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Dopamine agonist-induced dyskinesias are correlated to both firing pattern and frequency alterations of pallidal neurones in the MPTP-treated monkey.

Despite the importance and frequency of levodopa-induced dyskinesias, little is known about their causal mechanisms. In this study, electrophysiological single-unit recordings of the neuronal activity of the globus pallidus internalis (GPi), the main basal ganglia output structure, and the globus pallidus externalis (GPe) were recorded continuously in both normal and 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine treated subhuman primates before and after the administration of three dopamine agonists--apomorphine (a dopaminergic mixed agonist), SKF-38393 (a D1 partial agonist) and piribedil (a D2/D3 agonist)--at doses known to induce dyskinesias in the parkinsonian monkey. Changes in both the firing frequency and the firing pattern were analysed in relation to behavioural modifications. In both the normal and the parkinsonian monkey, the three agonists induced a decrease in the mean firing frequency of GPi neurones, although dyskinesias were induced only in the parkinsonian animals. In this situation, the improvement of parkinsonian motor abnormalities was correlated with the decrease in GPi firing frequency, whereas firing pattern changes were concomitant with the onset of dyskinesias. Moreover, firing frequency seemed to be decreased excessively during dyskinesias. The results indicate that the electrophysiological mechanism of dyskinesia involves an excessive decrease in GPi firing frequency and a modification of the firing pattern. However, the similarity between the induced decrease in firing frequency in normal and parkinsonian animals underlines the need for dopamine depletion in the induction of dyskinesias.

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine↗

Selective postsynaptic inhibition of tonic-firing neurons in substantia gelatinosa by mu-opioid agonist.

BACKGROUND: Spinal substantia gelatinosa (SG) is a site of action of administered and endogenous opioid agonists and is an important element in the system of antinociception. However, little is known about the types of neurons serving as specific postsynaptic targets for opioid action within the SG. To study the spinal mechanisms of opioidergic analgesia, the authors compared the action of mu-opioid agonist [D-Ala, N-Me-Phe, Gly-ol]-enkephalin (DAMGO) on SG neurons with different intrinsic firing properties. METHODS: Whole cell patch clamp recordings from spinal cord slices of Wistar rats were used to study the sensitivity of SG neurons to DAMGO. RESULTS: Three groups of neurons with distinct distributions in SG were classified: tonic-, adapting-, and delayed-firing neurons. DAMGO at 1 microm concentration selectively hyperpolarized all tonic-firing neurons tested, whereas none of the adapting- or delayed-firing neurons were affected. The effect of DAMGO on tonic-firing neurons was due to activation of G protein-coupled inward-rectifier K conductance, which could be blocked by 500 microm Ba and 500 microm Cs but increased by 50 microm baclofen. As a functional consequence of DAMGO action, a majority of tonic-firing neurons changed their pattern of intrinsic firing from tonic to adapting. CONCLUSIONS: It is suggested that tonic-firing neurons, presumably functioning as excitatory interneurons, are primary postsynaptic targets for administered and endogenous opioid agonists in spinal SG. Functional transition of cells in this group from tonic to adapting firing mode may represent an important mechanism facilitating opioidergic analgesia.

Analgesics, Opioid↗

Burst-firing sharpens frequency-tuning in primary auditory cortex.

Frequency-tuning in 46 high-firing single units from primary auditory cortex of ketamine-anaesthetized cats was studied separately for isolated-spike firing and burst spike firing. The tuning curve for burst firing was significantly narrower than for the overall firing rate condition and, consequently, much narrower than for the isolated spikes. The burst firing was found in excess of that predicted from a modulated Poisson process, so the results cannot be explained on basis of a change in firing rate criterion. We propose that burst firing in auditory cortex may selectively enhance frequency tuning dynamically controlled by the behavioural state of the animal as well as its stimulus history. Thus burst firing may have functional implications for cortical processing.

Acoustic Stimulation↗

Muscarinic modulation of intrinsic burst firing in rat hippocampal neurons.

Intracellular recordings in rat hippocampal slices were used to examine how exogenous and endogenous cholinergic agonists modulate the firing pattern of intrinsically burst-firing pyramidal cells. About 24% of CA1 pyramidal cells generated all-or-none, high-frequency bursts of fast action potentials in response to intracellular injection of long positive current pulses. Application of carbachol (5 microM) converted burst firing in these neurons into regular trains of independent spikes. Acetylcholine (5 microM) exerted a similar effect, provided acetylcholine esterase activity was blocked with neostigmine (2 microM). Atropine (1 microM) reversed this cholinergic effect, indicating its mediation by muscarinic receptors. Cholinergic agonists also caused mild neuronal depolarization but the block of intrinsic burst firing was independent of this effect. Repetitive stimulation of cholinergic fibres in the presence of neostigmine (2 microM) evoked a slow cholinergic excitatory postsynaptic potential (EPSP) lasting about a minute. During the slow EPSP, burst firing could not be evoked by depolarizing pulses and the neurons fired in regular mode. These effects were prevented by pretreatment with atropine (1 microM). Exogenously applied cholinergic agonists and endogenously released acetylcholine also reduced spike frequency accommodation and suppressed the long-duration afterhyperpolarization in burst-firing pyramidal cells in an atropine-sensitive manner. A membrane-permeable cAMP analogue (8-bromo-cAMP; 1 microM) also reduced frequency accommodation and blocked the long-duration afterhyperpolarization, but did not affect intrinsic burst firing at all. Taken together, the data show that muscarinic receptor stimulation transforms the stereotyped, phasic response of burst-firing neurons into stimulus-graded, tonic discharge.

8-Bromo Cyclic Adenosine Monophosphate↗

Models of ensemble firing of muscle spindle afferents recorded during normal locomotion in cats.

1. The aim of this work was to compare the ability of several mathematical models to predict the firing characteristics of muscle spindle primary afferents recorded chronically during normal stepping in cats. 2. Ensemble firing profiles of nine hamstring spindle primary (presumed group Ia) afferents were compiled from stored data from 132 step cycles. Three sets of profiles corresponding to slow, medium and fast steps were generated by averaging groups of step cycles aligned to peak muscle length in each cycle. 3. Five models obtained from the literature were compared. Each of these models was used to predict the spindle firing profiles from the averaged muscle length signals. The models were also used in the reverse direction, namely to predict muscle length from the firing profiles. A sixth model incorporating some key aspects of the other models was also included in the comparisons. 4. Five of the models predicted spindle firing well, with root mean square (r.m.s.) errors lower than 14 % of the modulation depth of the target profiles. The key variable in achieving good predictions was muscle velocity, the best fits being obtained with power-law functions of velocity, with an exponent of 0.5 or 0.6 (i.e. spindle firing rate is approximately proportional to the square root of muscle velocity). The fits were slightly improved by adding small components of EMG signal to mimic fusimotor action linked to muscle activation. The modest relative size of EMG-linked fusimotor action may be related to the fact that hamstring muscles are not strongly recruited in stepping. 5. Length was predicted very accurately from firing profiles with the inverse of the above models, indicating that the nervous system could in principle process spindle firing in a relatively simple way to give accurate information on muscle length. 6. The responses of the models to standard ramp-and-hold displacements at 10 mm s-1 were also studied (i.e. velocities that were an order of magnitude lower than that during stepping). In these cases components of spindle primary response related to length as well as velocity were needed for good fits. Because these length-related components detracted from rather than improved predictions of the step cycle data, an attenuation of length dependence at high muscle velocities emerged as a possibility. 7. We conclude that in this study we have identified models and parameters that may be used to predict spindle afferent firing from the time course of muscle length in the cat step cycle.

Animals↗

Mechanisms and consequences of action potential burst firing in rat neocortical pyramidal neurons.

1. Electrophysiological recordings and pharmacological manipulations were used to investigate the mechanisms underlying the generation of action potential burst firing and its postsynaptic consequences in visually identified rat layer 5 pyramidal neurons in vitro. 2. Based upon repetitive firing properties and subthreshold membrane characteristics, layer 5 pyramidal neurons were separated into three classes: regular firing and weak and strong intrinsically burst firing. 3. High frequency (330 +/- 10 Hz) action potential burst firing was abolished or greatly weakened by the removal of Ca2+ (n = 5) from, or by the addition of the Ca2+ channel antagonist Ni2+ (250-500 microm; n = 8) to, the perfusion medium. 4. The blockade of apical dendritic sodium channels by the local dendritic application of TTX (100 nM; n = 5) abolished or greatly weakened action potential burst firing, as did the local apical dendritic application of Ni2+ (1 mM; n = 5). 5. Apical dendritic depolarisation resulted in low frequency (157 +/- 26 Hz; n = 6) action potential burst firing in regular firing neurons, as classified by somatic current injection. The intensity of action potential burst discharges in intrinsically burst firing neurons was facilitated by dendritic depolarisation (n = 11). 6. Action potential amplitude decreased throughout a burst when recorded somatically, suggesting that later action potentials may fail to propagate axonally. Axonal recordings demonstrated that each action potential in a burst is axonally initiated and that no decrement in action potential amplitude is apparent in the axon > 30 microm from the soma. 7. Paired recordings (n = 16) from synaptically coupled neurons indicated that each action potential in a burst could cause transmitter release. EPSPs or EPSCs evoked by a presynaptic burst of action potentials showed use-dependent synaptic depression. 8. A postsynaptic, TTX-sensitive voltage-dependent amplification process ensured that later EPSPs in a burst were amplified when generated from membrane potentials positive to -60 mV, providing a postsynaptic mechanism that counteracts use-dependent depression at synapses between layer 5 pyramidal neurons.

Action Potentials↗

The firing rates of human motoneurones voluntarily activated in the absence of muscle afferent feedback.

1. To quantify the net influence of muscle afferent feedback on the firing rates of human motoneurones, the discharge frequencies of single motor axons in the common peroneal nerve were recorded during sustained voluntary efforts performed in the absence of feedback from the target muscle. These data were compared with the firing rates of single motor units in the intact tibialis anterior muscle. In five subjects, recordings were made from fifty-two motor axons innervating tibialis anterior during acute deafferentation and paralysis of the dorsiflexor muscles produced by anaesthetic block of the nerve distal to the recording site. 2. Maximal sustainable firing rates were determined for twenty-four motoneurons, twelve of which were classified as relatively low threshold (estimated recruitment level < or = 10% maximal) and six as high threshold. Mean firing rates of the low-threshold motoneurones (21.7 +/- 2.7 Hz; +/- S.E.M.) were significantly higher than those of the high-threshold motoneurones (14.0 +/- 4.4 Hz). The mean firing rate of the twenty-four deafferented motoneurones during maximal efforts to contract the paralysed muscle was 18.6 +/- 1.9 Hz, significantly lower than the maximal firing rates of single motor units recorded from the normally innervated tibialis anterior muscle (28.2 +/- 0.6 Hz). 3. During half-maximal efforts, the mean firing rate of eight deafferented motoneurones (10.8 +/- 1.1 Hz) was significantly lower than that of intact motor units (16.5 +/- 0.2 Hz). A similar finding was apparent during minimal efforts; the mean discharge frequency of seven deafferented motoneurones during weak voluntary efforts was 6.0 +/- 0.9 Hz, compared with 7.3 +/- 0.13 Hz for intact motor units. Overall, the range of motoneurone firing rates (from minimal to maximal levels of voluntary effort) was significantly affected by the acute deafferentation, but was shifted significantly to lower rates. 4. During sustained maximal voluntary efforts of at least 30 s duration the firing rate of deafferented motoneurones decreased over the first 5 s but was then maintained, i.e. there was no progressive decline as occurs with normally innervated motor units during fatiguing contractions. This observation supports a reflex origin for the normal decline in motoneurone discharge. 5. It is concluded that muscle afferents in the common peroneal nerve provide a net facilitation to the tibialis anterior motoneurone pool, reflexly increasing the motor output at all levels of voluntary drive by approximately one-third.

Action Potentials↗

Inputs from upper airway affect firing of respiratory-associated midbrain neurons.

In 16 decerebrated unanesthetized cats, we studied effects of neural inputs from upper airway on firing of 62 mesencephalic neurons that also developed respiratory-associated (RA) rhythmic firing when respiratory drive was high [Z. Chen, F. L. Eldridge, and P.G. Wagner. J. Physiol. (Lond.) 437: 305-325, 1991] and on firing of 16 neurons that did not develop the rhythmic firing (non-RA neurons). Activity in RA neurons increased after mechanical expansion of pharynx (45% of those tested) or larynx (68%) and after stimulation of glossopharyngeal (50%) or superior laryngeal nerves (77%). The increased neuronal firing occurred despite decreases or abolition of respiratory activity (expressed in phrenic nerve). Neuronal firing also increased after mechanical stimulation of nasal mucosa (66%) or by jets of air directed into the nares (48%) and after light brushing of nasal skin ( approximately 40%). Most stimuli led to decreased firing in a smaller number of neurons, and some neurons showed no response. None of the non-RA neurons developed an increase of firing after any of the stimuli, although one had decreased firing after stimulation of the superior laryngeal nerve. We conclude that inputs from the upper airway and nasal skin have independent modulatory effects on the same mesencephalic neurons that are stimulated by ascending rhythmic RA input from the medulla. These findings may have relevance to generation of the sensation of dyspnea.

Animals↗

Multiple firing of single muscle vasoconstrictor neurons during cardiac dysrhythmias in human heart failure.

Single vasoconstrictor nerve fibers in humans normally fire only once but have the capacity to fire as many as eight times, per cardiac interval. Our laboratory recently demonstrated that the mean firing frequency of individual vasoconstrictor fibers is more than doubled in the sympathoexcitation associated with congestive heart failure (Macefield VG, Rundqvist B, Sverrisdottir YB, Wallin BG, and Elam M. Circulation 100: 1708--1713, 1999). However, the propensity to fire only once per cardiac interval was retained. In the present retrospective study, we tested the hypothesis that vasoconstrictor fibers fire more than once per cardiac interval in response to transient sympathoexcitatory stimuli, providing one mechanism for further increase of an already augmented sympathetic discharge. Six patients with congestive heart failure (New York Heart Association functional class II--IV; left ventricular ejection range 13--37%, average 22%) were studied at rest and during premature ectopic heartbeats. Analyzed for a total of 60 premature beats, the average firing probability of 10 vasoconstrictor fibers increased from 61 to 80% in the prolonged cardiac interval (i.e., reduced diastolic pressure) after premature beats. The incidence of multiple within-burst firing increased markedly, with two spikes being more common than one. Our results illustrate two different mechanisms (increases in firing probability and multiple within-burst firing), and indirectly indicate a third mechanism (recruitment of previously silent fibers), for acute sympathoexcitatory responses.

Adult↗

Synchronization of motor-unit firings in several human muscles.

1. Synchronization of concurrently active motor-unit firings was studied in six human muscles performing isometric constant-force contractions at 30% of the maximal level. The myoelectric signal was detected with a quadrifilar needle electrode and was decomposed into its constituent motor-unit action-potential trains with the Precision Decomposition technique, whose accuracy has been proven previously. 2. Synchronization was considered as the tendency of two motor units to fire at fixed time intervals with respect to each other more often than would be expected if the motor units fired independently. A rigorous statistical technique was used to measure the presence of peaks in the cross-interval histogram of pairs of motor-unit action-potential trains. The location of the center of peak as well as their width and amplitude were measured. A synch index was developed to measure the percentage of firings that were synchronized. The percentage of concurrently active motor-unit pairs that contained synchronized firings was measured. 3. Synchronization of motor-unit firings was observed to occur in two modalities. The short-term modality was seen as a peak in the cross-interval histogram centered about zero-time delay (0.5 +/- 2.9 ms, mean +/- SD) and with an average width of 4.5 +/- 2.5 ms. The long-term modality was seen as a peak centered at latencies ranging from 8 to 76 ms. On the average, the peaks of the long-term synchronization were 36% lower but had approximately the same width as the peaks for the short-term synchronization. Short-term synchronization was seen in 60% of the motor-unit paris, whereas long-term synchronization was seen in 10% of the pairs. 4. Short-term synchronization occurred in bursts of consecutive firings, ranging in number from 1 to 10, with 91% of all synchronized firing occurring in groups of 1 or 2; and the bursts of discharges appeared at sporadic times during the contraction. 5. The amount of synchronization in motor-unit pairs was found to be low. In the six muscles that were tested, an average of 8.0% of all the firings were short-term synchronized, and an average of 1.0% were long-term synchronized. The synch index was statistically indistinguishable (P = 0.07-0.89) among the different muscles and among 9 of the 11 subjects tested. 6. Sixty percent of concurrently active motor-unit pairs displayed short-term synchronization, 10% of the pairs displayed long-term synchronization, and 8% displayed both modalities.(ABSTRACT TRUNCATED AT 400 WORDS)

Adult↗

Whole-cell analysis of ionic currents underlying the firing pattern of neurons in the gustatory zone of the nucleus tractus solitarii.

1. Previous work from this laboratory has shown that rostral nucleus tractus solitarii (rNTS) neurons can be separated into four different classes on the basis of responses to a current injection paradigm consisting of membrane hyperpolarization immediately followed by a depolarizing pulse. These classes have been termed Group I, II, III, and IV neurons. The regular repetitive firing discharge pattern of Group I cells is changed into an irregular spike train by membrane hyperpolarization. Hyperpolarization of Group II neurons delays the firing discharge induced by depolarization. Hyperpolarization had the least effect on the discharge pattern of Group III neurons. The discharge pattern of Group IV neurons consisted of a short burst of spikes. We used whole-cell recordings and pharmacological channel blockers in an in vitro brain stem slice preparation to determine the ionic basis for the repetitive firing properties of rNTS neurons. 2. Application of 4-aminopyridine (4-AP, 1 mM) decreased input resistance and increased action potential duration in all groups of neurons. However, the discharge pattern of Group I, III, and IV neurons was either unaltered or slightly modified by 4-AP. In contrast the delay in firing of Group II cells induced by hyperpolarization was strongly reduced and in some cases completely suppressed by application of 4-AP. This suggests that a 4-AP-sensitive conductance primarily underlies the firing pattern of Group II cells. 3. Voltage-clamp recordings revealed that the delay in Group II neurons is due to a transient outward potassium current that is partially inactivated around the resting membrane potential. Hyperpolarization removed this inactivation, causing a delay in the firing of the cell. The potassium current was blocked by 4-AP. A similar current was occasionally seen in neurons of the other groups. On the basis of its voltage and pharmacological dependence this current was presumed to be an A-current (IKA). 4. Blockade of calcium currents by a low-calcium (0.5 mM) saline containing 2 mM Co2+ depressed the excitability of rNTS cells. For Group II neurons the delay in firing activity was increased. In the other groups the repetitive firing pattern was suppressed. In addition the amplitude of the afterhyperpolarization occurring after a short train of action potentials was substantially reduced. This indicates that calcium currents (ICa) and calcium-activated potassium currents (IKCa) contribute to the repetitive firing properties of rNTS neurons. 5. In about half of Group I, III, and IV neurons an additional property was found.(ABSTRACT TRUNCATED AT 400 WORDS)

4-Aminopyridine↗

Temporal firing patterns of Purkinje cells in the cerebellar ventral paraflocculus during ocular following responses in monkeys I. Simple spikes.

The simple-spike firing frequency of 30 Purkinje cells (P cells) in the ventral paraflocculus (VPFL) of alert monkeys was studied in relation to vertical slow eye movements, termed ocular following response (OFR), induced by large-field visual motions of different velocities and durations. To quantitatively analyze the relationship between eye movement and firing frequency, an inverse dynamics representation of the eye movement was used for reconstructing the temporal waveform of firing. Coefficients of eye-acceleration, velocity, and position, bias, and time lag between firing and eye movement were estimated by least-square error method. In the regression analyses for each stimulus condition, 86% (146/170) of the well-modulated temporal firing patterns taken from those 30 P cells were reconstructed successfully from eye movement. The model with acceleration, velocity, and position terms, which we used, was shown as the best among several potential models by Cp statistics, consistent with t-test of significance of each term. Reliable coefficients were obtained from 75% (109/146) of the well-reconstructed firing patterns of 28 cells among 30. The estimated coefficients were larger (statistically significant) for slow stimuli than for fast stimuli, suggesting changes in sensitivities under different conditions. However, firing patterns of each cell under several different conditions were frequently well reconstructed by an inverse dynamics representation with a single set of coefficients (13 cells among 21). This indicates that the relationships between P cell firing and OFR are roughly linear in those stimulus ranges. The estimated coefficients for acceleration and velocity suggested that the VPFL P cells properly encode the dynamic components of the motor command during vertical OFR. As for the positional component, however, these P cells are correlated with eye movement in the opposite direction. In the regression analysis without positional component, remarkable differences between observed and reconstructed firing patterns were noted especially in the initial phase of the movements, indicating that the negative positional component was not negligible during OFR. Thus we conclude that, during OFR, the VPFL P cells cannot provide the necessary final motor command, and other brain regions, downstream neural structures, or other types of P cells must provide lacking position-dependent motor commands. This finding about the negative correlation with the position is in the opposite sign with previous studies obtained from the fixation and the smooth pursuit movement. From these comparisons, how the VPFL contributes to a part of the final motor command or how other brain regions complement the VPFL is suggested to be different for early and late phases of the movements.

Action Potentials↗

Temporal firing patterns of Purkinje cells in the cerebellar ventral paraflocculus during ocular following responses in monkeys II. Complex spikes.

Many theories of cerebellar motor learning propose that complex spikes (CS) provide essential error signals for learning and modulate parallel fiber inputs that generate simple spikes (SS). These theories, however, do not satisfactorily specify what modality is represented by CS or how information is conveyed by the ultra-low CS firing rate (1 Hz). To further examine the function of CS and the relationship between CS and SS in the cerebellum, CS and SS were recorded in the ventral paraflocculus (VPFL) of awake monkeys during ocular following responses (OFR). In addition, a new statistical method using a generalized linear model of firing probability based on a binomial distribution of the spike count was developed for analysis of the ultra-low CS firing rate. The results of the present study showed that the spatial coordinates of CS were aligned with those of SS and the speed-tuning properties of CS and SS were more linear for eye movement than retinal slip velocity, indicating that CS contain a motor component in addition to the sensory component identified in previous studies. The generalized linear model to reproduce firing probability confirmed these results, demonstrating that CS conveyed high-frequency information with its ultra-low firing frequency and conveyed both sensory and motor information. Although the temporal patterns of the CS were similar to those of the SS when the sign was reversed and magnitude was amplified approximately 50 times, the velocity/acceleration coefficient ratio of the eye movement model, an aspect of the CS temporal firing profile, was less than that of the SS, suggesting that CS were more sensory in nature than SS. A cross-correlation analysis of SS that are triggered by CS revealed that short-term modulation, that is, the brief pause in SS caused by CS, does not account for the reciprocal modulation of SS and CS. The results also showed that three major aspects of the CS and SS individual cell firing characteristics were negatively correlated on a cell-to-cell basis: the preferred direction of stimulus motion, the mean percent change in firing rate induced by upward stimulus motion, and patterns of temporal firing probability. These results suggest that CS may contribute to long-term interactions between parallel and climbing fiber inputs, such as long-term depression and/or potentiation.

Action Potentials↗

Hand dominance and motor unit firing behavior.

Daily preferential use was shown to alter physiological and mechanical properties of skeletal muscle. This study was aimed at revealing differences in the control strategy of muscle pairs in humans who show a clear preference for one hand. We compared the motor unit (MU) recruitment and firing behavior in the first dorsal interosseous (FDI) muscle of both hands in eight male volunteers whose hand preference was evaluated with the use of a standard questionnaire. Myoelectric signals were recorded while subjects isometrically abducted the index finger at 30% of the maximal voluntary contraction (MVC) force. A myoelectric signal decomposition technique was used to accurately identify MU firing times from the myoelectric signal. In MUs of the dominant hand, mean values for recruitment threshold, initial firing rate, average firing rate at target force, and discharge variability were lower when compared with the nondominant hand. Analysis of the cross-correlation between mean firing rate and muscle force revealed cross-correlation peaks of longer latency in the dominant hand than in the nondominant side. This lag of the force output with respect to fluctuations in the firing behavior of MUs is indicative of a greater mechanical delay in the dominant FDI muscle. MVC force was not significantly different across muscle pairs, but the variability of force at the submaximal target level was higher in the nondominant side. The presence of lower average firing rates, lower recruitment thresholds, and greater firing rate/force delay in the dominant hand is consistent with the notion of an increased percentage of slow twitch fibers in the preferentially used muscle, allowing twitch fusion and force buildup to occur at lower firing rates. It is suggested that a lifetime of preferred use may cause adaptations in the fiber composition of the dominant muscle such that the mechanical effectiveness of its MUs increased.

Action Potentials↗

Noise adaptation in integrate-and fire neurons.

The statistical spiking response of an ensemble of identically prepared stochastic integrate-and-fire neurons to a rectangular input current plus gaussian white noise is analyzed. It is shown that, on average, integrate-and-fire neurons adapt to the root-mean-square noise level of their input. This phenomenon is referred to as noise adaptation. Noise adaptation is characterized by a decrease in the average neural firing rate and an accompanying decrease in the average value of the generator potential, both of which can be attributed to noise-induced resets of the generator potential mediated by the integrate-and-fire mechanism. A quantitative theory of noise adaptation in stochastic integrate-and-fire neurons is developed. It is shown that integrate-and-fire neurons, on average, produce transient spiking activity whenever there is an increase in the level of their input noise. This transient noise response is either reduced or eliminated over time, depending on the parameters of the model neuron. Analytical methods are used to prove that nonleaky integrate-and-fire neurons totally adapt to any constant input noise level, in the sense that their asymptotic spiking rates are independent of the magnitude of their input noise. For leaky integrate-and-fire neurons, the long-run noise adaptation is not total, but the response to noise is partially eliminated. Expressions for the probability density function of the generator potential and the first two moments of the potential distribution are derived for the particular case of a nonleaky neuron driven by gaussian white noise of mean zero and constant variance. The functional significance of noise adaptation for the performance of networks comprising integrate-and-fire neurons is discussed.

Acclimatization↗

The effects of ultraviolet-B radiation on the toxicity of fire-fighting chemicals.

The interactive effects of ultraviolet (UV) and fire-retardant chemicals were evaluated by exposing rainbow trout (Oncorhyncus mykiss) juveniles and tadpoles of southern leopard frogs (Rana sphenocephala) to six fire-retardant formulations with and without sodium ferrocyanide (yellow prussiate of soda [YPS]) and to YPS alone under three simulated UV light treatments. Yellow prussiate of soda is used as a corrosion inhibitor in some of the fire-retardant chemical formulations. The underwater UV intensities measured were about 2 to 10% of surface irradiance measured in various aquatic habitats and were within tolerance limits for the species tested. Mortality of trout and tadpoles exposed to Fire-Trol GTS-R, Fire-Trol 300-F, Fire-Trol LCA-R, and Fire-Trol LCA-F was significantly increased in the presence of UV radiation when YPS was present in the formulation. The boreal toad (Bufo boreas), listed as endangered by the state of Colorado (USA), and southern leopard frog were similar in their sensitivity to these chemicals. Photoenhancement of fire-retardant chemicals can occur in a range of aquatic habitats and may be of concern even when optical clarity of water is low; however, other habitat characteristics can also reduce fire retardant toxicity.

Ammonia↗

Evaluation of motor unit firing rates by standard concentric needle electromyography.

Motor unit firing rates at slight voluntary contraction were studied by standard concentric needle electromyography. Employing digital signal analysis techniques firing rates of motor units (MU) could be evaluated as long as four or less different MUs were activated in the vicinity of the concentric needle electrode. The extension of the recording area is defined by the recording properties of the electrode and the upper limit of rise-time for all MUPs being evaluated. Distant MUs, generating volume conducted potentials with rise-times greater than 0.8 ms, were excluded. In biceps muscles of 15 healthy controls the firing rate of the MU activated first was evaluated at that moment, when a second MU was recruited and was found to be 12.1 +/- 2.1 Hz (mean +/- S.D., n = 40). The firing rate of the fastest MU out of 2, 3, or 4 simultaneously active MUs was 10.7 +/- 2.5 Hz, 10.9 +/- 2.5 Hz and 10.6 +/- 2.4 Hz respectively. Hence at low innervation level there is no increase of firing rate with rising number of activated MUs. The upper normal limit of MU firing rate (3 sigma interval) is calculated as 17 Hz, irrespective whether 1, 2, 3 or 4 MUs are active within the recording area. Fifteen patients with partially denervated biceps muscles were investigated. Maximal firing rates were increased in 10 patients, all showing moderate or severe paresis (grade 1-3). In 10 patients suffering from myopathies firing rates always were normal. The presented data may serve as an additional criterion in evaluating MU firing rates during standard clinical EMG.

Action Potentials↗

[Electrical activities of bursting-firing neurons in epileptic network reestablishment of rat hippocampus].

The purpose of our present work was to study the discharge of bursting-firing neurons (BFNs) in ipsilateral or contralateral hippocampus (HPC), and its relations to the reestablishment of local epileptic networks. The experiments were performed on 140 Sprague Dawley male rats (150-250 g). Acute tetanization (60 Hz, 2 s, 0.4 -0.6 mA) of the right posterior dorsal hippocampus (ATPDH) was administered to establish rat epilepsy model. The single unit discharges and the depth electrographs were simultaneously recorded from ipsilateral or contralateral HPC. In other experimental rats, acute tetanization of the right anterior dorsal HPC (ATADH) was used. Extracellular unit discharges in the CA1 region were simultaneously recorded from bilateral anterior dorsal hippocampi. Analysis of hippocampal BFN firing patterns before or after administration of the tetanization was focused on according to their location in the HPC epileptic networks in vivo. Single unit discharges of 138 hippocampal neurons were recorded from ipsilateral and/or contralateral anterior dorsal HPC. Of the 138 neurons recorded, 19 were BFNs. 13 BFNs were tetanus-evoked and the remaining 6 were spontaneous ones. The evoked reactions of the single hippocampal neuron induced by the tetanization mainly included: (1) the firing patterns of the BFNs in ipsilateral anterior dorsal HPC were obviously modulated by the ATPDH from tonic firing into rhythmic bursting. The bursting interspike intervals (BISI) decreased. (2) There were mild modulations of the firing patterns of the BFNs in contralateral anterior dorsal HPC following post-inhibition of the firing rate of single neuron induced by the ATPDH. The interspike intervals (ISI) increased obviously. (3) Post-facilitation of rhythmic bursting-firing of the BFNs in contralateral anterior dorsal HPC was induced by ATADH; both the ISI and the IBI increased. (4) Synchronous or asynchronous rhythmic bursting-firing of the BFNs and the network epileptiform events ipsilateral or contralateral anterior dorsal HPC were elicited by the ATPDH. The results obtained suggest that bursting-firing of single BFNs is produced by the ATPDH in the anterior dorsal HPC along the longitudinal axis of the ipsilateral HPC or across the hemisphere to the opposite HPC. Rhythmic activities of the BFN may be implicated in the epileptic network reestablishment of the HPC. On the other hand, synaptic modulation of the BFN temporal series might be responsible for pathophysiological information transmission in the HPC-epileptic network.

Animals↗