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At least 343 records · Page 19Linked to original sources
PubMed1989

Antidromically identified striatonigral projection neurons in the chronically implanted behaving rat: relations of cell firing to amphetamine-induced behaviors.

The effects of systematically administered amphetamine (0.25-5.0 mg/kg, sc) on neostriatal neurons recorded in chronically implanted behaving rats were studied. Projection neurons, identified by antidromic activation from the substantia nigra, fired very infrequently during most predrug behaviors (e.g., median rate, 0.02 spikes per second during locomotion; 17 of 18 fired less than 1 spike per second during all rated behaviors). Nonantidromic cells also tended to fire slowly (median rate, 0.02 spikes per second during locomotion; 20 of 24 cells fired less than 1 spike per second). Cells of both type showed up to 10-fold variations in firing rate across behaviors. For most neurons, amphetamine caused a reduction in the firing rate during related pre- and postdrug behaviors. For instance, the firing rate of 28 of 42 neurons was reduced during the initial amphetamine-induced locomotion as compared with the rate during predrug locomotion. Moreover, with the higher doses of amphetamine, there was a further reduction in firing rate corresponding to the transition from locomotion to stereotypies. In contrast to previous studies, which suggest that amphetamine generally increases neostriatal firing rate in behaving animals, these results suggest that amphetamine inhibits the numerous slowly firing neostriatal neurons, many of which were identified as projection neurons. Thus amphetamine alters the magnitude and pattern of neostriatal control of its neural targets.

Action Potentials↗
PubMed1997

Modulation of the firing activity of noradrenergic neurones in the rat locus coeruleus by the 5-hydroxtryptamine system.

1. The aim of the present study was to investigate the putative modulation of locus coeruleus (LC) noradrenergic (NA) neurones by the 5-hydroxytryptaminergic (5-HT) system by use of in vivo extracellular unitary recordings and microiontophoresis in anaesthetized rats. To this end, the potent and selective 5-HT1A receptor antagonist WAY 100635 (N-[2-[4(2-methoxyphenyl)-1-piperazinyl]-N-(2-pyridinyl) cyclohexanecarboxamide trihydroxychloride) was used. 2. In the dorsal hippocampus, both local (by microiontophoresis, 20 nA) and systemic (100 micrograms kg-1, i.v.) administration of WAY 100635 antagonized the suppressant effect of microiontophorectically-applied 5-HT on the firing activity of CA3 pyramidal neurones, indicating its antagonistic effect on postsynaptic 5-HT1A receptors. 3. WAY 100635 and 5-HT failed to modify the spontaneous firing activity of LC NA neurones when applied by microiontophoresis. However, the intravenous injection of WAY 100635 (100 micrograms kg-1) readily suppressed the spontaneous firing activity of LC NA neurones. 4. The lesion of 5-HT neurones with the neurotoxin 5,7-dihydroxytryptamine increased the spontaneous firing activity of LC NA neurones and abolished the suppressant effect of WAY 100635 on the firing activity of LC NA neurones. 5. In order to determine the nature of the 5-HT receptor subtypes mediating the suppressant effect of WAY 100635 on NA neurone firing activity, several 5-HT receptor antagonists were used. The selective 5-HT3 receptor antagonist BRL 46470A (10 and 100 micrograms kg-1, i.v.), the 5-HT1D receptor antagonist GR 127935 (100 micrograms kg-1, i.v.) and the 5-HT1A/1B receptor antagonist (-)-pindolol (15 mg kg-1, i.p.) did not prevent the suppressant effect of WAY 100635 on the firing activity of LC NA neurones. However, the suppressant effect of WAY 100635 was prevented by the non-selective 5-HT receptor antagonists spiperone (1 mg kg-1, i.v.) and metergoline (1 mg kg-1, i.v.), by the 5-HT2 receptor antagonist ritanserin (500 micrograms kg-1, i.v.). It was also prevented by the 5-HT1A receptor/alpha 1D-adrenoceptor antagonist BMY 7378 (1 mg kg-1, i.v.) and by the alpha 1-adrenoceptor antagonist prazosin (100 micrograms kg-1, i.v.). 6. These data support the notion that the 5-HT system tonically modulates NA neurotransmission since the lesion of 5-HT neurones enhanced the LC NA neurones firing activity and the suppressant effect of WAY 100635 on the firing activity of NA neurones was abolished by this lesion. However, the location of the 5-HT1A receptors involved in this complex circuitry remains to be elucidated. It is concluded that the suppressant effect of WAY 100635 on the firing activity of LC NA neurones is due to an enhancement of the function of 5-HT neurones via a presynaptic 5-HT1A receptor. In contrast, the postsynaptic 5-HT receptor mediating this effect of WAY 100635 on NA neurones appears to be of the 5-HT2A subtype.

Animals↗
PubMed2005

Restraint increases dopaminergic burst firing in awake rats.

In anesthetized animals, dopamine neurons fire in tonic and phasic firing modes hypothesized to be regulated by dissociable circuit mechanisms. Salient events critical to learning, reward processing, and attentional selection elicit transient phasic bursts. It is unclear, however, how burst activity contributes to sustained firing patterns in awake animals and if behavioral conditions known to affect dopaminergic neurotransmission change impulse activity levels. Acute stress is known to increase extracellular dopamine in the striatum and the prefrontal cortex. In this study, we have used multiunit recording to define and follow activity patterns in single dopaminergic neurons across days and to determine how restraint, a model of acute stress, changes tonic and phasic firing patterns. Long-term recording shows that a population of 23 putative dopamine neurons has heterogeneous firing profiles under baseline conditions. In all, 62% showed significant burst activity under resting conditions, while others showed predominantly regular (17%) or random (21%) activity patterns. Restraint increased mean firing rate in all dopamine neurons, but preferentially increased burst firing in neurons with higher burst rates under resting conditions. Finally, we show that increased burst firing can persist 24 h after a single exposure to stress. These data indicate that subsets of dopamine neurons may be sensitive to circuit mechanisms activated by stress and that persistent changes in burst firing may be evidence of synaptic plasticity. Furthermore, increased burst firing may be a mechanism through which stress augments extracellular dopamine in selected terminal regions.

Action Potentials↗
PubMed2000

Bond strength of three porcelains to two forms of titanium using two firing atmospheres.

STATEMENT OF PROBLEM: Problems with casting and porcelain bonding are encountered when titanium is used in metal-porcelain restorations. The oxidation characteristics of titanium are the main problem. The bonding mechanisms in titanium-porcelain systems are complex and poorly understood. PURPOSE: An in vitro investigation was performed to evaluate the bonding characteristics of 3 titanium-porcelain systems in various firing conditions. MATERIAL AND METHODS: This study evaluated the bonding strength of 3 commercial titanium porcelains fired in a vacuum and in an argon atmosphere to cast and noncast commercially pure titanium, using a 3-point bending test according to DIN 13927 and SEM with energy-dispersive spectrometry analysis. The results were compared with an Ni-Cr alloy and a conventional porcelain that was chosen as a control. RESULTS: The Ni-Cr-conventional porcelain system fired in an argon atmosphere had significantly higher bond strength than the other systems (P<.001). In addition, the bond strength of the titanium-spark erosion-Noritake Ti22 combination, fired in an argon atmosphere, was significantly higher than the other titanium-porcelain groups, which had results similar to those obtained with the vacuum-fired, Ni-Cr-conventional porcelain and argon-fired titanium-cast-Noritake Ti22 groups. On the other hand, the bond strength of the titanium-TiBond and titanium-Vita Titankeramik groups was below the lower limit value in the DIN 13927 standard for the 3-point bending test (25 MPa). Although the results of the Duncan multiple range test showed that firing in an argon atmosphere did not affect the bond strength of the titanium-Vita Titankeramik groups, the titanium-spark erosion-TiBond group, or the titanium-cast-Noritake Ti22 group, argon firing improved the bond strengths of the Ni-Cr-conventional porcelain group, the titanium-cast-TiBond group, and the titanium-spark erosion-Noritake Ti22 porcelain group. It was also found that there were no significant differences between the bond strengths of cast and non-cast titanium groups; an exception was the titanium TiBond groups in which the porcelain was fired in a vacuum. CONCLUSION: The oxide layer produced on titanium was considered to have a potentially adverse effect on titanium-porcelain bonding. It was also concluded that matching the titanium-porcelain combination is the main determinant for optimal bonding. Firing in an argon atmosphere that limited the oxidation of titanium improved the titanium-porcelain bond in some of the groups.

Analysis of Variance↗
PubMed2005

DNA replication origins fire stochastically in fission yeast.

DNA replication initiates at discrete origins along eukaryotic chromosomes. However, in most organisms, origin firing is not efficient; a specific origin will fire in some but not all cell cycles. This observation raises the question of how individual origins are selected to fire and whether origin firing is globally coordinated to ensure an even distribution of replication initiation across the genome. We have addressed these questions by determining the location of firing origins on individual fission yeast DNA molecules using DNA combing. We show that the firing of replication origins is stochastic, leading to a random distribution of replication initiation. Furthermore, origin firing is independent between cell cycles; there is no epigenetic mechanism causing an origin that fires in one cell cycle to preferentially fire in the next. Thus, the fission yeast strategy for the initiation of replication is different from models of eukaryotic replication that propose coordinated origin firing.

DNA Replication↗
PubMed1998

Fatal anaphylaxis due to fire ant stings.

Imported fire ants (Solenopsis invicta and Solenopsis richteri) are the source of a potentially lethal environmental hazard in the southeastern United States. Because of their resistance to natural and chemical control, fire ants can overwhelm their environment, causing destruction of land and animals. Fire ants can also cause a variety of health problems in humans, ranging from simple stings to anaphylaxis and death. We present a case of a 30-year-old woman who died of anaphylaxis following multiple fire ant stings. At autopsy, multiple skin lesions characteristic of those produced by fire ant stings were present on her arm. Postmortem blood samples were positive for imported fire ant venom-specific IgE antibodies (5654 ng/ml) and tryptase (12 ng/ml). Deaths caused by imported fire ant stings are rare but are likely to become more common as the fire ant population expands. In this report, we review deaths due to fire ant stings, discuss postmortem laboratory findings, and stress the importance of recognizing the characteristic skin lesions produced by fire ants.

Adult↗
PubMed2005

Ectopic firing due to artificial venous stasis in rat lumbar spinal canal stenosis model: a possible pathogenesis of neurogenic intermittent claudication.

STUDY DESIGN: An electrophysiologic analysis was performed on a chronic lumbar spinal stenosis model of rats. The effects of venous stasis on ectopic firing originating in the nerve root were investigated. OBJECTIVES: To elucidate the mechanisms of neurogenic intermittent claudication in lumbar spinal canal stenosis. SUMMARY OF BACKGROUND DATA: Neurogenic intermittent claudication has been known as a characteristic symptom of lumbar spinal canal stenosis (LSCS), but the pathogenesis is poorly understood. Venous stasis of cauda equina has been speculated as a possible factor in the development of symptoms of the lower extremities while walking. On the other hand, ectopic firing originating in the dorsal root ganglia is thought to play an important role in the development of radicular pain or abnormal sensation. However, a direct association between venous stasis and ectopic firing has been never demonstrated. METHODS: Using 10 Wistar rats, the LSCS group was prepared by inserting two silicone strips into the L3 and L5 dorsal epidural spaces. Another 10 animals were treated without silicone insertion as a sham group. Fourteen days later, the ectopic firing originating in the L5 nerve root was antidromically recorded from the distal stump of the severed sural nerve. After recording initial spontaneous firing, the posterior vena cava was clamped for 60 seconds to simulate a transient venous stasis and the changes in firing were analyzed. RESULTS: None of the animals in the sham group showed a significant change in firing due to venous stasis. In contrast, most animals in the LSCS group showed a marked increase in firing during the venous stasis with some latency and then returned to the initial firing state after the release of the clamp. This phenomenon was repeated as long as the animals were maintained. CONCLUSIONS: We demonstrated that ectopic firing was elicited by venous stasis only in the LSCS animals. Therefore, the venous stasis may be a major factor of neurogenic intermittent claudication.

Animals↗
PubMed1999

The effect of firing on the excitability of a model motoneurone and its implications for cortical stimulation.

1. To help clarify the use of measurements of 'excitability', a simple model motoneurone receiving noisy tonic background excitation was tested with brief stimuli. Its response was determined from its PSTH (post-stimulus time histogram). The tonic background was varied from well below to well above the threshold for tonic firing. The conclusions should apply to many other neurones. 2. The response of the model to a stimulus depended upon a number of factors, including stimulus strength, synaptic membrane noise and especially whether or not the background drive elicited tonic firing. With the onset of firing, the shape of the stimulus-response curve changed drastically and the model then responded to the smallest stimulus without a threshold. When the drive was subthreshold, increasing the background excitation always increased the response to a given stimulus. However, what happened when the tonic drive exceeded the threshold for tonic firing depended upon the stimulus strength. With weak stimuli, the response increased with the drive to reach a plateau level where it was independent of the background firing rate; this occurred for stimuli comparable in size to the synaptic noise. With stronger stimuli, the response rose to a maximum for very low firing rates, but then decreased by up to 50 % to a plateau for high firing rates. Increasing the membrane noise reduced or abolished the maximum. 3. The model was also used to simulate a monosynaptic conditioning-testing paradigm. The effect of a given conditioning stimulus was then found to change with the onset of firing, including when the strength of the testing stimulus was adjusted to make the size of the test response the same in the presence and absence of firing. 4. The behaviour of real motoneurones can be expected to be at least as complex with the transition from silence to firing, so H reflex and other tests of 'excitability' must then be treated with caution. In particular, as has been observed experimentally, the response of a unit may decrease with increasing background excitation, as well as with inhibition. 5. Transferring the findings to corticospinal neurones makes it unlikely that the magnitude of the descending volley elicited by a given cortical stimulus ('excitability') will always increase with the initial level of cortical activity. In addition, the appreciable threshold for transcranial magnetic stimulation during voluntary contraction suggests that it first excites axons rather than the neural pacemakers.

Cerebral Cortex↗
PubMed1988

Firing patterns of midbrain dopamine neurons: differences between A9 and A10 cells.

Dopamine neurons of the substantia nigra (A9) and the ventral tegmental area (A10), giving rise to the nigrostriatal and mesolimbic dopamine pathways, respectively, are commonly supposed to show similar electrophysiological activity. There are, however, instances where the two systems are differently modulated. To assess possible physiological differences in the neuronal activity of A9 and A10 neurons, randomly sampled single cells were extracellularly recorded in the chloral hydrate-anaesthetized male rat. In addition to firing rate, the degree of burst firing and the regularity of firing were quantitatively analysed. Our results show that although A9 and A10 do not differ in firing rates, A10 neuronal activity is markedly less regular and shows a higher degree of burst firing, as judged from analysis of inter-spike time interval histograms. Mean burst firing values were 3% for the A9, and 23% for the A10 neurons. Regularity was described by variation coefficients of inter-spike time interval histograms. The mean variation coefficient was 38.4% in the A9 group and 63.8% in the A10 group, i.e. the A10 neuronal firing was less regular. The difference in regularity is partly, but not fully, dependent on the difference in burst firing. Previous biochemical and physiological studies strongly support the functional significance of modulatory changes in midbrain dopamine-cell firing patterns. Since the firing pattern of midbrain dopamine cells seems to be controlled by synaptic inputs, our results indicate a higher tonic modulatory influence on the A10 than on the A9 neurons. Thus the present results imply the pharmacological possibility of preferentially affecting A10 versus A9 dopamine cell function.

Action Potentials↗
PubMed1994

Sensory input and burst firing output of rat and cat thalamocortical cells: the role of NMDA and non-NMDA receptors.

1. Intracellular and patch-clamp recordings were obtained from thalamocortical (TC) cells in the rat and cat dorsal lateral geniculate nucleus (dLGN) in vitro to study the role of N-methyl-D-aspartate (NMDA) and non-NMDA receptors in the synaptic potential and burst firing evoked by electrical stimulation of the optic tract. 2. At membrane potentials more positive than -65 mV, the sensory synaptic potential consisted of a fast EPSP that was followed by a smaller, slower component. At membrane potentials more negative than -65 mV, this slower component became more prominent owing to the presence of a low-threshold (LT) Ca2+ potential, which in turn evoked a high-frequency (> 150 Hz) burst of action potentials. The lower, but not the upper limit of the range of membrane potential over which burst firing occurred was dependent on the amplitude of the fast EPSP. 3. The non-NMDA receptor antagonists 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX, 5-10 microM) and 1-(4-amino-phenyl)-4-methyl-7,8-methylene-dioxy-5H-2,3- benzodiazepine (GYKI 52466, 100 microM) greatly depressed the fast EPSP, abolished the burst firing generated by the LT Ca2+ potential, and left a relatively small, slow EPSP, which was sensitive to the NMDA antagonist DL-2-amino-5-phosphonovaleric acid (DL-AP5, 50-100 microM). 4. In the absence of CNQX or GYKI 52466, DL-AP5 depressed the slow but not the fast EPSP. DL-AP5 also increased the latency of the first action potential evoked by the LT Ca2+ potential or even abolished the LT Ca2+ potential and associated burst firing. The latter effect was only present when this type of firing occurred within a small membrane potential range. 5. DL-AP5 had no effect on the properties of the LT Ca2+ current IT, indicating that its effect on the burst firing was not mediated by a direct action on IT. 6. The response of TC cells to high-frequency (100 Hz) stimulation consisted of an initial burst firing response, followed by a sustained depolarization that could reach firing threshold. This sustained depolarization was markedly depressed by DL-AP5 but not by CNQX. 7. These results demonstrate that with low-frequency stimulation of the sensory afferents, the generation of TC cell output in the rat and cat dLGN is mainly controlled by non-NMDA receptors, while the contribution of NMDA receptors is limited to the burst firing generated by the LT Ca2+ potential, and depends on the membrane potential range over which this type of firing occurs.(ABSTRACT TRUNCATED AT 400 WORDS)

2-Amino-5-phosphonovalerate↗
PubMed1996

Relationship of firing intervals of human motor units to the trajectory of post-spike after-hyperpolarization and synaptic noise.

1. Interspike interval distributions from human motor units of a variety of muscles were analysed to assess the role of synaptic noise in excitation. The time course of the underlying post-spike after-hyperpolarization (AHP) was deduced by applying a specially developed transform to the interval data. Different firing rates were studied both by varying the firing voluntarily, and by selecting subpopulations of spikes for a given firing rate from long recordings with slight variations in frequency. 2. At low firing rates the interval histograms had an exponential tail. Thus at long intervals, the motoneurone was randomly excited by noise and its post-spike AHP was complete. This contrasts with the firing produced by intracellular current injection in the cat, when the membrane potential increases linearly until threshold is reached. The interval histogram was therefore analysed with the aid of a model of synaptic excitation to deduce the mean 'trajectory' of membrane voltage in the last part of the interspike interval. 3. The computer model, described in the Appendix, was used to determine the effect of the mean level of membrane potential on the probability of a spike being excited, per unit time, during an on-going interspike interval. All variables were treated as voltages, with synaptic noise simulated by time-smoothed Gaussian noise. This enabled an interval distribution to be transformed into a segment of the underlying trajectory of the membrane potential; the potential was expressed in terms of the noise amplitude and the spike threshold. 4. At low firing rates, the equilibrium value of the membrane voltage trajectory lay well below threshold; the deviation typically corresponded to the standard deviation of the noise or more. The noise standard deviation was estimated to be about 2 mV. 5. With increasing mean firing rate, the near-threshold portion of the trajectory obtainable from the histogram occurred earlier, was steeper and rose to a higher level. Trajectories for different firing rates fell on the same curve after shifting them vertically by varying amounts. The curve was taken to represent the AHP of the motoneurone and was closely exponential. The shift of the trajectory gave its mean synaptic drive. The duration of the AHP varied between units and was longer than average for units from soleus muscle. 6. Further modelling showed that summation of noise with the AHP can explain the well-known changes in discharge variability that occur as firing rate increases. 7. It is concluded that synaptic noise plays a major role in the excitation of tonically firing human motoneurones and that the noiseless motoneurone with a linear trajectory provides an inadequate model for the conscious human. This is of interest in relation to various standard measures of human motor unit activity such as short-term synchronization.

Action Potentials↗
PubMed2003

A modeling study suggests complementary roles for GABAA and NMDA receptors and the SK channel in regulating the firing pattern in midbrain dopamine neurons.

Midbrain dopaminergic (DA) neurons in vivo exhibit two major firing patterns: single-spike firing and burst firing. The firing pattern expressed is dependent on both the intrinsic properties of the neurons and their excitatory and inhibitory synaptic inputs. Experimental data suggest that the activation of N-methyl-D-aspartate (NMDA) and GABAA receptors is a crucial contributor to the initiation and suppression of burst firing, respectively, and that blocking Ca(2+)-activated potassium SK channels can facilitate burst firing. A multi-compartmental model of a DA neuron with a branching structure was developed and calibrated based on in vitro experimental data to explore the effects of different levels of activation of NMDA and GABAA receptors as well as the modulation of the SK current on the firing activity. The simulated tonic activation of GABAA receptors was calibrated by taking into account the difference in the electrotonic properties in vivo versus in vitro. Although NMDA-evoked currents are required for burst generation in the model, currents evoked by GABAA-receptor activation can also regulate the firing pattern. For example, the model predicts that increasing the level of NMDA receptor activation can produce excessive depolarization that prevents burst firing, but a concurrent increase in the activation of GABAA receptors can restore burst firing. Another prediction of the model is that blocking the SK channel current in vivo will facilitate bursting, but not as robustly as blocking the GABAA receptors.

Animals↗
PubMed2004

Visual response properties of burst and tonic firing in the mouse dorsal lateral geniculate nucleus.

Thalamic relay cells fire action potentials in two modes: burst and tonic. Previous studies in cats have shown that these two modes are associated with significant differences in the visual information carried by spikes in the dorsal lateral geniculate nucleus (dLGN). Here we describe the visual response properties of burst and tonic firing in the mouse dLGN. Extracellular recordings of activity in single geniculate cells were performed under halothane and nitrous oxide anesthesia in vivo. After confirming that the criteria used to isolate burst spikes from these recordings identify firing events with properties described for burst firing in other species and preparations, we show that burst firing in the mouse dLGN occurs during visual stimulation. We then compare burst and tonic firing across a wide range of visual response characteristics. While the two firing modes do not differ with respect to spatial summation or spatial frequency tuning, they show significant differences in the temporal domain. Burst spikes are phase advanced relative to their tonic counterparts. Burst firing is also more rectified, possesses sharper temporal frequency tuning, and prefers lower temporal frequencies than tonic firing. In addition, contrast-response curves are more step-like for burst responses. Finally, we present analyses that describe the stimulus detection abilities and spike timing reliability of burst and tonic firing.

Action Potentials↗
PubMed2002

Regulation of firing response gain by calcium-dependent mechanisms in vestibular nucleus neurons.

Behavioral reflexes can be modified by experience via mechanisms that are largely unknown. Within the circuitry for the vestibuloocular reflex (VOR), neurons in the medial vestibular nucleus (MVN) show adaptive changes in firing rate responses that are correlated with VOR gain (the ratio of evoked eye velocity to input head velocity). Although changes in synaptic strength are typically assumed to underlie gain changes in the VOR, modulation of intrinsic ion channels that dictate firing could also play a role. Little is known, however, about how ion channel function or regulation contributes to firing responses in MVN neurons. This study examined contributions of calcium-dependent currents to firing responses in MVN neurons recorded with whole cell patch electrodes in rodent brain stem slices. Firing responses were remarkably linear over a wide range of firing rates and showed modest spike frequency adaptation. Firing response gain, the ratio of evoked firing rate to input current, was reduced by increasing extracellular calcium and increased either by lowering extracellular calcium or with antagonists to SK- and BK-type calcium-dependent potassium channels and N- and T-type calcium channels. Blockade of SK channels occluded gain increases via N-type calcium channels, while blocking BK channels occluded gain increases via presumed T-type calcium channels, indicating specific coupling of potassium channels and their calcium sources. Selective inhibition of Ca(2+)/calmodulin-dependent kinase II and broad-spectrum inhibition of phosphatases modulated gain via BK-dependent pathways, indicating that firing responses are tightly regulated. Modulation of firing response gain by phosphorylation provides an attractive mechanism for adaptive control of VOR gain.

Amiloride↗
PubMed1988

Repetitive firing properties of phrenic motoneurons in the cat.

1. Using both rectangular- and ramp-shaped intracellularly injected currents, the repetitive firing properties of 23 antidromically identified phrenic motoneurons were determined in anesthetized, paralyzed, and artificially ventilated cats during hypocapnic apnea. In response to rectangular depolarizing current injections, regular repetitive firing was observed in all cells. 2. At the beginning of a rectangular current pulse, the firing pattern was characterized by high frequency of firing that rapidly adapted to a much lower steady-state value. The relationship between the reciprocal of the first interspike interval (F1-2) and injected current was described by an initial linear portion of shallow slope, followed by a much steeper segment that smoothly reached a plateau value. The plateau value of F1-2 did not change with further increase in injected current. 3. The steady-state firing frequency versus injected current relationship was represented by a line of shallow slope over the entire range of injected currents. The slope of this line ranged between 1.1 and 4.5 Hz/nA. 4. A weaker correlation between minimal firing frequency for continuous activity and the reciprocal of the after hyperpolarization duration (1/AHPdur) was found for phrenic motoneurons than exists for lumbosacral motoneurons (26). Comparison of AHP shape at different levels of repetitive firing revealed that the slopes of the ascending portions of the AHP were similar except at the higher injected currents. Further, in the same cells during natural inspiratory activity the ascending part of the AHP was similar to that observed during current injection. 5. Depolarizing current ramps (approximately 1-s duration) were injected into 11 phrenic motoneurons. Instantaneous firing frequency was directly proportional to the intensity of the instantaneous injected current and independent of the rate of change of current for the range of ramp slopes tested (5-80 nA/s). Ramp-and-hold current injections were done in three motoneurons, and the peak instantaneous firing frequency showed little adaptation during the hold maneuver. 6. During hypocapnic apnea, we mimicked the expiratory-phase inhibition and inspiratory-phase excitation of phrenic motoneurons by injecting a 1-s depolarizing current ramp that was immediately preceded by a 1-s hyperpolarizing current ramp of the same absolute peak current intensity. Compared with the effects of positive current ramps alone the spike onsets during the negative-positive current ramp paradigm were either facilitated or retarded. Various ionic mechanisms are suggested for these effects as well as their function in determining the onset of firing during natur

Animals↗
PubMed1993

Effects of transient depolarizing potentials on the firing rate of cat neocortical neurons.

1. The effects of excitatory postsynaptic potentials (EPSPs) on interspike intervals (ISIs) of neocortical neurons can be mimicked by pulse potentials (PPs) produced by current injection. The present report documents the dependence of the ISI shortening on the amplitudes of PPs and EPSPs and on the firing rate of the affected neuron. 2. In rhythmically firing necortical neurons, the ISI shortenings caused by PPs arriving at specific times in the ISI can be described by a shortening-delay (S-D) curve. The S-D curve yields three measures of the PPs' ability to shorten the ISI: 1) the mean ISI shortening, S; 2) the maximum shortening, Smax; and 3) the effective interval, defined as the portion of the ISI in which the PP consistently shortens the ISI. For PPs ranging between 80 microV and 3.6 mV (and cells firing at 25 imp/s), the mean shortening increased with amplitude h as S (ms) = 1.2*h (mV)1.24 (r = 0.94; P < 0.01). Smax increased linearly with amplitude as 4.9 ms/mV (r = 0.86, P < 0.01). The effective interval (as a percentage of the ISI) increased slightly with PP amplitude and had a mean value of 65 +/- 21% (mean +/- SD). 3. S-D curves obtained with stimulus-evoked EPSPs varied with EPSP amplitude in a manner similar to those of PPs. The relations obtained for stimulus-evoked EPSPs were not statistically different from those obtained for PPs in the same cells. 4. To determine the effect of firing rate. PPs were applied while neurons fired at frequencies ranging from 8 to 71 imp/s. Both S and Smax were approximately inversely proportional to the baseline firing rate (fo) and could be described as: S or Smax = kfo-m. The mean value of the exponent m (+/- SD) was 0.96 +/- 0.25 for S and 1.2 +/- 0.4 for Smax. These values were not statistically different from a value of 1 (1 group, 2-tailed t test). The effective interval did not vary significantly with firing rate. 5. The dependence of S on PP amplitude and baseline firing rate was incorporated into an expression for the average change in firing rate (delta f) produced by PPs occurring at rate fs: delta f = 0.03 h1.24 fs. The delta f increased with PP amplitude but did not vary significantly with the baseline firing rate. The values of delta f calculated from the S-D curves matched the values that were computed directly from the spike trains.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1997

Computer simulation of the responses of human motoneurons to composite 1A EPSPS: effects of background firing rate.

Two compartmental models of spinal alpha motoneurons were constructed to explore the relationship between background firing rate and response to an excitatory input. The results of these simulations were compared with previous results obtained from human motoneurons and discussed in relation to the current model for repetitively firing human motoneurons. The morphologies and cable parameters of the models were based on two type-identified cat motoneurons previously reported in the literature. Each model included five voltage-dependent channels that were modeled using Hodgkin-Huxley formalism. These included fast Na+ and K+ channels in the initial segment and fast Na+ and K+ channels as well as a slow K+ channel in the soma compartment. The density and rate factors for the slow K+ channel were varied until the models could reproduce single spike AHP parameters for type-identified motoneurons in the cat. Excitatory synaptic conductances were distributed along the equivalent dendrites with the same density described for la synapses from muscle spindles to type-identified cat motoneurons. Simultaneous activation of all synapses on the dendrite resulted in a large compound excitatory postsynaptic potential (EPSP). Brief depolarizing pulses injected into a compartment of the equivalent dendrite resulted in pulse potentials (PPs), which resembled the compound EPSPs. The effects of compound EPSPs and PPs on firing probability of the two motoneuron models were examined during rhythmic firing. Peristimulus time histograms, constructed between the stimulus and the spikes of the model motoneuron, showed excitatory peaks whose integrated time course approximated the time course of the underlying EPSP or PP as has been shown in cat motoneurons. The excitatory peaks were quantified in terms of response probability, and the relationship between background firing rate and response probability was explored. As in real human motoneurons, the models exhibited an inverse relationship between response probability and background firing rate. The biophysical properties responsible for the relationship between response probability and firing rate included the shapes of the membrane voltage trajectories between spikes and nonlinear changes in PP amplitude during the interspike interval at different firing rates. The results from these simulations suggest that the relationship between response probability and background firing rate is an intrinsic feature of motoneurons. The similarity of the results from the models, which were based on the properties of cat motoneurons, and those from human motoneurons suggests that the biophysical properties governing rhythmic firing in human motoneurons are similar to those of the cat.

Cell Membrane↗
PubMed1998

Regulation of action-potential firing in spiny neurons of the rat neostriatum in vivo.

Both silent and spontaneously firing spiny projection neurons have been described in the neostriatum, but the reason for their differences in firing activity are unknown. We compared properties of spontaneously firing and silent spiny neurons in urethan-anesthetized rats. Neurons were identified as spiny projection neurons after labeling by intracellular injection of biocytin. The threshold for action-potential firing was measured under three different conditions: 1) electrical stimulation of the contralateral cerebral cortex, 2) brief directly applied current pulses, and 3) spontaneous action-potentials occurring during spontaneous episodes of depolarization ( state). The average membrane potential and the amplitude of noiselike fluctuations of membrane potential in the state were determined by fitting a Gaussian curve to the membrane-potential distribution. All neurons in the sample exhibited spontaneous membrane potential shifts between a hyperpolarized state and a depolarized state, but not all fired action potentials while in the state. The difference between the spontaneously firing and the silent spiny neurons was in the average membrane potential in the state, which was significantly more depolarized in the spontaneously firing than in the silent spiny neurons. There were no significant differences in the threshold, the amplitude of the noiselike fluctuations of membrane potential in the state, or in the proportion of time that the membrane potential was in the state. In both spontaneously firing and silent neurons, the threshold for action potentials evoked by current pulses was significantly higher than for those evoked by cortical stimulation. Application of more intense current pulses that reproduced the excitatory postsynaptic potential rate of rise produced firing at correspondingly lower thresholds. Because the membrane potential in the state is mainly determined by the balance between the synaptic drive and the outward potassium conductances activated in the subthreshold range of membrane potentials, either or both of these factors may determine whether firing occurs in response to spontaneous afferent activity.

Action Potentials↗