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PubMed2000

Depression of neuronal firing rates in somatosensory and posterior parietal cortex during object acquisition in a prehension task.

Prehension is an object-oriented behavior consisting of four components: reach, grasp, manipulation, and release. To determine how such actions are represented in primary somatosensory (S-I) and posterior parietal cortex (PPC), we used digital video to synchronize spike trains of neurons recorded in Brodmann's areas 3b, 1, 2, 5, and 7 with the hand kinematics as monkeys performed a prehension task. Statistical analyses indicated that one-third of task-modulated neurons showed significantly depressed firing rates during object acquisition and/or manipulation. This population was dominated by neurons innervated by deep receptors that sensed extension movements of the fingers, or by tactile receptors in hairy skin sensing stretch. Grasp-inhibited responses were the most common type. Tonic firing rates of these cells dropped significantly during approach as the hand was preshaped for grasping, or at contact when grasp was initiated, and persisted until hand motion ceased or as the grip relaxed. Maximum suppression of firing occurred at grasp completion. Their lack of specificity for particular hand behaviors formed the inhibitory counterpart of broadly tuned cells that fired prolonged bursts during grasp and manipulatory stages of prehension. The remainder of the task-inhibited population showed biphasic responses. Firing rates were significantly depressed during grasping and manipulation when the hand interacted directly with the object, but were enhanced prior to contact, when the hand was preshaped (approach-tuned), or upon relaxation of grasp and release of the object from the hand (loweror relax-tuned). Grasp-inhibited responses occurred primarily in S-I, whereas biphasic inhibitory activity was recorded mainly in PPC. Suppression of activity within these populations may thereby increase the saliency of excitatory responses to acquisition and manipulation of objects. Reduction of firing during prehension might also signal the flexed postures used to retain objects in the hand, rather than a generalized gating of sensory information. The similarity of responses to active and passive extension movements suggests that the inhibitory responses may provide important postural and motor information about the hand kinematics when performing skilled tasks.

Action Potentials↗

PubMed1999

A joint interspike interval difference stochastic spike train analysis: detecting local trends in the temporal firing patterns of single neurons.

We introduce a stochastic spike train analysis method called joint interspike interval difference (JISID) analysis. By design, this method detects changes in firing interspike intervals (ISIs), called local trends, within a 4-spike pattern in a spike train. This analysis classifies 4-spike patterns that have similar incremental changes. It characterizes the higher-order serial dependence in spike firing relative to changes in the firing history. Mathematically, this spike train analysis describes the statistical joint distribution of consecutive changes in ISIs, from which the serial dependence of the changes in higher-order intervals can be determined. It is similar to the joint interspike interval (JISI) analysis, except that the joint distribution of consecutive ISI differences (ISIDs) is quantified. The graphical location of points in the JISID scatter plot reveals the local trends in firing (i.e., monotonically increasing, monotonically decreasing, or transitional firing). The trajectory of these points in the serial-JISID plot traces the time evolution of these trends represented by a 5-spike pattern, while points in the JISID scatter plot represent trends of a 4-spike pattern. We provide complete theoretical interpretations of the JISID analysis. We also demonstrate that this method indeed identifies firing trends in both simulated spike trains and spike trains recorded from cultured neurons.

Animals↗

PubMed2005

Effect of sodium channel blocker (mexiletine) on pathological ectopic firing pattern in a rat chronic constriction nerve injury model.

We studied the efficacy of mexiletine as a sodium channel blocker for neuropathic pain by investigating the effect of mexiletine on the pathological ectopic firing pattern in a chronic constriction nerve injury (CCI) model. The experiment was conducted with 60 male Wistar rats. The CCI model was created by loosely ligating the sciatic nerve. After breeding 7 days, the frequency and pattern of ectopic firing antidromically recorded from the sural nerve and the amplitude of antidromic sensory nerve-evoked potential were analyzed. The CCI rats were given an intravenous injection of normal saline and mexiletine (5 or 15 mg/kg). Mexiletine significantly suppressed spontaneous firing frequency, an on-off firing pattern that consisted of cyclic bursting spikes and ectopic firing generation under the hypoxic condition. Mexiletine did not influence the amplitude of A-delta component in the antidromic sensory nerve-evoked potential. Mexiletine suppressed ectopic firing by blocking activity of the abnormal sodium channel at the nerve-injured site and dorsal root ganglion without blocking nerve conduction. This study suggests that mexiletine is useful for treating neuropathic pain in peripheral neuropathy.

Animals↗

PubMed2005

Dynamics of the instantaneous firing rate in response to changes in input statistics.

We review and extend recent results on the instantaneous firing rate dynamics of simplified models of spiking neurons in response to noisy current inputs. It has been shown recently that the response of the instantaneous firing rate to small amplitude oscillations in the mean inputs depends in the large frequency limit f on the spike initiation dynamics. A particular simplified model, the exponential integrate-and-fire (EIF) model, has a response that decays as 1/f in the large frequency limit and describes very well the response of conductance-based models with a Hodgkin-Huxley type fast sodium current. Here, we show that the response of the EIF instantaneous firing rate also decays as 1/f in the case of an oscillation in the variance of the inputs for both white and colored noise. We then compute the initial transient response of the firing rate of the EIF model to a step change in its mean inputs and/or in the variance of its inputs. We show that in both cases the response speed is proportional to the neuron stationary firing rate and inversely proportional to a 'spike slope factor' Delta(T) that controls the sharpness of spike initiation: as 1/Delta(T) for a step change in mean inputs, and as 1/Delta(T) (2) for a step change in the variance in the inputs.

Action Potentials↗

PubMed2006

Factors affecting phase synchronization in integrate-and-fire oscillators.

Step changes in input current are known to induce partial phase synchrony in ensembles of leaky integrate-and-fire neurons operating in the oscillatory or "regular firing" regime. An analysis of this phenomenon in the absence of noise is presented based on the probability flux within an ensemble of generalized integrate-and-fire neurons. It is shown that the induction of phase synchrony by a step input can be determined by calculating the ratio of the voltage densities obtained from fully desynchronized ensembles firing at the pre and post-step firing rates. In the limit of low noise and in the absence of phase synchrony, the probability density as a function of voltage is inversely proportional to the time derivative along the voltage trajectory. It follows that the magnitude of phase synchronization depends on the degree to which a change in input leads to a uniform multiplication of the voltage derivative over the range from reset to spike threshold. This analysis is used to investigate several factors affecting phase synchronization including high firing rates, inputs modeled as conductances rather than currents, peri-threshold sodium currents, and spike-triggered potassium currents. Finally, we show that without noise, the equilibrium ensemble density is proportional to the phase response curve commonly used to analyze oscillatory systems.

Action Potentials↗

PubMed1993

Diverse firing properties of single motor units in the inner and outer portions of the guinea pig anterior digastric muscle.

Microwire recordings from the histochemically heterogeneous inner compartment of the guinea pig anterior digastric muscle (ADG) revealed tonic firing of single motor units, which were spontaneously active and could also be recruited following orofacial afferent stimulation and during rhythmic jaw movements (RJM). As units with tonic firing were not observed in the homogeneously fast-twitch outer ADG, the tonic units were classified as slow-twitch motor units. Irregular patterns of motor-unit firing at variable frequencies were observed after orofacial stimulation and during RJM in the outer and inner compartments. The irregular firing pattern of units in the fast-twitch outer compartment was characterized by shorter and less variable bursts than that of units in the heterogeneous inner compartment. A phasic, centrally driven firing pattern was observed during RJM in outer and inner ADG units. The firing frequency of some of these units was modulated during the rhythmical bursts. It is suggested that, as in limb muscles, functionally specialized ADG motor units are recruited in an orderly sequence, starting with spontaneously active, slow-twitch units in the inner compartment, continuing with fast-twitch units recruited upon enhancement of the synaptic drive (as in the case of orofacial stimulation), and ending with massive, rhythmical recruitment of slow- and fast-twitch units during RJM.

Action Potentials↗

PubMed1985

Comprehensive treatment of chronic fire setting in a severely disordered boy.

A comprehensive, multidimensional treatment strategy was designed for a severely behaviorally disordered 10-year-old boy with a 7-year history of setting fires. The study replicates a previous study designed to suppress fire setting, teach appropriate substitute behavior and increase awareness of the consequences of fire setting. Three additional components were added to the original treatment program: relaxation training, a response cost for fire setting, and a visit to a hospital burn unit (overt sensitization). Follow-up data 1 year later indicate that treatment was successful in extinguishing all fire-setting behaviors. The additional treatment components presented in this paper may add to the efficacy and sustained durability of treatment gains in difficult, low frequency fire setting behavior.

Behavior Therapy↗

PubMed1981

Spontaneous firing patterns of identified spiny neurons in the rat neostriatum.

Spontaneous firing patterns of 94 unidentified neurons and 34 identified spiny neurons were compared in the neostriatum of locally anesthetized immobilized rats. Intracellular and extracellular recordings were analyzed using first order interval histograms and autocorrelograms, and neurons were identified by their somatodendritic morphology after intracellular injection of horseradish peroxidase. All neostriatal neurons tended to fire in irregular phasic bursts of activity. Considerable variation in mean firing rate, burst duration, interburst interval and the occurrence and rate of firing between bursts was apparent in both groups of neurons. There was no apparent difference between spiny neurons and the sample of unidentified extracellularly recorded neurons along any of these firing pattern parameters. Intracellular recordings from identified spiny neurons revealed noisy irregular periods of maintained 5-20 mV membrane depolarizations which corresponded to the occurrence of bursts of firing in spontaneously active neurons. These depolarizations occurred in neostriatal neurons exhibiting no spontaneous activity but were of insufficient amplitude to trigger impulse activity.

Animals↗

PubMed1983

(-)-Sulpiride activates the firing rate and tyrosine hydroxylase activity of dopaminergic neurons in unanesthetized rats.

The effect of i.v. sulpiride on the firing rate of dopaminergic neurons in the substantia nigra, pars compacta (SN-DA cells) and tyrosine hydroxylase (TH) activity in the caudate nucleus was studied. In rats, paralyzed with succinylcholine and artificially respirated, (-)-sulpiride (10-50 mg/kg) produced a dose-related increase in the firing rate of SN-DA cells and in TH activity. On the contrary, in rats anesthetized with halothane, (-)-sulpiride (up to 50 mg/kg) activated neither dopaminergic firing nor TH activity. However, (-)-sulpiride (10-25 mg/kg) readily reversed the inhibitory effect of i.v. apomorphine (25 micrograms/kg) on dopaminergic firing in both anesthetized and unanesthetized rats. Since sulpiride fails to inhibit DA-sensitive adenylate cyclase, it may be concluded that DA receptors, whose blockade results in increased dopaminergic firing and TH activation, are not coupled with this enzyme. Moreover, the results indicate that the mechanism responsible for firing and TH stimulation is inhibited by halothane anesthesia. The latter significantly decreased also the stimulant effect of i.v. haloperidol on striatal TH activity.

Animals↗

PubMed1991

Low doses of gamma-hydroxybutyric acid stimulate the firing rate of dopaminergic neurons in unanesthetized rats.

In unanesthetized rats the intravenous (i.v.) administration of gamma-hydroxybutyric acid (GHB) at the doses of 50-400 mg/kg produced a dose-related stimulation (10-56%) of the firing rate of dopaminergic (DA) neurons in the pars compacta of the substantia nigra. Doses of 1000 and 1500 mg/kg inhibited the firing rate almost completely. In unanesthetized rats the intraperitoneal injection of GHB at the dose of 750 mg/kg produced a brief initial stimulation (23%) followed by a modest reduction in the firing rate (29%). On the other hand, in chloral hydrate-anesthetized rats the i.v. administration of GHB at cumulative doses of up to 200 mg/kg failed to modify the firing rate of DA neurons, while a cumulative dose of 400 mg/kg suppressed neuronal firing. The results indicate that sub-anesthetic doses of GHB stimulate the firing rate of DA neurons in unanesthetized rats.

Anesthesia, General↗

PubMed1993

Subthalamic nucleus lesion regularizes firing patterns in globus pallidus and substantia nigra pars reticulata neurons in rats.

Subthalamic nucleus lesion altered the statistical properties of the firing patterns of globus pallidus and substantia nigra pars reticulata neurons recorded in urethane anesthetized rats by increasing the proportion of cells in both structures that fired with a very highly regular pattern (from approximately 25% to approximately 50%). In all cases, the most regularly firing neurons fired at a higher mean rate than did more slowly firing neurons. In contrast, globus pallidus lesion shifted the pattern of substantia nigra neurons towards more irregular firing and induced a bursty pattern in two neurons.

Action Potentials↗

PubMed1995

Reduction in firing rate of substantia nigra pars reticulata neurons by valproate: influence of different types of anesthesia in rats.

Nondopaminergic, presumably GABAergic neurons in the substantia nigra pars reticulata (SNR) are thought to function as a gating mechanism for seizure propagation. Systemic administration of anticonvulsant doses of the antiepileptic drug valproate (VPA) has previously been reported to inhibit the firing of nondopaminergic SNR neurons in anesthetized but not in awake, paralyzed and locally anesthetized rats, suggesting that the findings in anesthetized rats were due to an interaction between VPA and the general anesthetic used. In the present study, we determined the influence of different anesthetic measures on the effect of an anticonvulsant dose of VPA (100 mg/kg) on extracellularly recorded spontaneous single unit activity of nondopaminergic SNR neurons in rats. Rats were anesthetized by continuous infusion of the general anesthetic chloral hydrate, the dissociative anesthetic ketamine or the narcotic opioid fentanyl, or were only locally anesthetized and paralyzed. VPA significantly reduced SNR firing in all groups with a time course that matched its anticonvulsant time course in rodents. However, VPA's inhibitory effect on SNR firing was significantly less marked under anesthesia with chloral hydrate than in any of the other groups, indicating that this anesthetic suppresses the action of VPA, which may be related to an interaction with GABA-related processes in the SNR. The closest approximation to the effect of VPA in awake rats was obtained under anesthesia with ketamine, while VPA's inhibitory action on SNR neuronal firing seemed to be enhanced in the fentanyl group, which exhibited the highest baseline firing rates of all groups. Determination of VPA in the SN showed that the difference in VPA's inhibitory effect on SNR neurons was not secondary to differences in local drug concentrations. The data demonstrate that VPA is capable of significantly slowing the spontaneous activity of nondopaminergic SNR neurons, but that the magnitude of this effect depends on the anesthetic measures used. In view of the presumed role of SNR neurons in seizure propagation and the finding that VPA consistently inhibits these neurons at an anticonvulsant dose, the present data suggest that suppression of spontaneous SNR neuronal firing may be an important mechanism through which VPA exerts its anticonvulsant properties.

Anesthetics↗

PubMed1988

The motor unit firing rate and the power spectrum of EMG in humans.

The EMG power spectrum is influenced by many factors such as the conduction velocity of the muscle fiber, the action potential of the motor unit, the number of motor units firing near the electrode, and the recording conditions. Model studies of the relation between motor unit firing rate and power spectrum of EMG have produced conflicting results. To examine this relation in vivo the brachial biceps muscle was examined in 14 controls at a force of 10% of maximum. The motor unit firing intervals were obtained from 164 motor units, sampled with a single fiber electrode. The EMG was sampled at 10 sites in each muscle with a concentric electrode and the power spectrum was obtained using fast Fourier transformation. The mean power frequency of the interference pattern as well as the relative power at 1400 Hz both decreased with increasing motor unit firing intervals between subjects. The study thus indicates that the amount of high frequencies in the power spectrum is greater in a subject with a high firing rate of the motor units than in a subject with a low firing rate.

Adolescent↗

PubMed1992

Spontaneous firing level distinguishes the effects of NMDA and non-NMDA receptor antagonists on the ganglion cells in the cat retina.

Different responses of retinal ganglion cells to iontophoretically applied NMDA receptor antagonists and non-NMDA receptor antagonists were studied in anaesthetized cats. Cells with normal range of spontaneous firing and those with abnormally high spontaneous firing levels showed a different response to these drugs. Both visually driven and spontaneous firing of cells with 'normal' spontaneous firing level were blocked by non-NMDA receptor antagonists, but not by NMDA receptor antagonists which often raised spontaneous firing. In contrast, the responses of cells with abnormally high spontaneous firing level were blocked effectively by NMDA antagonists including MK-801, an NMDA channel blocker, as well as by non-NMDA receptor antagonists. The results suggest that under normal physiological conditions, NMDA receptors which are not involved in synaptic transmission may play a role in reducing the resting discharge level of the retinal ganglion cells. NMDA receptors, however, appear to open ion channels in response to glutamate input when ganglion cells become abnormally depolarized.

2-Amino-5-phosphonovalerate↗

PubMed1993

Effect of temperature on limitation by MK-801 of firing of action potentials by spinal cord neurons in cell culture.

The anticonvulsant, MK-801, limited sustained high frequency repetitive firing of sodium-dependent action potentials by mouse spinal cord neurons in monolayer dissociated cell culture. Limitation was voltage- and temperature-dependent and was accompanied by decreasing rate of rise of action potentials until firing ceased during the 400 ms depolarizations. The IC50 for limitation was 2 x 10(-7) M at 37 degrees C, 6.4 x 10(-7) M at 35 degrees C, and 4 x 10(-5) M at 23 degrees C. The relationship between the percentage of neurons capable of sustained repetitive firing and MK-801 concentration at 33 degrees C was biphasic. The first phase (about 50%) of limitation had IC50a = 1.5 x 10(-7) M, and the second had IC50b = 2 x 10(-4) M; the midpoint of the connecting plateau was 10(-5) M. At temperatures below 37 degrees C, the current needed to achieve maximal firing increased. The maximal rate of rise, maximal firing frequency and sensitivity to MK-801 of action potentials elicited by 1 ms stimuli decreased at temperatures below 37 degrees C. Passive membrane properties were unchanged. Slow firing and a temperature-sensitive conformational change in voltage-activated sodium channels could account for the higher concentrations of MK-801 required to block sodium-dependent action potentials at temperatures below 37 degrees C.

Action Potentials↗

PubMed1994

S-adenosyl-L-methionine modulates firing rate of dorsal motor nucleus of the vagus neurones in vitro.

We used the patch clamp technique applied to an in vitro brain slice preparation to examine the changes in firing activity of single dorsal vagal motoneurones exposed to S-adenosyl-methionine. In approximately 70% of the neurones tested, S-adenosyl-L-methionine (1-100 microM) decreased the spontaneously occurring firing in a dose dependent manner; the plateau decrease was 40 +/- 6%. The peak effect was observed approximately 5 min after the superfusion with S-adenosyl-L-methionine was started, and was usually reversible upon wash out of S-adenosyl-L-methionine from the superfusing chamber. No effect of the control salt of S-adenosyl-L-methionine, 1,4-butane-disulfonate.NA (100 microM), was observed. The frequency of discharge observed upon depolarization steps from hyperpolarized potentials was reduced to 34 +/- 17% (n = 11) of control upon S-adenosyl-L-methionine (100 microM) superfusion; no effect of S-adenosyl-L-methionine was observed on the action potential threshold. Preincubation with adenosine receptor antagonists, 8-cyclopentyl-1,3-dipropylxanthine (DPCPX, 10 nM) and 3,7-dimethyl-1-propargylxanthine (DMPX, 50 microM), reversed the S-adenosyl-L-methionine-induced inhibition of firing rate, and in fact, in the presence of these adenosine antagonists, S-adenosyl-L-methionine increased the firing rate of vagal motoneurones. This excitation of vagal motoneurones was blocked by pretreatment with S-adenosyl-homocysteine (100 microM), an inhibitor of methylation reactions. It is concluded that the inhibitory activity of S-adenosyl-L-methionine on the firing rate of vagal motoneurones is due to its metabolic transformation into adenosine which then acts on adenosine receptors. The excitatory effect on firing rate appears to be due to other actions, possibly including methylation reactions of key components of signal transduction mechanisms.

Action Potentials↗

PubMed1994

Evaluation of some properties of an opaque porcelain fired simultaneously with the body porcelain.

Recently, a porcelain-fused-to-metal opaque porcelain was introduced that does not require a separate firing before application of the body porcelain. The objective of this study was to determine the properties of this new opaque porcelain and its ability to bond to metal. The properties studied included flexural strength, linear firing shrinkage, coefficient of thermal expansion, powder particle size, and ability to bond to body porcelain and dental alloys. Sintering of this opaque porcelain was complete when fired at 1760 degrees F (960 degrees C) with a linear firing shrinkage of 13.1% +/- 0.2%. No boundary between the opaque and body porcelains could be found with a scanning electron microscope after firing at 1760 degrees F (960 degrees C). The mean flexural strengths were 99 +/- 7 and 101 +/- 8 MPa respectively, for this opaque porcelain and a conventional opaque porcelain, and were not significantly different as assessed with Student's t-test (p = 0.548). The coefficients of thermal expansion for this opaque porcelain was 13.3 +/- 0.2 x 10(-6)/degrees C. Particle size analysis showed a 63% increase in the particles below 5 microns for this opaque porcelain and bonding to two alloys was adequate as indicated by its cohesive failure. Simultaneous firing of this special opaque porcelain and body porcelain produced satisfactory sintering, strength, and bonding to metal.

Chemical Phenomena↗

PubMed1988

Clonidine regularizes substantia nigra dopamine cell firing.

The effects of clonidine on the activity of single substantia nigra dopamine neurons were studied in the chloral hydrate anesthetized rat. Although clonidine did not affect the firing rate of the cells, it regularized the firing pattern and decreased burst firing at 2-8 micrograms kg-1 i.v. These effects were antagonized by the alpha 2-antagonist yohimbine. Yohimbine (1.0 mg kg-1) deregularized the firing pattern and increased the firing rate as well as the burst firing. The regularization produced by clonidine is discussed in terms of synaptic efficacy. The results might explain the therapeutic effects of clonidine in certain neuropsychiatric disorders.

Action Potentials↗