4.5%), thalamus (2%), internal capsule (10%) and genu of the corpus callosum (7%). The enlarged OFC volume in adults after AIE is consistent with previous imaging studies in human adolescents. AIE treatment was associated with significant increases in the expression of several extracellular matrix (ECM) proteins in the adult OFC including WFA (55%), Brevican (32%), Neurocan (105%), Tenacin-C (25%), and HABP (5%). These findings are consistent with AIE causing persistent changes in brain structure that could contribute to a lack of behavioral flexibility.

  10. Adolescent binge ethanol treatment alters adult brain regional volumes, cortical extracellular matrix protein and behavioral flexibility

    PubMed Central

    Coleman, Leon Garland; Liu, Wen; Oguz, Ipek; Styner, Martin; Crews, Fulton T.

    2014-01-01

    Adolescents binge drink more than any other age group, increasing risk of disrupting the development of the frontal cortex. We hypothesized that adolescent binge drinking would lead to persistent alterations in adulthood. In this study, we modeled adolescent weekend underage binge-drinking, using adolescent mice (post-natal days [P] 28–37). The adolescent intermittent binge ethanol (AIE) treatment includes 6 binge intragastric doses of ethanol in an intermittent pattern across adolescence. Assessments were conducted in adulthood following extended abstinence to determine if there were persistent changes in adults. Reversal learning, open field and other behavioral assessments as well as brain structure using magnetic imaging and immunohistochemistry were determined. We found AIE did not impact adult Barnes Maze learning. However, AIE did cause reversal learning deficits in adults. AIE also caused structural changes in the adult brain. AIE was associated with adulthood volume enlargements in specific brain regions without changes in total brain volume. Enlarged regions included the orbitofrontal cortex (OFC, 4%), cerebellum (4.5%), thalamus (2%), internal capsule (10%) and genu of the corpus callosum (7%). The enlarged OFC volume in adults after AIE is consistent with previous imaging studies in human adolescents. AIE treatment was associated with significant increases in the expression of several extracellular matrix (ECM) proteins in the adult OFC including WFA (55%), Brevican (32%), Neurocan (105%), Tenacin-C (25%), and HABP (5%). These findings are consistent with AIE causing persistent changes in brain structure that could contribute to a lack of behavioral flexibility. PMID:24275185

  11. Group III/IV locomotor muscle afferents alter motor cortical and corticospinal excitability and promote central fatigue during cycling exercise

    PubMed Central

    Sidhu, Simranjit K.; Weavil, Joshua C.; Mangum, Tyler S.; Jessop, Jacob E.; Richardson, Russell S.; Morgan, David E.; Amann, Markus

    2017-01-01

    Objective To investigate the influence of group III/IV muscle afferents on the development of central fatigue and corticospinal excitability during exercise. Methods Fourteen males performed cycling-exercise both under control-conditions (CTRL) and with lumbar intrathecal fentanyl (FENT) impairing feedback from leg muscle afferents. Transcranial magnetic- and cervicomedullary stimulation was used to monitor cortical versus spinal excitability. Results While fentanyl-blockade during non-fatiguing cycling had no effect on motor-evoked potentials (MEPs), cervicomedullary-evoked motor potentials (CMEPs) were 13 ± 3% higher (P < 0.05), resulting in a decrease in MEP/CMEP (P < 0.05). Although the pre- to post-exercise reduction in resting twitch was greater in FENT vs. CTRL (−53 ± 3% vs. −39 ± 3%; P < 0.01), the reduction in voluntary muscle activation was smaller (−2 ± 2% vs. −10 ± 2%; P < 0.05). Compared to the start of fatiguing exercise, MEPs and CMEPs were unchanged at exhaustion in CTRL. In contrast, MEPs and MEP/CMEP increased 13 ± 3% and 25 ± 6% in FENT (P < 0.05). Conclusion During non-fatiguing exercise, group III/IV muscle afferents disfacilitate, or inhibit, spinal motoneurons and facilitate motor cortical cells. In contrast, during exhaustive exercise, group III/IV muscle afferents disfacilitate/inhibit the motor cortex and promote central fatigue. Significance Group III/IV muscle afferents influence corticospinal excitability and central fatigue during whole-body exercise in humans. PMID:27866119

  12. Relationship between early motor milestones and severity of restricted and repetitive behaviors in children and adolescents with autism spectrum disorder.

    PubMed

    Uljarević, Mirko; Hedley, Darren; Alvares, Gail A; Varcin, Kandice J; Whitehouse, Andrew J O

    2017-03-16

    This study explored the relationships between the later age of achievement of early motor milestones, current motor atypicalities (toe walking), and the severity of restricted and repetitive behaviors (RRBs) in individuals with autism spectrum disorder (ASD). Parents of 147 children and adolescents with ASD (Mage  = 8.09 years, SD = 4.28; 119 males) completed an early developmental milestones questionnaire and the Social Responsiveness Scale as a measure of Insistence on Sameness (IS) and Repetitive Mannerisms (RM). Two hierarchical regression analyses were conducted to test whether RM and IS behaviors were predicted by early motor milestones, or current toe walking. The final model predicting RM accounted for 15% of the variance (F = 3.02, p = .009), with toe walking as a unique and independent predictor of RM scores (t = 3.568, p = .001). The final model predicting IS accounted for 19.1% of variance in IS scores (F = 4.045, p = .001), with chronological age (CA) (t = 2.92, p = .004), age when first standing (t = 2.09, p = .038), and toe walking (t = 2.53, p = .013) as unique independent predictors. Toe walking (t = 2.4, p = .018) and age when first sitting (t = 2.08, p = .04) predicted the severity of RRBs on the Autism Diagnostic Observation Schedule (F = 2.334, p = .036). Our study replicates previous findings on the relationship between concurrent motor impairments and RRBs, and provides the first evidence for the association between RRBs and age of attainment of early motor milestones. Autism Res 2017. © 2017 International Society for Autism Research, Wiley Periodicals, Inc.

  13. The anaesthetic combination of ketamine/midazolam does not alter the acquisition of spatial and motor tasks in adult mice.

    PubMed

    Valentim, A M; Olsson, I A S; Antunes, L M

    2013-01-01

    The ketamine/midazolam association of a dissociative with a sedative agent is used for the induction and maintenance of anaesthesia in laboratory animals. Anaesthesia may interfere with research results through side-effects on the nervous system, such as memory impairment. It is known that ketamine and midazolam affect cognition; however, their effects have not been clarified when used in a context of balanced anaesthesia. Thus, this study evaluated the effects of ketamine/midazolam on the acquisition of motor and of a spatial memory task in adult mice. Twenty-eight C57BL/6 adult male mice were divided into three groups: untreated control, treated with ketamine/midazolam (75 mg/kg / 10 mg/kg) and treated with midazolam (10 mg/kg) groups. Respiratory rate, heart rate and systolic pressure were measured every 5 min in the animals treated with ketamine/midazolam, as this was the only group that exhibited loss of the righting reflex. One day after treatment, animals were tested in the open field, rotarod and radial arm maze. There were no differences between treatments regarding open-field activity, rotarod performance or number of working and reference memory errors in the radial arm maze task. In conclusion, the learning process of spatial and motor tasks was not disrupted by the anaesthetic combination of ketamine/midazolam. These results suggest its safe use in adult mice in projects where acquisition of a spatial and motor task is necessary.

  14. Rapid Amygdala Kindling Causes Motor Seizure and Comorbidity of Anxiety- and Depression-Like Behaviors in Rats

    PubMed Central

    Chen, Shang-Der; Wang, Yu-Lin; Liang, Sheng-Fu; Shaw, Fu-Zen

    2016-01-01

    Amygdala kindling is a model of temporal lobe epilepsy (TLE) with convulsion. The rapid amygdala kindling has an advantage on quick development of motor seizures and for antiepileptic drugs screening. The rapid amygdala kindling causes epileptogenesis accompanied by an anxiolytic response in early isolation of rat pups or depressive behavior in immature rats. However, the effect of rapid amygdala kindling on comorbidity of anxiety- and depression-like behaviors is unexplored in adult rats with normal breeding. In the present study, 40 amygdala stimulations given within 2 days were applied in adult Wistar rats. Afterdischarge (AD) and seizure stage were recorded throughout the amygdala kindling. Anxiety-like behaviors were evaluated by the elevated plus maze (EPM) test and open field (OF) test, whereas depression-like behaviors were assessed by the forced swim (FS) and sucrose consumption (SC) tests. A tonic-clonic convulsion was provoked in the kindle group. Rapid amygdala kindling resulted in a significantly lower frequency entering an open area of either open arms of the EPM or the central zone of an OF, lower sucrose intake, and longer immobility of the FS test in the kindle group. Our results suggest that rapid amygdala kindling elicited severe motor seizures comorbid with anxiety- and depression-like behaviors. PMID:27445726

  15. The effects of chronic intracortical microstimulation on neural tissue and fine motor behavior

    NASA Astrophysics Data System (ADS)

    Rajan, Alexander T.; Boback, Jessica L.; Dammann, John F.; Tenore, Francesco V.; Wester, Brock A.; Otto, Kevin J.; Gaunt, Robert A.; Bensmaia, Sliman J.

    2015-12-01

    Objective. One approach to conveying sensory feedback in neuroprostheses is to electrically stimulate sensory neurons in the cortex. For this approach to be viable, it is critical that intracortical microstimulation (ICMS) causes minimal damage to the brain. Here, we investigate the effects of chronic ICMS on the neuronal tissue across a variety of stimulation regimes in non-human primates. We also examine each animal’s ability to use their hand—the cortical representation of which is targeted by the ICMS—as a further assay of possible neuronal damage. Approach. We implanted electrode arrays in the primary somatosensory cortex of three Rhesus macaques and delivered ICMS four hours per day, five days per week, for six months. Multiple regimes of ICMS were delivered to investigate the effects of stimulation parameters on the tissue and behavior. Parameters included current amplitude (10-100 μA), pulse train duration (1, 5 s), and duty cycle (1/1, 1/3). We then performed a range of histopathological assays on tissue near the tips of both stimulated and unstimulated electrodes to assess the effects of chronic ICMS on the tissue and their dependence on stimulation parameters. Main results. While the implantation and residence of the arrays in the cortical tissue did cause significant damage, chronic ICMS had no detectable additional effect; furthermore, the animals exhibited no impairments in fine motor control. Significance. Chronic ICMS may be a viable means to convey sensory feedback in neuroprostheses as it does not cause significant damage to the stimulated tissue.

  16. Sensory gating of an embryonic zebrafish interneuron during spontaneous motor behaviors.

    PubMed

    Knogler, Laura D; Drapeau, Pierre

    2014-01-01

    In all but the simplest monosynaptic reflex arcs, sensory stimuli are encoded by sensory neurons that transmit a signal via sensory interneurons to downstream partners in order to elicit a response. In the embryonic zebrafish (Danio rerio), cutaneous Rohon-Beard (RB) sensory neurons fire in response to mechanical stimuli and excite downstream glutamatergic commissural primary ascending (CoPA) interneurons to produce a flexion response contralateral to the site of stimulus. In the absence of sensory stimuli, zebrafish spinal locomotor circuits are spontaneously active during development due to pacemaker activity resulting in repetitive coiling of the trunk. Self-generated movement must therefore be distinguishable from external stimuli in order to ensure the appropriate activation of touch reflexes. Here, we recorded from CoPAs during spontaneous and evoked fictive motor behaviors in order to examine how responses to self-movement are gated in sensory interneurons. During spontaneous coiling, CoPAs received glycinergic inputs coincident with contralateral flexions that shunted firing for the duration of the coiling event. Shunting inactivation of CoPAs was caused by a slowly deactivating chloride conductance that resulted in lowered membrane resistance and increased action potential threshold. During spontaneous burst swimming, which develops later, CoPAs received glycinergic inputs that arrived in phase with excitation to ipsilateral motoneurons and provided persistent shunting. During a touch stimulus, short latency glutamatergic inputs produced cationic currents through AMPA receptors that drove a single, large amplitude action potential in the CoPA before shunting inhibition began, providing a brief window for the activation of downstream neurons. We compared the properties of CoPAs to those of other spinal neurons and propose that glycinergic signaling onto CoPAs acts as a corollary discharge signal for reflex inhibition during movement.

  17. Protective effect of montelukast against quinolinic acid/malonic acid induced neurotoxicity: possible behavioral, biochemical, mitochondrial and tumor necrosis factor-α level alterations in rats.

    PubMed

    Kalonia, H; Kumar, P; Kumar, A; Nehru, B

    2010-11-24

    The present study has been designed to explore the protective effect of montelukast (leukotriene receptor antagonist) against intrastriatal quinolinic acid (QA; 300 nmol) and malonic acid (MA; 6 μmol) induced Huntington's like symptoms in rats. Quinolinic acid has been reported to induce excitotoxicity by stimulating the N-methyl-D-aspartate receptor, causing calcium overload which in turn leads to the neurodegeneration. On the other hand, MA, being a reversible inhibitor of mitochondrial enzyme complex-II, leads to energy crisis and free radical generation. Recent studies have reported the therapeutic potential of leukotriene receptor antagonists in different neurodegenerative disorders. However, their exact role is yet to be established. The present study accordingly, is an attempt to investigate the effect of montelukast against QA and MA induced behavioral, biochemical and molecular alterations in rat striatum. Oxidative stress, mitochondrial enzyme complex and tumor necrosis factor-alpha (TNF-α) were evaluated on day 21st and 14th post intrastriatal QA and MA treatment, respectively. Findings of the present study demonstrate significant alteration in the locomotor activity and motor coordination as well as oxidative burden (increased lipid peroxidation, nitrite concentration and decreased endogenous antioxidants), mitochondrial enzyme complex (I, II and IV) activities and TNF-α level, in both intrastriatal QA and MA treated animals. Further, montelukast (0.4, 0.8 mg/kg p.o.) treatment for 21 and 14 days respectively, attenuated the behavioral alterations, oxidative stress, mitochondrial dysfunction and TNF-α level in these models of Huntington's disease in a significant manner. In conclusion, the present study emphasizes the neuroprotective potential of montelukast in the therapeutic management of Huntington like symptoms.

  18. Dynamic microglial alterations underlie stress-induced depressive-like behavior and suppressed neurogenesis.

    PubMed

    Kreisel, T; Frank, M G; Licht, T; Reshef, R; Ben-Menachem-Zidon, O; Baratta, M V; Maier, S F; Yirmiya, R

    2014-06-01

    The limited success in understanding the pathophysiology of major depression may result from excessive focus on the dysfunctioning of neurons, as compared with other types of brain cells. Therefore, we examined the role of dynamic alterations in microglia activation status in the development of chronic unpredictable stress (CUS)-induced depressive-like condition in rodents. We report that following an initial period (2-3 days) of stress-induced microglial proliferation and activation, some microglia underwent apoptosis, leading to reductions in their numbers within the hippocampus, but not in other brain regions, following 5 weeks of CUS exposure. At that time, microglia displayed reduced expression of activation markers as well as dystrophic morphology. Blockade of the initial stress-induced microglial activation by minocycline or by transgenic interleukin-1 receptor antagonist overexpression rescued the subsequent microglial apoptosis and decline, as well as the CUS-induced depressive-like behavior and suppressed neurogenesis. Similarly, the antidepressant drug imipramine blocked the initial stress-induced microglial activation as well as the CUS-induced microglial decline and depressive-like behavior. Treatment of CUS-exposed mice with either endotoxin, macrophage colony-stimulating factor or granulocyte-macrophage colony-stimulating factor, all of which stimulated hippocampal microglial proliferation, partially or completely reversed the depressive-like behavior and dramatically increased hippocampal neurogenesis, whereas treatment with imipramine or minocycline had minimal or no anti-depressive effects, respectively, in these mice. These findings provide direct causal evidence that disturbances in microglial functioning has an etiological role in chronic stress-induced depression, suggesting that microglia stimulators could serve as fast-acting anti-depressants in some forms of depressive and stress-related conditions.

  19. How does environmental enrichment reduce repetitive motor behaviors? Neuronal activation and dendritic morphology in the indirect basal ganglia pathway of a mouse model.

    PubMed

    Bechard, Allison R; Cacodcar, Nadia; King, Michael A; Lewis, Mark H

    2016-02-15

    Repetitive motor behaviors are observed in many neurodevelopmental and neurological disorders (e.g., autism spectrum disorders, Tourette syndrome, fronto-temporal dementia). Despite their clinical importance, the neurobiology underlying these highly stereotyped, apparently functionless behaviors is poorly understood. Identification of mechanisms that mediate the development of repetitive behaviors will aid in the discovery of new therapeutic targets and treatment development. Using a deer mouse model, we have shown that decreased indirect basal ganglia pathway activity is associated with high levels of repetitive behavior. Environmental enrichment (EE) markedly attenuates the development of such aberrant behaviors in mice, although mechanisms driving this effect are unknown. We hypothesized that EE would reduce repetitive motor behaviors by increasing indirect basal ganglia pathway function. We assessed neuronal activation and dendritic spine density in basal ganglia of adult deer mice reared in EE and standard housing. Significant increases in neuronal activation and dendritic spine densities were observed only in the subthalamic nucleus (STN) and globus pallidus (GP), and only for those mice that exhibited an EE-induced decrease in repetitive motor behavior. As the STN and GP lie within the indirect pathway, these data suggest that EE-induced attenuation of repetitive motor behaviors is associated with increased functional activation of the indirect basal ganglia pathway. These results are consistent with our other findings highlighting the importance of the indirect pathway in mediating repetitive motor behaviors.

  20. How does environmental enrichment reduce repetitive motor behaviors? Neuronal activation and dendritic morphology in the indirect basal ganglia pathway of a mouse model

    PubMed Central

    Bechard, Allison R.; Cacodcar, Nadia; King, Michael A.; Lewis, Mark H.

    2015-01-01

    Repetitive motor behaviors are observed in many neurodevelopmental and neurological disorders (e.g. autism spectrum disorders, Tourette syndrome, fronto-temporal dementia). Despite their clinical importance, the neurobiology underlying these highly stereotyped, apparently functionless behaviors is poorly understood. Identification of mechanisms that mediate the development of repetitive behaviors will aid in the discovery of new therapeutic targets and treatment development. Using a deer mouse model, we have shown that decreased indirect basal ganglia pathway activity is associated with high levels of repetitive behavior. Environmental enrichment (EE) markedly attenuates the development of such aberrant behaviors in mice, although mechanisms driving this effect are unknown. We hypothesized that EE would reduce repetitive motor behaviors by increasing indirect basal ganglia pathway function. We assessed neuronal activation and dendritic spine density in basal ganglia of adult deer mice reared in EE and standard housing. Significant increases in neuronal activation and dendritic spine densities were observed only in the subthalamic nucleus (STN) and globus pallidus (GP), and only for those mice that exhibited an EE-induced decrease in repetitive motor behavior. As the STN and GP lie within the indirect pathway, these data suggest that EE-induced attenuation of repetitive motor behaviors is associated with increased functional activation of the indirect basal ganglia pathway. These results are consistent with our other findings highlighting the importance of the indirect pathway in mediating repetitive motor behaviors. PMID:26620495

  1. A Temporal Predictive Code for Voice Motor Control: Evidence from ERP and Behavioral Responses to Pitch-shifted Auditory Feedback

    PubMed Central

    Behroozmand, Roozbeh; Sangtian, Stacey; Korzyukov, Oleg; Larson, Charles R.

    2016-01-01

    The predictive coding model suggests that voice motor control is regulated by a process in which the mismatch (error) between feedforward predictions and sensory feedback is detected and used to correct vocal motor behavior. In this study, we investigated how predictions about timing of pitch perturbations in voice auditory feedback would modulate ERP and behavioral responses during vocal production. We designed six counterbalanced blocks in which a +100 cents pitch-shift stimulus perturbed voice auditory feedback during vowel sound vocalizations. In three blocks, there was a fixed delay (500, 750 or 1000 ms) between voice and pitch-shift stimulus onset (predictable), whereas in the other three blocks, stimulus onset delay was randomized between 500, 750 and 1000 ms (unpredictable). We found that subjects produced compensatory (opposing) vocal responses that started at 80 ms after the onset of the unpredictable stimuli. However, for predictable stimuli, subjects initiated vocal responses at 20 ms before and followed the direction of pitch shifts in voice feedback. Analysis of ERPs showed that the amplitudes of the N1 and P2 components were significantly reduced in response to predictable compared with unpredictable stimuli. These findings indicate that predictions about temporal features of sensory feedback can modulate vocal motor behavior. In the context of the predictive coding model, temporally-predictable stimuli are learned and reinforced by the internal feedforward system, and as indexed by the ERP suppression, the sensory feedback contribution is reduced for their processing. These findings provide new insights into the neural mechanisms of vocal production and motor control. PMID:26835556

  2. A temporal predictive code for voice motor control: Evidence from ERP and behavioral responses to pitch-shifted auditory feedback.

    PubMed

    Behroozmand, Roozbeh; Sangtian, Stacey; Korzyukov, Oleg; Larson, Charles R

    2016-04-01

    The predictive coding model suggests that voice motor control is regulated by a process in which the mismatch (error) between feedforward predictions and sensory feedback is detected and used to correct vocal motor behavior. In this study, we investigated how predictions about timing of pitch perturbations in voice auditory feedback would modulate ERP and behavioral responses during vocal production. We designed six counterbalanced blocks in which a +100 cents pitch-shift stimulus perturbed voice auditory feedback during vowel sound vocalizations. In three blocks, there was a fixed delay (500, 750 or 1000 ms) between voice and pitch-shift stimulus onset (predictable), whereas in the other three blocks, stimulus onset delay was randomized between 500, 750 and 1000 ms (unpredictable). We found that subjects produced compensatory (opposing) vocal responses that started at 80 ms after the onset of the unpredictable stimuli. However, for predictable stimuli, subjects initiated vocal responses at 20 ms before and followed the direction of pitch shifts in voice feedback. Analysis of ERPs showed that the amplitudes of the N1 and P2 components were significantly reduced in response to predictable compared with unpredictable stimuli. These findings indicate that predictions about temporal features of sensory feedback can modulate vocal motor behavior. In the context of the predictive coding model, temporally-predictable stimuli are learned and reinforced by the internal feedforward system, and as indexed by the ERP suppression, the sensory feedback contribution is reduced for their processing. These findings provide new insights into the neural mechanisms of vocal production and motor control.

  3. Environmental prenatal stress eliminates brain and maternal behavioral sex differences and alters hormone levels in female rats.

    PubMed

    Del Cerro, M C R; Ortega, E; Gómez, F; Segovia, S; Pérez-Laso, C

    2015-07-01

    Environmental prenatal stress (EPS) has effects on fetuses that are long-lasting, altering their hormone levels, brain morphology and behavior when they reach maturity. In previous research, we demonstrated that EPS affects the expression of induced maternal behavior (MB), the neuroendocrine system, and morphology of the sexually dimorphic accessory olfactory bulb (AOB) involved in reproductive behavior patterns. The bed nucleus of the accessory olfactory tract (BAOT) is another vomeronasal (VN) structure that plays an inhibitory role in rats in the expression of induced maternal behavior in female and male virgins. In the present study, we have ascertained whether the behavioral, neuroendocrine, and neuromorphological alterations of the AOB found after EPS also appear in the BAOT. After applying EPS to pregnant rats during the late gestational period, in their female offspring at maturity we tested induced maternal behavior, BAOT morphology and plasma levels of testosterone (T), estradiol (E2), progesterone (P), adrenocorticotropic hormone (ACTH) and corticosterone (Cpd B). EPS: a) affected the induction of MB, showed a male-like pattern of care for pups, b) elevated plasma levels of Cpd B and reduced E2 in comparison with the controls, and c) significantly increased the number of BAOT neurons compared to the control females and comparable to the control male group. These findings provide further evidence that stress applied to pregnant rats produces long-lasting behavioral, endocrine and neuroanatomical alterations in the female offspring that are evident when they become mature.

  4. Exercise effects on motor and affective behavior and catecholamine neurochemistry in the MPTP-lesioned mouse.

    PubMed

    Gorton, Lori M; Vuckovic, Marta G; Vertelkina, Nina; Petzinger, Giselle M; Jakowec, Michael W; Wood, Ruth I

    2010-12-01

    This study used 1-methyl-4-phenyl-1,2,3,6,-tetrahydropyridine (MPTP) in mice to determine if exercise improves behavior and dopamine (DA) and serotonin (5HT) content. Male C57BL/6 mice received MPTP (4 x 20mg/kg) or saline. They remained sedentary or exercised by treadmill or voluntary running wheel for 6 weeks (n=8/group). Saline-treated mice ran significantly faster on running wheels (22.8+/-1.0m/min) than on treadmill (8.5+/-0.5m/min), and MPTP lesion did not reduce voluntary exercise (19.3+/-1.5m/min, p>0.05). There was a significant effect of both lesion and exercise on overall Rotarod performance (ORP): MPTP lesion reduced ORP, while treadmill exercise increased ORP vs sedentary mice (p<0.05). MPTP increased anxiety in the marble-burying test: sedentary lesioned mice buried more marbles (74.0+/-5.2%) than sedentary controls (34.8+/-11.8%, p<0.05). Conversely, exercise reduced anxiety on the elevated plus maze. Among saline-treated mice, those exposed to voluntary wheel-running showed an increased percent of open arm entries (49.8+/-3.5%, p<0.05) relative to sedentary controls (36.2+/-4.0%, p<0.05). Neither MPTP nor exercise altered symptoms of depression measured by sucrose preference or tail suspension. MPTP significantly reduced DA in striatum (in sedentary lesioned mice to 42.1+/-3.0% of saline controls), and lowered 5HT in amygdala and striatum (in sedentary lesioned mice to 86.1+/-4.1% and 66.5+/-8.2% of saline controls, respectively); exercise had no effect. Thus, exercise improves behavior in a model of DA depletion, without changes in DA or 5HT.

  5. Development and Validation of a Computational Model for Predicting the Behavior of Plumes from Large Solid Rocket Motors

    NASA Technical Reports Server (NTRS)

    Wells, Jason E.; Black, David L.; Taylor, Casey L.

    2013-01-01

    Exhaust plumes from large solid rocket motors fired at ATK's Promontory test site carry particulates to high altitudes and typically produce deposits that fall on regions downwind of the test area. As populations and communities near the test facility grow, ATK has become increasingly concerned about the impact of motor testing on those surrounding communities. To assess the potential impact of motor testing on the community and to identify feasible mitigation strategies, it is essential to have a tool capable of predicting plume behavior downrange of the test stand. A software package, called PlumeTracker, has been developed and validated at ATK for this purpose. The code is a point model that offers a time-dependent, physics-based description of plume transport and precipitation. The code can utilize either measured or forecasted weather data to generate plume predictions. Next-Generation Radar (NEXRAD) data and field observations from twenty-three historical motor test fires at Promontory were collected to test the predictive capability of PlumeTracker. Model predictions for plume trajectories and deposition fields were found to correlate well with the collected dataset.

  6. Stepper motor

    NASA Technical Reports Server (NTRS)

    Dekramer, Cornelis

    1994-01-01

    The purpose of this document is to describe the more commonly used permanent magnet stepper motors for spaceflight. It will discuss the mechanical and electrical aspects of the devices, their torque behavior, those parameters which need to be controlled and measured, and test methods to be employed. It will also discuss torque margins, compare these to the existing margin requirements, and determine the applicability of these requirements. Finally it will attempt to generate a set of requirements which will be used in any stepper motor procurement and will fully characterize the stepper motor behavior in a consistent and repeatable fashion.

  7. Altered hippocampal function before emotional trauma in rats susceptible to PTSD-like behaviors.

    PubMed

    Nalloor, Rebecca; Bunting, Kristopher M; Vazdarjanova, Almira

    2014-07-01

    Posttraumatic stress disorder (PTSD) is an anxiety disorder that occurs after experiencing a traumatic event. Susceptibility to PTSD exists, as only some trauma-exposed individuals develop this condition. Investigating susceptibilities in animal models can contribute to understanding the etiology of the disorder. We previously reported an animal model which allows reliable pre-classification of rats as susceptible (Sus) or resistant (Res) to developing a PTSD-like phenotype after a later trauma. Here we report that Sus, compared to Res, rats have altered hippocampal function, along the septo-temporal axis, prior to experiencing a traumatic event. In Experiment I, Res and Sus rats explored a novel box twice. Using a cellular imaging method for assessing plasticity-related immediate-early gene expression in large neuronal ensembles, Arc/Homer1a catFISH, we show that Sus rats have smaller vCA3 ensembles during the second exploration. This suppressed vCA3 activation in Sus rats was not due to a difference in exploratory behavior, or to a difference in Arc/Homer1a expression in the basolateral amygdala (BLA). BLA is a main source of inputs to vCA3, but both the ensemble size and overlap of BLA ensembles activated during the two explorations was similar to that of Res rats. Additionally, Sus rats had significant 'infidelity' in their dorsal hippocampal representations of the second event: a lower overlap, compared to Res rats, of Arc/Homer1a-expressing ensembles activated during the two explorations (the size of the ensembles were similar to those of Res rats). These differences were revealed only in conditions of relatively low stress, because they were not observed when Sus and Res rats experienced fear conditioning (Experiment II). Combined, the findings show that altered hippocampal function exists before experiencing emotional trauma in susceptible rats and suggest that this is a risk factor for PTSD.

  8. Autism-related Neuroligin-3 Mutation Alters Social Behavior and Spatial Learning

    PubMed Central

    Jaramillo, Thomas C.; Liu, Shunan; Pettersen, Ami; Birnbaum, Shari G; Powell, Craig M.

    2014-01-01

    LAY ABSTRACT Mutations in neuroligin genes have been identified in association with autism. This manuscript provides characterization of a specific mutation in the neuroligin-3 gene that has been associated with autism in two brothers. The resulting autism model has alterations in social and cognitive function reminiscent of autism in patients. This model will be useful to understand the role of neuroligin dysfunction as a rare cause of autism. SCIENTIFIC ABSTRACT Multiple candidate genes have been identified for autism spectrum disorders. While some of these genes reach genome-wide significance, others, such as the R451C point mutation in the synaptic cell adhesion molecule neuroligin-3, appear to be rare. Interestingly, two brothers with the same R451C point mutation in neuroligin-3 present clinically on seemingly disparate sides of the autism spectrum. These clinical findings suggest genetic background may play a role in modifying the penetrance of a particular autism-associated mutation. Animal models may contribute additional support for such mutations as functionally relevant and can provide mechanistic insights. Previously, in collaboration with the Südhof laboratory, we reported that mice with an R451C substitution in neuroligin-3 displayed social deficits and enhanced spatial learning. While some of these behavioral abnormalities have since been replicated independently in the Südhof laboratory, observations from the Crawley laboratory failed to replicate these findings in a similar neuroligin-3 mutant mouse model and suggested that genetic background may contribute to variation in observations across laboratories. Therefore we sought to replicate our findings in the neuroligin-3 R451C point mutant knockin mouse model (NL3R451C) in a different genetic background. We backcrossed our NL3R451C mouse line onto a 129S2/SvPasCrl genetic background and repeated a subset of our previous behavioral testing. NL3R451C mice on a 129S2/SvPasCrl displayed social

  9. Early functional impairment of sensory-motor connectivity in a mouse model of spinal muscular atrophy

    PubMed Central

    Mentis, George Z.; Blivis, Dvir; Liu, Wenfang; Drobac, Estelle; Crowder, Melissa E.; Kong, Lingling; Alvarez, Francisco J.; Sumner, Charlotte J.; O'Donovan, Michael J.

    2011-01-01

    SUMMARY To define alterations of neuronal connectivity that occur during motor neuron degeneration, we characterized the function and structure of spinal circuitry in spinal muscular atrophy (SMA) model mice. SMA motor neurons show reduced proprioceptive reflexes that correlate with decreased number and function of synapses on motor neuron somata and proximal dendrites. These abnormalities occur at an early stage of disease in motor neurons innervating proximal hindlimb muscles and medial motor neurons innervating axial muscles, but only at end-stage disease in motor neurons innervating distal hindlimb muscles. Motor neuron loss follows afferent synapse loss with the same temporal and topographical pattern. Trichostatin A, which improves motor behavior and survival of SMA mice, partially restores spinal reflexes illustrating the reversibility of these synaptic defects. De-afferentation of motor neurons is an early event in SMA and may be a primary cause of motor dysfunction that is amenable to therapeutic intervention. PMID:21315257

  10. Early functional impairment of sensory-motor connectivity in a mouse model of spinal muscular atrophy.

    PubMed

    Mentis, George Z; Blivis, Dvir; Liu, Wenfang; Drobac, Estelle; Crowder, Melissa E; Kong, Lingling; Alvarez, Francisco J; Sumner, Charlotte J; O'Donovan, Michael J

    2011-02-10

    To define alterations of neuronal connectivity that occur during motor neuron degeneration, we characterized the function and structure of spinal circuitry in spinal muscular atrophy (SMA) model mice. SMA motor neurons show reduced proprioceptive reflexes that correlate with decreased number and function of synapses on motor neuron somata and proximal dendrites. These abnormalities occur at an early stage of disease in motor neurons innervating proximal hindlimb muscles and medial motor neurons innervating axial muscles, but only at end-stage disease in motor neurons innervating distal hindlimb muscles. Motor neuron loss follows afferent synapse loss with the same temporal and topographical pattern. Trichostatin A, which improves motor behavior and survival of SMA mice, partially restores spinal reflexes, illustrating the reversibility of these synaptic defects. Deafferentation of motor neurons is an early event in SMA and may be a primary cause of motor dysfunction that is amenable to therapeutic intervention.

  11. Fish Oil Diet Associated with Acute Reperfusion Related Hemorrhage, and with Reduced Stroke-Related Sickness Behaviors and Motor Impairment

    PubMed Central

    Pascoe, Michaela C.; Howells, David W.; Crewther, David P.; Constantinou, Nicki; Carey, Leeanne M.; Rewell, Sarah S.; Turchini, Giovanni M.; Kaur, Gunveen; Crewther, Sheila G.

    2014-01-01

    Ischemic stroke is associated with motor impairment and increased incidence of affective disorders such as anxiety/clinical depression. In non-stroke populations, successful management of such disorders and symptoms has been reported following diet supplementation with long chain omega-3-polyunsaturated-fatty-acids (PUFAs). However, the potential protective effects of PUFA supplementation on affective behaviors after experimentally induced stroke and sham surgery have not been examined previously. This study investigated the behavioral effects of PUFA supplementation over a 6-week period following either middle cerebral artery occlusion or sham surgery in the hooded-Wistar rat. The PUFA diet supplied during the acclimation period prior to surgery was found to be associated with an increased risk of acute hemorrhage following the reperfusion component of the surgery. In surviving animals, PUFA supplementation did not influence infarct size as determined 6 weeks after surgery, but did decrease omega-6-fatty-acid levels, moderate sickness behaviors, acute motor impairment, and longer-term locomotor hyperactivity and depression/anxiety-like behavior. PMID:24567728

  12. Fish oil diet associated with acute reperfusion related hemorrhage, and with reduced stroke-related sickness behaviors and motor impairment.

    PubMed

    Pascoe, Michaela C; Howells, David W; Crewther, David P; Constantinou, Nicki; Carey, Leeanne M; Rewell, Sarah S; Turchini, Giovanni M; Kaur, Gunveen; Crewther, Sheila G

    2014-01-01

    Ischemic stroke is associated with motor impairment and increased incidence of affective disorders such as anxiety/clinical depression. In non-stroke populations, successful management of such disorders and symptoms has been reported following diet supplementation with long chain omega-3-polyunsaturated-fatty-acids (PUFAs). However, the potential protective effects of PUFA supplementation on affective behaviors after experimentally induced stroke and sham surgery have not been examined previously. This study investigated the behavioral effects of PUFA supplementation over a 6-week period following either middle cerebral artery occlusion or sham surgery in the hooded-Wistar rat. The PUFA diet supplied during the acclimation period prior to surgery was found to be associated with an increased risk of acute hemorrhage following the reperfusion component of the surgery. In surviving animals, PUFA supplementation did not influence infarct size as determined 6 weeks after surgery, but did decrease omega-6-fatty-acid levels, moderate sickness behaviors, acute motor impairment, and longer-term locomotor hyperactivity and depression/anxiety-like behavior.

  13. Enhancement of extinction learning attenuates ethanol-seeking behavior and alters plasticity in the prefrontal cortex.

    PubMed

    Gass, Justin T; Trantham-Davidson, Heather; Kassab, Amanda S; Glen, William B; Olive, M Foster; Chandler, L Judson

    2014-05-28

    Addiction is a chronic relapsing disorder in which relapse is often initiated by exposure to drug-related cues. The present study examined the effects of mGluR5 activation on extinction of ethanol-cue-maintained responding, relapse-like behavior, and neuronal plasticity. Rats were trained to self-administer ethanol and then exposed to extinction training during which they were administered either vehicle or the mGluR5 positive allosteric modulator 3-cyano-N-(1,3-diphenyl-1H-pyrazol-5-yl) or CDPPB. CDPPB treatment reduced active lever responding during extinction, decreased the total number of extinction sessions required to meet criteria, and attenuated cue-induced reinstatement of ethanol seeking. CDPPB facilitation of extinction was blocked by the local infusion of the mGluR5 antagonist 3-((2-methyl-4-thiazolyl)ethynyl) pyridine into the infralimbic (IfL) cortex, but had no effect when infused into the prelimbic (PrL) cortex. Analysis of dendritic spines revealed alterations in structural plasticity, whereas electrophysiological recordings demonstrated differential alterations in glutamatergic neurotransmission in the PrL and IfL cortex. Extinction was associated with increased amplitude of evoked synaptic PrL and IfL NMDA currents but reduced amplitude of PrL AMPA currents. Treatment with CDPPB prevented the extinction-induced enhancement of NMDA currents in PrL without affecting NMDA currents in the IfL. Whereas CDPPB treatment did not alter the amplitude of PrL or IfL AMPA currents, it did promote the expression of IfL calcium-permeable GluR2-lacking receptors in both abstinence- and extinction-trained rats, but had no effect in ethanol-naive rats. These results confirm changes in the PrL and IfL cortex in glutamatergic neurotransmission during extinction learning and demonstrate that manipulation of mGluR5 facilitates extinction of ethanol cues in association with neuronal plasticity.

  14. Exposure to altered gravity during specific developmental periods differentially affects growth, development, the cerebellum and motor functions in male and female rats

    NASA Astrophysics Data System (ADS)

    Nguon, K.; Ladd, B.; Sajdel-Sulkowska, E. M.

    2006-01-01

    We previously reported that perinatal exposure to hypergravity affects cerebellar structure and motor coordination in rat neonates. In the present study, we explored the hypothesis that neonatal cerebellar structure and motor coordination may be particularly vulnerable to the effects of hypergravity during specific developmental stages. To test this hypothesis, we compared neurodevelopment, motor behavior and cerebellar structure in rat neonates exposed to 1.65 G on a 24-ft centrifuge during discrete periods of time: the 2nd week of pregnancy [gestational day (G) 8 through G15; group A], the 3rd week of pregnancy (G15 through birth on G22/G23; group B), the 1st week of nursing [birth through postnatal day (P) 6; group C], the 2nd and 3rd weeks of nursing (P6 through P21; group D), the combined 2nd and 3rd weeks of pregnancy and nursing (G8 through P21; group E) and stationary control (SC) neonates (group F). Prenatal exposure to hypergravity resulted in intrauterine growth retardation as reflected by a decrease in the number of pups in a litter and lower average mass at birth. Exposure to hypergravity immediately after birth impaired the righting response on P3, while the startle response in both males and females was most affected by exposure during the 2nd and 3rd weeks after birth. Hypergravity exposure also impaired motor functions, as evidenced by poorer performance on a rotarod; while both males and females exposed to hypergravity during the 2nd and 3rd weeks after birth performed poorly on P21, male neonates were most dramatically affected by exposure to hypergravity during the second week of gestation, when the duration of their recorded stay on the rotarod was one half that of SC males. Cerebellar mass was most reduced by later postnatal exposure. Thus, for the developing rat cerebellum, the postnatal period that overlaps the brain growth spurt is the most vulnerable to hypergravity. However, male motor behavior is also affected by midpregnancy exposure to

  15. Short and long term neuro-behavioral alterations in type 1 diabetes mellitus pediatric population

    PubMed Central

    Litmanovitch, Edna; Geva, Ronny; Rachmiel, Marianna

    2015-01-01

    Type 1 diabetes mellitus (T1DM) is one of the most prevalent chronic conditions affecting individuals under the age of 18 years, with increasing incidence worldwide, especially among very young age groups, younger than 5. There is still no cure for the disease, and therapeutic goals and guidelines are a challenge. Currently, despite T1DM intensive management and technological interventions in therapy, the majority of pediatric patients do not achieve glycemic control goals. This leads to a potential prognosis of long term diabetic complications, nephrological, cardiac, ophthalmological and neurological. Unfortunately, the neurological manifestations, including neurocognitive and behavioral complications, may present soon after disease onset, during childhood and adolescence. These manifestations may be prominent, but at times subtle, thus they are often not reported by patients or physicians as related to the diabetes. Furthermore, the metabolic mechanism for such manifestations has been inconsistent and difficult to interpret in practical clinical care, as reported in several reviews on the topic of brain and T1DM. However, new technological methods for brain assessment, as well as the introduction of continuous glucose monitoring, provide new insights and information regarding brain related manifestations and glycemic variability and control parameters, which may impact the clinical care of children and youth with T1DM. This paper provides a comprehensive review of the most recently reported behavioral, cognitive domains, sleep related, electrophysiological, and structural alterations in children and adolescences from a novel point of view. The review focuses on reported impairments based on duration of T1DM, its timeline, and modifiable disease related risk parameters. These findings are not without controversy, and limitations of data are presented in addition to recommendations for future research direction. PMID:25789107

  16. Common behaviors alterations after extremely low-frequency electromagnetic field exposure in rat animal model.

    PubMed

    Mahdavi, Seyed Mohammad; Sahraei, Hedayat; Rezaei-Tavirani, Mostafa; Najafi Abedi, Akram

    2016-01-01

    Naturally, the presence of electromagnetic waves in our living environment affects all components of organisms, particularly humans and animals, as the large part of their body consists of water. In the present study, we tried to investigate the relation between exposure to the extremely low-frequency electromagnetic field (ELF-EMF) and common behaviors such as body weight, food and water intake, anorexia (poor appetite), plasma glucose concentration, movement, rearing and sniffing in rats. For this purpose, rats were exposed to 40  Hz ELF-EMF once a day for 21 days, then at days 1, 3, 7, 14 and 21 after exposure, any changes in the above-mentioned items were assessed in the exposed rats and compared to the non-exposed group as control. Body weight of irradiated rats significantly increased only a week after exposure and decreased after that. No significant change was observed in food and water intake of irradiated rats compared to the control, and the anorexia parameter in the group exposed to ELF-EMF was significantly decreased at one and two weeks after irradiation. A week after exposure, the level of glucose was significantly increased but at other days these changes were not significant. Movements, rearing and sniffing of rats at day 1 after exposure were significantly decreased and other days these changes did not follow any particular pattern. However, the result of this study demonstrated that exposure to ELF-EMF can alter the normal condition of animals and may represent a harmful impact on behavior.

  17. Artificial Outdoor Nighttime Lights Associate with Altered Sleep Behavior in the American General Population

    PubMed Central

    Ohayon, Maurice M.; Milesi, Cristina

    2016-01-01

    Study Objectives: Our study aims to explore the associations between outdoor nighttime lights (ONL) and sleep patterns in the human population. Methods: Cross-sectional telephone study of a representative sample of the general US population age 18 y or older. 19,136 noninstitutionalized individuals (participation rate: 83.2%) were interviewed by telephone. The Sleep-EVAL expert system administered questions on life and sleeping habits; health; sleep, mental and organic disorders (Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision; International Classification of Sleep Disorders, Second Edition; International Classification of Diseases, 10th Edition). Individuals were geolocated by longitude and latitude. Outdoor nighttime light measurements were obtained from the Defense Meteorological Satellite Program's Operational Linescan System (DMSP/OLS), with nighttime passes taking place between 19:30 and 22:30 local time. Light data were correlated precisely to the geolocation of each participant of the general population sample. Results: Living in areas with greater ONL was associated with delayed bedtime (P < 0.0001) and wake up time (P < 0.0001), shorter sleep duration (P < 0.01), and increased daytime sleepiness (P < 0.0001). Living in areas with greater ONL also increased the dissatisfaction with sleep quantity and quality (P < 0.0001) and the likelihood of having a diagnostic profile congruent with a circadian rhythm disorder (P < 0.0001). Conclusions: Although they improve the overall safety of people and traffic, nighttime lights in our streets and cities are clearly linked with modifications in human sleep behaviors and also impinge on the daytime functioning of individuals living in areas with greater ONL. Citation: Ohayon MM, Milesi C. Artificial outdoor nighttime lights associate with altered sleep behavior in the american general population. SLEEP 2016;39(6):1311–1320. PMID:27091523

  18. An Scn1a epilepsy mutation in Scn8a alters seizure susceptibility and behavior

    PubMed Central

    Makinson, Christopher D.; Dutt, Karoni; Lin, Frank; Papale, Ligia A.; Shankar, Anupama; Barela, Arthur J.; Liu, Robert; Goldin, Alan L.; Escayg, Andrew

    2015-01-01

    Understanding the role of SCN8A in epilepsy and behavior is critical in light of recently identified human SCN8A epilepsy mutations. We have previously demonstrated that Scn8amed and Scn8amed-jo mice carrying mutations in the Scn8a gene display increased resistance to flurothyl and kainic acid-induced seizures; however, they also exhibit spontaneous absence seizures. To further investigate the relationship between altered SCN8A function and epilepsy, we introduced the SCN1A-R1648H mutation, identified in a family with generalized epilepsy with febrile seizures plus (GEFS+), into the corresponding position (R1627H) of the mouse Scn8a gene. Heterozygous R1627H mice exhibited increased resistance to some forms of pharmacologically and electrically induced seizures and the mutant Scn8a allele ameliorated the phenotype of Scn1a-R1648H mutants. Hippocampal slices from heterozygous R1627H mice displayed decreased bursting behavior compared to wild-type littermates. Paradoxically, at the homozygous level, R1627H mice did not display increased seizure resistance and were susceptible to audiogenic seizures. We furthermore observed increased hippocampal pyramidal cell excitability in heterozygous and homozygous Scn8a-R1627H mutants, and decreased interneuron excitability in heterozygous Scn8a-R1627H mutants. These results expand the phenotypes associated with disruption of the Scn8a gene and demonstrate that an Scn8a mutation can both confer seizure protection and increase seizure susceptibility. PMID:26410685

  19. Properties of the Driving Behavior Survey Among Individuals with Motor Vehicle Accident-Related Posttraumatic Stress Disorder

    PubMed Central

    Clapp, Joshua D.; Baker, Aaron S.; Litwack, Scott D.; Sloan, Denise M.; Beck, J. Gayle

    2014-01-01

    Data suggest anxious drivers may engage in problematic behaviors that place themselves and others at increased risk of negative traffic events. Three domains of problematic behavior – exaggerated safety/caution, performance deficits, and hostile/aggressive behaviors – previously were identified during development of the Driving Behavior Survey (DBS), a novel measure of anxiety-related behavior. Extending this research, the current study examined the psychometric properties of DBS scores among individuals with posttraumatic stress disorder (PTSD) subsequent to motor vehicle trauma (N = 40). Internal consistencies and 12-week test-retest reliabilities for DBS scales ranged from good to excellent. Comparison of scores to normative student data indicated dose-response relationships for safety/caution and performance deficit subscales, with increased frequency of anxious behavior occurring within the PTSD sample. Associations with standard clinical measures provide additional evidence for anxiety-related driving behavior as a unique marker of functional impairment, distinct from both avoidance and disorder-specific symptoms. PMID:24325891

  20. Targeting Dyrk1A with AAVshRNA Attenuates Motor Alterations in TgDyrk1A, a Mouse Model of Down Syndrome

    PubMed Central

    Ortiz-Abalia, Jon; Sahún, Ignasi; Altafaj, Xavier; Andreu, Núria; Estivill, Xavier; Dierssen, Mara; Fillat, Cristina

    2008-01-01

    Genetic-dissection studies carried out with Down syndrome (DS) murine models point to the critical contribution of Dyrk1A overexpression to the motor abnormalities and cognitive deficits displayed in DS individuals. In the present study we have used a murine model overexpressing Dyrk1A (TgDyrk1A mice) to evaluate whether functional CNS defects could be corrected with an inhibitory RNA against Dyrk1A, delivered by bilateral intrastriatal injections of adeno-associated virus type 2 (AAVshDyrk1A). We report that AAVshDyrk1A efficiently transduced HEK293 cells and primary neuronal cultures, triggering the specific inhibition of Dyrk1A expression. Injecting the vector into the striata of TgDyrk1A mice resulted in a restricted, long-term transduction of the striatum. This gene therapy was found to be devoid of toxicity and succeeded in normalizing Dyrk1A protein levels in TgDyrk1A mice. Importantly, the behavioral studies of the adult TgDyrk1A mice treated showed a reversal of corticostriatal-dependent phenotypes, as revealed by the attenuation of their hyperactive behavior, the restoration of motor-coordination defects, and an improvement in sensorimotor gating. Taken together, the data demonstrate that normalizing Dyrk1A gene expression in the striatum of adult TgDyrk1A mice, by means of AAVshRNA, clearly reverses motor impairment. Furthermore, these results identify Dyrk1A as a potential target for therapy in DS. PMID:18940310

  1. The Relationship between Instructor Misbehaviors and Student Antisocial Behavioral Alteration Techniques: The Roles of Instructor Attractiveness, Humor, and Relational Closeness

    ERIC Educational Resources Information Center

    Claus, Christopher J.; Booth-Butterfield, Melanie; Chory, Rebecca M.

    2012-01-01

    Using rhetorical/relational goal theory as a guiding frame, we examined relationships between instructor misbehaviors (i.e., indolence, incompetence, and offensiveness) and the likelihood of students communicating antisocial behavioral alteration techniques (BATs). More specifically, the study focused on whether students' perceptions of instructor…

  2. Effect of wettability alteration on long-term behavior of fluids in subsurface

    SciTech Connect

    Bandara, Uditha C.; Palmer, Bruce J.; Tartakovsky, Alexandre M.

    2016-01-13

    Wettability is an important factor affecting fluid behavior in the subsurface, including oil, gas, and supercritical CO$_2$ in deep geological reservoirs. For example, CO$_2$ is generally assumed to behave as a non-wetting fluid, which favors safe storage. However, because of chemical heterogeneity of the reservoirs, mixed wettability conditions can exist. Furthermore, recent experiments suggest that with time, the wettability of super-critical CO$_2$ may change from non-wetting to partially-wetting due to changes in electrostatic interactions. These changes are caused by chemical reactions between dissolved CO$_2$ and its environment. To date, the effect of wettability alteration and mixed wettability on the long term fate of injected CO$_2$ has not well been studied. Here, we use the multiphase Pairwise Force Smoothed Particle Hydrodynamics (PF-SPH) Model to study complex pore-scale processes involved in geological CO$_2$ sequestration, including the effect of spatial and temporal wettability variations on long-term distribution of CO$_2$ in porous media. Results reveal that in the absence of dissolution of supercritical CO$_2$ and precipitation of carbonate minerals (mineral trapping), the amount of trapped supercritical CO$_2$ significantly decreases as the wettability of the porous media changes from brine-wet to partial-wet or CO$_2$-wet.

  3. Low dose effects of a Withania somnifera extract on altered marble burying behavior in stressed mice

    PubMed Central

    Dey, Amitabha; Chatterjee, Shyam Sunder; Kumar, Vikas

    2016-01-01

    Aim: Withania somnifera root (WSR) extracts are often used in traditionally known Indian systems of medicine for prevention and cure of psychosomatic disorders. The reported experiment was designed to test whether low daily oral doses of such extracts are also effective in suppressing marble burying behavior in stressed mice or not. Materials and Methods: Groups of mice treated with 10, 20, or 40 mg/kg daily oral doses of WSR were subjected to a foot shock stress-induced hyperthermia test on the 1st, 5th, 7th, and 10th day of the experiment. On the 11th and 12th treatment days, they were subjected to marble burying tests. Stress response suppressing effects of low dose WSR were estimated by its effects on body weight and basal core temperature of animals during the course of the experiment. Results: Alterations in bodyweight and basal core temperature triggered by repeated exposures to foot shock stress were absent even in the 10 mg/kg/day WSR treated group, whereas the effectiveness of the extract in foot shock stress-induced hyperthermia and marble burying tests increased with its increasing daily dose. Conclusion: Marble burying test in stressed mice is well suited for identifying bioactive constituents of W. somnifera like medicinal plants with adaptogenic, anxiolytic and antidepressant activities, or for quantifying pharmacological interactions between them. PMID:27366354

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

    PubMed

    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.

  5. Developmental Exposure to Aroclor 1254 Alters Migratory Behavior in Juvenile European Starlings (Sturnus vulgaris).

    PubMed

    Flahr, Leanne M; Michel, Nicole L; Zahara, Alexander R D; Jones, Paul D; Morrissey, Christy A

    2015-05-19

    Birds exposed to endocrine disrupting chemicals during development could be susceptible to neurological and other physiological changes affecting migratory behaviors. We investigated the effects of ecologically relevant levels of Aroclor 1254, a polychlorinated biphenyl (PCB) mixture, on moult, fattening, migratory activity, and orientation in juvenile European starlings (Sturnus vulgaris). Birds were orally administered 0 (control), 0.35 (low), 0.70 (intermediate), or 1.05 (high) μg Aroclor 1254/g-body weight by gavage from 1 through 18 days posthatch and later exposed in captivity to a photoperiod shift simulating an autumn migration. Migratory activity and orientation were examined using Emlen funnel trials. Across treatments, we found significant increases in mass, fat, and moulting and decreasing plasma thyroid hormones over time. We observed a significant increase in activity as photoperiod was shifted from 13L:11D (light:dark) to 12L:12D, demonstrating that migratory condition was induced in captivity. At 12L:12D, control birds oriented to 155.95° (South-Southeast), while high-dosed birds did not. High-dosed birds showed a delayed orientation to 197.48° (South-Southwest) under 10L:14D, concomitant with apparent delays in moult. These findings demonstrate how subtle contaminant-induced alterations during development could lead to longer-scale effects, including changes in migratory activity and orientation, which could potentially result in deleterious effects on fitness and survival.

  6. 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.

  7. Alteration of the behavioral effects of nicotine by chronic caffeine exposure.

    PubMed

    Tanda, G; Goldberg, S R

    2000-05-01

    The prevalence of tobacco smoking and coffee drinking place nicotine and caffeine among the most used licit drugs in many societies and their consumption is often characterised by concurrent use. The pharmacological basis for any putative interaction between these drugs remains unclear. Some epidemiological reports support anecdotal evidence, which suggests that smokers consume caffeine to enhance the effects of nicotine. This paper reviews various aspects of the pharmacology of caffeine and nicotine, in humans and experimental animals, important for the understanding of the interactions between these drugs. In particular, recent experiments are reviewed in which chronic exposure to caffeine in the drinking water of rats facilitated acquisition of self-adminstration behavior, enhanced nicotine-induced increases in dopamine levels in the shell of the nucleus accumbens and altered the dopaminergic component of a nicotine discrimination. These studies provide evidence that the rewarding and subjective properties of nicotine can be changed by chronic caffeine exposure and indicate that caffeine exposure may be an important environmental factor in shaping and maintaining tobacco smoking.

  8. Mutations in the circadian gene period alter behavioral and biochemical responses to ethanol in Drosophila.

    PubMed

    Liao, Jennifer; Seggio, Joseph A; Ahmad, S Tariq

    2016-04-01

    Clock genes, such as period, which maintain an organism's circadian rhythm, can have profound effects on metabolic activity, including ethanol metabolism. In turn, ethanol exposure has been shown in Drosophila and mammals to cause disruptions of the circadian rhythm. Previous studies from our labs have shown that larval ethanol exposure disrupted the free-running period and period expression of Drosophila. In addition, a recent study has shown that arrhythmic flies show no tolerance to ethanol exposure. As such, Drosophila period mutants, which have either a shorter than wild-type free-running period (perS) or a longer one (perL), may also exhibit altered responses to ethanol due to their intrinsic circadian differences. In this study, we tested the initial sensitivity and tolerance of ethanol exposure on Canton-S, perS, and perL, and then measured their Alcohol Dehydrogenase (ADH) and body ethanol levels. We showed that perL flies had slower sedation rate, longer recovery from ethanol sedation, and generated higher tolerance for sedation upon repeated ethanol exposure compared to Canton-S wild-type flies. Furthermore, perL flies had lower ADH activity and had a slower ethanol clearance compared to wild-type flies. The findings of this study suggest that period mutations influence ethanol induced behavior and ethanol metabolism in Drosophila and that flies with longer circadian periods are more sensitive to ethanol exposure.

  9. Alcohol during adolescence selectively alters immediate and long-term behavior and neurochemistry.

    PubMed

    Maldonado-Devincci, Antoniette M; Badanich, Kimberly A; Kirstein, Cheryl L

    2010-02-01

    Alcohol use increases across adolescence and is a concern in the United States. In humans, males and females consume different amounts of alcohol depending on the age of initiation, and the long-term consequences of early ethanol consumption are not readily understood. The purpose of our work was to better understand the immediate and long-term impact of ethanol exposure during adolescence and the effects it can have on behavior and dopaminergic responsivity. We have assessed sex differences in voluntary ethanol consumption during adolescence and adulthood and the influence of binge ethanol exposure during adolescence. We have observed that males are sensitive to passive social influences that mediate voluntary ethanol consumption, and early ethanol exposure induces long-term changes in responsivity to ethanol in adulthood. Exposure to moderate doses of ethanol during adolescence produced alterations in dopamine in the nucleus accumbens septi during adolescence and later in adulthood. Taken together, all of these data indicate that the adolescent brain is sensitive to the impact of early ethanol exposure during this critical developmental period.

  10. Effect of wettability alteration on long-term behavior of fluids in subsurface

    NASA Astrophysics Data System (ADS)

    Bandara, Uditha C.; Palmer, Bruce J.; Tartakovsky, Alexandre M.

    2016-04-01

    Wettability is an important factor affecting fluid behavior in the subsurface, including oil, gas, and supercritical hbox {CO}_2 in deep geological reservoirs. For example, hbox {CO}_2 is generally assumed to behave as a non-wetting fluid, which favors safe storage. However, because of chemical heterogeneity of the reservoirs, mixed wettability conditions can exist. Furthermore, recent experiments suggest that with time, the wettability of super-critical hbox {CO}_2 may change from non-wetting to partially wetting due to changes in electrostatic interactions. These changes are caused by chemical reactions between dissolved hbox {CO}_2 and its environment. To date, the effect of wettability alteration and mixed wettability on the long-term fate of injected hbox {CO}_2 has not well been studied. Here, we use the multiphase pairwise force smoothed particle hydrodynamics model to study complex pore-scale processes involved in geological hbox {CO}_2 sequestration, including the effect of spatial and temporal wettability variations on long-term distribution of hbox {CO}_2 in porous media. Results reveal that in the absence of dissolution of supercritical hbox {CO}_2 and precipitation of carbonate minerals (mineral trapping), the amount of trapped supercritical hbox {CO}_2 significantly decreases as the wettability of the porous media changes from brine-wet to partial-wet or hbox {CO}_2-wet.

  11. Altered diurnal pattern of steroid hormones in relation to various behaviors, external factors and pathologies: A review.

    PubMed

    Collomp, K; Baillot, A; Forget, H; Coquerel, A; Rieth, N; Vibarel-Rebot, N

    2016-10-01

    The adrenal and gonadal stress steroids [i.e., cortisol, testosterone and dehydroepiandrosterone (DHEA)] have gathered considerable attention in the last few decades due to their very broad physiological and psychological actions. Their diurnal patterns have become a particular focus following new data implicating altered diurnal hormone patterns in various endocrine, behavioral and cardiovascular risk profiles. In this review of the current literature, we present a brief overview of the altered diurnal patterns of these hormones that may occur in relation to chronic stress, nutritional behaviors, physical exercise, drugs and sleep deprivation/shift. We also present data on the altered diurnal hormone patterns implicated in cardiometabolic and psychiatric/neurologic diseases, cancer and other complex pathologies. We consider the occasionally discrepant results of the studies, and summarize the current knowledge in this new field of interest, underlining the potential effects on both biological and psychological functioning, and assess the implications of these effects. Last, we conclude with some practical considerations and perspectives.

  12. Prenatal Alcohol Exposure and Chronic Mild Stress Differentially Alter Depressive- and Anxiety-Like Behaviors in Male and Female Offspring

    PubMed Central

    Hellemans, Kim G. C.; Verma, Pamela; Yoon, Esther; Yu, Wayne K.; Young, Allan H.; Weinberg, Joanne

    2016-01-01

    Background Fetal Alcohol Spectrum Disorder (FASD) is associated with numerous neuro behavioral alterations, as well as disabilities in a number of domains, including a high incidence of depression and anxiety disorders. Prenatal alcohol exposure (PAE) also alters hypothalamic-pituitary-adrenal (HPA) function, resulting in increased responsiveness to stressors and HPA dysregulation in adulthood. Interestingly, data suggest that pre-existing HPA abnormalities may be a major contributory factor to some forms of depression, particularly when an individual is exposed to stressors later in life. We tested the hypothesis that exposure to stressors in adulthood may unmask an increased vulnerability to depressive- and anxiety-like behaviors in PAE animals. Methods Male and female offspring from prenatal alcohol (PAE), pair-fed (PF), and ad libitumfed control (C) treatment groups were tested in adulthood. Animals were exposed to 10 consecutive days of chronic mild stress (CMS), and assessed in a battery of well-validated tasks sensitive to differences in depressive- and / or anxiety-like behaviors. Results We report here that the combination of PAE and CMS in adulthood increases depressive- and anxiety-like behaviors in a sexually dimorphic manner. PAE males showed impaired hedonic responsivity (sucrose contrast test), locomotor hyperactivity (open field), and alterations in affiliative and nonaffiliative social behaviors (social interaction test) compared to control males. By contrast, PAE and, to a lesser extent, PF, females showed greater levels of “behavioral despair” in the forced swim test, and PAE females showed altered behavior in the final 5 minutes of the social interaction test compared to control females. Conclusions These data support the possibility that stress may be a mediating or contributing factor in the psychopathologies reported in FASD populations. PMID:20102562

  13. Passive or simulated displacement of one arm (but not its mirror reflection) modulates the involuntary motor behavior of the other arm.

    PubMed

    Brun, C; Metral, M; Chancel, M; Kavounoudias, A; Luyat, M; Guerraz, M

    2015-01-29

    Recent studies of both healthy and patient populations have cast doubt on the mirror paradigm's beneficial effect on motor behavior. Indeed, the voluntary arm displacement that accompanies reflection in the mirror may be the determining factor in terms of the motor behavior of the contralateral arm. The objective of the present study was to assess the respective effects of mirror reflection and arm displacement (whether real or simulated) on involuntary motor behavior of the contralateral arm following sustained, isometric contraction (Kohnstamm phenomenon). Our results revealed that (i) passive displacement of one arm (displacement of the left arm via a motorized manipulandum moving at 4°/s) influenced the velocity of the Kohnstamm phenomenon (forearm flexion occurring shortly after the cessation of muscle contraction) in the contralateral arm and (ii) mirror vision had no effect. Indeed, the velocity of the Kohnstamm phenomenon tended to be adjusted to match the velocity of the passive displacement of the other arm. In a second experiment, arm displacement was simulated by vibrating the triceps at 25, 50 or 75 Hz. Results showed that the velocity of the Kohnstamm phenomenon in one arm increased with the vibration frequency applied to the other arm. Our results revealed the occurrence of bimanual coupling because involuntary displacement of one arm was regulated by muscle-related information generated by the actual or simulated displacement of the other arm. In line with the literature data on voluntary motor behavior, our study failed to evidence an additional impact of mirror vision on involuntary motor behavior.

  14. Collective behavior of minus-ended motors in mitotic microtubule asters gliding toward DNA.

    PubMed

    Athale, Chaitanya A; Dinarina, Ana; Nedelec, Francois; Karsenti, Eric

    2014-02-01

    Microtubules (MTs) nucleated by centrosomes form star-shaped structures referred to as asters. Aster motility and dynamics is vital for genome stability, cell division, polarization and differentiation. Asters move either toward the cell center or away from it. Here, we focus on the centering mechanism in a membrane independent system of Xenopus cytoplasmic egg extracts. Using live microscopy and single particle tracking, we find that asters move toward chromatinized DNA structures. The velocity and directionality profiles suggest a random-walk with drift directed toward DNA. We have developed a theoretical model that can explain this movement as a result of a gradient of MT length dynamics and MT gliding on immobilized dynein motors. In simulations, the antagonistic action of the motor species on the radial array of MTs leads to a tug-of-war purely due to geometric considerations and aster motility resembles a directed random-walk. Additionally, our model predicts that aster velocities do not change greatly with varying initial distance from DNA. The movement of asymmetric asters becomes increasingly super-diffusive with increasing motor density, but for symmetric asters it becomes less super-diffusive. The transition of symmetric asters from superdiffusive to diffusive mobility is the result of number fluctuations in bound motors in the tug-of-war. Overall, our model is in good agreement with experimental data in Xenopus cytoplasmic extracts and predicts novel features of the collective effects of motor-MT interactions.

  15. Adaptive intermittent control: A computational model explaining motor intermittency observed in human behavior.

    PubMed

    Sakaguchi, Yutaka; Tanaka, Masato; Inoue, Yasuyuki

    2015-07-01

    It is a fundamental question how our brain performs a given motor task in a real-time fashion with the slow sensorimotor system. Computational theory proposed an influential idea of feed-forward control, but it has mainly treated the case that the movement is ballistic (such as reaching) because the motor commands should be calculated in advance of movement execution. As a possible mechanism for operating feed-forward control in continuous motor tasks (such as target tracking), we propose a control model called "adaptive intermittent control" or "segmented control," that brain adaptively divides the continuous time axis into discrete segments and executes feed-forward control in each segment. The idea of intermittent control has been proposed in the fields of control theory, biological modeling and nonlinear dynamical system. Compared with these previous models, the key of the proposed model is that the system speculatively determines the segmentation based on the future prediction and its uncertainty. The result of computer simulation showed that the proposed model realized faithful visuo-manual tracking with realistic sensorimotor delays and with less computational costs (i.e., with fewer number of segments). Furthermore, it replicated "motor intermittency", that is, intermittent discontinuities commonly observed in human movement trajectories. We discuss that the temporally segmented control is an inevitable strategy for brain which has to achieve a given task with small computational (or cognitive) cost, using a slow control system in an uncertain variable environment, and the motor intermittency is the side-effect of this strategy.

  16. Disruption of motor behavior and injury to the CNS induced by 3-thienylboronic acid in mice.

    PubMed

    Farfán-García, E D; Pérez-Rodríguez, M; Espinosa-García, C; Castillo-Mendieta, N T; Maldonado-Castro, M; Querejeta, E; Trujillo-Ferrara, J G; Soriano-Ursúa, M A

    2016-09-15

    The scarcity of studies on boron containing compounds (BCC) in the medicinal field is gradually being remedied. Efforts have been made to explore the effects of BCCs due to the properties that boron confers to molecules. Research has shown that the safety of some BCCs is similar to that found for boron-free compounds (judging from the acute toxicological evaluation). However, it has been observed that the administration of 3-thienylboronic acid (3TB) induced motor disruption in CD1 mice. In the current contribution we studied in deeper form the disruption of motor performance produced by the intraperitoneal administration of 3TB in mice from two strains (CD1 and C57BL6). Disruption of motor activity was dependent not only on the dose of 3TB administered, but also on the DMSO concentration in the vehicle. The ability of 3TB to enter the Central Nervous System (CNS) was evidenced by Raman spectroscopy as well as morphological effects on the CNS, such as loss of neurons yielding biased injury to the substantia nigra and striatum at doses ≥200mg/kg, and involving granular cell damage at doses of 400mg/kg but less injury in the motor cortex. Our work acquaints about the use of this compound in drug design, but the interesting profile as neurotoxic agent invite us to study it regarding the damage on the motor system.

  17. Collective behavior of minus-ended motors in mitotic microtubule asters gliding toward DNA

    NASA Astrophysics Data System (ADS)

    Athale, Chaitanya A.; Dinarina, Ana; Nedelec, Francois; Karsenti, Eric

    2014-02-01

    Microtubules (MTs) nucleated by centrosomes form star-shaped structures referred to as asters. Aster motility and dynamics is vital for genome stability, cell division, polarization and differentiation. Asters move either toward the cell center or away from it. Here, we focus on the centering mechanism in a membrane independent system of Xenopus cytoplasmic egg extracts. Using live microscopy and single particle tracking, we find that asters move toward chromatinized DNA structures. The velocity and directionality profiles suggest a random-walk with drift directed toward DNA. We have developed a theoretical model that can explain this movement as a result of a gradient of MT length dynamics and MT gliding on immobilized dynein motors. In simulations, the antagonistic action of the motor species on the radial array of MTs leads to a tug-of-war purely due to geometric considerations and aster motility resembles a directed random-walk. Additionally, our model predicts that aster velocities do not change greatly with varying initial distance from DNA. The movement of asymmetric asters becomes increasingly super-diffusive with increasing motor density, but for symmetric asters it becomes less super-diffusive. The transition of symmetric asters from superdiffusive to diffusive mobility is the result of number fluctuations in bound motors in the tug-of-war. Overall, our model is in good agreement with experimental data in Xenopus cytoplasmic extracts and predicts novel features of the collective effects of motor-MT interactions.

  18. Negative childhood experiences alter a prefrontal-insular-motor cortical network in healthy adults: A preliminary multimodal rsfMRI-fMRI-MRS-dMRI study

    PubMed Central

    Duncan, Niall W.; Hayes, Dave J.; Wiebking, Christine; Tiret, Brice; Pietruska, Karin; Chen, David Q.; Rainville, Pierre; Marjańska, Malgorzata; Mohammid, Omar; Doyon, Julien; Hodaie, Mojgan; Northoff, Georg

    2016-01-01

    Research in humans and animals has shown that negative childhood experiences (NCE) can have long-term effects on the structure and function of the brain. Alterations have been noted in grey and white matter, in the brain’s resting state, on the glutamatergic system, and on neural and behavioural responses to aversive stimuli. These effects can be linked to psychiatric disorder such as depression and anxiety disorders that are influenced by excessive exposure to early life stressors. The aim of the current study was to investigate the effect of NCEs on these systems. Resting state functional MRI (rsfMRI), aversion task fMRI, glutamate magnetic resonance spectroscopy (MRS), and diffusion magnetic resonance imaging (dMRI) were combined with the Childhood Trauma Questionnaire (CTQ) in healthy subjects to examine the impact of NCEs on the brain. Low CTQ scores, a measure of NCEs, were related to higher resting state glutamate levels and higher resting state entropy in the medial prefrontal cortex (mPFC). CTQ scores, mPFC glutamate and entropy, correlated with neural BOLD responses to the anticipation of aversive stimuli in regions throughout the aversion-related network, with strong correlations between all measures in the motor cortex and left insula. Structural connectivity strength, measured using mean fractional anisotropy, between the mPFC and left insula correlated to aversion-related signal changes in the motor cortex. These findings highlight the impact of NCEs on multiple inter-related brain systems. In particular, they highlight the role of a prefrontal-insular-motor cortical network in the processing and responsivity to aversive stimuli and its potential adaptability by NCEs. PMID:26287448

  19. Mutation of Gtf2ird1 from the Williams-Beuren syndrome critical region results in facial dysplasia, motor dysfunction, and altered vocalisations.

    PubMed

    Howard, Monique L; Palmer, Stephen J; Taylor, Kylie M; Arthurson, Geoffrey J; Spitzer, Matthew W; Du, Xin; Pang, Terence Y C; Renoir, Thibault; Hardeman, Edna C; Hannan, Anthony J

    2012-03-01

    Insufficiency of the transcriptional regulator GTF2IRD1 has become a strong potential explanation for some of the major characteristic features of the neurodevelopmental disorder Williams-Beuren syndrome (WBS). Genotype/phenotype correlations in humans indicate that the hemizygous loss of the GTF2IRD1 gene and an adjacent paralogue, GTF2I, play crucial roles in the neurocognitive and craniofacial aspects of the disease. In order to explore this genetic relationship in greater detail, we have generated a targeted Gtf2ird1 mutation in mice that blocks normal GTF2IRD1 protein production. Detailed analyses of homozygous null Gtf2ird1 mice have revealed a series of phenotypes that share some intriguing parallels with WBS. These include reduced body weight, a facial deformity resulting from localised epidermal hyperplasia, a motor coordination deficit, alterations in exploratory activity and, in response to specific stress-inducing stimuli; a novel audible vocalisation and increased serum corticosterone. Analysis of Gtf2ird1 expression patterns in the brain using a knock-in LacZ reporter and c-fos activity mapping illustrates the regions where these neurological abnormalities may originate. These data provide new mechanistic insight into the clinical genetic findings in WBS patients and indicate that insufficiency of GTF2IRD1 protein contributes to abnormalities of facial development, motor function and specific behavioural disorders that accompany this disease.

  20. How does transcranial DC stimulation of the primary motor cortex alter regional neuronal activity in the human brain?

    PubMed

    Lang, Nicolas; Siebner, Hartwig R; Ward, Nick S; Lee, Lucy; Nitsche, Michael A; Paulus, Walter; Rothwell, John C; Lemon, Roger N; Frackowiak, Richard S

    2005-07-01

    Transcranial direct current stimulation (tDCS) of the primary motor hand area (M1) can produce lasting polarity-specific effects on corticospinal excitability and motor learning in humans. In 16 healthy volunteers, O positron emission tomography (PET) of regional cerebral blood flow (rCBF) at rest and during finger movements was used to map lasting changes in regional synaptic activity following 10 min of tDCS (+/-1 mA). Bipolar tDCS was given through electrodes placed over the left M1 and right frontopolar cortex. Eight subjects received anodal or cathodal tDCS of the left M1, respectively. When compared to sham tDCS, anodal and cathodal tDCS induced widespread increases and decreases in rCBF in cortical and subcortical areas. These changes in rCBF were of the same magnitude as task-related rCBF changes during finger movements and remained stable throughout the 50-min period of PET scanning. Relative increases in rCBF after real tDCS compared to sham tDCS were found in the left M1, right frontal pole, right primary sensorimotor cortex and posterior brain regions irrespective of polarity. With the exception of some posterior and ventral areas, anodal tDCS increased rCBF in many cortical and subcortical regions compared to cathodal tDCS. Only the left dorsal premotor cortex demonstrated an increase in movement related activity after cathodal tDCS, however, modest compared with the relatively strong movement-independent effects of tDCS. Otherwise, movement related activity was unaffected by tDCS. Our results indicate that tDCS is an effective means of provoking sustained and widespread changes in regional neuronal activity. The extensive spatial and temporal effects of tDCS need to be taken into account when tDCS is used to modify brain function.

  1. Cholinergic and Dopaminergic Alterations in Nigrostriatal Neurons Are Involved in Environmental Enrichment Motor Protection in a Mouse Model of Parkinson's Disease.

    PubMed

    Hilario, Willyan Franco; Herlinger, Alice Laschuk; Areal, Lorena Bianchine; de Moraes, Lívia Silveira; Ferreira, Tamara Andrea Alarcon; Andrade, Tassiane Emanuelle Servane; Martins-Silva, Cristina; Pires, Rita Gomes Wanderley

    2016-12-01

    Parkinson's disease (PD) is the second most common neurodegenerative disease in the world, being characterized by dopaminergic neurodegeneration of substantia nigra pars compacta. PD pharmacotherapy has been based on dopamine replacement in the striatum with the dopaminergic precursor 3,4-dihydroxyphenylalanine (L-DOPA) and/or with dopaminergic agonists, alongside anticholinergic drugs in order to mitigate the motor abnormalities. However, these practices neither prevent nor stop the progression of the disease. Environmental enrichment (EE) has effectively prevented several neurodegenerative processes, mainly in preclinical trials. Several studies have demonstrated that EE induces biological changes, bearing on cognitive enhancement, neuroprotection, and on the attenuation of the effects of stress, anxiety, and depression. Herein, we investigated whether EE could prevent the motor, biochemical, and molecular abnormalities in a murine model of PD induced by 1-methyl-4-phenyl-2,3-dihydropyridine (MPTP). Our results show that EE does not prevent the dopaminergic striatal depletion induced by MPTP, despite having averted the MPTP-induced hyperlocomotion. However, it was able to slow down and avoid, respectively, the 3,4-dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA) depletion. Analysis of dopaminergic mRNA alterations in the midbrain showed that D1R expression was increased by MPTP, while the normal expression level of this receptor was restored by EE. As for the cholinergic system, MPTP led to a decrease in the ChAT gene expression while increasing the expression of both AChE and M1R. EE attenuated and prevented-respectively-ChAT and M1R gene expression alterations triggered by MPTP in the midbrain. Overall, our data brings new evidence supporting the neuroprotective potential of EE in PD, focusing on the interaction between dopaminergic and cholinergic systems.

  2. Thalamocortical Projections onto Behaviorally Relevant Neurons Exhibit Plasticity during Adult Motor Learning.

    PubMed

    Biane, Jeremy S; Takashima, Yoshio; Scanziani, Massimo; Conner, James M; Tuszynski, Mark H

    2016-03-16

    Layer 5 neurons of the neocortex receive direct and relatively strong input from the thalamus. However, the intralaminar distribution of these inputs and their capacity for plasticity in adult animals are largely unknown. In slices of the primary motor cortex (M1), we simultaneously recorded from pairs of corticospinal neurons associated with control of distinct motor outputs: distal forelimb versus proximal forelimb. Activation of ChR2-expressing thalamocortical afferents in M1 before motor learning produced equivalent responses in monosynaptic excitation of neurons controlling the distal and proximal forelimb, suggesting balanced thalamic input at baseline. Following skilled grasp training, however, thalamocortical input shifted to bias activation of corticospinal neurons associated with control of the distal forelimb. This increase was associated with a cell-specific increase in mEPSC amplitude but not presynaptic release probability. These findings demonstrate distinct and highly segregated plasticity of thalamocortical projections during adult learning.

  3. Increasing Maternal or Post-Weaning Folic Acid Alters Gene Expression and Moderately Changes Behavior in the Offspring

    PubMed Central

    Kuizon, Salomon; Buenaventura, Diego; Stapley, Nathan W.; Ruocco, Felicia; Begum, Umme; Guariglia, Sara R.; Brown, W. Ted; Junaid, Mohammed A.

    2014-01-01

    Background Studies have indicated that altered maternal micronutrients and vitamins influence the development of newborns and altered nutrient exposure throughout the lifetime may have potential health effects and increased susceptibility to chronic diseases. In recent years, folic acid (FA) exposure has significantly increased as a result of mandatory FA fortification and supplementation during pregnancy. Since FA modulates DNA methylation and affects gene expression, we investigated whether the amount of FA ingested during gestation alters gene expression in the newborn cerebral hemisphere, and if the increased exposure to FA during gestation and throughout the lifetime alters behavior in C57BL/6J mice. Methods Dams were fed FA either at 0.4 mg or 4 mg/kg diet throughout the pregnancy and the resulting pups were maintained on the diet throughout experimentation. Newborn pups brain cerebral hemispheres were used for microarray analysis. To confirm alteration of several genes, quantitative RT-PCR (qRT-PCR) and Western blot analyses were performed. In addition, various behavior assessments were conducted on neonatal and adult offspring. Results Results from microarray analysis suggest that the higher dose of FA supplementation during gestation alters the expression of a number of genes in the newborns’ cerebral hemispheres, including many involved in development. QRT-PCR confirmed alterations of nine genes including down-regulation of Cpn2, Htr4, Zfp353, Vgll2 and up-regulation of Xist, Nkx6-3, Leprel1, Nfix, Slc17a7. The alterations in the expression of Slc17a7 and Vgll2 were confirmed at the protein level. Pups exposed to the higher dose of FA exhibited increased ultrasonic vocalizations, greater anxiety-like behavior and hyperactivity. These findings sugg