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Firing Patterns (firing + pattern)
Selected AbstractsEffect of Interictal Spikes on Single-Cell Firing Patterns in the HippocampusEPILEPSIA, Issue 4 2007Jun-Li Zhou Summary:,Purpose: The interictal EEG spike(s) is the hallmark of the epileptic EEG. While focal interictal spike (IS) have been associated with transitory cognitive impairment, with the type of deficit dependent on where in the cortex the IS arises, the mechanism by which IS result in transitory dysfunction is not known. The purpose of this study was to determine the effect of IS on single-cell firing patterns in freely moving rats with a prior history of seizures. Methods: We studied IS in two seizure models; pilocarpine-induced status epilepticus and recurrent flurothyl models. The effect of spontaneous hippocampal spikes on action potentials (APs) of CA1 cells in rats walking in a familiar environment was investigated using 32 extracellular electrodes. We also compared the effect of spikes on two types of hippcampal cells; place cells that discharge rapidly only when the rat's head is in a specific part of the environment, the so-called firing field, and interneurons, which are a main source of inhibition in the hippocampus. Results: IS were associated with a decreased likelihood of AP compared with IS-free portions of the record. Compared to pre-IS baseline, IS were followed by significant decreases in CA1 APs for periods up to 2 s following the IS in both models. When occurring in flurries, IS were associated with a pronounced decrease in APs. The response to IS was cell-dependent; IS resulted in decreases in AP firing after the IS in interneurons but not place cells. Conclusions: This study demonstrates that IS have substantial effects on cellular firing in the hippocampus and that these effects last far longer than the spike and slow wave. Furthermore, the effect of IS on cellular firing was cell specific, affecting interneurons more than place cells. These findings suggest that IS may contribute to seizure-induced cognitive impairment by altering AP firing in a cell-specific manner. [source] Effects of Potassium Concentration on Firing Patterns of Low-Calcium Epileptiform Activity in Anesthetized Rat Hippocampus: Inducing of Persistent Spike ActivityEPILEPSIA, Issue 4 2006Zhouyan Feng Summary:,Purpose: It has been shown that a low-calcium high-potassium solution can generate ictal-like epileptiform activity in vitro and in vivo. Moreover, during status epileptiform activity, the concentration of [K+]o increases, and the concentration of [Ca2+]o decreases in brain tissue. Therefore we tested the hypothesis that long-lasting persistent spike activity, similar to one of the patterns of status epilepticus, could be generated by a high-potassium, low-calcium solution in the hippocampus in vivo. Methods: Artificial cerebrospinal fluid was perfused over the surface of the exposed left dorsal hippocampus of anesthetized rats. A stimulating electrode and a recording probe were placed in the CA1 region. Results: By elevating K+ concentration from 6 to 12 mM in the perfusate solution, the typical firing pattern of low-calcium ictal bursts was transformed into persistent spike activity in the CA1 region with synaptic transmission being suppressed by calcium chelator EGTA. The activity was characterized by double spikes repeated at a frequency ,4 Hz that could last for >1 h. The analysis of multiple unit activity showed that both elevating [K+]o and lowering [Ca2+]o decreased the inhibition period after the response of paired-pulse stimulation, indicating a suppression of the after-hyperpolarization (AHP) activity. Conclusions: These results suggest that persistent status epilepticus,like spike activity can be induced by nonsynaptic mechanisms when synaptic transmission is blocked. The unique double-spike pattern of this activity is presumably caused by higher K+ concentration augmenting the frequency of typical low-calcium nonsynaptic burst activity. [source] Neurochemical identification of stereotypic burst-firing neurons in the rat dorsal raphe nucleus using juxtacellular labelling methodsEUROPEAN JOURNAL OF NEUROSCIENCE, Issue 1 2007Mihály Hajós Abstract Recent electrophysiological studies have discovered evidence of heterogeneity of 5-hydroxytryptamine (5-HT) neurons in the mesencephalic raphe nuclei. Of particular interest is a subpopulation of putative 5-HT neurons that display many of the electrophysiological properties of presumed 5-HT-containing neurons (regular and slow firing of single spikes with a broad waveform) but fire spikes in short, stereotyped bursts. In the present study we investigated the chemical identity of these neurons in rats utilizing in vivo juxtacellular labelling methods. Of ten dorsal raphe nucleus (DRN) neurons firing short stereotyped bursts within an otherwise regular firing pattern, all exhibited immunoreactivity for either 5-HT (n = 6) or the 5-HT synthesizing enzyme, tryptophan hydroxylase (TRH; n = 2) or both (n = 2). Supporting pharmacological experiments demonstrated that the burst firing DRN neurons demonstrated equal sensitivity to 5-HT1A agonism and ,1 -adrenoceptor antagonism to single spiking DRN neurons that we have previously identified as 5-HT-containing. Collectively these data provide direct evidence that DRN neurons that exhibit stereotyped burst firing activity are 5-HT containing. The presence of multiple types of electrophysiologically distinct midbrain 5-HT neurons is discussed. [source] Muscarinic control of graded persistent activity in lateral amygdala neuronsEUROPEAN JOURNAL OF NEUROSCIENCE, Issue 11 2006Alexei V. Egorov Abstract The cholinergic system is crucially involved in several cognitive processes including attention, learning and memory. Muscarinic actions have profound effects on the intrinsic firing pattern of neurons. In principal neurons of the entorhinal cortex (EC), muscarinic receptors activate an intrinsic cation current that causes multiple self-sustained spiking activity, which represents a potential mechanism for transiently sustaining information about novel items. The amygdala appears to be important for experience-dependent learning by emotional arousal, and cholinergic muscarinic influences are essential for the amygdala-mediated modulation of memory. Here we show that principal neurons from the lateral nucleus of the amygdala (LA) can generate intrinsic graded persistent activity that is similar to EC layer V cells. This firing behavior is linked to muscarinic activation of a calcium-sensitive non-specific cation current and can be mimicked by stimulation of cholinergic afferents that originate from the nucleus basalis of Meynert (n. M). Moreover, we demonstrate that the projections from the n. M. are essential and sufficient for the control and modulation of graded firing activity in LA neurons. We found that activation of these cholinergic afferents (i) is required to maintain and to increase firing rates in a graded manner, and (ii) is sufficient for the graded increases of stable discharge rates even without an associated up-regulation of Ca2+. The induction of persistent activity was blocked by flufenamic acid or 2-APB and remained intact after Ca2+ -store depletion with thapsigargin. The internal ability of LA neurons to generate graded persistent activity could be essential for amygdala-mediated memory operations. [source] Kv1 currents mediate a gradient of principal neuron excitability across the tonotopic axis in the rat lateral superior oliveEUROPEAN JOURNAL OF NEUROSCIENCE, Issue 2 2004Margaret Barnes-Davies Abstract Principal neurons of the lateral superior olive (LSO) detect interaural intensity differences by integration of excitatory projections from ipsilateral bushy cells and inhibitory inputs from the medial nucleus of the trapezoid body. The intrinsic membrane currents active around firing threshold will form an important component of this binaural computation. Whole cell patch recording in an in vitro brain slice preparation was employed to study conductances regulating action potential (AP) firing in principal neurons. Current-clamp recordings from different neurons showed two types of firing pattern on depolarization, one group fired only a single initial AP and had low input resistance while the second group fired multiple APs and had a high input resistance. Under voltage-clamp, single-spiking neurons showed significantly higher levels of a dendrotoxin-sensitive, low threshold potassium current (ILT). Block of ILT by dendrotoxin-I allowed single-spiking cells to fire multiple APs and indicated that this current was mediated by Kv1 channels. Both neuronal types were morphologically similar and possessed similar amounts of the hyperpolarization-activated nonspecific cation conductance (Ih). However, single-spiking cells predominated in the lateral limb of the LSO (receiving low frequency sound inputs) while multiple-firing cells dominated the medial limb. This functional gradient was mirrored by a medio-lateral distribution of Kv1.1 immunolabelling. We conclude that Kv1 channels underlie the gradient of LSO principal neuron firing properties. The properties of single-spiking neurons would render them particularly suited to preserving timing information. [source] Innervation of interneurons immunoreactive for VIP by intrinsically bursting pyramidal cells and fast-spiking interneurons in infragranular layers of juvenile rat neocortexEUROPEAN JOURNAL OF NEUROSCIENCE, Issue 1 2002Jochen F. Staiger Abstract Cortical columns contain specific neuronal populations with characteristic sets of connections. This wiring forms the structural basis of dynamic information processing. However, at the single-cell level little is known about specific connectivity patterns. We performed experiments in infragranular layers (V and VI) of rat somatosensory cortex, to clarify further the input patterns of inhibitory interneurons immunoreactive (ir) for vasoactive intestinal polypeptide (VIP). Neurons in acute slices were electrophysiologically characterized using whole-cell recordings and filled with biocytin. This allowed us to determine their firing pattern as regular-spiking, intrinsically bursting and fast-spiking, respectively. Biocytin was revealed histochemically and VIP immunohistochemically. Sections were examined for contacts between the axons of the filled neurons and the VIP-ir targets. Twenty pyramidal cells and five nonpyramidal (inter)neurons were recovered and sufficiently stained for further analysis. Regular-spiking pyramidal cells displayed no axonal boutons in contact with VIP-ir targets. In contrast, intrinsically bursting layer V pyramidal cells showed four putative single contacts with a proximal dendrite of VIP neurons. Fast-spiking interneurons formed contacts with two to six VIP neurons, preferentially at their somata. Single as well as multiple contacts on individual target cells were found. Electron microscopic examinations showed that light-microscopically determined contacts represent sites of synaptic interactions. Our results suggest that, within infragranular local cortical circuits, (i) fast-spiking interneurons are more likely to influence VIP cells than are pyramidal cells and (ii) pyramidal cell input probably needs to be highly convergent to fire VIP target cells. [source] Discharge patterns of neurons in the medial pontobulbar reticular formation during fictive mastication in the rabbitEUROPEAN JOURNAL OF NEUROSCIENCE, Issue 10 2001K.-G. Westberg Abstract In this study, we describe functional characteristics of neurons forming networks generating oral ingestive motor behaviours. Neurons in medial reticular nuclei on the right side of the brainstem between the trigeminal and hypoglossal motor nuclei were recorded in anaesthetized and paralysed rabbits during two types of masticatory-like motor patterns induced by electrical stimulation of the left (contralateral) or right (ipsilateral) cortical masticatory areas. Sixty-seven neurons in nucleus reticularis pontis caudalis (nPontc), nucleus reticularis parvocellularis (nParv), and nucleus reticularis gigantocellularis (Rgc) were studied. These were classified as phasic or tonic depending on their firing pattern during the fictive jaw movement cycle. Phasic neurons located in the dorsal part of nPontc were active during the jaw opening phase, whilst those in dorsal nParv tended to fire during the closing phase. In most neurons, burst duration and firing frequency changed between the two motor patterns, but there was little change in phase of firing. Tonic units were mainly recorded in the ventral half of nPontc, and at the junction between Rgc and caudal nParv. Cortical inputs with short latency from the contralateral masticatory area were more frequent in phasic (82%) than tonic (44%) neurons, whilst inputs from the ipsilateral cortex were equal in the two subgroups (57% and 56%). Phasic neurons had significantly shorter mean contralateral than ipsilateral cortical latencies, whilst there was no difference among tonic neurons. Intra- and perioral primary afferent inputs activated both types of neurons at oligo-synaptic latencies. Our results show that subpopulations of neurons in medial reticular nuclei extending from the caudal part of the trigeminal motor nucleus to the rostral third of the hypoglossal motor nucleus are active during the fictive masticatory motor behaviour. Unlike masticatory neurons in the lateral tegmentum, the medial subpopulations are spatially organized according to discharge pattern. [source] An oscillatory interference model of grid cell firingHIPPOCAMPUS, Issue 9 2007Neil Burgess Abstract We expand upon our proposal that the oscillatory interference mechanism proposed for the phase precession effect in place cells underlies the grid-like firing pattern of dorsomedial entorhinal grid cells (O'Keefe and Burgess (2005) Hippocampus 15:853,866). The original one-dimensional interference model is generalized to an appropriate two-dimensional mechanism. Specifically, dendritic subunits of layer II medial entorhinal stellate cells provide multiple linear interference patterns along different directions, with their product determining the firing of the cell. Connection of appropriate speed- and direction- dependent inputs onto dendritic subunits could result from an unsupervised learning rule which maximizes postsynaptic firing (e.g. competitive learning). These inputs cause the intrinsic oscillation of subunit membrane potential to increase above theta frequency by an amount proportional to the animal's speed of running in the "preferred" direction. The phase difference between this oscillation and a somatic input at theta-frequency essentially integrates velocity so that the interference of the two oscillations reflects distance traveled in the preferred direction. The overall grid pattern is maintained in environmental location by phase reset of the grid cell by place cells receiving sensory input from the environment, and environmental boundaries in particular. We also outline possible variations on the basic model, including the generation of grid-like firing via the interaction of multiple cells rather than via multiple dendritic subunits. Predictions of the interference model are given for the frequency composition of EEG power spectra and temporal autocorrelograms of grid cell firing as functions of the speed and direction of running and the novelty of the environment. © 2007 Wiley-Liss, Inc. [source] Phase precession and phase-locking of hippocampal pyramidal cellsHIPPOCAMPUS, Issue 3 2001Amitabha Bose Abstract We propose that the activity patterns of CA3 hippocampal pyramidal cells in freely running rats can be described as a temporal phenomenon, where the timing of bursts is modulated by the animal's running speed. With this hypothesis, we explain why pyramidal cells fire in specific spatial locations, and how place cells phase-precess with respect to the EEG theta rhythm for rats running on linear tracks. We are also able to explain why wheel cells phase-lock with respect to the theta rhythm for rats running in a wheel. Using biophysically minimal models of neurons, we show how the same network of neurons displays these activity patterns. The different rhythms are the result of inhibition being used in different ways by the system. The inhibition is produced by anatomically and physiologically diverse types of interneurons, whose role in controlling the firing patterns of hippocampal cells we analyze. Each firing pattern is characterized by a different set of functional relationships between network elements. Our analysis suggests a way to understand these functional relationships and transitions between them. Hippocampus 2001;11:204,215. © 2001 Wiley-Liss, Inc. [source] Differential expression of connexin 43 in the chick tangential vestibular nucleusJOURNAL OF NEUROSCIENCE RESEARCH, Issue 5 2003Anastas Popratiloff Abstract The chick tangential nucleus is a major vestibular nucleus whose principal cells receive convergent inputs from primary vestibular and nonvestibular fibers and participate in the vestibular reflexes. During development, the principal cells gradually acquire the mature firing pattern in part by losing a specific potassium current around hatching (H). Here we focus on characterizing the expression of connexin 43 (Cx43), a gap junction protein found mainly between astrocytes in the mature brain. The astrocytic syncytium plays an important role in maintaining extracellular potassium ion balance in the brain. Accordingly, it is important to characterize the potential of this syncytium to communicate during the critical developmental age of hatching. Using fluorescence immunocytochemistry, we investigated whether Cx43 staining was concentrated in specific cellular compartments at H1 by applying well-known markers for astrocytes (glial fibrillary acidic protein; GFAP), oligodendrocytes (antimyelin), neurons (microtubule-associated protein 2), and synaptic terminals (synaptotagmin). GFAP-positive astrocytes and GFAP-negative nonneuronal cells around the principal cell bodies were labeled with Cx43, suggesting that Cx43 was expressed exclusively by nonneuronal cells near the neuronal elements. Next, the developmental pattern of expression of Cx43 was studied at embryonic day 16 (E16), H1, and H9. At E16, Cx43 was present weakly as random small clusters in the tangential nucleus, whereas, at H1, overall staining became localized, with increases in size, brightness, and number of immunostained clusters. Finally, at H9, Cx43 staining decreased, but cluster size and location remained unchanged. These results suggest that Cx43 is developmentally regulated with a peak at birth and is associated primarily with astrocytes and nonneuronal cells near the principal cell bodies. © 2003 Wiley-Liss, Inc. [source] Cortical versus spinal dysfunction in amyotrophic lateral sclerosisMUSCLE AND NERVE, Issue 5 2006Shahram Attarian MD Abstract Little is known about the possible link between cortical and spinal motor neuron dysfunction in amyotrophic lateral sclerosis (ALS). We correlated the characteristics of the responses to transcranial magnetic stimulation (TMS) with the electromechanical properties and firing pattern of single motor units (MUs) tested in nine ALS patients, three patients with Kennedy's disease, and 15 healthy subjects. In Kennedy's disease, 19 of 22 MUs were markedly enlarged with good electromechanical coupling and discharged with great variability. Their excitatory responses increased with MU size. In ALS, 17 of 34 MUs with excitatory responses behaved as in Kennedy's disease. By contrast, 28 MUs with nonsignificant responses showed poor electromechanical coupling and high firing rates, whereas 28 MUs with inhibitory responses showed moderate functional alterations. This result indicates that in ALS as in Kennedy's disease, sprouting of corticospinal axons may occur on surviving motoneurons. A clear relationship exists between the responsiveness of MUs to TMS and their functional state. Muscle Nerve, 2006 [source] Motoneurons: A preferred firing range across vertebrate species?MUSCLE AND NERVE, Issue 5 2002T. George Hornby PhD Abstract The term "preferred firing range" describes a pattern of human motor unit (MU) unitary discharge during a voluntary contraction in which the profile of the spike-frequency of the MU's compound action potential is dissociated from the profile of the presumed depolarizing pressure exerted on the unit's spinal motoneuron (MN). Such a dissociation has recently been attributed by inference to the presence of a plateau potential (PP) in the active MN. This inference is supported by the qualitative similarities between the firing pattern of human MUs during selected types of relatively brief muscle contraction and that of intracellularly stimulated, PP-generating cat MNs in a decerebrate preparation, and turtle MNs in an in vitro slice of spinal cord. There are also similarities between the stimulus-response behavior of intracellularly stimulated turtle MNs and human MUs during the elaboration of a slowly rising voluntary contraction. This review emphasizes that there are a variety of open issues concerning the PP. Nonetheless, a rapidly growing body of comparative vertebrate evidence supports the idea that the PP and other forms of non-linear MN behavior play a major role in the regulation of muscle force, from the lamprey to the human. © 2002 Wiley Periodicals, Inc. Muscle Nerve 25: 000,000, 2002 [source] Firing properties and functional connectivity of substantia nigra pars compacta neurones recorded with a multi-electrode array in vitroTHE JOURNAL OF PHYSIOLOGY, Issue 10 2010Nicola Berretta Dopamine (DA) neurones of the substantia nigra pars compacta (SNc) are involved in a wide variety of functions, including motor control and reward-based learning. In order to gain new insights into the firing properties of neuronal ensembles in the SNc, we recorded extracellular single units from spontaneously active neurones, using a multi-electrode array (MEA) device in midbrain slices. The majority of neurones (50.21%) had a low firing frequency (1,3 Hz) and a stable pacemaker-like pattern, while others (44.84%) were irregular, but still firing at a low rate. The remaining population (4.95%) comprised neurones with a regular higher firing rate (5,10 Hz). High rate neurones, on the whole, were insensitive to DA (30 ,m), while low rate neurones were mostly inhibited by DA, although responding either with a prominent or a weak inhibition. However, we recorded low rate regular neurones that were insensitive to DA, or irregular low rate neurones excited by DA. Interestingly, we found pairs of active neurones (12.10 ± 3.14%) with a significant proportion of spikes occurring synchronously. Moreover, the crosscorrelation probability in each pair tended to increase in response to DA. In conclusion, MEA recordings in midbrain slices reveal a much more complex picture than previously reported with regard to the firing pattern and DA sensitivity of spontaneously active SNc neurones. Moreover, the study opens new prospectives for the in vitro investigation of functional connectivity in the midbrain dopaminergic system, thus proposing new targets for the pharmacological treatment of DA-dependent neurological disorders. [source] Rebound bursts following inhibition: how dopamine modifies firing pattern in subthalamic neuronsTHE JOURNAL OF PHYSIOLOGY, Issue 8 2008Steven W. Johnson No abstract is available for this article. [source] Consistent dynamics suggests tight regulation of biophysical parameters in a small network of bursting neuronsDEVELOPMENTAL NEUROBIOLOGY, Issue 14 2006Attila Szücs Abstract The neuronal firing patterns in the pyloric network of crustaceans are remarkably consistent among animals. Although this characteristic of the pyloric network is well-known, the biophysical mechanisms underlying the regulation of the systems output are receiving renewed attention. Computer simulations of the pyloric network recently demonstrated that consistent motor output can be achieved from neurons with disparate biophysical parameters among animals. Here we address this hypothesis by pharmacologically manipulating the pyloric network and analyzing the emerging voltage oscillations and firing patterns. Our results show that the pyloric network of the lobster stomatogastric ganglion maintains consistent and regular firing patterns even when entire populations of specific voltage-gated channels and synaptic receptors are blocked. The variations of temporal parameters used to characterize the burst patterns of the neurons as well as their intraburst spike dynamics do not display statistically significant increase after blocking the transient K-currents (with 4-aminopyridine), the glutamatergic inhibitory synapses (with picrotoxin), or the cholinergic synapses (with atropine) in pyloric networks from different animals. These data suggest that in this very compact circuit, the biophysical parameters are cell-specific and tightly regulated. © 2006 Wiley Periodicals, Inc. J Neurobiol, 2006 [source] Effect of Interictal Spikes on Single-Cell Firing Patterns in the HippocampusEPILEPSIA, Issue 4 2007Jun-Li Zhou Summary:,Purpose: The interictal EEG spike(s) is the hallmark of the epileptic EEG. While focal interictal spike (IS) have been associated with transitory cognitive impairment, with the type of deficit dependent on where in the cortex the IS arises, the mechanism by which IS result in transitory dysfunction is not known. The purpose of this study was to determine the effect of IS on single-cell firing patterns in freely moving rats with a prior history of seizures. Methods: We studied IS in two seizure models; pilocarpine-induced status epilepticus and recurrent flurothyl models. The effect of spontaneous hippocampal spikes on action potentials (APs) of CA1 cells in rats walking in a familiar environment was investigated using 32 extracellular electrodes. We also compared the effect of spikes on two types of hippcampal cells; place cells that discharge rapidly only when the rat's head is in a specific part of the environment, the so-called firing field, and interneurons, which are a main source of inhibition in the hippocampus. Results: IS were associated with a decreased likelihood of AP compared with IS-free portions of the record. Compared to pre-IS baseline, IS were followed by significant decreases in CA1 APs for periods up to 2 s following the IS in both models. When occurring in flurries, IS were associated with a pronounced decrease in APs. The response to IS was cell-dependent; IS resulted in decreases in AP firing after the IS in interneurons but not place cells. Conclusions: This study demonstrates that IS have substantial effects on cellular firing in the hippocampus and that these effects last far longer than the spike and slow wave. Furthermore, the effect of IS on cellular firing was cell specific, affecting interneurons more than place cells. These findings suggest that IS may contribute to seizure-induced cognitive impairment by altering AP firing in a cell-specific manner. [source] Episodic ataxia type 1 mutations in the KCNA1 gene impair the fast inactivation properties of the human potassium channels Kv1.4-1.1/Kv,1.1 and Kv1.4-1.1/Kv,1.2EUROPEAN JOURNAL OF NEUROSCIENCE, Issue 11 2006Paola Imbrici Abstract Episodic ataxia type 1 (EA1) is an autosomal dominant neurological disorder characterized by constant muscle rippling movements (myokymia) and episodic attacks of ataxia. Several heterozygous point mutations have been found in the coding sequence of the voltage-gated potassium channel gene KCNA1 (hKv1.1), which alter the delayed-rectifier function of the channel. Shaker -like channels of different cell types may be formed by unique hetero-oligomeric complexes comprising Kv1.1, Kv1.4 and Kv,1.x subunits. Here we show that the human Kv,1.1 and Kv,1.2 subunits modulated the functional properties of tandemly linked Kv1.4-1.1 wild-type channels expressed in Xenopus laevis oocytes by (i) increasing the rate and amount of N-type inactivation, (ii) slowing the recovery rate from inactivation, (iii) accelerating the cumulative inactivation of the channel and (iv) negatively shifting the voltage dependence of inactivation. To date, the role of the human Kv1.4-1.1, Kv1.4-1.1/Kv,1.1 and Kv1.4-1.1/Kv,1.2 channels in the aetiopathogenesis of EA1 has not been investigated. Here we also show that the EA1 mutations E325D, V404I and V408A, which line the ion-conducting pore, and I177N, which resides within the S1 segment, alter the fast inactivation and repriming properties of the channels by decreasing both the rate and degree of N-type inactivation and by accelerating the recovery from fast inactivation. Furthermore, the E325D, V404I and I177N mutations shifted the voltage dependence of the steady-state inactivation to more positive potentials. The results demonstrate that the human Kv,1.1 and Kv,1.2 subunits regulate the proportion of wild-type Kv1.4-1.1 channels that are available to open. Furthermore, EA1 mutations alter heteromeric channel availability which probably modifies the integration properties and firing patterns of neurones controlling cognitive processes and body movements. [source] Functional screening of traditional antidepressants with primary cortical neuronal networks grown on multielectrode neurochipsEUROPEAN JOURNAL OF NEUROSCIENCE, Issue 2 2006Alexandra Gramowski Abstract We optimized the novel technique of multielectrode neurochip recordings for the rapid and efficient screening of neuroactivity. Changes in the spontaneous activity of cultured networks of primary cortical neurons were quantified to evaluate the action of drugs on the firing dynamics of complex network activity. The multiparametric assessment of electrical activity changes caused by psychoactive herbal extracts from Hypericum, Passiflora and Valeriana, and various combinations thereof revealed a receptor-specific and concentration-dependent inhibition of the firing patterns. The spike and burst rates showed significant substance-dependent effects and significant differences in potency. The effects of specific receptor blockades on the inhibitory responses provided evidence that the herbal extracts act on gamma-amino butyric acid (GABA) and serotonin (5-HT) receptors, which are recognized targets of pharmacological antidepressant treatment. A biphasic effect, serotonergic stimulation of activity at low concentrations that is overridden by GABAergic inhibition at higher concentrations, is apparent with Hypericum alone and the triple combination of the extracts. The more potent neuroactivity of the triple combination compared to Hypericum alone and the additive effect of Passiflora and Valeriana suggest a synergy between constituent herbal extracts. The extracts and their combinations affected the set of derived activity parameters in a concomitant manner suggesting that all three constituent extracts and their combinations have largely similar modes of action. This study also demonstrates the sensitivity, selectivity and robustness of neurochip recordings for high content screening of complex mixtures of neuroactive substances and for providing multiparametric information on neuronal activity changes to assess the therapeutic potential of psychoactive substances. [source] Neurons with distinctive firing patterns, morphology and distribution in laminae V,VII of the neonatal rat lumbar spinal cordEUROPEAN JOURNAL OF NEUROSCIENCE, Issue 3 2003Péter Szűcs Abstract It is generally accepted that neurons in the ventral spinal grey matter, a substantial proportion of which can be regarded as constituents of the spinal motor apparatus, receive and integrate synaptic inputs arising from various peripheral, spinal and supraspinal sources. Thus, a profound knowledge concerning the integrative properties of interneurons in the spinal ventral grey matter appears to be essential for a fair understanding of operational principles of spinal motor neural assemblies. Using the whole cell patch clamp configuration in a correlative physiological and morphological experimental approach, here we demonstrate that the intrinsic membrane properties of neurons vary widely in laminae V,VII of the ventral grey matter of the neonatal rat lumbar spinal cord. Based on their firing patterns in response to depolarizing current steps, we have classified the recorded neurons into four categories: ,phasic', ,repetitive', ,single' and ,slow'. Neurons with firing properties characteristic of the ,phasic', ,repetitive' and ,single' cells have previously been reported also in the superficial and deep spinal dorsal horn, but this is the first account in the literature in which ,slow' neurons have been recovered and described in the spinal cord. The physiological heterogeneity in conjunction with the morphological correlation and distribution of neurons argues that different components of motor neural assemblies in the spinal ventral grey matter possess different signal processing characteristics. [source] Comparison of the firing patterns of human postganglionic sympathetic neurones and spinal , motoneurones during brief burstsEXPERIMENTAL PHYSIOLOGY, Issue 1 2004Vaughan G. Macefield Focal recordings from individual postganglionic sympathetic neurones in awake human subjects have revealed common firing properties. One of the most striking features is that they tend to fire only once per sympathetic burst. Why this should be so is not known, but we propose that the short duration of the burst may limit the number of times a sympathetic neurone can fire. Indeed, while the normal variation in cardiac interval and burst duration is too narrow to reveal a correlation between burst duration and the number of spikes generated, we know that spike generation is doubled when burst duration is doubled following ectopic heart beats. To test the hypothesis that the burst duration constrains the firing of individual sympathetic neurones to one per burst, we used the human skeletomotor system as a model for the sympathetic nervous system, which allowed us to vary burst duration and amplitude experimentally. Intramuscular recordings were made from 27 single motor units (, motoneurones) in the tibialis anterior or soleus muscles of seven subjects; multiunit EMG activity was recorded via surface electrodes and blood pressure was recorded continuously. Subjects were instructed to generate EMG bursts of varying amplitude in the intervals between heart beats. By constraining the firing of , motoneurones to brief (,400 ms) bursts we could emulate real sympathetic bursts. Individual motoneurones generated 0,7 spikes during the emulated sympathetic bursts, with firing patterns similar to those exhibited by real sympathetic neurones. Eleven motor units showed significant positive linear correlations between the number of spikes they generated within a burst and its amplitude, whereas for 17 motor units there were significant positive correlations between the number of spikes and burst duration. This indicates that burst duration is a major determinant of the number of times an , motoneurone will fire during a brief burst, and we suggest that the same principle may explain the firing pattern typical of human sympathetic neurones. [source] Role of active movement in place-specific firing of hippocampal neuronsHIPPOCAMPUS, Issue 1 2005Eun Young Song Abstract The extent of external and internal factors contributing to location-specific firing of hippocampal place cells is currently unclear. We investigated the role of active movement in location-specific firing by comparing spatial firing patterns of hippocampal neurons, while rats either ran freely or rode a motorized cart on the same circular track. Most neurons changed their spatial firing patterns across the two navigation conditions ("remapping"), and they were stably maintained across repeated active or passive navigation sessions. These results show that active movement is a critical factor in determining place-specific firing of hippocampal neurons. This could explain why passive displacement is not an effective way of acquiring spatial knowledge for subsequent active navigation in an unfamiliar environment. © 2004 Wiley-Liss, Inc. [source] Phase precession and phase-locking of hippocampal pyramidal cellsHIPPOCAMPUS, Issue 3 2001Amitabha Bose Abstract We propose that the activity patterns of CA3 hippocampal pyramidal cells in freely running rats can be described as a temporal phenomenon, where the timing of bursts is modulated by the animal's running speed. With this hypothesis, we explain why pyramidal cells fire in specific spatial locations, and how place cells phase-precess with respect to the EEG theta rhythm for rats running on linear tracks. We are also able to explain why wheel cells phase-lock with respect to the theta rhythm for rats running in a wheel. Using biophysically minimal models of neurons, we show how the same network of neurons displays these activity patterns. The different rhythms are the result of inhibition being used in different ways by the system. The inhibition is produced by anatomically and physiologically diverse types of interneurons, whose role in controlling the firing patterns of hippocampal cells we analyze. Each firing pattern is characterized by a different set of functional relationships between network elements. Our analysis suggests a way to understand these functional relationships and transitions between them. Hippocampus 2001;11:204,215. © 2001 Wiley-Liss, Inc. [source] Role of endogenous acetylcholine in the control of the dopaminergic system via nicotinic receptorsJOURNAL OF NEUROCHEMISTRY, Issue 3 2010Uwe Maskos J. Neurochem. (2010) 114, 641,646. Abstract Nicotinic acetylcholine receptors (nAChRs) are pentameric membrane protein receptors activated by the addictive drug, nicotine. However, sometimes underestimated, under physiological conditions the endogenous neurotransmitter acetylcholine is the agonist. In this mini-review, I will discuss the evidence in favour of an important role for this cholinergic activation of the dopaminergic (DAergic) system. I will focus on the literature implicating the action of acetylcholine on the somato-dendritic compartment of these neurons. This modulation is responsible for a variety of phenotypes in knock-out animals of nAChR subunits. These include locomotion, exploratory behaviour, dopamine (DA) release, and DA neuron firing patterns. The novel techniques brought to bear on these analyses, lentiviral re-expression, and repression, of nAChR subunits, and transgenic expression of hypersensitive receptors will be discussed. [source] Specificity of muscle action after anterior cruciate ligament injuryJOURNAL OF ORTHOPAEDIC RESEARCH, Issue 6 2003Glenn N. Williams Abstract Neuromuscular control is believed to be a critical factor in dynamic knee stability. The purpose of this study was to evaluate voluntary muscle control in anterior cruciate ligament deficient (ACL-D) and uninjured people. Twenty athletes of similar age participated in this study. Subjects performed a target-matching protocol that required them to produce isometric moments about the knee with fine control in flexion, extension, varus, and valgus (i.e., loads were generated in the plane perpendicular to the long axis of the shank). Electromyographic data were collected from 10 muscles that span the knee. A specificity index was calculated for each muscle to describe how fine-tuned (specific) its muscle activity pattern was with respect to its principal direction of action in the load plane. Diminished specificity of muscle action was observed in 8 of 10 muscles in the ACL-D subjects' involved knees when compared with the activity patterns from their uninvolved knees and those from the uninjured subjects' knees. The vastus lateralis muscle was especially affected. Increased and more global co-contraction was also observed in the ACL-D limbs. The alterations in muscle firing patterns observed in this study are consistent with diminished neuromuscular control. © 2003 Orthopaedic Research Society. Published by Elsevier Science Ltd. All rights reserved. [source] Neuronal activity in the globus pallidus of multiple system atrophy patientsMOVEMENT DISORDERS, Issue 12 2004Luiz C.M. Pereira MD Abstract The pathophysiological changes in neural activity that characterize multiple system atrophy (MSA) are largely unknown. We recorded the activity of pallidal neurons in 3 patients with clinical and radiological features of MSA who underwent unilateral microelectrode-guided pallidotomy for disabling parkinsonism. Findings in these patients were compared with 4 control patients with a clinical diagnosis of Parkinson's disease (PD). The position, firing rates, and firing patterns of single neurons in the pallidal complex were analyzed in both MSA and PD patients. The mean spontaneous firing rate of neurons in the internal segment of the globus pallidus internus (GPii) was significantly lower in MSA than in PD patients. There were no significant differences between MSA and PD patients, however, in firing rates of neurons in the external globus pallidus (GPe) or in the external segment of GPi (GPie). In addition, no significant differences in firing pattern were found between MSA and PD patients. In conclusion, this study has shown that firing rates of neurons in GPii but not in GPie and GPe are different in MSA patients compared with that in PD patients, a finding that may reflect the poor clinical results of pallidotomy reported in patients with MSA. © 2004 Movement Disorder Society [source] Novel antiepileptic drug levetiracetam decreases dyskinesia elicited by L -dopa and ropinirole in the MPTP-lesioned marmosetMOVEMENT DISORDERS, Issue 11 2003Michael P. Hill PhD Abstract Long-term dopamine replacement therapy of Parkinson's disease leads to the occurrence of dyskinesias. Altered firing patterns of neurons of the internal globus pallidus, involving a pathological synchronization/desynchronization process, may contribute significantly to the genesis of dyskinesia. Levetiracetam, an antiepileptic drug that counteracts neuronal (hyper)synchronization in animal models of epilepsy, was assessed in the MPTP,lesioned marmoset model of Parkinson's disease, after coadministration with (1) levodopa (L -dopa) or (2) ropinirole/L -dopa combination. Oral administration of levetiracetam (13,60 mg/kg) in combination with either L -dopa (12 mg/kg) alone or L -dopa (8 mg/kg)/ropinirole (1.25 mg/kg) treatments was associated with significantly less dyskinesia, in comparison to L -dopa monotherapy during the first hour after administration. Thus, new nondopaminergic treatment strategies targeting normalization of abnormal firing patterns in basal ganglia structures may prove useful as an adjunct to reduce dyskinesia induced by dopamine replacement therapy without affecting its antiparkinsonian action. © 2003 Movement Disorder Society [source] Excitatory synaptic potentials in spastic human motoneurons have a short rise-timeMUSCLE AND NERVE, Issue 1 2005Nina L. Suresh PhD Abstract This study assessed whether changes in size or time-course of excitatory postsynaptic potentials (EPSPs) in motoneurons innervating spastic muscle could induce a greater synaptic response, and thereby contribute to reflex hyperexcitability. We compared motor unit (MU) firing patterns elicited by tendon taps applied to both spastic and contralateral (nonspastic) biceps brachii muscle in hemiparetic stroke subjects. Based on recordings of 115 MUs, significantly shortened EPSP rise times were present on the spastic side, but with no significant differences in estimated EPSP amplitude. These changes may contribute to hyperexcitable reflex responses at short latency, but the EPSP amplitude changes appear insufficient to account for global differences in reflex excitability. Muscle Nerve, 2005 [source] The Effect of Fatigue on the Timing of Electrical Stimulation-Evoked Muscle Contractions in People with Spinal Cord InjuryNEUROMODULATION, Issue 3 2004Peter J. Sinclair PhD Abstract This study investigated the activation dynamics of electrical stimulation-evoked muscle contractions performed by individuals with spinal cord injury (SCI). The purpose was to determine whether electrical stimulation (ES) firing patterns during cycling exercise should be altered in response to fatigue-induced changes in the time taken for force to rise and fall with ES. Seven individuals with SCI performed isometric contractions and pedaled a motorized cycle ergometer with stimulation applied to the quadriceps muscles. Both exercise conditions were performed for five minutes while the patterns of torque production were recorded. ES-evoked knee extension torque fell by 75% under isometric conditions, and the rate of force rise and decline decreased in proportion to torque (r = 0.91, r = 0.94, respectively). There was no change in the time for torque to rise to 50% of maximum levels. The time for torque to decline did increase slightly, but only during the first minute of exercise. Cycling power output fell approximately 50% during the five minutes of exercise, however, there was no change in the time taken for torque to rise or fall. The magnitude of ES-evoked muscle torques decline substantially with fatigue, however, the overall pattern of torque production remained relatively unchanged. These results suggest there is no need to alter stimulation firing patterns to accommodate fatigue during ES-evoked exercise. [source] Intrinsic properties and mechanisms of spontaneous firing in mouse cerebellar unipolar brush cellsTHE JOURNAL OF PHYSIOLOGY, Issue 2 2007Marco J. Russo Neuronal firing patterns are determined by the cell's intrinsic electrical and morphological properties and are regulated by synaptic interactions. While the properties of cerebellar neurons have generally been studied in much detail, little is known about the unipolar brush cells (UBCs), a type of glutamatergic interneuron that is enriched in the granular layer of the mammalian vestibulocerebellum and participates in the representation of head orientation in space. Here we show that UBCs can be distinguished from adjacent granule cells on the basis of differences in membrane capacitance, input resistance and response to hyperpolarizing current injection. We also show that UBCs are intrinsically firing neurons. Using action potential clamp experiments and whole-cell recordings we demonstrate that two currents contribute to this property: a persistent TTX-sensitive sodium current and a ruthenium red-sensitive, TRP-like cationic current, both of which are active during interspike intervals and have reversal potentials positive to threshold. Interestingly, although UBCs are also endowed with a large Ih current, this current is not involved in their intrinsic firing, perhaps because it activates at voltages that are more hyperpolarized than those associated with autonomous activity. [source] Differential targeting and functional specialization of sodium channels in cultured cerebellar granule cellsTHE JOURNAL OF PHYSIOLOGY, Issue 3 2005Nancy Osorio The ion channel dynamics that underlie the complex firing patterns of cerebellar granule (CG) cells are still largely unknown. Here, we have characterized the subcellular localization and functional properties of Na+ channels that regulate the excitability of CG cells in culture. As evidenced by RT-PCR and immunocytochemical analysis, morphologically differentiated CG cells expressed Nav1.2 and Nav1.6, though both subunits appeared to be differentially regulated. Nav1.2 was localized at most axon initial segments (AIS) of CG cells from 8 days in vitro DIV 8 to DIV 15. At DIV 8, Nav1.6 was found uniformly throughout somata, dendrites and axons with occasional clustering in a subset of AIS. Accumulation of Nav1.6 at most AIS was evident by DIV 13,14, suggesting it is developmentally regulated at AIS. The specific contribution of these differentially distributed Na+ channels has been assessed using a combination of methods that allowed discrimination between functionally compartmentalized Na+ currents. In agreement with immunolocalization, we found that fast activating,fully inactivating Na+ currents predominate at the AIS membrane and in the somatic plasma membrane. [source] | |||||||||||||||||||||||||