Pyramidal unit activity in unanesthetized cats

Pyramidal unit activity in unanesthetized cats at rest and during voluntary movement was recorded by a microelectrode technique from the motor cortex for the forelimb. Some pyramidal neurons were not spontaneously active. The conduction velocity along the axon of these neurons was sometimes high (up to 71.5 m/sec), sometimes low (up to 11.2 m/sec). The remaining pyramidal neurons had spontaneous activity with a mean frequency of 1.29 to 43 spikes/sec. Analysis of interspike interval histograms of spontaneous activity and of autocorrelation histograms showed grouping of the spikes into volleys in most pyramidal neurons (irrespective of the conduction velocity). During voluntary movements the change in the activity of many pyramidal units correlated with changes in the EMG. The firing rate of the pyramidal neurons under these circumstances began to rise at least 50 msec before the increase in amplitude of the EMG and it remained high throughout the movement. The firing rate of most neurons during movement was 40–60/sec. The results are compared with those obtained by other workers who studied pyramidal unit activity of monkeys during voluntary movement.     

Potentiation of ketamine effects on the spiking activity in the lateral geniculate nucleus by rapid eye movement (REM) sleep deprivation.

In cats prepared for chronic recording of sleep, an investigation was made on the effects of an anaesthetic agent, ketamine [cl-581, 2-(O-chlorophenyl)-2-methylaminocyclohexamine HCl] and rapid eye movement (REM) sleep deprivation on spiking activity recorded from lateral geniculate (LGN) nucleus. In normal cats most of the LGN spikes occurring during sleep are found in REM sleep. Follwoing injection of 10 mg/kg of ketamine a substantial increase of slow wave sleep (SWS) spikes occurred. While selective REM sleep deprivation had the same effects, combined influences of ketamine and REM-sleep deprivation led to a marked potentiation of their individual effects probably by simultaneous stimulation of the neurone system which determines the endogenous electrical activity of LGN cells.     

Firing properties of substantia nigra dopaminergic neurons in freely moving rats

Single unit recordings were obtained from putative dopaminergic neurons in the substantia nigra of awake, freely moving rats. The cells exhibited waveforms, range of firing rates and types of firing patterns identical to those of identified DA neurons of anesthetized or paralyzed rats. Two firing patterns were observed: single spike activity and a bursting mode with spikes of progressively diminished amplitude and increased duration within each burst. The degree of burst firing varied considerably among the cells and individual cells sometimes switched from one pattern of firing (e.g. predominantly single spike) to another (e.g. bursting), although the determinants of these transitions are, at this time, unclear. Putative DA neurons were inhibited by i.v. apomorphine and excited by i.v. haloperidol. Haloperidol also reversed the apomorphine-induced inhibition of firing. Inhibitions and excitations were associated with a reduction and elevation, respectively, in burst firing. The effects of the two drugs were identical to their effects in immobilized rats. In several cases, a putative DA neuron was observed to fire all of its spikes in near coincidence with at least one other cell with identical electrophysiological characteristics. This form of interaction (i.e. presumed electrical coupling) between DA cells is only rarely observed in anesthetized or paralyzed rats and may play a significant role in the normal functioning of the nigrostriatal DA system.     

Serotonin (5-HT2) receptor mediated enhancement of cortical unit activity.

Simultaneous single-unit and intracortical activity were recorded from neocortical neurons in urethane-anaesthetized rats to investigate the role of serotonin (5-HT) in modifying cortical excitability. Units, at a depth of 775-1100 microns from the pial surface, discharged in a burst-pause pattern that was correlated with slow wave activity. Application of noxious somatic stimulation resulted in cortical desynchronization and altered the pattern of unit activity such that firing was continuous, i.e., the pauses were eliminated. Intravenous administration of the mixed 5-HT1C/5-HT2 antagonists (cinanserin, cyproheptadine, ketanserin, and ritanserin) prevented both desynchronization and the change in unit activity induced by noxious stimulation within 2.5-15 min of the injection. The basic pattern of burst-pause activity remained intact, but the number of spikes per burst was typically reduced, whereas interburst intervals were increased. Iontophoretic application of these antagonists onto cortical neurons resulted in actions similar to those observed following systemic administration. Intravenous and iontophoretic application of m-trifluomethylphenylpiperazine (5-HT1C agonist, 5-HT2 antagonist) resulted in actions indistinguishable from those observed with the above antagonists, from which we conclude 5-HT2 and not 5-HT1C receptors mediate the alteration in unit activity observed with noxious stimulation. The results are discussed with respect to an interaction between N-methyl-D-aspartate and 5-HT2 receptors leading to the enhanced unit activity observed with noxious stimulation.     

Ripple-associated high-firing interneurons in the hippocampal CA1 region

By simultaneously recording the activity of individual neurons and field potentials in freely behaving mice, we found two types of interneurons firing at high frequency in the hippocampal CA1 region, which had high correlations with characteristic sharp wave-associated ripple oscillations (100–250 Hz) during slow-wave sleep. The firing of these two types of interneurons highly synchronized with ripple oscillations during slow-wave sleep, with strongly increased firing rates corresponding to individual ripple episodes. Interneuron type I had at most one spike in each sub-ripple cycle of ripple episodes and the peak firing rate was 310±33.17 Hz. Interneuron type II had one or two spikes in each sub-ripple cycle and the peak firing rate was 410±47.61 Hz. During active exploration, their firing was phase locked to theta oscillations with the highest probability at the trough of theta wave. Both two types of interneurons increased transiently their firing rates responding to the startling shake stimuli. The results showed that these two types of high-frequency interneurons in the hippocampal CA1 region were involved in the modulation of the hippocampal neural network during different states.     

Chloral hydrate anesthesia alters the responsiveness of dorsal raphe neurons to psychoactive drugs

The effects of several psychoactive drugs on raphe unit activity in freely moving cats was compared with drug-induced effects in chloral hydrate anesthetized cats. The anesthesia greatly potentiated the depressant effects of LSD, phenoxybenzamine, clonidine, methiothepin, clozapine, and chlorimipramine on raphe units, but partially antagonized the depressant effects of diazepam. These results demonstrate that apparently discrepant reports of the affects of these drugs on raphe neurons in anesthetized rats versus freely moving cats are attributable to the use of anesthesia in rat studies. These data underscore the importance of conducting such drug studies in awake, freely moving animals, for which the results would be far more relevant to the issue of human drug use.     

Ripple-associated high-firing interneurons in the hippocampal CA1 region

By simultaneously recording the activity of individual neurons and field potentials in freely behaving mice, we found two types of interneurons firing at high frequency in the hippocampal CA1 region, which had high correlations with characteristic sharp wave-associated ripple oscillations (100―250 Hz) during slow-wave sleep. The firing of these two types of interneurons highly synchronized with ripple oscillations during slow-wave sleep, with strongly increased firing rates corresponding to individual ripple episodes. Interneuron type I had at most one spike in each sub-ripple cycle of ripple episodes and the peak firing rate was 310±33.17 Hz. Interneuron type II had one or two spikes in each sub-ripple cycle and the peak firing rate was 410±47.61 Hz. During active exploration, their firing was phase locked to theta oscillations with the highest probability at the trough of theta wave. Both two types of interneurons increased transiently their firing rates responding to the startling shake stimuli. The results showed that these two types of high-frequency interneurons in the hippocampal CA1 region were involved in the modulation of the hippocampal neural network during different states.     

The role of the medial preoptic area in the organization of paradoxical sleep

Influence of electrical stimulation of the medial preoptic area of cats on characteristics of paradoxical sleep and activity of medial preoptic neurons were studied in the course of sleep-waking cycle. Low-frequency stimulation of this structure in the state of slow-wave sleep evoked short-latency electrocortical desynchronization and induced transition to paradoxical sleep or paradocical sleep-like state. The same stimulation during the whole period of paradoxical sleep results in a reduction of its duration, practically complete disappearance of tonic stage, and increase in the density of rapid eye movements in phasic stage. The vast majority of meurons in the medial preoptic area decreased their firing rates during quiet waking and slow-wave sleep and dramatically increased their activity during paradoxical sleep. More than 50% of such neurons displayed activation 20-70 s prior to the appearance of electrocorticographic correlates of paradoxical sleep. Some neurons were selectively active during paradoxical sleep. Approximately 50% of cells increased their firing rates a few seconds prior to and/or during series of rapid eye movements. The results suggest that the medial preoptic area contains the units of the executive system (network) of paradoxical sleep and are involved in the mechanisms of neocortical desynchronization.     

Effect of extracellular polarization on unit activity in the lateral geniculate bodies

Unit responses of the lateral geniculate bodies (LGB) to polarization of the cells through the recording microelectrode were investigated in acute experiments on cats anesthetized with Nembutal. Under the influence of anodic polarization the firing rate of the LGB cells clearly increased. Complete adaptation of the cells to the polarizing current was not observed during the time intervals investigated (5–10 min). Cathodic polarization by a current of 5–50 nA induced inhibitory effects; neurons with a single type of spontaneous activity under these circumstances generated volleys of 2–5 spikes. Off-responses were recorded in 75–85% of neurons. It is postulated that complex changes in unit activity produced by polarization may be due to the structural characteristics of the functional connections of the LGB neurons investigated. The change to grouped activity on the part of many of the neurons under the influence of cathodic polarization is evidently explained by the specific functional pattern of the synaptic system of the LGB cells.Institute of Experimental Medicine, Academy of Medical Sciences of the USSR, Leningrad. Translated from Neirofiziologiya, Vol. 4, No. 2, pp. 130–140, March–April, 1972.     

Globus Pallidus External Segment Neuron Classification in Freely Moving Rats: A Comparison to Primates

Globus Pallidus external segment (GPe) neurons are well-characterized in behaving primates. Based on their firing properties, these neurons are commonly divided into two distinct groups: high frequency pausers (HFP) and low frequency bursters (LFB). However, no such characterization has been made for behaving rats. The current study characterizes and categorizes extracellularly recorded GPe neurons in freely moving rats, and compares these results to those obtained by extracellular recordings in behaving primates using the same analysis methods. Analysis of our data recorded in rats revealed two distinct neuronal populations exhibiting firing-pattern characteristics that are similar to those obtained in primates. These characteristic firing patterns are conserved between species although the firing rate is significantly lower in rats than in primates. Significant differences in waveform duration and shape were insufficient to create a reliable waveform-based classification in either species. The firing pattern analogy may emphasize conserved processing properties over firing rate per-se. Given the similarity in GPe neuronal activity between human and non-human primates in different pathologies, our results encourage information transfer using complementary studies across species in the GPe to acquire a better understanding of the function of this nucleus in health and disease.     

Selective discharge of pontine neurons during the postural atonia produced by an anticholinesterase in the decerebrate cat.

I. Episodes of postural atonia associated with bursts of REM similar to those which occur spontaneously either in the intact preparation during desynchronized sleep, or in the chronic decorticate or decerebrate preparations, can be elicited in acute decerebrate cats following intravenous injection of small doses of an anticholinesterase. The present experiments were performed in precollicular decerebrate animals in order to identify the pontine neurons which show increases in their firing rate related in time with the appearance of the cataplectic episodes. In particular long-term recordings of single units were obtained before, during and after the episodes of postural atonia produced by i.v. injection of 0.03-0.1 mg/kg of eserine sulphate. Spontaneous discharge rates were used to measure the selectivity of each individual unit, i.e., the tendency of the unit to discharge more during the cataplectic episode than during the postural rigidity. The physiological data obtained from neurons histologically localized in different nuclear groups were then averaged. 2. Neurons localized in the pontine reticular formation as well as in the region of the locus coeruleus and the raphe system showed low rates of discharge when rigidity was present. The same units, however, showed a remarkable increase in firing rate which preceded by several tenths of seconds the onset of postural atonia and lasted throughout the cataplectic episodes. 3. The neurons of the pontine reticular formation had a selectivity which was higher than that of the neurons located in the locus coeruleus-raphe system; moreover the cells of the gigantocellular tegmental field (FTG) had the highest selectivity of all pontine reticular structures studied. 4. The relation of the discharge rate curves to the occurrence of the cataplectic episodes suggests that these neurons constitute output elements of a generator system for postural atonia. It is postulated that these pontine reticular neurons are directly involved in the activation of the bulbospinal inhibitory system, which is finally responsible for the abolition of the decerebrate rigidity. 5. During cataplectic episodes these pontine neurons showed some clustered discharges which appeared in association with bursts of eye movements. In most instances, however, there was no constant relationship of the unit activity to individual eye movements. Moreover large phasic increases in firing rate appeared also during the intervals between successive bursts of REM. 6. The striking increase in firing rate of the FTG neurons observed during the cataplectic episodes cannot be attributed to an increased excitatory input to these neurons. In fact excitatory influences following intense somatic stimulation are unlikely to occur during the cataplectic episodes; moreover the response of these neurons to intense somatosensory stimulations did not reach rates comparable with those occurring spontaneously during the induced cataplectic episodes...     

Responses of neurons in the rostral ventrolateral medulla to whole body rotations: comparisons in decerebrate and conscious cats

The responses to vestibular stimulation of brain stem neurons that regulate sympathetic outflow and blood flow have been studied extensively in decerebrate preparations, but not in conscious animals. In the present study, we compared the responses of neurons in the rostral ventrolateral medulla (RVLM), a principal region of the brain stem involved in the regulation of blood pressure, to whole body rotations of conscious and decerebrate cats. In both preparations, RVLM neurons exhibited similar levels of spontaneous activity (median of ～17 spikes/s). The firing of about half of the RVLM neurons recorded in decerebrate cats was modulated by rotations; these cells were activated by vertical tilts in a variety of directions, with response characteristics suggesting that their labyrinthine inputs originated in otolith organs. The activity of over one-third of RVLM neurons in decerebrate animals was altered by stimulation of baroreceptors; RVLM units with and without baroreceptor signals had similar responses to rotations. In contrast, only 6% of RVLM neurons studied in conscious cats exhibited cardiac-related activity, and the firing of just 1% of the cells was modulated by rotations. These data suggest that the brain stem circuitry mediating vestibulosympathetic reflexes is highly sensitive to changes in body position in space but that the responses to vestibular stimuli of neurons in the pathway are suppressed by higher brain centers in conscious animals. The findings also raise the possibility that autonomic responses to a variety of inputs, including those from the inner ear, could be gated according to behavioral context and attenuated when they are not necessary.     

Factors affecting slow regular firing in the suprachiasmatic nucleus in vitro

In isolated slices of hypothalamus, suprachiasmatic nucleus (SCN) neurons were recorded intracellularly. Blockade of Ca++ channels increased spike duration, eliminating an early component of the afterhyperpolarization (AHP) that followed evoked spikes. The duration and reversal potential of AHPs were, however, unaffected, suggesting that only an early, fast component of the AHP was Ca(++)-dependent. Unlike other central neurons that exhibit pacemaker activity, therefore, SCN neurons do not display a pronounced, long-lasting Ca(++)-dependent AHP. Extracellular Ba++ and intracellular Cs+ both revealed slow depolarizing potentials evoked either by depolarizing current injection, or by repolarization following large hyperpolarizations. They had different effects on the shape of spikes and the AHPs that followed them, however. Cs+, which blocks almost all K+ channels, dramatically reduced resting potential, greatly increased spike duration (to tens of milliseconds), and blocked AHPs completely. In contrast, Ba++ had little effect on resting potential and produced only a small increase in spike duration, depressing an early Ca(++)-dependent component and a later Ca(++)-independent component of the AHP. The relatively weak pacemaker activity of SCN neurons appears to involve voltage-dependent activation of at least one slowly inactivating inward current, which brings the cells to firing threshold and maintains tonic firing; both Ca(++)-dependent and Ca(++)-independent K+ channels, which repolarize cells after spikes and maintain interspike intervals; and Ca++ channels, which contribute to activation of Ca(++)-activated K+ currents and may also contribute to slow depolarizing potentials. In the absence of powerful synaptic inputs, SCN neurons express a pacemaker activity that is sufficient to maintain an impressively regular firing pattern. Slow, repetitive activation of optic input, however, increases local circuit activity to such an extent that the normal pacemaker potentials are overridden and firing patterns are altered. Since SCN neurons are very small and have large input resistances, they are particularly susceptible to synaptic input.     

Patterns of spontaneous activity in single rat olfactory receptor neurons are different in normally breathing and tracheotomized animals

Spontaneous firing of olfactory receptor neurons (ORNs) was recently shown to be required for the survival of ORNs and the maintenance of their appropriate synaptic connections with mitral cells in the olfactory bulb. ORN spontaneous activity has never been described or characterized quantitatively in mammals. To do so we have made extracellular single unit recordings from ORNs of freely breathing (FB) and tracheotomized (TT) rats. We show that the firing behavior of TT neurons was relatively simple: they tended to fire spikes at the same average frequency according to purely random (Poisson) or simple (Gamma or Weibull) statistical laws. A minority of them were bursting with relatively infrequent and short bursts. The activity of FB neurons was less simple: their firing rates were more diverse, some of them showed trends or were driven by breathing. Although more of them were regular, only a minority could be described by simple laws; the majority displayed random bursts with more spikes than the bursts of TT neurons. In both categories bursts and isolated spikes (outside bursts) occurred completely at random. The spontaneous activity of ORNs in rats resembles that of frogs, but is higher, which may be due to a difference in body temperature. These results suggest that, in addition to the intrinsic thermal noise, spontaneous activity is provoked in part by mechanical, thermal, or chemical (odorant molecules) effects of air movements due to respiration, this extrinsic part being naturally larger in FB neurons. It is suggested that spontaneous activity may be modulated by respiration. Because natural sampling of odors is synchronized with breathing, such modulation may prepare and keep olfactory bulb circuits tuned to process odor stimuli.     

Acute NMDA Receptor Antagonism Disrupts Synchronization of Action Potential Firing in Rat Prefrontal Cortex

Antagonists of N-methyl-D-aspartate receptors (NMDAR) have psychotomimetic effects in humans and are used to model schizophrenia in animals. We used high-density electrophysiological recordings to assess the effects of acute systemic injection of an NMDAR antagonist (MK-801) on ensemble neural processing in the medial prefrontal cortex of freely moving rats. Although MK-801 increased neuron firing rates and the amplitude of gamma-frequency oscillations in field potentials, the synchronization of action potential firing decreased and spike trains became more Poisson-like. This disorganization of action potential firing following MK-801 administration is consistent with changes in simulated cortical networks as the functional connections among pyramidal neurons become less clustered. Such loss of functional heterogeneity of the cortical microcircuit may disrupt information processing dependent on spike timing or the activation of discrete cortical neural ensembles, and thereby contribute to hallucinations and other features of psychosis induced by NMDAR antagonists.     

Brainstem neurons responsible for postural, masseter or pharyngeal muscle atonia during paradoxical sleep in freely-moving cats

In this mini review, we summarize our findings regarding the brainstem neurons responsible for the postural, masseter, or pharyngeal muscle atonia observed during paradoxical sleep (PS) in freely moving cats. Both the pons and medulla contain neurons showing tonic activation selective to PS and atonia, referred to as PS/atonia-on-neurons. The PS/atonia-on neurons, characterized by their most slow conducting property and located in the peri-locus coeruleus alpha (peri-LCa) and adjacent LCa of the mediodorsal pontine tegmentum, play a critical executive role in the somatic and orofacial muscle atonia observed during PS. Slow conducting medullary PS/atonia-on neurons located in the nuclei reticularis magnocellularis (Mc) and parvocellularis (Pc) may play a critical executive role in the generation of, respectively, antigravity or orofacial muscle atonia during PS. In addition, either tonic or phasic cessation of activity of medullary serotonergic neurons may play an important role in the atonia of genioglossus muscles during PS via a mechanism of disfacilitation.     

Functional interrelation of the brain structures of the cat during the generation of rhythmic activity. I. The frequency characteristics of the electroencephalogram

The similarity of frequency parameters of electroencephalograms (EEG) recorded from visual, associative and sensorimotor cortical area, caudate nucleus and several thalamic nuclei have been analysed using the period analysis of EEG and cluster analysis of data obtained to clarify the functional interrelationships between these parts of the brain during generation of rhythmic activity of different types. Functional interrelationships between brain structures in freely moving cats during the states of drowsiness and slow-wave sleep have been shown to differ from "classical" thalamo-cortical pacemaker relations.     

Modulation of the basal forebrain neural activity related to efficiency of reaching for food movements in rat

In the course of learning, single unit activity of basal forebrain neurons was recorded in freely moving rats. Modulation of the neural activity related to efficiency of reaching for food movements was observed between a 40% of the recorded neurons. The firing-rate of such neurons increased during retrieval of the food. Conversely, the activity of these neurons decreased or did not change during unsuccessful movements. In the most neurons (57.1%) the modulation of the activity was observed at the second half of time interval of the movement, but before finishing its. Some neurons (35.7%) changed their activity after the movements.     

Slow Oscillations of the Purkinje Cell Firing Rate Induced by Electrical Stimulation of the Locus Coeruleus in Rats

In anesthetized Wistar rats, we studied the effect of electrical stimulation of the locus coeruleus (LC) on the firing rates of Purkinje cells using spectral analysis. The frequency of extracellularly recorded activity of Purkinje cells was measured before and during the 1st, 5th, 6th, and 11th min after cessation of 10-sec-long LC stimulations. Spectral analysis of the Purkinje cell firing rates (imp./bin, the bin duration was 2^-8 sec) for 60- to 120-sec-long intervals was performed using fast Fourier transformation after digital conversion of unitary spikes. Mean power spectra of the Purkinje cell firing rates (derived from 8-sec-long consecutive epochs at a sampling rate of 256 sec^-1) showed an increase in the slow frequency range (0.1-1.0 Hz) after LC stimulation, particularly due to the slowest components (below 0.5 Hz). This effect lasted more than 1 min and usually less than 6 min after cessation of LC stimulation and could be interpreted as the development of slow oscillations in the Purkinje cell firing. Our results suggest that slow oscillations of the firing rate of cerebellar output neurons, induced by LC stimulation, reflect a specific coordination of the cerebellar neuronal activities (important for a central norepinephrine influence) in regulation of different pathological states.     

Impact of intrinsic properties and synaptic factors on the activity of neocortical networks in vivo.

To investigate the relative impact of intrinsic and synaptic factors in the maintenance of the membrane potential of cat neocortical neurons in various states of the network, we performed intracellular recordings in vivo. Experiments were done in the intact cortex and in isolated neocortical slabs of anesthetized animals, and in naturally sleeping and awake cats. There are at least four different electrophysiological cell classes in the neocortex. The responses of different neuronal classes to direct depolarization result in significantly different responses in postsynaptic cells. The activity patterns observed in the intact cortex of anesthetized cats depended mostly on the type of anesthesia. The intracellular activity in small neocortical slabs was composed of silent periods, lasting for tens of seconds, during which only small depolarizing potentials (SDPs, presumed miniature synaptic potentials) were present, and relatively short-lasting (a few hundred milliseconds) active periods. Our data suggest that minis might be amplified by intrinsically-bursting neurons and that the persistent Na+ current brings neurons to firing threshold, thus triggering active periods. The active periods in neurons were composed of the summation of synaptic events and intrinsic depolarizing currents. In chronically-implanted cats, slow-wave sleep was characterized by active (depolarizing) and silent (hyperpolarizing) periods. The silent periods were absent in awake cats. We propose that both intrinsic and synaptic factors are responsible for the transition from silent to active states found in naturally sleeping cats and that synaptic depression might be responsible for the termination of active states during sleep. In view of the unexpected high firing rates of neocortical neurons during the depolarizing epochs in slow-wave sleep, we suggest that cortical neurons are implicated in short-term plasticity processes during this state, in which the brain is disconnected from the outside world, and that memory traces acquired during wakefulness may be consolidated during sleep.