Responses of motor cortex neurons of the cat to auditory stimulation and their role in the instrumental food reflex

The responses of motor cortex neurons in the cat to the presentation of a single auditory click and a series of 10 clicks presented with 1,000/sec frequency were studied under conditions of chronic experiments before and after the development of an instrumental food reflex. After reflex development a single presentation of a positive conditioned stimulus (single click) markedly influenced for 7 sec the appearance of instrumental movements. At the same time, the immediate responses of motor cortex neurons to presentation of the conditioned auditory stimulus had no impact on the appearance in the motor cortex of discharges leading to the realization of instrumental movements. Consequently, motor cortex neurons do not require activation from afferent sensory inputs for the generation of such discharges. The immediate neuronal responses to conditioned stimulation did not inhibit the realization of the instrumental reflex. It is proposed that they are associated with the realization of motor function in the unconditioned defensive response evoked by the presentation of an auditory stimulus. The presence or absence of responses to auditory conditioned stimulation was dependent upon the signal meaning of the stimulus, its physical parameters, and the degree of excitability of the animal.A. A. Bogomolets Institute of Physiology, Academy of Sciences of the Ukrainian SSR, Kiev. Translated from Neirofiziologiya, Vol. 17, No. 4, pp. 539–550, July–August, 1985.     

Participation of midbrain periaqueductal gray matter in defense conditioning in rats

Responses of neurons of the periaqueductal gray matter (PAG) were studied in chronic experiments on cats during formation and extinction of a defensive conditioned reflex to sound and its differential inhibition. In response to conditioned stimulation these neurons developed phasic-tonic spike responses up to 3 sec in duration. During combination of stimuli these responses were formed long before the conditioned reflex and disappeared long after the latter was extinguished. In the case of an established conditioned reflex, the onset of spike responses occurred 100–200 msec before the appearance of motor responses. An increase in spike activity of tonic character in neurons of PAG preceded voluntary movements by 100–500 msec. The responses of these neurons to presentation of a differential stimulus consisted of groups of spikes 150–200 msec in duration. They were formed with difficulty, and their manifestation was made even more difficult by an interruption during the experiment and by preceding positive stimuli. On the basis of the results a conditioned reflex can be regarded as the result of a multilevel hierarchic process of readjustment of unit activity, which begins in the nonspecific structures of the midbrain.A. A. Bogomolets Institute of Physiology, Academy of Sciences of the Ukrainian SSR, Kiev. Translated from Neirofiziologiya, Vol. 15, No. 3, pp. 278–287, May–June, 1983.     

Dynamics of single unit activity in the association cortex of waking cats during defensive conditioning

Responses of neurons in association area 5 during defensive conditioning to acoustic stimulation were studied in chronic experiments on cats. As a rule the neurons responded by excitation to presentation of conditioned and unconditioned stimuli. During the conditioned reflex unit responses usually appeared in the first 50 msec after the beginning of acoustic stimulation, i.e., they were connected with the action of the conditioned stimulus and not with manifestations of conditioned-reflex motion. The most significant changes in responses of cortical association units were observed in the initial period of conditioning. During stabilization of the conditioned reflex, responses of some neurons became stabilized, whereas in other neurons the spontaneous activity and intensity of responses increased, and in a third group the response to one of the stimuli disappeared. This last result indicates a switch during conditioning from polysensory unit responses to monosensory specialized responses. Extinctive inhibition was found to consist of a gradual decrease in the level of the spike discharge and its approximation to spontaneous activity, i.e., to be passive in character.A. A. Bogomolets Institute of Physiology, Academy of Sciences of the Ukrainian SSR, Kiev. Translated from Neirofiziologiya, Vol. 10, No. 6, pp. 563–572, November–December, 1978.     

Responses of somatic cortical neurons during the conditioned placing reflex in cats

Unit activity was studied in areas 3 and 4 during the conditioned placing reflex in cats. Responses of somatic cortical neurons in this case were shown to develop comparatively late — 80–100 or, more often, 200–450 msec after the conditioned stimulus. In the motor cortex responses preceded movement by 50–550 msec, whereas in the somatosensory cortex they usually began simultaneously with or after the beginning of the movement. Judging from responses of somatic cortical neurons, the placing reflex is realized by the same neuronal mechanism as the corresponding voluntary movement. The differential stimulus and positive conditioned stimulus, after extinction of the conditioned placing reflex, evoked short-latency spike responses lasting 250–350 msec in the same neurons as took part in the reflex itself. In these types of internal inhibition, responses of the neurons were thus initially excitatory in character. Participation of the neurons in the conditioned placing reflex and its extinction, disinhibition, and differentiation, is the result of a change in the time course of excitatory processes and is evidently connected with differential changes in the efficiency of the various synaptic inputs of the neuron.A. A. Bogomolets Institute of Physiology, Academy of Sciences of the Ukrainian SSR, Kiev. Translated from Neirofiziologiya, Vol. 14, No. 4, pp. 392–401, July–August, 1982.     

Dynamics of cortical unit responses during defensive conditioning to sound

Several phases were distinguished in single-unit responses in areas 3 and 4 during defensive conditioning to acoustic stimulation: an initial response, short inhibition of the spike discharge, early and late after-discharges, and changes arising after the end of acoustic stimulation. The initial spike response appeared or intensified (if present already) in the first period of defensive conditioning parallel with an increase in spontaneous unit activity. After-discharges appeared later. The conditioned-reflex movement usually began 100–400 msec after stimulation began. This latent period of the first movement was the same whether for a real conditioned reflex or an after-discharge. Comparison of the latent periods of conditioned movements with the phases of the unit responses showed that the conditioned responses of the cortical neuron were primarily modified after-discharges of neurons evoked by a conditioned stimulus. Differential unit responses to acoustic stimulation, also based on after-discharges, were formed just as actively as positive. The basic role of reinforcement during conditioning is not to increase the excitability of the neurons, which is important in connection with their acquisition of polysensory properties, but to modify the after-discharges of the neurons.A. A. Bogomolets Institute of Physiology, Academy of Sciences of the Ukrainian SSR, Kiev. Translated from Neirofiziologiya, Vol. 10, No. 4, pp. 339–347, July–August, 1978.     

Role of the midbrain periaqueductal gray matter in conditioned reflexes

Unit activity in the midbrain periaqueductal gray matter (PGM) during an instrumental placing reflex, its extinction, differentiation, and conditioned inhibition, was studied in chronic experiments on cats. Spike responses 1–2 sec in duration in 69 (36.7%) of 182 neurons preceded by 400–800 msec the beginning of conditioned-reflex and voluntary intertrial movements. These advanced responses appeared 200 msec before the corresponding advance responses of motor cortical neurons. Fifty-eight neurons (30.9%) responded directly to acoustic stimulation with a latent period of 10–50 msec for 2–6 sec, 19 neurons (10.1%) generated double responses, linked with both the acoustic stimulus and subsequent conditioned-reflex movement, and 42 neurons (22.3%) did not respond to acoustic stimulation, although individual neurons of this group changed the level of their spontaneous activity in response to repeated conditioned stimulation, and this change was maintained for some tens of minutes. Extinction, differentiation, and conditioned inhibition all abolished conditioned-reflex movements, but each type of internal inhibition was accompanied by its own characteristic changes in the firing pattern of PGM neurons. Functional independence of neurons of the first and second groups was demonstrated during extinction and recovery of the conditioned-reflex. The results indicate the important role of PGM not only in the mechanism of the conditioned reflex, but also in the development of its internal inhibition.A. A. Bogomolets Institute of Physiology, Academy of Sciences of the Ukrainian SSR, Kiev. Translated from Neirofiziologiya, Vol. 16, No. 3, pp. 403–419, May–June, 1984.     

Unitary activity in the cat motor cortex during a conditioned postural adjustment reflex

Unitary activity in the motor cortex (area 4) during a conditioned postural adjustment reflex was investigated in cats. Responses of the overwhelming majority of neurons connected with conditioned-reflex placing movements were activational in type. They consisted of several components and preceded the movements themselves by 50–600 msec. During realization of incorrect responses to presentation of a differential stimulus and of "spontaneous" interstimulus movements, the unitary responses were similar in direction but differed in their lower intensity and, in most cases, they appeared simultaneously with these movements. In the course of extinction both the conditioned-reflex movements and the corresponding unitary responses disappeared simultaneously. The technique of formation of a conditioned postural adjustment reflex suggested in this paper can be used to from natural, well-coordinated forelimb movements in animals in response to conditioned stimulation which are necessary initial components of more complex behavioral motor responses.A. A. Bogomolets Institute of Physiology, Academy of Sciences of the Ukrainian SSR, Kiev. Translated from Neirofiziologiya, Vol. 16, No. 6, pp. 745–753, November–December, 1984.     

Interaction between visceral,somatic, and visual excitation on single neurons of the lateral geniculate body in cats

Acute experiments on cats anesthetized with pentobarbital and immobilized with diplacin or listhenon showed that visceral and somatic excitation may either facilitate or inhibit single unit activity in the lateral geniculate body evoked by photic stimulation. The manifestations of facilitation were: a modulatory type of enhancement of responses of silent neurons and neurons with a low level of spontaneous activity; enhancement of responses accompanied by simultaneous depression of spontaneous activity — a sensory contrast effect; enhancement of long-latency responses; appearance of a short-latency discharge from cells with an inhibitory response to light; the appearance of responses to light in neurons not responding previously or stabilization of responses in neurons responding to light irregularly. The inhibitory effects were manifested as immediate inhibition of responses, usually long-latency, and the filling up of the inhibitory pauses of the response to light with spikes, leading to a decrease in the signal-noise ratio. Somatic stimulation was more effective and more frequently evoked facilitation of responses to light (in 74% of cells). Similar results were obtained by stimulation of the mesencephalic reticular formation. Visceral excitation gave rise to facilitatory and inhibitory effects to an almost equal degree. The results show that excitation arising as the result of visceral and somatic stimulation affects the conduction of visual information in the neuronal system of the lateral geniculate body.Ivano-Frankovsk Medical Institute. Institute of Experimental Medicine, Academy of Medical Sciences of the USSR, Leningrad. Translated from Neirofiziologiya, Vol. 5, No. 6, pp. 636–643, November–December, 1973.     

Spontaneous and evoked unit activity of the septum and hippocampus transplated into the rat neocortex

Embryonic septal and hippocampal tissue was transplanted into a cavity formed by removal of part of the parietal cortex of adult rats by suction. By extracellular recording 4–6 months after the operation cells with spontaneous activity with a frequency of 3.6±0.4 Hz, characterized by an irregular, stochastic spike distribution, were detected in the graft. About 90% of cells responded to electrical stimulation of neighboring cortical areas after a latent period of 5–43 msec. The most stable responses appeared to stimulation with frequencies of 5–10 Hz; in most cases the evoked discharge was followed by a period of inhibition of spontaneous activity (100–700 msec). The same number of cells responded to tactile stimulation of the body surface and vibrissae of the recipient animal. Specific responses of different types with latent periods of between 50 and 600 msec were observed. Normalization of unit activity of intracerebral grafts compared with activity of cells in tissue developing in the anterior chamber of the eye, and their functional integration with the recipient's brain are discussed.Institute of Biological Physics, Academy of Sciences of the USSR, Pushchino-on-Oka. Translated from Neirofiziologiya, Vol. 17, No. 2, pp. 160–168, March–April, 1985.     

Effect of noradrenalin and serotonin on responses of area CA3 neurons evoked in guinea pig hippocampal slices by electrical stimulation of mossy fibers

The effect of noradrenalin (NA) and serotonin (5-HT) on responses of area CA₃ cells evoked by electrical stimulation of mossy fibers was studied in slices of guinea pig hippocampus survivingin vitro. Both substances, which modify the general level and organization of spontaneous activity, also affected responses of area CA₃ cells. Changes in magnitude and structure of the response usually correlated with corresponding changes in spontaneous activity. In certain cases NA, which lowered the frequency of spontaneous activity but increased its relative content of "complex discharges" and also the number of reduced action potentials in the complex discharge, also led to an increase in the response to stimulation. 5-HT evoked periodic grouped activity in some cells and led to the appearance of such grouped discharges for the first time in the responses of other cells. Unlike NA, 5-HT caused prolonged (up to 40 min) after-facilitation of the response and an increase in spontaneous discharge frequency.Institute of Biological Physics, Academy of Sciences of the USSR, Pushchino-on-Oka. Translated from Neirofiziologiya, Vol. 14, No. 4, pp. 410–417, July–August, 1982.     

Effects of acetylcholine and cholinergic transmission blockers on neuronal spike activity in the cat motor cortex associated with conditioned reflex

The effects of direct application of acetylcholine (ACh) and m- and n-cholinoreceptor blockers on test cells were investigated in waking cats having developed instrumental lever-pressing conditioned reflex. Changes were recorded in both spontaneous and invoked firing activity in a functionally homogeneous group of motor cortex cells, in which increased discharge rate usually preceded the start of conditioned reflex movements. It was found, however, that ACh increased spontaneous activity considerably in some of the neurons tested and reduced it moderately in others. Atropine sharply reduced background activity in cortical neurons while preserving spike response to presentation of a conditioned stimulus and n-cholino-blockers such as hexonium and (occasionally) tubocurarine inhibited spike response produced by conditioned stimuli; background activity was slightly inhibited by hexonium and reinforced by tubocurarine. It was concluded that ACh put out by cholinergic fibers helps to maintain background firing activity level in cortical neurons under naturally occurring conditions, acting via m-cholinoreceptors, whereas factors influencing generation of spike discharges associated with performance of conditioned reflex movements are mediated by n-cholinoreceptors.A. A. Bogomolets Institute of Physiology, Academy of Sciences of the Ukrainian SSR, Kiev. Translated from Neirofiziologiya, Vol. 21, No. 5, pp. 579–589, September–October, 1989.     

Spontaneous activity of auditory cortical neurons of waking cats at rest and during defensive conditioning

The results of a computerized statistical analysis of 366 realizations of spontaneous spike activity of 181 neurons in the primary auditory cortex (area 50) of waking cats at rest and during defensive conditioning are described. In both situations the parameters of spontaneous activity of most neurons differed from those of a random flow. Conditioning led, on the one hand, to a stable increase in the frequency of spontaneous activity in intertrial periods and, on the other hand, judging from changes in the mean firing rate, the coefficients of variation of the length of the interspike intervals, the histograms of their distribution, and also the increase in the number of neurons with different forms of correlation between interspike intervals, to an increase in its stability (degree of organization).A. A. Bogomolets Institute of Physiology, Academy of Sciences of the Ukrainian SSR, Kiev. Translated from Neirofiziologiya, Vol. 10, No. 3, pp. 227–238, May–June, 1978.     

Intracellular responses of primary auditory cortical neurons to tones of different frequencies and to electrical stimulation of spiral ganglion fibers in cat

Experiments on cats anesthetized with pentobarbital showed that, depending on the intensity and frequency of acoustic stimulation, neurons in auditory area AI give responses of EPSP, EPSP-spike-IPSP, EPSP-IPSP, and IPSP type. Presentation of a tone of characteristic or near-characteristic frequency and above-threshold intensity, and also electrical stimulation of nerve fibers of the spiral ganglion, innervating the central zone of the receptive field of the neuron, evoke in most cases a response of EPSP-spike-IPSP type. Tone differing considerably in frequency from the characteristic, and electrical stimulation of peripheral zones of the receptive field, evoked responses of EPSP-IPSP or IPSP type. The range of frequencies of tones to which, at threshold intensity, an action potential is generated by the neuron is considerably narrower than the range of frequencies of tones evoking an EPSP and IPSP. Above the intensity of tone threshold IPSP is an invariable component of the response of most neurons in area AI. The appearance of an IPSP in the neuron is accompanied by depression of spontaneous activity and the neuronal response to testing stimulation. Two types of IPSP were distinguished: One type is a component of the EPSP-spike-IPSP response and arises during excitation of auditory receptors located in the central part of the receptive field of the neuron, the other arises during excitation of receptors located at the periphery of the field, and which project to neurons with other characteristic frequencies. The former arise after spike excitation of the neuron, the latter after EPSP or primarily.A. A. Bogomolets Institute of Physiology, Academy of Sciences of the Ukrainian SSR, Kiev. Translated from Neirofiziologiya, Vol. 16, No. 1, pp. 123–131, January–February, 1984.     

Responses of limbic cortical neurons during instrumental conditioned reflexes in cats

Unit activity in cortical areas 24 and 32 was studied during conditioned placing reflex formation in cats. Neuronal responses in the limbic cortex of trained animals correlated with acoustic stimulation, the motor response, and also with the presentation of food reinforcement. In untrained animals 16% of neurons responded to acoustic stimulation. After training the number of neurons responding to sound in area 32 increased to 51.3%. Of the total number of neurons, 34.6% responded by initial excitation and 26.7% by inhibition of spike activity. The latent period of these responses was about 50 msec and their duration up to 200 msec. Similar but weaker responses were observed in area 24. Short-latency activation responses to conditioned and differential stimulation were similar in character. It is suggested that after training processes taking place in the limbic cortex may contribute to better perception of both conditioned and differential acoustic stimuli, irrespective of their functional significance.A. A. Bogomolets Institute of Physiology, Academy of Sciences of the Ukrainian SSR, Kiev. Translated from Neirofiziologiya, Vol. 16, No. 2, pp. 201–208, March–April, 1984.     

After-effects of repetitive stimulation in spinal neurons

Spontaneous activity of interneurons before and after repetitive stimulation at 0.1–0.5/sec was recorded in acute experiments on spinal cats and kittens. Using the dynamic selective correlation method a search was made for areas of spontaneous activity with the same distribution of action potentials in time as in the averaged evoked response to a single stimulus. In the case of some neurons portions of the background which correlate reliably in structure with the evoked response repeated at an interval equal to or a multiple of the interval of stimulation. Reproduction of the rhythm of stimulation in the spontaneous activity is intensified with an increase in the total duration of preceding stimulation with the same input and shows positive correlation with the degree of posttetanic potentiation. The facts obtained are evidence of prolonged after-processes in spinal neurons.Institute of Experimental Medicine, Academy of Medical Sciences of the USSR, Leningrad. Translated from Neirofiziologiya, Vol. 5, No. 3, pp. 272–280, May–June, 1973.     

Role of Acetylcholine in the Modulation of Activity of Neocortical Neurons in Awake Animals Performing an Instrumental Conditioned Reflex

We studied modulatory effects of the cholinergic system on the activity of sensorimotor cortex neurons related to realization of an instrumental conditioned placing reflex. Experiments were carried out on awake cats; multibarrel glass microelectrodes were used for extracellular recording of impulse activity of neurons in the sensorimotor cortex and iontophoretic application of synaptically active agents within the recording region. The background and reflex-related activity was recorded in the course of realization of conditioned movements, and then changes of spiking induced by applications of the testing substances were examined. Applications of acetylcholine and carbachol resulted in increases in the intensity of impulse reactions of neocortical neurons evoked by presentation of an acoustic signal and in simultaneous shortening of the response latencies. An agonist of muscarinic receptors, pylocarpine, exerted a similar effect on the evoked activity of sensorimotor cortex neurons. Blockers of muscarinic receptors, atropine and scopolamine, vice versa, sharply suppressed impulse reactions of cortical neurons to afferent stimulation and simultaneously increased latencies of these responses. Applications of an agonist of nicotinic receptors, nicotine, was accompanied by suppression of impulse neuronal responses, an increase in the latency of spike reactions to presentation of a sound signal, and a corresponding increase in the latency of a conditioned motor reaction. In contrast, application of an antagonist of nicotinic receptors, tubocurarine, significantly intensified neuronal spike responses and shortened their latency. The mechanisms underlying the effects of antagonists of membrane muscarinic and nicotinic cholinoreceptors and the role of activation of these receptors in the modulation of activity of pyramidal and non-pyramidal neocortical neurons related to realization of the instrumental motor reflex are discussed.     

Responses of caudate neurons to clicks in chronic experiments on cats

Spontaneous and evoked unit activity in response to repeated application of clicks at a frequency of 0.3–2.0 Hz in the caudate nucleus was studied by an extracellular recording technique in chronic experiments on cats. Four types of spontaneous unit activity in the caudate nucleus were distinguished. Altogether 44% of neurons tested responded by changes in spontaneous activity to clicks. Five types of responses of caudate neurons to clicks were discovered: phasic excitation, phasic inhibition, tonic activation, tonic inhibition, and mixed tonic responses; the commonest type was tonic activation. During prolonged stimulation by clicks extinction of the phasic responses was not observed. Complete or partial extinction of tonic responses in the course of frequent repetition of stimulation was observed in 33% of responding neurons. The question of possible convergence of specific and nonspecific influences on caudate neurons is discussed.A. A. Bogomolets Institute of Physiology, Academy of Sciences of the Ukrainian SSR, Kiev. Translated from Neirofiziologiya, Vol. 12, No. 1, pp. 28–35, January–February, 1980.     

Effects of serotonin on neuronal response induced in the sensorimotor cortex by tactile and conditioned acoustic stimuli

Neuronal firing response in the sensorimotor cortex to tactile (non-conditioned) and acoustic (conditioned) stimuli was investigated in trained cats before and after iontophoretic application of serotonin and lysergide. Three functionally distinct groups of neurons were identified from the response produced by presenting tactile and acoustic stimuli. Applying serotonin was found to facilitate preliminary and residual spike response induced by tactile stimulation; it also facilitates and modulates response in many cortical neurons to conditioned stimuli. Facilitation takes the form of reduced latency of response and increased numbers of spikes in response to conditioned stimulus presentation, especially at the initial phase of response to sound and immediately after the onset of conditioned reflex motion. Additional neurons formerly unresponsive to acoustic stimuli joined in the reaction under the effects of serotonin. Changed response patterns often evolve following minor fluctuations in background activity level. It is suggested that facilitation of response following iontophoretic serotonin application in the neocortex is associated with activation of excitatory serotonin receptors (S₂). The lysergide-induced increase in background and evoked activity noted during experimentation can apparently be put down to blockade of inhibitory serotonon (S_1B) receptors.A. A. Bogomolets Institute of Physiology, Academy of Sciences of the Ukrainian SSR, Kiev. Translated from Neirofiziologiya, Vol. 22, No. 3, pp. 337–347, May–June, 1990.     

Unit responses of the secondary somatosensory cortex during defensive conditioning in cats

Unit responses in the secondary somatosensory cortex during the formation and extinction of a defensive conditioned reflex to acoustic stimulation were investigated in chronic experiments on cats. In 21 of 28 neurons tested during defensive conditioning the firing pattern changed in accordance with the character of responses to electric shock reinforcement. Two types of conditioned-reflex unit responses were distinguished: excitatory and inhibitory. Most neurons responding to the conditioned stimulus by activation did so during the first 50 msec, which was 80–100 msec before the conditioned motor response. Considerable variability of the unit responses was observed during conditioning. By the time of stabilization of the conditioned-reflex connections the unit response to the conditioned stimulus was stable in form. The pattern of extinction of the conditioned unit activity was expressed as a decrease in the discharge frequency in responses of excitatory type and disinhibition of activity in the case of inhibitory responses.A. A. Bogomolets Institute of Physiology, Academy of Sciences of the Ukrainian SSR, Kiev, Translated from Neirofiziologiya, Vol. 9, No. 3, pp. 232–238, May–June, 1977.     

Formation of spontaneous and evoked unit activity in organotypical hippocampal tissue culture

Spontaneous and evoked single unit activity of Ammon's horn and the dentate fascia was investigated by extracellular recording in organotypical explants of neonatal mouse hippocampus during the first 2 weeks in culture. Three main types of spontaneous activity were observed: single, group, and volley. After the fifth to sixth day in culture the neurons were found to respond to stimulation of the entorhinal cortex and dentate fascia. Both short-latency (evidently monosynaptic) and long-latency responses were observed, and they usually varied if the stimulus was repeated. The appearance of evoked unit activity in the explants is considered to be due to maturation of synaptic contacts at axon endings of granule cells and perforant path, the formation of which continues during culture.Brain Institute, Academy of Medical Sciences of the USSR, Moscow. Translated from Neirofiziologiya, Vol. 9, No. 3, pp. 257–266, May–June, 1977.