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.     

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.     

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.     

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.     

Response of recticular and dorsal thalamic nuclei neurons during extinction of conditioned implementation in the cat

Unit activity in 66 neurons of the reticular (R) nucleus and 31 neurons of the ventropostrolateral nuclei of the thalamus, and 14 neurons of the posterolateral nuclear complex, the pulvinar, were studied during extinction of the conditioned food implementation reflex. The number of R neurons that had responded to initial excitation in the first 300 msec after the conditional stimulus (CS) decreased with the extinction. Simultaneous disappearance of conditioned-reflex placement movements and late excitatory and inhibitory responses of R and dorsal thalamic nuclei neurons with latent periods exceeding 300 msec was also observed. Extinction of the conditioned reflex (CR) led to a significant lowering of background activity in two-thirds of investigated R and other thalamic nuclear neurons. This suggests that efferent effects from the reticular nucleus are decreased during Cr extinction.A. A. Bogomolets Institute of Physiology, Academy of Sciences of the USSR, Kiev. Translated from Neirofiziologiya, Vol. 23, No. 1, pp. 3–8, January–February, 1991.     

Neuronal response in the cat parietal association cerebral cortex (area 5) during performance of conditioned reflex motion

Responses in 160 neurons of the cat parietal cortex were investigated during the performance of instrumental food reflex (lever pressing) during experiments involving presentation of a conditioned acoustic stimulus. Discharge rate changed in 49% of neurons during the period preceding the conditioned reflex movement. Three basic types of cell with an excitatory response pattern were discovered apart from a small group showing suppression of activity, each differently involved in the process of conditioned reflex movement performance. Excitation arose in neurons of the first type 200±52.9 msec (average) before the onset of the conditioned reflex movement, reaching its peak discharge rate as the animal placed its paw on the lever. The former parameter was 605±54.2 msec for the second type of neuron, with firing rate peaking between the start of electromyographic response and the completion of lever pressing. The same parameter measured 1,000–2,000 msec in the third type and activation took the form of a diffuse increase in discharge rate without a clear-cut peak occurring during performance of the instrumental reflex. Findings would suggest the involvement of the parietal cortex neuronal system in the triggering as well as the follow-through of conditioned reflex motion.A. A. Bogomolets Institute of Physiology, Academy of Sciences of the Ukrainian SSR, Kiev. Translated from Neirofiziologiya, Vol. 19, No. 2, pp. 223–231, March–April, 1987.     

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.     

Neuronal responses in area 7 of the cat cortex during defensive conditioning

Responses of neurons in area 7 of the parietal association cortex during and after formation of a defensive conditioned reflex to sound were recorded in waking cats. Changes in spike responses of the neurons as a result of the onset of conditioned reflex limb movements were observed in 68% of neurons. Spike responses of neurons formed as a result of learning appeared only if conditioned-reflex limb movements appeared, and they were not observed if, for some reason or other, movements were absent after presentation of the positive conditioned stimulus or on extinction of the reflex. Responses of 46% neurons to conditioned stimulation preceded the conditioned-reflex motor responses by 50–450 msec. The remaining responding neurons were recruited into the response after the beginning of movement. Characteristic spike responses of neurons to the conditioned stimulus appeared 500–900 msec before the beginning of movement and, in the case of appearance of special, "prolonged" motor responses of limb withdrawal, evoked by subsequent reinforcing stimulation.     

Effect of response inhibition in cat motor cortex neurons during the expectation of conditioning stimulus

The spike responses of the motor cortex neurons (area 4) associated with forelimb movement were studied in awake cats earlier trained to perform placing motor reactions. Responses produced by the same neurons were compared in two situations: 1) when a sound-click conditioning stimulus (CS) was applied in isolation; 2) when a CS followed a preliminary warning stimulus (WS), a light flash, with a 100–1000 msec delay. During the reflex initiation by combined action of the WS and CS, response components that occurred prior to the placing movement (PM) performance under isolated CS action weakened and arrived 50–150 msec later; yet, response components that appeared in the same situation simultaneously with PM onset or later remained unchanged. PM latent periods were not changed when WS was applied. The temporal interval between WS and CS was characterized by depression of neuronal activity; depression duration was determined by the interstimulus delay. It is conceivable that the described transformations in spike responses of cortical neurons occurred due to changes in the sensory direction of the animal's attention; this direction, in all cases, is a crucial factor in the formation of neuronal activity in the cortex.Translated from Neirofiziologiya, Vol. 25, No. 1, pp. 21–27, January–February, 1993.t     

Analysis of spike discharge of a neuron population in the cat motor cortex during a conditioned change of posture reflex

Spike responses of area 4 neurons in the projection area of the contralateral forelimb to acoustic stimulation (1 sec), which became the conditioned stimulus after training, and to dropping of the platform beneath the test limb, which served as reinforcing stimulus, were studied in trained and untrained cats. Responses only of those neurons which were activated during a passive movement caused by dropping of the platform were studied. In trained animals the number of these neurons which responded to the conditioned stimulus if a reflex occurred was 100%, and in the absence of conditioned-reflex movements to the conditioned stimulus it was 70%, much greater than the number of neurons responding to the same acoustic stimulus in untrained animals (45%). On peristimulus histograms of responses of the test neuron population in untrained and trained animals to acoustic stimulation (in the absence of movements) only the initial spike response with a latent period of under 50 msec and a duration of up to 100 msec could be clearly distinguished. In the presence of reflex movement multicomponent spike responses were observed: an initial spike response and early and late after-responses linked with performance of conditioned-reflex limb flexion. Early after-responses 100–200 msec in duration, appearing after a latent period of 100–150 msec, were linked to the time of application of the conditioned stimulus, whereas the appearance and duration of late after-responses were determined by the time of onset of conditioned-reflex movement. The magnitude of the neuronal response to reinforcement in trained animals does not depend on the appearance of the conditioned movement.A. A. Bogomolets Institute of Physiology, Academy of Sciences of the Ukrainian SSR, Kiev. Translated from Neirofiziologiya, Vol. 17, No. 1, pp. 93–102, January–February, 1985.     

Single unit activity related to acoustic stimulus meaning in the cat auditory cortex during instrumental food reflex

Responses of 93 neurons to isolated presentation of a single click and a series of 10 clicks with following frequency of 1000 Hz and responses of 66 neurons after the click had become a positive conditioned stimulus, and a series of 10 clicks had become a differential, negative stimulus, were investigated in chronic experiments on cats. Formation and realization of differential inhibition of an instrumental food reflex was shown not to lead to strengthening of inhibition in the auditory cortex, and the process of differential inhibition itself within the primary auditory cortex is not essentially an inhibitory process. Identical changes were found in responses of auditory cortical neurons to both positive and negative conditioned stimuli after training, evidence that neurons of the primary auditory cortex play a similar role in realization of the instrumental reflex and in its differential inhibition. It is suggested that the presence of groups of neurons responding by excitation or inhibition only to presentation of a stimulus with definite informative value is of great importance for differentiation.A. A. Bogomolets Institute of Physiology, Academy of Sciences of the Ukranian SSR, Kiev. Translated from Neirofiziologiya, Vol. 17, No. 2, pp. 212–221, March–April, 1985.     

Neuronal response in the cat parietal association cortex to conditioned and non-conditioned acoustic stimuli

Neuronal response in the cat association cortex (area 5) to conditioned and non-conditioned acoustic stimulation was investigated. Numbers of neurons responding to a conditioned acoustic stimulus according to the traditional reflex pattern were twice as high. Numbers of inhibitory neuronal responses to the stimulus increased when instrumental reflex occurred. Neurons were found which only reacted to a conditioned acoustic stimulus in the absence of conditioned reflex movement occurring with instrumental food reflex. Although findings do not exclude the possibility of this cortical area contributing to the analysis of sensory signals and evaluation of their biological significance, it might be supposed that its main functional property lies in its involvement in the process of initiating behavioral response to a conditioned response.A. A. Bogomolets Institute of Physiology, Academy of Sciences of the Ukrainian SSR, Kiev. Translated from Neirofiziologiya, Vol. 20, No. 5, pp. 637–645, September–October, 1988.     

Inhibitory influence of supplementary extraneous stimulation upon neuronal responses in the sensorimotor cortex of the cat during a conditioned reflex

Using alert rabbits trained to perform placing movements in response to a sound click, we investigated impulse responses (IR) of neurons of the somatosensory cortex preceding realization of the reflex by 50–150 msec. When a brief extraneous stimulation (light flashes, audible tone, electrical stimulation of a limb) was applied after initiation of the reflex, learned movements with the earlier behavioral parameters (latent periods and duration) were maintained. However, the IR of neurons to the presentation of a conditioned stimulus (CS) was of lesser intensity and arose 50–250 msec later. A constant extraneous stimulation (an audible tone, a forced stream of air upon the muzzle) or a decrease in the intensity of the CS administered to the threshold of hearing resulted in similar changes in the neuronal responses upon the application of the CS, but the parameters of the learned movements were maintained. We suggest that the cause of these changes in neuronal responses is increased exteroceptive attention to extraneous stimulation to additional extraneous stimulation.A. A. Bogomolets Institute of Physiology, Academy of Sciences of the Ukrainian SSR, Kiev. Translated from Neirofiziologiya, Vol. 23, No. 2, pp. 174–181, March–April, 1991.     

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.     

Transformation of the afferent tactile signal into a motor command in the cat motor cortex

Activity of 112 neurons of the precruciate motor cortex in cats was studied during a forelimb placing reaction to tactile stimulation of its distal parts. The latent period of response of the limb to tactile stimulation was: for flexors of the elbow (biceps brachii) 30–40 msec, for the earliest reponses of cortical motor neurons about 20 msec. The biceps response was observed 5–10 msec after the end of stimulation of the cortex with a series of pulses lasting 25 msec. Two types of excitatory responses of the neurons were identified: responses of sensory type observed to each tactile stimulation of the limb and independent of the presence or absence of motion, and responses of motor type, which developed parallel with the motor response of the limb and were not observed in the absence of motion. The minimal latent period of the responses of motor type was equal to the latent period of the sensory responses to tactile stimulation (20±10 msec). Stimulation of the cortex through the recording microelectrode at the site of derivation of unit activity, which increased during active flexion of the forelimb at the elbow (11 stimuli at intervals of 2.5 msec, current not exceeding 25 µA), in 70% of cases evoked an electrical response in the flexor muscle of the elbow.M. V. Lomonosov Moscow State University. Translated from Neirofiziologiya, Vol. 9, No. 2, pp. 115–123, March–April, 1977.     

Neurons of the cat sensorimotor cortex: Responses related to differentiation of monomodal and heteromodal conditioning signals

Spike responses of the sensorimotor cortex neurons were studied in chronic experiments on cats trained to perform an operant reflex, a placing movement triggered by application of the distant stimuli. The responses recorded under conditions of differentiation of sound tones of various frequencies and of a heteromodal complex (light + tone) from its components were compared. The responses recorded from 125 neurons in 3 animals were analyzed. No neurons selectively responding either to monomodal or to heteromodal signals were found. Forty-five cells responded to positive signals by excitation or inhibition, irrespective of the signal modality. The shortest latencies of these responses were 30 and 40 msec, respectively. When inhibitory stimuli were applied, these neurons either generated much weaker responses, or did not respond at all. A correlation was found between the level of response depression and the level of differentiation of the signals by an animal. These findings allow us to hypothesize that the sensorimotor cortex does participate in differentiation of sensory signals, providing preparation for switching on the motor response after a positive stimulus or suppression of such a response after a negative one.Neirofiziologiya/Neurophysiology, Vol. 26, No. 4, pp. 251–261, July–August, 1994.     

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.     

Influence of food motivation on neuronal response of the cat somatic cortex during instrumental reflex

Spike activity in neurons of areas 3 and 4 was investigated in experiments on cats during the conditioned reflex response of placing the paw on a support both before and after feeding ad libitum. Ingestion of a feed consisting of a rapidly absorbed glucose dairy mix did not prevent the reflex taking place if the animals' favorite food was used as reinforcement. Background activity increased in two-thirds of the neurons after the feed; the tonic constituent of neuronal response declined substantially and repeated contraction of the biceps occurring at the same rate as locomotor movements disappeared. Difference in latency of response produced by the conditioned stimulus in the same neurons before and after feeding measured 50–300 msec during the experiment. Measurements of latency of placing motion remained largely unchanged. Changes in the latency of neuronal spike response were thus found to be interrelated with the intensity of the animal's motivational excitation. It is suggested that fluctuations in degree of food motivation lead to changes in cortico-subcortical relationships responsible for initiation and performance of conditioned movements in these animals.A. A. Bogomolets Institute of Physiology, Academy of Sciences of the Ukrainian SSR, Kiev. Translated from Neirofiziologiya, Vol. 19, No. 5, pp. 646–653, September–October, 1987.     

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.     

Functional properties distinguishing individual auditory cortical neurons

Responses of 246 auditory cortical neurons to paired and repetitive stimulation of geniculo-cortical fibers were studied in experiments on cats immobilized with tubocurarine. The refractory period (RP) varied from 1 to 200 msec in different neurons. For neurons excited antidromically it varied from 1 to 3 msec. Among neurons excited monosynaptically there were some with a short (1.3–6 msec), medium, (8–16 msec) or long (30–100 msec) refractory period. Most neurons excited polysynaptically had a RP of mean length. RPs 30–200 msec in length were due to inhibition arising in the neuron after conditioning stimulation. In some neurons, after a short (1.5–2.0 msec) initial period of refractoriness there was a temporary (for 2–3 msec) recovery of responsiveness, followed by another period of ineffectiveness of the testing stimulus lasting 30–100 msec. Barbiturates selectively inhibited long-latency unit responses in the auditory cortex and during their action the number of responding neurons with a mean RP decreased sharply. The results demonstrate functional heterogeneity of auditory cortical neurons responding to an incoming volley of afferent impulses.A. A. Bogomolets Institute of Physiology, Academy of Sciences of the Ukrainian SSR, Kiev. Translated from Neirofiziologiya, Vol. 5, No. 3, pp. 236–245, May–June, 1973.