Electrophysiological and morphological properties of neurons in the rat superior colliculus. I. Neurons in the intermediate layer.

To begin characterizing the neural elements underlying the dynamic properties of local circuits in the mammalian superior colliculus (SC), electrophysiological and morphological properties of individual neurons in the intermediate layer [stratum griseum intermediale (SGI)] were investigated using whole cell patch-clamp recording and intracellular staining with biocytin in slice preparations from young (17-22 days old) and adult rats (7-8 wk old). Voltage responses to depolarizing current pulses of 223 neurons recorded in young rats were classified into six subclasses: regular-spiking neurons (n = 113), interspike intervals during depolarizing current pulses were constant; late-spiking neurons (n = 48), initiation of repetitive firing was delayed markedly from the onset of depolarizing pulses because of a transient hyperpolarization caused by A-like currents; burst-spiking neurons (n = 29), transient burst firing due to low-threshold Ca(2+) channels were observed at the firing threshold level; fast-spiking neurons (n = 19), constant repetitive firings at frequencies >100 Hz were observed for the duration of the depolarizing pulse; neurons with marked spike frequency adaptation (n = 11), interspike intervals more than doubled due to spike frequency adaptation during depolarizing pulses; and neurons with rapid spike inactivation (n = 3), spike amplitude rapidly reduced, width increased during depolarizing pulses, and spiking was terminated after generating a few spikes. In response to hyperpolarizing current pulses, two different types of inward rectification were observed; time-dependent inward rectification by hyperpolarization-activated current (I(h); n = 29) and time-independent inward rectification (n = 111). Morphological analysis showed that neurons expressing time-dependent inward rectification by I(h) had large somata, extended divergent dendrites dorsally into the superficial layers, and projected axons ventrally and sometimes dorsally, all characteristic features of wide-field vertical cells. Other neurons exhibited heterogeneous morphological properties, such as multipolar, fusiform, horizontal, or pyramidal-shaped cells. In adult rats, a total of 44 neurons showed similar electrophysiological properties except for the last type. These results indicate that the local circuits of the SC include neurons with at least five different firing properties and two different rectification properties; each with distinct electrophysiological and morphological characteristics that may be correlated with the functional output of the SC.     

Dendritic Na+ current inactivation can increase cell excitability by delaying a somatic depolarizing afterpotential

Many central neurons support active dendritic spike backpropagation mediated by voltage-gated currents. Active spikes in dendrites have been shown capable of providing feedback to the soma to influence somatic excitability and firing dynamics through a depolarizing afterpotential (DAP). In pyramidal cells of the electrosensory lobe of weakly electric fish, Na(+) spikes in dendrites undergo a frequency-dependent broadening that enhances the DAP to increase somatic firing frequency. We use a combination of dynamical analysis and electrophysiological recordings to demonstrate that spike broadening in dendrites is primarily caused by a cumulative inactivation of dendritic Na(+) current. We further show that a reduction in dendritic Na(+) current increases excitability by decreasing the interspike interval and promoting burst firing. This process arises when inactivation of dendritic Na(+) current shifts the latency of the dendritic spike to delay the arrival of the DAP sufficiently to increase its impact on somatic membrane potential despite a reduction in dendritic excitability. Furthermore, the relationship between dendritic Na(+) current density and somatic excitability is nonmonotonic, as intermediate levels of dendritic Na(+) current exert the greatest excitatory influence. These results reveal that temporal shifts in dendritic spike firing provide a novel means for backpropagating spikes to influence the final output of a cell.     

Phasic stimulation of the locus coeruleus: Effects on activity in the lateral geniculate nucleus

Neurons in the locus coeruleus (LC) encode information related to behavioral state in a tonic pattern of firing and information related to the occurrence of a sensory stimulus in a phasic pattern of firing. The effects of phasic stimulation of the LC (6 pulses at 30 Hz), designed to approximate its physiological activation by sensory stimuli, were studied in the lateral geniculate nucleus (LGN) of anesthetized rats. Phasic stimulation of the LC significantly increased neuronal firing in the LGN with a mean latency 320 ms from onset of stimulation. Receiver operating characteristic analyses on a trial-by-trial basis showed that phasic LC stimulation can result in a highly discriminable signal in the LGN. This increased neuronal firing rate in the LGN was specific for the site of stimulation and was reduced by the norepinephrine synthesis inhibitor αmethyl-p-tyrosine and by intravenous WB-4101 (α₁-receptor antagonist). Neurons in the LGN have a singlespike firing mode when sensory information is faithfully relayed from retina to cortex and a burst-firing mode when the transfer of this information is degraded. Phasic LC stimulation reduced burst firing (2–5 ms interspike intervals, ISIs) at low frequencies ( ≤4 Hz) in the LGN, and for some neurons there was an absolute decrease in burst-like ISIs after LC stimulation, despite an increase in mean firing rate.     

Membrane properties of principal neurons of the lateral superior olive

In the lateral superior olive (LSO) the firing rate of principal neurons is a linear function of inter-aural sound intensity difference (IID). The linearity and regularity of the "chopper response" of these neurons have been interpreted as a result of an integration of excitatory ipsilateral and inhibitory contralateral inputs by passive soma-dendritic cable properties. To account for temporal properties of this output, we searched for active time- and voltage-dependent nonlinearities in whole cell recordings from a slice preparation of the rat LSO. We found nonlinear current-voltage relations that varied with the membrane holding potential. Repetitive regular firing, supported by voltage oscillations, was evoked by current pulses injected from holding potentials near rest, but the response was reduced to an onset spike of fixed short latency when the pulse was injected from de- or hyperpolarized holding potentials. The onset spike was triggered by a depolarizing transient potential that was supported by T-type Ca(2+)-, subthreshold Na(+)-, and hyperpolarization-activated (I(H)) conductances sensitive, respectively, to blockade with Ni2+, tetrodotoxin (TTX), and Cs+. In the hyperpolarized voltage range, the I(H), was largely masked by an inwardly rectifying K+ conductance (I(KIR)) sensitive to blockade with 200 microM Ba2+. In the depolarized range, a variety of K+ conductances, including A-currents sensitive to blockade with 4-aminopyridine (4-AP) and additional tetraethylammonium (TEA)-sensitive currents, terminated the transient potential and firing of action potentials, supporting a strong spike-rate adaptation. The "chopper response," a hallmark of LSO principal neuron firing, may depend on the voltage- and time-dependent nonlinearities. These active membrane properties endow the LSO principal neurons with an adaptability that may maintain a stable code for sound direction under changing conditions, for example after partial cochlear hearing loss.     

Effects of the action of microwave-frequency electromagnetic radiation on the spike activity of neurons in the supraoptic nucleus of the hypothalamus in rats

Acute experiments on white rats anesthetized with Nembutal (40 mg/kg, i.p.) were performed with extracellular recording and analysis of background spike activity from neurons in the supraoptic nucleus of the hypothalamus after exposure to electromagnetic radiation in the millimeter range. The distribution of neurons was determined in terms of the degree of regularity, the nature of the dynamics of neural streams, and the modalities of histograms of interspike intervals; the mean neuron spike frequency was calculated, along with the coefficient of variation of interspike intervals. These studies demonstrated changes in the background spike activity, predominantly affecting the internal structure of the spike streams recorded. The major changes were in the duration of interspike intervals and the degree of regularity of spike activity. Statistically significant changes in the mean spike frequencies of neuron populations in individual frequency ranges were also seen. __________ Translated from Rossiiskii Fiziologicheskii Zhurnal imeni I. M. Sechenova, Vol. 91, No. 12, pp. 1398–1406, December, 2005.     

Repetitive firing and oscillatory activity of pyramidal-like bursting neurons in the rat subiculum

 Electrophysiological characterization of neurons within the rat subiculum was carried out with intracellular recordings in an in vitro slice preparation. Subicular neurons responded to threshold pulses of depolarizing current delivered at a resting membrane potential (RMP) of –65.7±5.8 mV (mean±SD, n=85) with an initial burst of three to five fast action potentials that rode on a depolarizing envelope and was terminated by an afterhyperpolarization (burst AHP) (duration 113±35 ms; peak amplitude 2.7±0.6 mV, n=10). Tonic firing replaced the bursting mode at membrane potential less negative than –55 mV. Suprathreshold depolarizing pulses evoked at RMP both an initial burst and successive tonic firing. Intracellular staining with biocytin showed morphological features typical of pyramidal cells (n=8). The relationship between frequency of repetitive firing and injected current (f–I) revealed that the burst firing frequency (250–300 Hz) was only slightly influenced by the amount of injected current. By contrast, the f–I curve of the tonic firing phase depended upon current intensity: it displayed an initial segment that increased at first linearly and then turned into a plateau for both the early and the late inter-spike intervals. The frequency of the tonic firing declined only slightly with time, thus suggesting a lack of adaptation. During tonic firing, each single action potential was followed by a fast AHP and a depolarizing afterpotential. Termination of repetitive firing was followed by an AHP (spike-train AHP; duration 223±101 ms, peak amplitude 5.6±2.4 mV, n=17). Fast spike-train and burst AHPs were reduced by bath application of the Ca²⁺-channel blockers Co²⁺(2 mM) and Cd²⁺(1 mM) (n=8), thus suggesting the participation of Ca²⁺-dependent K⁺ conductances in these AHPs. Subicular bursting neurons generated persistent, subthreshold voltage oscillations at 5.3±1 Hz (n=20) during steady depolarization positive to –60 mV; at values positive to –55 mV, the oscillatory activity could trigger clusters of single action potentials with a periodicity of 0.9–2 Hz. Oscillations were not prevented by application of excitatory amino acid receptor and GABA_A receptor antagonists (n=5), Ca²⁺-channel blockers (n=5), or Cs⁺ (3 mM; n=4), but were abolished by the Na⁺-channel blocker tetrodotoxin (1 μM; n=6). Our findings demonstrate that pyramidal-like subicular neurons generate both bursting and non-adapting tonic firing, depending upon their membrane potential. These neurons also display oscillatory activity in the range of theta frequency that depends on the activation of a voltage-gated Na⁺ conductance. These electrophysiological properties may play a role in the process of signals arising from the hippocampal formation before being funnelled towards other limbic structures. Received: 20 May 1996 / Accepted: 6 November 1996     

The effects of vibration on the baseline spike activity of neurons in the superior vestibular nucleus

The characteristics of the baseline spike activity of neurons in the superior vestibular nucleus of rats were studied after exposure to vibration for five, 10, and 15 days using a computerized method for recording and analyzing interspike intervals. The distributions of neurons in terms of their regularity, their dynamic types, and the modalities of their interspike interval histograms were assessed. In intact animals, the mean spike frequency was 14.0 ± 1.4 Hz. Changes in the main measures were seen at different durations of exposure to vibration, along with a significant increase in the mean neuron spike frequency. The results demonstrate changes in the level of the functional state of neurons in the superior vestibular nucleus after exposure to vibration. The characteristics and significance of the results are discussed. __________ Translated from Rossiiskii Fiziologicheskii Zhurnal imeni I. M. Sechenova, Vol. 91, No. 8, pp. 885–892, August, 2005.     

Electrophysiological and repetitive firing properties of neurons in the superficial/middle layers of the human neocortex maintained in vitro

Conventional intracellular recordings were made from neurons located in the superficial/middle layers of human temporal neocortical slices obtained from patients undergoing neurosurgical procedures for the treatment of epilepsy or brain tumour. In most of the neurons, inward membrane rectification was observed when the cell was depolarized or hyperpolarized from rest by intracellular injection of positive or negative current pulses. Bath application of tetrodotoxin abolished the depolarizing inward rectification, but not the anomalous rectification in the hyperpolarizing direction. Single action potential firing was followed by a fast afterhyperpolarization, a depolarizing afterpotential and a medium afterhyperpolarization, while a slower afterhyperpolarization was seen following repetitive firing. Blockade of Ca² channels with Cd² diminished all three types of afterhyperpolarization. Although the repetitive firing pattern in all cells indicated that they discharge in a regular-spiking fashion, 63% of the cells fired tonically in the initial part of discharge, while the remaining 37% of the cells fired phasically. Frequencycurrent plot for the initial interspike intervals during long depolarizing pulses revealed primary and secondary ranges of firing. Spike frequency adaptation was also observed. In conclusion, our experiments indicate that human neocortical cells in the superficial/middle layers display electrophysiological characteristics that are similar to those described in rodent and feline neocortices.     

Intracellular recordings from medial septal neurons during hippocampal theta rhythm

 The electrophysiological properties of neurons of the medial septal nucleus and the nucleus of the diagnonal band of Broca (MS/DB) were studied using intracellular methods in urethane-anesthetized rats. Three types of rhythmically bursting neurons were identified in vivo on the basis of their action potential shapes and durations, afterhyperpolarizations (AHPs), membrane characteristics, firing rates and sensitivities to the action of muscarinic antagonist: (1) Cells with short-duration action potentials and no AHPs (2 of 34 rhythmic cells, 6%) had high firing rates and extremely reliable bursts with 6–16 spikes per theta cycle, which were highly resistant to scopolamine action. (2) Cells with short-duration action potentials and short-duration AHPs (8 of 34 rhythmic cells, 24%) also had high firing rates and reliable bursts with 4–13 spikes per theta cycle, phase-locked to the negative peak of the dentate theta wave. Hyperpolarizing current injection revealed a brief membrane time constant, time-dependent membrane rectification and a burst of firing at the break. Depolarizing current steps produced high-frequency repetitive trains of action potentials without spike frequency adaptation. The action potential and membrane and characteristics of this cell type are consistent with those described for GABAergic septal neurons. Many of these neurons retained their theta-bursting pattern in the presence of muscarinic antagonist. (3) Cells with long-duration action potentials and long-duration AHPs (24 of 34 rhythmic cells, 70%) had low firing rates, and usually only 1–3 spikes per theta cycle, locked mainly to the positive peak of the dentate theta rhythm. Hyperpolarizing current injection revealed a long membrane time constant and a break potential; a depolarizing pulse caused a train of action potentials with pronounced spike frequency adaptation. The action potential and membrane properties of this cell type are consistent with those reported for cholinergic septal neurons. The theta-related rhythmicity of this cell type was abolished by muscarinic antagonists. The phasic inhibition of ”cholinergic” MS/DB neurons by ”GABAergic” MS/DB neurons, followed by a rebound of their firing, is proposed as a mechanism contributing to recruitment of the whole MS/DB neuronal population into the synchronized rhythmic bursting pattern of activity that underlies the occurrence of the hippocampal theta rhythm. Received: 5 February 1996 / Accepted: 6 November 1996     

Conditional spike backpropagation generates burst discharge in a sensory neuron

Backpropagating dendritic Na(+) spikes generate a depolarizing afterpotential (DAP) at the soma of pyramidal cells in the electrosensory lateral line lobe (ELL) of weakly electric fish. Repetitive spike discharge is associated with a progressive depolarizing shift in somatic spike afterpotentials that eventually triggers a high-frequency spike doublet and subsequent burst afterhyperpolarization (bAHP). The rhythmic generation of a spike doublet and bAHP groups spike discharge into an oscillatory burst pattern. This study examined the soma-dendritic mechanisms controlling the depolarizing shift in somatic spike afterpotentials, and the mechanism by which spike doublets terminate spike discharge. Intracellular recordings were obtained from ELL pyramidal somata and apical dendrites in an in vitro slice preparation. The pattern of spike discharge was equivalent in somatic and dendritic regions, reflecting the backpropagation of spikes from soma to dendrites. There was a clear frequency-dependent threshold in the transition from tonic to burst discharge, with bursts initiated when interspike intervals fell between approximately 3-7 ms. Removal of all backpropagating spikes by dendritic TTX ejection revealed that the isolated somatic AHPs were entirely stable at the interspike intervals that generated burst discharge. As such, the depolarizing membrane potential shift during repetitive discharge could be attributed to a potentiation of DAP amplitude. Potentiation of the DAP was due to a frequency-dependent broadening and temporal summation of backpropagating dendritic Na(+) spikes. Spike doublets were generated with an interspike interval close to, but not within, the somatic spike refractory period. In contrast, the interspike interval of spike doublets always fell within the longer dendritic refractory period, preventing backpropagation of the second spike of the doublet. The dendritic depolarization was thus abruptly removed from one spike to the next, allowing the burst to terminate when the bAHP hyperpolarized the membrane. The transition from tonic to burst discharge was dependent on the number and frequency of spikes invoking dendritic spike summation, indicating that burst threshold depends on the immediate history of cell discharge. Spike frequency thus represents an important condition that determines the success of dendritic spike invasion, establishing an intrinsic mechanism by which backpropagating spikes can be used to generate a rhythmic burst output.     

Comparative analysis of the baseline spike activity of neurons in the fastigial nucleus of the cerebellum at different durations of exposure to vibration

Acute experiments on Nembutal-anesthetized (40 mg/kg, i.p.) white rats with extracellular recording and analysis of baseline spine activity of neurons in the fastigial nucleus of the cerebellum were performed in normal conditions and after exposure to vibration for 5, 10, and 15 days. The distribution of neurons in terms of the regularity and dynamics of spike flows and the modality of interspike interval histograms were determined, along with the mean neuron spike frequency and the coefficient of variation of interspike intervals. The results showed that the most significant changes in neuron activity in fastigial nucleus cells were formed during the first ten days of vibration. On day 15, there was a tendency for measures to return to control levels. __________ Translated from Rossiiskii Fiziologicheskii Zhurnal imeni I. M. Sechenova, Vol. 91, No. 6, pp. 601–610, June, 2005.     

A fast transient outward current in layer II/III neurons of rat perirhinal cortex

The perirhinal cortex (PRC) is a supra-modal cortical area that collects and integrates information originating from uni- and multi-modal neocortical regions, transmits it to the hippocampus, and receives a feedback from the hippocampus itself. The elucidation of the mechanisms that underlie the specific excitable properties of the different PRC neuronal types appears as an important step toward the understanding of the integrative functions of PRC. In this study, we investigated the biophysical properties of the transient, I _A-type K⁺ current recorded in pyramidal neurons acutely dissociated from layers II/III of PRC of the rat (P8–P16). The current activated at about −50 mV and showed a fast monoexponential decay (τ_h >> 14 ms at −30 to +10 mV). I _A recovery from inactivation also had a monoexponential time course. No significant differences in the biophysical properties or current density of I _A were found in pyramidal neurons from rats of different ages. Application of 4-AP (1–5 mM) reversibly and selectively blocked I _A, and in current clamp conditions it increased spike duration and shortened the delay of the first spike during repetitive firing evoked by sustained depolarizing current injection. These properties are similar to those of the I _A found in thalamic neurons and other cortical pyramidal neurons. Our results suggest that I _A contributes to spike repolarization and to regulate both spike onset timing and firing frequency in PRC neurons.     

Regularity and latency of units in ventral cochlear nucleus: implications for unit classification and generation of response properties

1. The responses of neurons in the ventral cochlear nucleus (VCN) of decerebrate cats are described with regard to their regularity of discharge and latency. Regularity is measured by estimating the mean and standard deviation of interspike intervals as a function of time during responses to short tone bursts (25 ms). This method extends the usual interspike-interval analysis based on interval histograms by allowing the study of temporal changes in regularity during transient responses. The coefficient of variation (CV), equal to the ratio of standard deviation to mean interspike interval, is used as a measure of irregularity. Latency is measured as the mean and standard deviation of the latency of the first spike in response to short tone bursts, with 1.6-ms rise times. 2. The regularity and latency properties of the usual PST histogram response types are shown. Five major PST response type classes are used: chopper, primary-like, onset, onset-C, and unusual. The presence of a prepotential in a unit's action potentials is also noted; a prepotential implies that the unit is recorded from a bushy cell. 3. Units with chopper PST histograms give the most regular discharge. Three varieties of choppers are found. Chop-S units (regular choppers) have CVs less than 0.35 that are approximately constant during the response; chop-S units show no adaptation of instantaneous rate, as measured by the inverse of the mean interspike interval. Chop-T units have CVs greater than 0.35, show an increase in irregularity during the response and show substantial rate adaptation. Chop-U units have CVs greater than 0.35, show a decrease in irregularity during the response, and show a variety of rate adaptation behaviors, including negative adaptation (an increase in rate during a short-tone response). Irregular choppers (chop-T and chop-U units) rarely have CVs greater than 0.5. Choppers have the longest latencies of VCN units; all three groups have mean latencies at least 1 ms longer than the shortest auditory nerve (AN) fiber mean latencies. 4. Chopper units are recorded from stellate cells in VCN (35, 42). Our results for chopper units suggest a model for stellate cells in which a regularly firing action potential generator is driven by the summation of the AN inputs to the cell, where the summation is low-pass filtered by the membrane capacitance of the cell.(ABSTRACT TRUNCATED AT 400 WORDS)     

Reactions and functional relationships between nonrespiratory neurons in the medulla oblongata after central application of penicillin

Changes in impulse activity of nonrespiratory neurons in the medulla oblongata produced by central administration of penicillin were studied in acute experiments on narcotized immobilized rats. The mean firing frequency increased in most neurons. The peaks on histograms for the distribution of interspike intervals were shifted toward shorter intervals and their amplitude increased; the type of distribution was also changed. Tonic activity of neurons was transformed into burst activity. Study of auto- and cross-correlation histograms for neuronal pairs showed that hyperactivation of structures was accompanied by an increase in the degree of synchronization. These changes reflect the appearance of new functional relationships between neurons in the respiratory center. We found that nonrespiratory reticular neurons are involved in the mechanisms of normal and pathological respiratory rhythm generation and serve as a functionally labile component of the neuronal respiratory network. Translated fromByulleten’ Eksperimental’noi Biologii i Meditsiny, Vol. 138, No. 8, pp. 170–175, August, 2004     

Current-to-frequency transduction in CA1 hippocampal pyramidal cells: Slow prepotentials dominate the primary range firing

Summary (1)In order to study how hippocampal pyramidal cells transform a steady depolarization into discharges, CA1 pyramids (n = 32) were injected with 1.5 s long pulses of constant depolarizing current. (2) The firing in response to weak currents was in most cells, characterized by low frequency (0.2–5 Hz), slowly increasing depolarizations preceding each action potential (slow prepotentials, SPPs), a long latency (0.2–5 s) to the initial spike and lack of adaptation. (3) The SPPs, which lasted 30–2,000 ms, showed an increasing steepness with increasing current, and seemed to be a major regulating factor for the slow firing. (4) In response to stronger currents the discharge had a high initial frequency (100–350 Hz), followed by adaptation to steady state firing (5–50 Hz). Thirty of 32 cells showed a dip in the frequency (n = 5), or a pause (n = 25) lasting 250–1,000 ms between the initial burst of firing and the steady state. The pause occurred only at intermediate current strengths. (5) Additional spikes to the initial burst seemed to be recruited through the development of depolarizing waves. The initial slope of these waves resembled those of the SPPs. Similar waves occurred at the expected tune of occasionally missing spikes during steady state firing. (6) The variability (SD/mean) of the interspike intervals decreased with increasing frequency of firing. (7) The frequency-current (f/I) relation for the steady state firing showed a simple linear or convex shape, and lacked a secondary range. In contrast, the f/I plots for the initial few interspike intervals had both primary, secondary and tertiary ranges, like motoneurones.Supported by the Norwegian Research Council for Science and the Humanities and The National Institute of Health, USA     

Persistent Na+ current modifies burst discharge by regulating conditional backpropagation of dendritic spikes

The estimation and detection of stimuli by sensory neurons is affected by factors that govern a transition from tonic to burst mode and the frequency characteristics of burst output. Pyramidal cells in the electrosensory lobe of weakly electric fish generate spike bursts for the purpose of stimulus detection. Spike bursts are generated during repetitive discharge when a frequency-dependent broadening of dendritic spikes increases current flow from dendrite to soma to potentiate a somatic depolarizing afterpotential (DAP). The DAP eventually triggers a somatic spike doublet with an interspike interval that falls inside the dendritic refractory period, blocking spike backpropagiation and the DAP. Repetition of this process gives rise to a rhythmic dendritic spike failure, termed conditional backpropagation, that converts cell output from tonic to burst discharge. Through in vitro recordings and compartmental modeling we show that burst frequency is regulated by the rate of DAP potentiation during a burst, which determines the time required to discharge the spike doublet that blocks backpropagation. DAP potentiation is magnified through a positive feedback process when an increase in dendritic spike duration activates persistent sodium current (I(NaP)). I(NaP) further promotes a slow depolarization that induces a shift from tonic to burst discharge over time. The results are consistent with a dynamical systems analysis that shows that the threshold separating tonic and burst discharge can be represented as a saddle-node bifurcation. The interaction between dendritic K(+) current and I(NaP) provides a physiological explanation for a variable time scale of bursting dynamics characteristic of such a bifurcation.     

Relationship between repetitive firing and afterhyperpolarizations in human neocortical neurons.

1. Human neocortical neurons fire repetitively in response to long depolarizing current injections. The slope of the relationship between average firing frequency and injected current (f-I slope) was linear or bilinear in these cells. The mean steady-state f-I slope (average of the last 500 ms of a 1-s firing episode) was 57.8 Hz/nA. The instantaneous firing rate decreased with time during a 1-s constant-current injection (spike frequency adaptation). Also, human neurons exhibited habituation in response to a 1-s current stimulus repeated every 2 s. 2. Afterhyperpolarizations (AHPs) reflect the active ionic conductances after action potentials. We studied AHPs with the use of intracellular recordings and pharmacological manipulations in the in vitro slice preparation to 1) gain insight into the ionic mechanisms underlying the AHPs and 2) elucidate the role that the underlying currents play in the functional behavior of human cortical neurons. 3. We have classified three AHPs in human neocortical neurons on the basis of their time courses: fast, medium, and slow. The amplitude of the AHPs was dependent on stimulus intensity and duration, number and frequency of spikes, and membrane potential. 4. The fast AHP had a reversal potential of -65 mV and was eliminated in extracellular Co2+, tetraethylammonium (TEA) or 4-aminopyridine, and intracellular TEA or CsCl. These manipulations also caused an increase in spike width. 5. The medium AHP had a reversal potential of -90 to -93 mV (22-24 mV hyperpolarized from mean resting potential). This AHP was reduced by Co2+, apamin, tubocurare, muscarine, norepinephrine (NE), and serotonin (5-HT). Pharmacological manipulations suggest that the medium AHP is produced in part by 1) a Ca-dependent K+ current and 2) a time-dependent anomalous rectifier (IH). 6. The slow AHP reversed at -83 to -87 mV (14-18 mV hyperpolarized from mean resting potential). This AHP was diminished by Co2+, muscarine, NE, and 5-HT. The pharmacology of the slow AHP suggests that a Ca-dependent K+ current with slow kinetics contributes to this AHP. 7. The currents involved in the fast AHP are important in spike repolarization, control of interspike interval during repetitive firing, and prevention of burst firing. Currents underlying the medium and slow AHPs influence the interspike interval during repetitive firing and produce spike frequency adaptation and habituation.     

Spike-dependent depolarizing afterpotentials contribute to endogenous bursting in gonadotropin releasing hormone neurons

Pulsatile secretion of gonadotropin releasing hormone in mammals is thought to depend on repetitive and prolonged bursts of action potentials in specific neuroendocrine cells. We have previously described episodes of electrical activity in isolated gonadotropin releasing hormone neurons, but the intrinsic mechanisms underlying the generation of spike bursts are unknown. In acutely isolated gonadotropin releasing hormone neurons, which had been genetically targeted to express enhanced green fluorescent protein, current pulses generated spike-mediated depolarizing afterpotentials in 69% of cells. Spike-dependent depolarizing afterpotentials could evoke bursts of action potentials that lasted for tens of seconds. Brief pulses of glutamate (as short as 1 ms), which simulated excitatory postsynaptic potentials, also triggered spike-mediated depolarizing afterpotentials and episodic activity. These data indicate that spike-dependent depolarizing afterpotentials, an endogenous mechanism in gonadotropin releasing hormone neurons, likely contribute to the episodic firing thought to underlie pulsatile secretion of gonadotropin releasing hormone. Furthermore, fast excitatory postsynaptic potentials mediated by glutamate can activate this intrinsic mechanism.     

Repeated sequences of interspike intervals in baroresponsive respiratory related neuronal assemblies of the cat brain stem

Many neurons exhibit spontaneous activity in the absence of any specific experimental perturbation. Patterns of distributed synchrony embedded in such activity have been detected in the brain stem, suggesting that it represents more than "baseline" firing rates subject only to being regulated up or down. This work tested the hypothesis that nonrandom sequences of impulses recur in baroresponsive respiratory-related brain stem neurons that are elements of correlational neuronal assemblies. In 15 Dial-urethan anesthetized vagotomized adult cats, neuronal impulses were monitored with microelectrode arrays in the ventral respiratory group, nucleus tractus solitarius, and medullary raphe nuclei. Efferent phrenic nerve activity was recorded. Spike trains were analyzed with cycle-triggered histograms and tested for respiratory-modulated firing rates. Baroreceptors were stimulated by unilateral pressure changes in the carotid sinus or occlusion of the descending aorta; changes in firing rates were assessed with peristimulus time and cumulative sum histograms. Cross-correlation analysis was used to test for nonrandom temporal relationships between spike trains. Favored patterns of interspike interval sequences were detected in 31 of 58 single spike trains; 18 of the neurons with significant sequences also had short-time scale correlations with other simultaneously recorded cells. The number of distributed patterns exceeded that expected under the null hypothesis in 12 of 14 data sets composed of 4-11 simultaneously recorded spike trains. The data support the hypothesis that baroresponsive brain stem neurons operate in transiently configured coordinated assemblies and suggest that single neuron patterns may be fragments of distributed impulse sequences. The results further encourage the search for coding functions of spike patterns in the respiratory network.     

Depression of spike adaptation and afterhyperpolarization by 4-aminopyridine in hippocampal neurons

In guinea pig hippocampal slices, 4-aminopyridine (4-AP) in concentrations of 100-500 microM reduced the adaptation of CA3 pyramidal neurons to depolarizing stimuli, resulting in a prolongation of repetitive firing during injection of long-lasting depolarizing currents. Concurrently, there was a decrease in the 'sag' of potential after spike bursts. Furthermore, 4-AP decreased or abolished the hyperpolarizing potential (the afterhyperpolarization) which normally followed repetitive firing of the neurons. The findings suggest that 4-AP could interfere with the Ca2+-activated K+ current in hippocampal CA3 pyramidal neurons.