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Excitability
Kinds of Excitability Terms modified by Excitability Selected AbstractsThe Influence of Gonadal Hormones on Neuronal Excitability, Seizures, and Epilepsy in the FemaleEPILEPSIA, Issue 9 2006Helen E. Scharfman Summary:, It is clear from both clinical observations of women, and research in laboratory animals, that gonadal hormones exert a profound influence on neuronal excitability, seizures, and epilepsy. These studies have led to a focus on two of the primary ovarian steroid hormones, estrogen and progesterone, to clarify how gonadal hormones influence seizures in women with epilepsy. The prevailing view is that estrogen is proconvulsant, whereas progesterone is anticonvulsant. However, estrogen and progesterone may not be the only reproductive hormones to consider in evaluating excitability, seizures, or epilepsy in the female. It seems unlikely that estrogen and progesterone would exert single, uniform actions given our current understanding of their complex pharmacological and physiological relationships. Their modulatory effects are likely to depend on endocrine state, relative concentration, metabolism, and many other factors. Despite the challenges these issues raise to future research, some recent advances have helped clarify past confusion in the literature. In addition, testable hypotheses have developed for complex clinical problems such as "catamenial epilepsy." Clinical and animal research, designed with the relevant endocrinological and neurobiological issues in mind, will help advance this field in the future. [source] Impaired M-Current and Neuronal ExcitabilityEPILEPSIA, Issue 2002Motohiro Okada Summary: ,Purpose: Benign familial neonatal convulsions (BFNC), a hereditary epilepsy, occurs specifically in newborns and remits spontaneously after this period. Several mutations of either KCNQ2 or KCNQ3, members of the KCNQ-related K+ -channel (KCNQ-channel) family, were identified as a cause of BFNC. Such mutations impair KCNQ-related M- current, an element of the inhibitory system in the central nervous system (CNS), and therefore are thought to result in neuronal hyperexcitability. Methods: To clarify the pathogenesis of BFNC, this study investigated the effects of the KCNQ channel on propagation of neuronal excitability using a 64-channel multielectrode dish (MED64) system for novel two-dimensional monitoring of evoked field potentials including fiber volley (FV) and field excitatory postsynaptic potential (fEPSP). Results: Dup996, a selective KCNQ-channel inhibitor, did not affect the amplitude of FV or fEPSP, but enhanced the FV and fEPSP propagation. The ,-aminobutyric acid (GABA)A -receptor antagonist, bicuculline, enhanced their propagation, whereas ,-amino-3-hydroxy-5-methyl-4-isoxazolepropionate (AMPA)/glutamate-receptor antagonist, DNQX, reduced both amplitude and propagation of fEPSP without affecting those of FV. Under the condition of GABAA -receptor blockade by bicuculline, Dup996 enhanced the amplitude of fEPSP and propagation of FV and fEPSP without affecting the amplitude of FV. Dup996 enhanced the stimulating effects of bicuculline on the propagation and amplitude of FV and fEPSP, but it did not affect the inhibiting effects of DNQX. Conclusions: These results suggest that the occurrence of BFNC cannot be produced by KCNQ-channel dysfunction alone but by reciprocal action between impaired KCNQ channel and the other unknown. [source] Abnormal Excitability of Hippocampal CA3 Neurons in Noda Epileptic Rat (NER): Alteration of Seizure with AgingEPILEPSIA, Issue 2000Ryosuke Hanaya Purpose: Noda epileptic rat (NER), a mutant found in thc colony of Crj:Wistar rats, spontaneously shows tonic-clonic convulsions approximately once every 30 hours from 8,16 weeks of age. A long-lasting dcpolarization shift accompanied by repetitivc firings are observed in hippocampal CA3 pyramidal neurons of NER with seizures. Using hippocampal slice preparations of NER, the present electrophysiologi- cal study was performed to elucidate whether this abnormal firing in CA3 neurons developed with age and if abnormality of Ca2+ channel was involved. Methods: Hippocampal slices (40Opm) werc prepared from NER and normal Wistar rats (age; 4,29 weeks). A single rectangular pulse stimulus composed of 0.1-ms duration was delivered to the mossy fibers every 5 seconds though a bipolar electrode placed in the granular cell layer of the dentate gyrus. Intracellular recording was made from the CA3 pyramidal cell using a microelectrode containing 3M KCI intracellular recordings. A Ca2+ spike was elicited by applying a depolarizing pulse (InA, 120ms) in the cell through the recording electrode under a blockadc of Na+ and K+ channels using 1 pM tetrodotoxin and I 0mM tctraethylammonium added to the artificial CSF, respectivcly. Nicardipine (I-IOOnM), a Ca2+ channel blocker, was applicd to the bath. Results: Thirty-seven slices from I9 NER and 6 slices from 4 normal Wishe rats were used. There were no obvious changes in the resting membrane potentials of CA3 neurons between NER and Wistar rats tested. When a single stimulus was delivered to the mossy fibers, a long-lasting depolarization shift accompanied by repetitive firings followed by after-hyperpolarization werc also obtained i n hippocampal CA3 neurons of young NER (4,5 weeks of age) before occurrence of any seizurcs, although the depolarization shift in younger NER was shorter than that in NER aged more than 6 weeks. These abnormal firings werc evokcd in 58% and 30% of all CA3 neurons tested in the younger and mature NER (6,1 5 weeks of age), respectively. Furthermore, abnormal firing was not elicited in NER aged after I6 weeks. Agc-matched Wistar rats showed only single action potentials without any depolarization shift with single mossy fiber stimulation. Bath application of nicardipine (IOnM) inhibited this long-lasting depolarization shift and the accompanying repetitive firing followed by afterhypcrpolarization without affecting the first spike induced by mossy fiber stimulations. Furthermore, nicai-dipine (IOnM) inhibited the Ca2+ spikes elicited by applying a depolarizing pulse in the neurons of NER with seizures, although a higher dose (100nM) did not affect those in Wistar rats. Conclusions: These findings indicate that abnormal excitability of the NER CA3 pyramidal neurons is probably due to abnormality in the Ca2+ channcls. The abnorinal excitability was observed in NER at an age when tonic-clonic convulsions were not detected, suggesting that thc hippocampus may probably scrve as an epileptogenic focus in younger NER and the seizure impulses originating i n this area are transinittcd to the new other seizurc foci in mature NER. [source] Saccadic eye movements evoked by microstimulation of striate cortexEUROPEAN JOURNAL OF NEUROSCIENCE, Issue 4 2003Edward J. Tehovnik Abstract Experiments were performed to assess the excitability of neural elements activated while inducing saccadic eye movements electrically from different cortical layers of striate cortex (area V1) in rhesus monkeys. Excitability was assessed by measuring current thresholds, saccadic latencies, chronaxies, and the effectiveness of anode-first vs. cathode-first pulses. Minimum current thresholds for the evocation of saccades (i.e. less than 5 µA) were observed when the deepest layers of V1 were stimulated. The shortest saccadic latencies were also observed at these depths. The shortest latency at 10 times the threshold current was 49 ms on average. The chronaxies of the elements mediating saccades were less in deep V1 (i.e. 0.17 ms) than in superficial V1 (i.e. 0.23 ms). Anode-first pulses were more effective at evoking saccades from superficial V1, whereas cathode-first pulses were more effective at evoking saccades from deep V1. These results indicate that the excitability properties of superficial and deep V1 are distinct for the generation of saccades. Moreover, the excitability of elements mediating saccades in V1 of monkeys is comparable to that of elements mediating phosphenes in human V1. [source] Change of Excitability in Brainstem and Cortical Visual Processing in Migraine Exhibiting AllodyniaHEADACHE, Issue 10 2006Koichi Shibata MD Background.,Clinical and neurophysiological manifestations of information processing associated with central sensitization are little known. Allodynic migraine (AM) can be caused by the sensitization of trigeminal neuron, but no study has reported on AM between attacks using blink reflex (BR) and pattern-reversal visual evoked potentials (PVEPs). Objective.,We explored the characteristics of AM between attacks associated with central sensitization using BR and PVEP. Methods.,We recruited 13 patients with interictal AM and 15 patients with nonallodynic migraine (NA), and 30 healthy subjects (HS). BRs were obtained using paired pulses delivered at the interstimulus interval (ISI) of 150, 300, and 500 ms. The ratio of the area in the R2 of the second to R2 of the first shock was measured for each ISI. PVEP were recorded with 2 spatial frequencies (0.5 and 4.0 cpd) and 2 low and high contrasts (29% and 98%, respectively). Amplitudes of P100 were measured. Results.,For BR, there were no significant differences in the ratio of the area of the R2 between the sides of stimulation, and the sides of headache. AM patients had less suppression of the R2 at the ISI of 150 and 300 ms when compared with the NA patients and HS. For PVEP, at 0.5, there were significant differences of amplitude between AM patients and HS, and between NA patients and HS in low and high contrast. At 4.0 cpd, there were significant differences of amplitude between AM patients and HS in low contrast, and between AM patients and HS, and NA patients and HS in high contrast. In AM patients, there was a significant difference of amplitude ratio between 0.5 and 4.0 cpd. Conclusions.,Our BR and PVEP study showed that migraine patients exhibiting allodynia may show central sensitization of brainstem trigeminal neuron and have contrast modulating dysfunction during the cortical visual processing of striate and extrastriate on visual cortex in-between attacks. [source] Visual Cortex Excitability in Migraine With and Without AuraHEADACHE, Issue 6 2001Wim M. Mulleners MD Objectives.,Previous research using transcranial magnetic stimulation has produced equivocal findings concerning thresholds for the generation of visual phosphenes in migraine with aura. These studies were methodologically varied and did not systematically address cortical excitability in migraine without aura. We therefore studied magnetophosphene thresholds in both migraine with aura and migraine without aura compared with headache-free controls. Methods.,Sixteen subjects with migraine with aura and 12 subjects with migraine without aura were studied and compared with 16 sex- and age-matched controls. Using a standardized transcranial magnetic stimulation protocol of the occipital cortex, we assessed the threshold stimulation intensity at which subjects just perceived phosphenes via a method of alternating course and fine-tuning of stimulator output. Results.,There were no significant differences across groups in the proportion of subjects seeing phosphenes. However, the mean threshold at which phosphenes were reported was significantly lower in both migraine groups (migraine with aura=47%, migraine without aura=46%) than in controls (66%). Moreover, there was no significant correlation between individual phosphene threshold and the time interval to the closest migraine attack. Conclusion.,Our findings confirm that the occipital cortex is hyperexcitable in the migraine interictum, both in migraine with and without aura. [source] Thyroid Hormone Action: Nongenomic Modulation of Neuronal Excitability in the HippocampusJOURNAL OF NEUROENDOCRINOLOGY, Issue 2 2009M. A. Caria Years of effort have failed to establish a generally-accepted mechanism of thyroid hormone (TH) action in the mature brain. Recently, both morphological and pharmacological evidence have supported a direct neuroactive role for the hormone and its triiodinated metabolites. However, no direct physiological validation has been available. We now describe electrophysiological studies in vivo in which we observed that local thyroxine (T4) administration promptly inhibited field excitatory postsynaptic potentials recorded in the dentate gyrus (DG) with stimulation of the medial perforant pathway, a result that was found to be especially pronounced in hypothyroid rats. In separate in vitro experiments, we observed more subtle but statistically significant responses of hippocampal slices to treatment with the hormone. The results demonstrate that baseline firing rates of CA1 pyramidal cells were modestly reduced by pulse-perfusion with T4. By contrast, administration of triiodothyronine (T3) was often noted to have modest enhancing effects on CA1 cell firing rates in hippocampal slices from euthyroid animals. Moreover, and more reliably, robust firing rate increases induced by norepinephrine were amplified when preceded by treatment with T3, whereas they were diminished by pretreatment with T4. These studies provide the first direct evidence for functional, nongenomic actions of TH leading to rapid changes in neuronal excitability in adult rat DG studied in vivo and highlight the opposing effects of T4 and T3 on norepinephrine-induced responses of CA1 cells studied in vitro. [source] Nesfatin-1 Influences the Excitability of Paraventricular Nucleus NeuronesJOURNAL OF NEUROENDOCRINOLOGY, Issue 2 2008C. J. Price Nesfatin-1 is a newly-discovered satiety peptide found in several nuclei of the hypothalamus, including the paraventricular nucleus. To begin to understand the physiological mechanisms underlying these satiety-inducing actions, we examined the effects of nesfatin-1 on the excitability of neurones in the paraventricular nucleus. Whole-cell current-clamp recordings from rat paraventricular nucleus neurones showed nesfatin-1 to have either hyperpolarising or depolarising effects on the majority of neurones tested. Both types of response were observed in neurones irrespective of classification based on electrophysiological fingerprint (magnocellular, neuroendocrine or pre-autonomic) or molecular phenotype (vasopressin, oxytocin, corticotrophin-releasing hormone, thyrotrophin-releasing hormone or vesicular glutamate transporter), determined using single cell reverse transcription-poylmerase chain reaction. Consequently, we provide the first evidence that this peptide, which is produced in the paraventricular nucleus, has effects on the membrane potential of a large proportion of different subpopulations of neurones located in this nucleus, and therefore identify nesfatin-1 as a potentially important regulator of paraventricular nucleus output. [source] In Vivo Modulation of Post-Spike Excitability in Vasopressin Cells by ,-Opioid Receptor ActivationJOURNAL OF NEUROENDOCRINOLOGY, Issue 8 2000C. H. Brown Abstract An endogenous ,-opioid agonist reduces the duration of phasic bursts in vasopressin cells. Non-synaptic post-spike depolarizing after-potentials underlie activity during bursts by increasing post-spike excitability and ,-receptor activation reduces depolarizing after-potential amplitude in vitro. To investigate the effects of ,-opioids on post-spike excitability in vivo, we analysed extracellular recordings of the spontaneous activity of identified supraoptic nucleus vasopressin cells in urethane-anaesthetized rats infused with Ringer's solution (n = 17) or the ,-agonist, U50,488H (2.5 µg/h at 0.5 µl/h; n = 23), into the supraoptic nucleus over 5 days. We plotted the mean hazard function for the interspike interval distributions as a measure of the post-spike excitability of these cells. Following each spike, the probability of another spike firing in vasopressin cells recorded from U50,488H infused nuclei was markedly reduced compared to Ringer's treated vasopressin cells. To determine whether U50,488H could reduce post-spike excitability in cells that displayed spontaneous phasic activity, we infused U50,488H (50 µg/h at 1 µl/h, i.c.v.), for 1,12 h while recording vasopressin cell activity. Nine of 10 vasopressin cells were silenced by i.c.v. U50,488H 15 ± 5 min into the infusion. Six cells exhibited spontaneous phasic activity before U50,488H infusion and recordings from three of these phasic cells were maintained until activity recovered; during U50,488H infusion, the activity of these three cells was irregular. Generation of the mean hazard function before and during U50,488H infusion revealed a reduction in post-spike excitability during U50,488H infusion. Thus, ,-receptor activation reduces post-spike excitability in vivo; this may reflect inhibition of depolarizing after-potentials and may thus underlie the reduction in burst duration of vasopressin cells caused by an endogenous ,-agonist in vivo. [source] Altered Motor Cortex Excitability to Magnetic Stimulation in Alcohol Withdrawal SyndromeALCOHOLISM, Issue 4 2010Raffaele Nardone Background:, Alcohol addiction is a complex brain disease caused by alterations in crucial neurotransmitter systems, including gamma-aminobutyric acid (GABA) and glutamate. These disturbances could be revealed by changes in cortical excitability parameters, as assessed by transcranial magnetic stimulation (TMS). This study was aimed to further investigate the complex pathophysiology of alcohol withdrawal syndrome (AWS). Methods:, Motor cortex excitability was examined in 13 subjects with AWS in a mild predelirial state, in 12 chronic alcoholics and in 15 age-matched control subjects, using a range of TMS protocols. Central motor conduction time, resting and active motor threshold, duration of the cortical silent period, short latency intracortical inhibition (SICI), and intracortical facilitation (ICF) to paired TMS were examined. Results:, Intracortical facilitation was significantly increased in the AWS patients when compared with the chronic alcoholics and the control subjects. The other TMS parameters did not differ significantly from the controls. Administration of a single oral dose of the glutamatergic antagonist riluzole in a subgroup of 8 patients significantly reduced ICF; motor threshold and SICI were not affected by riluzole. Conclusion:, Transcranial magnetic stimulation shows a selective increase in intracortical facilitation after ethanol withdrawal. Our findings support the theory that altered glutamatergic receptor function plays an important role in the pathogenesis of human alcohol withdrawal. This study provides further physiological evidence that antiglutamatergic approaches represent an efficacious alternative for treating alcohol withdrawal symptoms. [source] Restored Atrial Excitability After Late Recanalization in a Patient with Atrial Standstill and Acute Myocardial InfarctionPACING AND CLINICAL ELECTROPHYSIOLOGY, Issue 2 2002TAKA-AKI KOSHIMIZU KOSHIMIZU, T-A., et al.: Restored Atrial Excitability After Late Recanalization in a Patient with Atrial Standstill and Acute Myocardial Infarction. Atrial standstill is electrophysiologically characterized by the loss of spontaneous excitation in atrial muscle and the inability to cause action potential firing upon electrical stimulation. Clinical diagnosis of transient standstill of the right atrium was made in a patient with acute occlusion of the right coronary artery and acute renal failure. Percutaneous coronary intervention, performed 5 days after the onset, restored the coronary blood flow and resulted in full recovery of electrical activity and regular sinus rhythm. [source] The Comparative Effects of Drive and Test Stimulus Intensity on Myocardial Excitability and VulnerabilityPACING AND CLINICAL ELECTROPHYSIOLOGY, Issue 1 2000HOWARD S. FRIEDMAN The number and intensity of stimuli that set basic cycle length in cardiac electrophysiological studies can influence the electrical properties assessed by extrastimuli. The relative contribution of drive (S1) and test (S2) stimulus intensity in defining myocardial excitability and vulnerability has not been reported. The purpose of this investigation was to assess this interaction and to determine whether a trial and ventricular findings differed. The effects of S1 and S2 intensity on a trial and ventricular stimulus-intensity-refractory-period curves were determined in open-chest dogs: comparisons were made between curves with S1 intensity varied between diastolic threshold (DT) and 10 mA and S2 intensity maintained at DT and those with S, intensity maintained at DT and S2 intensity varied between DT and 10 mA. S1 -S2 was held constant and S1 -S2 varied. The effects of different stimulation sites, cycle length, number of stimulations, and neural blockade were assessed. S3 intensity amplification shifted atrial stimulus-intensity-refractory period curves in the direction of increased excitability and vulnerability; the changes were, more pronounced than those obtained by modulating S2 intensity. The changes produced by increasing S1 intensity were evident at different cycle lengths and were enhanced by an increased number of stimulations, but were not evident when S1 and S2 were delivered at different atrial sites. Although beta-blockade attenuated the effects of increasing S1 intensity somewhat, the addition of cholinergic blockade virtually abolished it. Ventricular refractoriness was also changed by modulation of S1 intensity, but the changes were less striking. In the atrium, modulation of S1 intensity has greater effects of stimulus-intensity-refractory-period relations than modulation ofS2 intensity; in the ventricle, the converse is true. [source] Personality in nonhuman primates: a review and evaluation of past researchAMERICAN JOURNAL OF PRIMATOLOGY, Issue 8 2010Hani D. Freeman Abstract Scientific reports of personality in nonhuman primates are now appearing with increasing frequency across a wide range of disciplines, including psychology, anthropology, endocrinology, and zoo management. To identify general patterns of research and summarize the major findings to date, we present a comprehensive review of the literature, allowing us to pinpoint the major gaps in knowledge and determine what research challenges lay ahead. An exhaustive search of five scientific databases identified 210 relevant research reports. These articles began to appear in the 1930s, but it was not until the 1980s that research on primate personality began to gather pace, with more than 100 articles published in the last decade. Our analyses of the literature indicate that some domains (e.g., sex, age, rearing conditions) are more evenly represented in the literature than are others (e.g., species, research location). Studies examining personality structure (e.g., with factor analysis) have identified personality dimensions that can be divided into 14 broad categories, with Sociability, Confidence/Aggression, and Fearfulness receiving the most research attention. Analyses of the findings pertaining to inter-rater agreement, internal consistency, test,retest reliability, generally support not only the reliability of primate personality ratings scales but also point to the need for more psychometric studies and greater consistency in how the analyses are reported. When measured at the level of broad dimensions, Extraversion and Dominance generally demonstrated the highest levels of inter-rater reliability, with weaker findings for the dimensions of Agreeableness, Emotionality, and Conscientiousness. Few studies provided data with regard to convergent and discriminant validity; Excitability and Dominance demonstrated the strongest validity coefficients when validated against relevant behavioral criterion measures. Overall, the validity data present a somewhat mixed picture, suggesting that high levels of validity are attainable, but by no means guaranteed. Discussion focuses on delineating major theoretical and empirical questions facing research and practice in primate personality. Am. J. Primatol. 72:653,671, 2010. © 2010 Wiley-Liss, Inc. [source] Excitability of human motor cortex inputs prior to graspTHE JOURNAL OF PHYSIOLOGY, Issue 1 2007Gita Prabhu Transcranial magnetic stimulation (TMS) was used to investigate corticospinal excitability during the preparation period preceding visually guided self-paced grasping. Previously we have shown that while subjects prepare to grasp a visible object, paired-pulse TMS at a specific interval facilitates motor-evoked potentials (MEPs) in hand muscles in a manner that varies with the role of the muscle in shaping the hand for the upcoming grasp. This anticipatory modulation may reflect transmission of inputs to human primary motor cortex (M1) for visuomotor guidance of hand shape. Conversely, single-pulse TMS is known to suppress MEPs during movement preparation. Here we investigate the time course of single- and paired-pulse MEP modulation. TMS was delivered over M1, at different time intervals after visual presentation of either a handle or a disc to healthy subjects. Participants were instructed to view the object, and later to grasp it when given a cue. During grasp there was a specific pattern of hand muscle activity according to the object grasped. MEPs were evoked in these muscles by TMS delivered prior to grasp. Paired-pulse MEPs were facilitated, whilst single-pulse MEPs were suppressed. The pattern of facilitation matched the object-specific pattern of muscle activity for TMS pulses delivered 150 ms or more after object presentation. However, this effect was not present when TMS was delivered immediately after object presentation, or if the delivery of TMS was given separately from the cue to perform the grasp action. These results suggest that object-related information for preparation of appropriate hand shapes reaches M1 only immediately preceding execution of the grasp. [source] Tests for presynaptic modulation of corticospinal terminals from peripheral afferents and pyramidal tract in the macaqueTHE JOURNAL OF PHYSIOLOGY, Issue 1 2006A. Jackson The efficacy of sensory input to the spinal cord can be modulated presynaptically during voluntary movement by mechanisms that depolarize afferent terminals and reduce transmitter release. It remains unclear whether similar influences are exerted on the terminals of descending fibres in the corticospinal pathway of Old World primates and man. We investigated two signatures of presynaptic inhibition of the macaque corticospinal pathway following stimulation of the peripheral nerves of the arm (median, radial and ulnar) and the pyramidal tract: (1) increased excitability of corticospinal axon terminals as revealed by changes in antidromically evoked cortical potentials, and (2) changes in the size of the corticospinal monosynaptic field potential in the spinal cord. Conditioning stimulation of the pyramidal tract increased both the terminal excitability and monosynaptic fields with similar time courses. Excitability was maximal between 7.5 and 10 ms following stimulation and returned to baseline within 40 ms. Conditioning stimulation of peripheral nerves produced no statistically significant effect in either measure. We conclude that peripheral afferents do not exert a presynaptic influence on the corticospinal pathway, and that descending volleys may produce autogenic terminal depolarization that is correlated with enhanced transmitter release. Presynaptic inhibition of afferent terminals by descending pathways and the absence of a reciprocal influence of peripheral input on corticospinal efficacy would help to preserve the fidelity of motor commands during centrally initiated movement. [source] Excitability of human muscle afferents studied using threshold tracking of the H reflexTHE JOURNAL OF PHYSIOLOGY, Issue 2 2002Cindy S.-Y. In human peripheral nerves, physiological evidence has been presented for a number of biophysical differences between cutaneous afferents and , motor axons. The differences in strength-duration properties for cutaneous afferents and motor axons in the median nerve have been attributed to greater expression of a persistent Na+ conductance (INa,P) on cutaneous afferents. However, it is unclear whether the biophysical properties of human group Ia afferents differ from those of cutaneous afferents. The present studies were undertaken to determine whether the properties of human group Ia afferents can be studied indirectly using ,threshold tracking' to measure the excitability changes in the H reflex, and to determine whether the excitability of group Ia afferents differs from that of cutaneous afferents. The strength-duration properties of the soleus H reflex and soleus motor axons were measured at rest and during sustained voluntary contractions. Similar experiments were performed on the median nerve at the wrist to study the strength-duration properties of cutaneous afferents, , motor axons and H reflex of the thenar muscles. In addition, the technique of ,latent addition' was used to determine whether there was a difference in a low-threshold conductance on soleus Ia afferent and motor axons. The present findings indicate that the strength-duration time constant (,SD) for the H reflex is longer than that for , motor axons, but similar to that for cutaneous afferents. There were no differences in ,SD for the soleus H reflex at rest and during contractions, suggesting that ,SD for the H reflex is largely unaffected by changes in synaptic or motoneurone properties. Finally, the difference in latent addition suggests that the longer ,SD of the soleus H reflex may indeed be due to greater activity of a persistent Na+ conductance on Ia afferents than on soleus , motor axons. [source] Aberrant Control of Motoneuronal Excitability in Amyotrophic Lateral Sclerosis: Excitatory Glutamate,/,D -Serine vs.CHEMISTRY & BIODIVERSITY, Issue 6 2010-Aminobutanoic Acid (GABA), Inhibitory Glycine/ Abstract The mechanism underlying selective motoneuronal loss in amyotrophic lateral sclerosis (ALS) remains uncertain. The pathogenesis appears to be a complex and multifactorial process. Glutamate excitotoxicity to motoneuron is one of the most intensely investigated targets for the treatment of ALS, and excessive motoneuronal excitation by glutamate through ionotropic glutamate receptors has been mainly demonstrated. However, development of clinically effective drug targeting glutamate is sometimes difficult, because some aspects of glutamergic signals also could be beneficial, as the injured neurons attempt to recruit endogenous recovery. This review is focused on identifying other mechanisms of imbalanced excitation in ALS motoneurons including excitation-modulating D -serine and inhibitory glycine/GABA. Further, validation of these mechanisms might ultimately lead us to new therapeutic targets for ALS. [source] Synaptic Control Of Motoneuron Excitability In Rodents: From Months To MillisecondsCLINICAL AND EXPERIMENTAL PHARMACOLOGY AND PHYSIOLOGY, Issue 1-2 2000Gd Funk SUMMARY 1. Motoneurons (MN) shape motor patterns by transforming inputs into action potential output. This transformation, excitability, is determined by an interaction between synaptic inputs and intrinsic membrane properties. Excitability is not static, but changes over multiple time scales. The purpose of the present paper is to review our recent data on synaptic factors important in the dynamic control of MN excitability over time scales ranging from weeks to milliseconds. 2. Developmental changes in modulation of MN excitability are well established. Noradrenergic potentiation of hypoglossal (XII) MN inspiratory activity in rhythmically active medullary slice preparations from rodents increases during the first two postnatal weeks. This is due to increasing ,1 - and ,-adrenoceptor excitatory mechanisms and to a decreasing inhibitory mechanism mediated by ,2 -adrenoceptors. Over a similar period, ATP potentiation of XII inspiratory activity does not change. 3. Motoneuron excitability may also change on a faster time scale, such as between different behaviours or different phases of a behaviour. Examination of this has been confounded by the fact that excitatory synaptic drives underlying behaviour can obscure smaller concurrent changes in excitability. Using the rhythmically active neonatal rat brain-stem,spinal cord preparation, we blocked excitatory inspiratory drive to phrenic MN (PMN) to reveal a reduction in PMN excitability specific to the inspiratory phase that: (i) arises from an inhibitory GABAergic input; (ii) is not mediated by recurrent pathways; and (iii) is proportional to and synchronous with the excitatory inspiratory input. We propose that the proportionality of the concurrent inhibitory and excitatory drives provides a means for phase- specific modulation of PMN gain. 4. Modulation across such diverse time scales emphasizes the active role that synaptic factors play in controlling MN excitability and shaping behaviour. [source] Ataxic mutant mice with defects in Ca2+ channel ,1A subunit gene: morphological and functional abnormalities in cerebellar cortical neuronsCONGENITAL ANOMALIES, Issue 2 2000Kazuhiko Sawada ABSTRACT This review summarizes recent studies in the morphological and functional abnormalities of cerebella in three ataxic mutant mice, i.e. tottering mouse, leaner mouse, and rolling mouse Nagoya (RMN). These mutants carry mutations in the Ca2+ channel ,1A subunit gene, and become useful models for human neurological diseases such as episodic ataxia type-2, familial hemiplegic migraine, and spinocerebellar ataxia type-6. All three mutants exhibited altered morphology of the Purkinje cells, ectopic synaptic contacts between granule cell axons (parallel fibers) and Purkinje cell dendritic spines and abnormal expression of tyrosine hydroxylase in Purkinje cells. In leaner mice, Purkinje cell loss was observed in alternating sagittal compartments of the cerebellar cortex corresponding to the Zebrin II-negative zones. The mutated Ca2+ channel ,1A subunit was highly expressed in granule and Purkinje cells, and the P-type Ca2+ currents in Purkinje cells were selectively reduced in the mutant mice. Therefore, we concluded that altered Ca2+ currents through the mutated Ca2+ channel ,1A subunit might be involved in the functional and morphological abnormalities in granule and Purkinje cells, and might result in expressions of behavioral phenotypes including ataxia. Increased levels of corticotropin-releasing factor and cholecystokinin in some climbing and mossy fibers were observed in RMN. These neuropeptides modulated the excitability of granule and Purkinje cells, indicating the possible expression of ataxic symptoms. [source] Changes in presumed motor cortical activity during fatiguing muscle contraction in humansACTA PHYSIOLOGICA, Issue 3 2010T. Seifert Abstract Aim:, Changes in sensory information from active muscles accompany fatiguing exercise and the force-generating capacity deteriorates. The central motor commands therefore must adjust depending on the task performed. Muscle potentials evoked by transcranial magnetic stimulation (TMS) change during the course of fatiguing muscle activity, which demonstrates activity changes in cortical or spinal networks during fatiguing exercise. Here, we investigate cortical mechanisms that are actively involved in driving the contracting muscles. Methods:, During a sustained submaximal contraction (30% of maximal voluntary contraction) of the elbow flexor muscles we applied TMS over the motor cortex. At an intensity below motor threshold, TMS reduced the ongoing muscle activity in biceps brachii. This reduction appears as a suppression at short latency of the stimulus-triggered average of rectified electromyographic (EMG) activity. The magnitude of the suppression was evaluated relative to the mean EMG activity during the 50 ms prior to the cortical stimulus. Results:, During the first 2 min of the fatiguing muscle contraction the suppression was 10 ± 0.9% of the ongoing EMG activity. At 2 min prior to task failure the suppression had reached 16 ± 2.1%. In control experiments without fatigue we did not find a similar increase in suppression with increasing levels of ongoing EMG activity. Conclusion:, Using a form of TMS which reduces cortical output to motor neurones (and disfacilitates them), this study suggests that neuromuscular fatigue increases this disfacilitatory effect. This finding is consistent with an increase in the excitability of inhibitory circuits controlling corticospinal output. [source] Probing the corticospinal link between the motor cortex and motoneurones: some neglected aspects of human motor cortical functionACTA PHYSIOLOGICA, Issue 4 2010N. C. Petersen Abstract This review considers the operation of the corticospinal system in primates. There is a relatively widespread cortical area containing corticospinal outputs to a single muscle and thus a motoneurone pool receives corticospinal input from a wide region of the cortex. In addition, corticospinal cells themselves have divergent intraspinal branches which innervate more than one motoneuronal pool but the synergistic couplings involving the many hand muscles are likely to be more diverse than can be accommodated simply by fixed patterns of corticospinal divergence. Many studies using transcranial magnetic stimulation of the human motor cortex have highlighted the capacity of the cortex to modify its apparent excitability in response to altered afferent inputs, training and various pathologies. Studies using cortical stimulation at ,very low' intensities which elicit only short-latency suppression of the discharge of motor units have revealed that the rapidly conducting corticospinal axons (stimulated at higher intensities) drive motoneurones in normal voluntary contractions. There are also major non-linearities generated at a spinal level in the relation between corticospinal output and the output from the motoneurone pool. For example, recent studies have revealed that the efficacy of the human corticospinal connection with motoneurones undergoes activity-dependent changes which influence the size of voluntary contractions. Hence, corticospinal drives must be sculpted continuously to compensate for the changing functional efficacy of the descending systems which activate the motoneurones. This highlights the need for proprioceptive monitoring of movements to ensure their accurate execution. [source] Electrophysiological determinants of hypokalaemia-induced arrhythmogenicity in the guinea-pig heartACTA PHYSIOLOGICA, Issue 4 2009O. E. Osadchii Abstract Aim:, Hypokalaemia is an independent risk factor contributing to arrhythmic death in cardiac patients. In the present study, we explored the mechanisms of hypokalaemia-induced tachyarrhythmias by measuring ventricular refractoriness, spatial repolarization gradients, and ventricular conduction time in isolated, perfused guinea-pig heart preparations. Methods:, Epicardial and endocardial monophasic action potentials from distinct left ventricular (LV) and right ventricular (RV) recording sites were monitored simultaneously with volume-conducted electrocardiogram (ECG) during steady-state pacing and following a premature extrastimulus application at progressively reducing coupling stimulation intervals in normokalaemic and hypokalaemic conditions. Results:, Hypokalaemic perfusion (2.5 mm K+ for 30 min) markedly increased the inducibility of tachyarrhythmias by programmed ventricular stimulation and rapid pacing, prolonged ventricular repolarization and shortened LV epicardial and endocardial effective refractory periods, thereby increasing the critical interval for LV re-excitation. Hypokalaemia increased the RV-to-LV transepicardial repolarization gradients but had no effect on transmural dispersion of APD90 and refractoriness across the LV wall. As determined by local activation time recordings, the LV-to-RV transepicardial conduction and the LV transmural (epicardial-to-endocardial) conduction were slowed in hypokalaemic heart preparations. This change was attributed to depressed diastolic excitability as evidenced by increased ventricular pacing thresholds. Conclusion:, These findings suggest that hypokalaemia-induced arrhythmogenicity is attributed to shortened LV refractoriness, increased critical intervals for LV re-excitation, amplified RV-to-LV transepicardial repolarization gradients and slowed ventricular conduction in the guinea-pig heart. [source] Modulation of rabbit sinoatrial node activation sequence by acetylcholine and isoproterenol investigated with optical mapping techniqueACTA PHYSIOLOGICA, Issue 4 2009D. V. Abramochkin Abstract Aims:, Changes in the rabbit sinoatrial node (SAN) activation sequence with the cholinergic and adrenergic factors were studied. The correlation between the sinus rhythm rate and the leading pacemaker site shift was determined. The hypothesis concerning the cholinergic suppression of nodal cell excitability as one of the mechanisms associated with pacemaker shift was tested. Methods:, A high-resolution optical mapping technique was used to register beat-to-beat changes in the SAN activation pattern under the influence of the cholinergic and adrenergic factors. Results:, Acetylcholine (10 ,m) and strong intramural parasympathetic nerve stimulation caused a pacemaker shift as well as rhythmic slowing and the formation of an inexcitable region in the central part of SAN. In this region the generation of action potentials was suppressed. The slowing of the sinus rhythm (which exceeded 12.8 ± 3.1% of the rhythm control rate) always accompanied the pacemaker shift. Isoproterenol (10, 100 nm, 1 ,m) and sympathetic postganglionic nerve stimulation also evoked a pacemaker shift but without formation of an inexcitable zone. The acceleration of the sinus rhythm, which exceeded 10.5 ± 1.3% of the control rate of the rhythm, always accompanied the shift. Conclusions:, Both cholinergic and adrenergic factors cause pacemaker shifts in the rabbit SAN. While modest changes in the sinus rhythm do not coincide with the pacemaker shift, greater changes always accompany the shift and may be caused by it, according to one hypothesis. The formation of an inexcitable zone at the place where the leading pacemaker is situated is one of the mechanisms associated with pacemaker shift. [source] An enhanced level of motor cortical excitability during the control of human standingACTA PHYSIOLOGICA, Issue 3 2009C. D. Tokuno Abstract Aim:, The study examined the role of the motor cortex in the control of human standing. Methods:, Subjects (n = 15) stood quietly with or without body support. The supported standing condition enabled subjects to stand with a reduced amount of postural sway. Peripheral electrical stimulation, transcranial magnetic stimulation (TMS) or transcranial electrical stimulation (TES) was applied to elicit a soleus (SOL) H-reflex, or motor-evoked potentials (MEPs) in the SOL and the tibialis anterior (TA). Trials were grouped based on the standing condition (i.e. supported vs. normal) as well as sway direction (i.e. forward and backward) while subjects were standing normally. Results:, During normal when compared to supported standing, the SOL H-reflex was depressed (,11 ± 4%), while the TMS-evoked MEPs from the SOL and TA were facilitated (35 ± 11% for the SOL, 51 ± 15% for the TA). TES-evoked SOL and TA MEPs were, however, not different between the normal and supported standing conditions. The data based on sway direction indicated that the SOL H-reflex, as well as the SOL TMS- and TES-evoked MEPs were all greater during forward when compared to backward sway. In contrast, the TMS- and TES-evoked MEPs from the TA were smaller when swaying forward as compared to backward. Conclusions:, The results indicated the presence of an enhanced cortical excitability because of the need to control for postural sway during normal standing. The increased cortical excitability was, however, unlikely to be involved in an on-going control of postural sway, suggesting that postural sway is controlled at the spinal and/or subcortical levels. [source] Protein kinase A modulates A-type potassium currents of larval zebrafish (Danio rerio) white muscle fibresACTA PHYSIOLOGICA, Issue 2 2009C. A. Coutts Abstract Aims:, Potassium (K+) channels are involved in regulating cell excitability and action potential shape. To our knowledge, very little is known about the modulation of A-type K+ currents in skeletal muscle fibres. Therefore, we sought to determine whether K+ currents of zebrafish white skeletal muscle were modulated by protein kinase A (PKA). Methods:, Pharmacology and whole-cell patch clamp were used to examine A-type K+ currents and action potentials associated with zebrafish white skeletal muscle fibres. Results:, Activation of PKA by a combination of forskolin + 3-isobutyl-1-methylxanthine (Fsk + IBMX) decreased the peak current density by ,60% and altered the inactivation kinetics of A-type K+ currents. The specific PKA inhibitor H-89 partially blocked the Fsk + IBMX-induced reduction in peak current density, but had no effect on the change in decay kinetics. Fsk + IBMX treatment did not shift the activation curve, but it significantly reduced the slope factor of activation. Activation of PKA by Fsk + IBMX resulted in a negative shift in the V50 of inactivation. H-89 prevented all Fsk + IBMX-induced changes in the steady-state properties of K+ currents. Application of Fsk + IBMX increased action potential amplitude, but had no significant effect on action potential threshold, half width or recovery rate, when fibres were depolarized with single pulses, paired pulses or with high-frequency stimuli. Conclusion:, PKA modulates the A-type K+ current in zebrafish skeletal muscle and affects action potential properties. Our results provide new insights into the role of A-type K+ channels in muscle physiology. [source] Could chronic pain and spread of pain sensation be induced and maintained by glial activation?ACTA PHYSIOLOGICA, Issue 1-2 2006E. Hansson Abstract An injury often starts with acute physiological pain, which becomes inflammatory or neuropathic, and may sometimes become chronic. It has been proposed recently that activated glial cells, astrocytes and microglia within the central nervous system could maintain the pain sensation even after the original injury or inflammation has healed, and convert it into chronic by altering neuronal excitability. Glial cell activation has also been proposed to be involved in the phenomenon of spread of pain sensation ipsilaterally or to the contralateral side (i.e. mirror image pain). Substance P and calcitonin gene-related peptide, released due to an inflammatory process, interact with the endothelial cells of the blood,spinal cord and blood,brain barriers. The barriers open partially and substances may influence adjacent glial cells. Such substances are also released from neurones carrying the ,pain message' all the way from the injury to the cerebral cortex. Pro-inflammatory cytokines may be released from the microglial cells, and astroglial Ca2+ -transients or oscillations may spread within the astroglial networks. One theory is that Ca2+ -oscillations could facilitate the formation of new synapses. These new synapses could establish neuronal contacts for maintaining and spreading the pain sensation. If this theory holds true, it is possible that Ca2+ waves, production of cytokines and growth factors could be modified by selective anti-inflammatory drugs to achieve a balance in the activities of the different intercellular and intracellular processes. This paper reviews current knowledge about glial mechanisms underlying the phenomena of chronic pain and spread of the pain sensation. [source] Contribution of neuroinflammation in burning mouth syndrome: indications from benzodiazepine useDERMATOLOGIC THERAPY, Issue 2008Fabrizio Guarneri ABSTRACT: Characterized by burning and painful oral sensations in absence of clinically significant mucosal abnormalities, the burning mouth syndrome is, despite numerous researches made, basically idiopathic and, consequently, difficult to treat effectively. Therapy with tricyclic antidepressants and benzodiazepines has been proposed, although the exact pathomechanism is not clear. The objective of this study is to define the possible reasons for the efficacy of benzodiazepines in the treatment of the burning mouth syndrome. Starting from the report of eight cases successfully treated with prazepam, the present authors examined the clinical features and the evidence from literature that support the possibility of a role of neuroinflammation in the pathogenesis of the burning mouth syndrome. Available data suggest that the nervous system could be crucial in the pathogenesis of the syndrome (altered perception of pain, disturbance of neural transmission, increased excitability, negative involvement of trigeminal-vascular system), and the present authors' experience lets them suppose a role for neuroinflammation. This hypothesis could also explain the positive response to benzodiazepines in some patients. The important role of neuroinflammation in dermatologic and oral diseases has been only recently investigated and acknowledged. Further studies on the connection between neuroinflammation and burning mouth syndrome could open interesting perspectives in the understanding and management of this difficult clinical condition. [source] Neuron-specific expression of atp6v0c2 in zebrafish CNSDEVELOPMENTAL DYNAMICS, Issue 9 2010Ah-Young Chung Abstract Vacuolar ATPase (V-ATPase) is a multi-subunit enzyme that plays an important role in the acidification of a variety of intracellular compartments. ATP6V0C is subunit c of the V0 domain that forms the proteolipid pore of the enzyme. In the present study, we investigated the neuron-specific expression of atp6v0c2, a novel isoform of the V-ATPase c-subunit, during the development of the zebrafish CNS. Zebrafish atp6v0c2 was isolated from a genome-wide analysis of the zebrafish mibta52b mutant designed to identify genes differentially regulated by Notch signaling. Whole-mount in situ hybridization revealed that atp6v0c2 is expressed in a subset of CNS neurons beginning several hours after the emergence of post-mitotic neurons. The ATP6V0C2 protein is co-localized with the presynaptic vesicle marker, SV2, suggesting that it is involved in neurotransmitter storage and/or secretion in neurons. In addition, the loss-of-function experiment suggests that ATP6V0C2 is involved in the control of neuronal excitability. Developmental Dynamics 239:2501,2508, 2010. © 2010 Wiley-Liss, Inc. [source] Epilepsy in fragile X syndromeDEVELOPMENTAL MEDICINE & CHILD NEUROLOGY, Issue 11 2002Elizabeth Berry-Kravis MD PhD Epilepsy is reported to occur in 10 to 20% of individuals with fragile X syndrome (FXS). A frequent seizure/EEG pattern in FXS appears to resemble that of benign focal epilepsy of childhood (BFEC, benign rolandic epilepsy). To evaluate seizure frequency and type in a Chicago FXS cohort, data regarding potential seizure history were reviewed for 136 individuals with FXS (age range 2 to 51 years: 113 males and 23 females). Seizures occurred in 15 males (13.3%) and one female (4.3%): of these, 12 had partial seizures. EEG findings were available for 35 individuals (13 of 16 with seizures and 22 of 120 without seizures) and showed an epileptiform abnormality in 10 (77%) individuals with seizures and five (23%) individuals without seizures - the most common epileptiform pattern being centrotemporal spikes. Seizures were easily controlled in 14 of the 16 individuals with seizures. Many individuals, including all with centrotemporal spikes, had remission of seizures in childhood. The most common seizure syndrome resembled BFEC and this pattern had the best prognosis for epilepsy remission. Deficiency of FMRP (fragile X mental retardation protein) appears to lead to increased neuronal excitability and susceptibility to epilepsy, but particularly seems to facilitate mechanisms leading to the BFEC pattern. [source] Development of the corticospinal system and hand motor function: central conduction times and motor performance testsDEVELOPMENTAL MEDICINE & CHILD NEUROLOGY, Issue 4 2000U M Fietzek Maturation of the corticospinal (CS) tract and hand motor function provide paradigms for central nervous system development. In this study, involving 112 participants (aged from 0.2 to 30 years), we evaluated central motor conduction times (CMCT) obtained with transcranial magnetic stimulation (TMS) during preinnervation conditions of facilitation and relaxation. Auditory reaction time, velocity of a ballistic movement of the arm, finger tapping, diadochokinesis, and fine motor visuomanual tracking were also examined. The maturation profiles for every parameter were calculated. CMCTs for the different preinnervation conditions reached adult values at different times and this could be explained by maturation of excitability at the cortical and spinal level. A stable phase for CMCTs and reaction time was reached during childhood. Parameters which measured motor speed and skill indicated that the development of these continued into adulthood. The maturation of the fast CS tract seems to be completed before the acquisition of the related motor performance has been accomplished. In conclusion, we could demonstrate that data from several neurophysiological methods can be combined and used to study the maturation of the function of the nervous system. This approach could allow appraisal of pathological conditions that show parallels with omissions or lack of developmental progress. [source] | |||||||||||||||||||||||||||||||