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.     

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 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 caudate neurons to acoustic stimulation in cats

Responses of 141 neurons of the caudate nucleus to acoustic stimuli — tones (500 and 2000 Hz) and clicks of different frequency (0.2 and 0.8/sec) and intensity (75, 80, 95 dB) — were recorded extracellularly in chronic experiments on cats. The responses recorded showed great variability with respect to character (phasic, tonic), structure (one or two phases of excitation), latent periods (from 7.5 to 300.0 msec), and burst discharge frequency (from 90 to 800 spikes/sec). Analysis of averaged poststimulus histograms and graphs of the dynamics of the responses showed that responses of 74% of neurons were much better expressed if less frequent stimuli were used: The regularity of the responses and the number of spikes in each response increased. Responses of neurons also increased and acquired a more distinct temporal structure if the intensity of the clicks increased. The character of responses to clicks and tones differed qualitatively in 17% of neurons studied: Phasic excitation arose in response to clicks, tonic changes in spike activity to tones. The particular features of responses of caudate neurons to acoustic stimulation with different parameters are discussed.A. A. Bogomolets Institute of Physiology, Academy of Sciences of the Ukrainian SSR, Kiev. Translated from Neirofiziologiya, Vol. 12, No. 6, pp. 588–595, November–December, 1980.     

Inhibitory effects of external stimulation on neuronal spike response in the cat association cortex during conditioning

The effects of external stimulus presentation on neuronal spike response induced in area 7 by conditioned and unconditioned stimuli were investigated in waking cats. Pointing reaction arising in response to the action of external stimuli led to the phasing out of spike response to unconditioned cutaneous stimulation, as well as depression or complete suppression of response in area 7 neurons to conditioned stimulus presentation, despite occurrence of conditioned reflex motion. External stimuli no longer exerted an inhibitory effect on the neuronal spike response induced by protracted use of conditioned and unconditioned stimuli. The fact that the conditioned lever-pressing reflex could occur either following or without neuronal spike response in area 7 would raise the question of whether neurons belonging to this area always participate directly in the triggering and occurrence of conditioned reflex motion.A. A. Bogomolets Institute of Physiology, Academy of Sciences of the Ukrainian SSR, Kiev. Translated from Neirofiziogiya, Vol. 22, No. 2, pp. 147–155, March–April, 1990.     

Neuron activity in the motor cortex of a cat with inhibition of a conditioned postural change reflex

A study was made of the neuron spike reactions in the primary motor cortex of the cat in the projection zone of the contralateral forelimb with external and internal inhibition of the conditioned reflex for posture change that consisted of shifting the body weight to the forelimb being studied. Spike responses of the neurons to extraneous stimuli and the conditioned signal were determined to a significant degree by the condition of the animal and its habituation to the signal used. In trained animals, the duration of responses to extraneous stimulation was shorter than in the nontrained. With external and internal inhibition, we observed simultaneous disappearance of conditioned reflex movements and the trace spike discharges connected with them. Frequently extraneous stimulations could suppress trace discharges even when learned movement was present. Extraneous stimulations of a different modality inhibited the reflex to different degrees. The change in neuron spike reaction connected with a conditioned reflex change in posture was similar to well-learned local reflex phenomena.A. A. Bogomol'ets Institute of Physiology, Academy of Sciences of the Ukrainian SSR, Kiev. Translated from Neirofiziologiya, Vol. 17, No. 4, pp. 489–500, July–August, 1985.     

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.     

Responses of neurons in cat primary somatosensory cortex to repetitive stimulation of vibrissae

Extra- and intracellular responses of neurons in the primary somatosensory cortex to repetitive mechanical stimulation of the vibrissae at different frequencies were studied in unanesthetized curarized adult cats. Unlike responses to electrical stimulation of the combined afferent input (the infraorbital nerve) spike discharges of neurons in response to vibrissal stimulation can reproduce rather higher frequencies of stimulation and their initial character changes more often in the course of the repetitive series. Most cortical neurons were characterized by limitation of the area of their peripheral receptive fields with an increase in the frequency of adequate repetitive stimulation. A group of cortical neurons was distinguished by its ability to respond to high-frequency stimulation and to generate burst discharges. Comparison of the frequency characteristics of spike responses of these cells and of inhibitory synaptic action in other cortical neurons led to the conclusion that this group of cells thus distinguished may be inhibitory cortical neurons. The role of interaction between excitatory and inhibitory processes arising in cortical neurons during repetitive stimulation of different areas of their receptive fields is discussed.A. A. Bogomolets Institute of Physiology, Academy of Sciences of the Ukrainian SSR, Kiev. Translated from Neirofiziologiya, Vol. 14, No. 2, pp. 164–171, March–April, 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.     

Synaptic responses of propriospinal neurons to stimulation of the stepping strip of the dorsolateral funiculus in cats

Synpatic responses were recorded extracellularly from single neurons at levels T12–T13 in response to microstimulation of the stepping strip of the dorsolateral funiculus in the thoracic and cervical portions of the spinal cord in cats decerebrated at the precollicular level [4]. The latent periods of these responses increased when the distance between the stepping point and recording point exceeded 20 mm, and when two stimuli had to be applied in order to evoke responses. Axons of neurons respondingtrans-synaptically to stimulation of the stepping strip were located on the boundary between the lateral and ventral funiculi close to the gray matter. Antidromic responses of neurons sending their axons in the caudal direction were found on average in 37% of cases, provided that the distance between the recording and stimulation points did not exceed 40 mm. Half of the neurons which generated synaptic responses to stimulation of spinal stepping points could be excited also by a series of three to six stimuli, applied to the mesencephalic locomotor point [15]. It is suggested that the neurons discovered may participate in the spread of activity toward the generator of stepping movements of the hind limb.Institute for Problems in Information Transmission, Academy of Sciences of the USSR, Moscow. M. V. Lomonosov Moscow State University. Translated from Neirofiziologiya, Vol. 17, No. 2, pp. 270–278, March–April, 1985.     

Involvement of mesencephalic reticular formation neurons in cat conditioned reflexes

Traditional defensive and operant food reflexes were used to investigate neuronal responses of the mesencephalic reticular formation. It was found that these neurons may be divided into different groups according to function, depending on how they respond to positive conditioning stimuli. Of the two main groups of neurons with sustained tonic reactions one is activated in response to positive acoustic conditioning stimulation; it no longer reacts to the same stimulus after extinction of the reflex, while the other only becomes involved in response to positive stimulation accompanying the initiation of movement. Neurons belonging to the second group begin to respond directly to acoustic stimulation after extinction of the conditioned reflex. Neurons of the mesencephalic reticular formation can thus exercise additional tonic ascending effects both in the production and inner inhibition of the conditioned reflex. The group of neurons with a phasic reaction, i.e., a double response (a direct response to sound and another produced by movement) displayed a drop in spontaneous activity during the shaping of inhibition of differentiation and of extinction in particular. It was found that the initial changes in the spike response of reticular formation neurons during conditioning and pseudo-conditioning are similar. There are thus grounds for stating that neurons of the mesencephalic reticular formation participate in the shaping, production, and inner inhibition of traditional and operant conditioned reflexes in a differentiated capacity rather than as a population reacting identically.A. A. Bogomolets Institute of Physiology, Academy of Sciences of the Ukrainian SSR, Kiev. Translated from Neirofiziologiya, Vol. 18, No. 2, pp. 161–171, March–April, 1986.     

Responses of cat pulvinar neurons to moving visual stimuli

Responses of 114 pulvinar neurons to moving visual stimuli were studied. Most (79) neurons possessed spontaneous activity (10–25 spikes/sec). Of 59 neurons tested, 31 responded to stimulation of both retinas and 28 to stimulation only of the contralateral retina. Of 114 neurons, 41 responded only to movement of black objects, while the rest responded to movement of both black and light objects. According to the character of their responses to movement the neurons were divided into two main groups. The first group consisted of neurons sensitive to the direction of motion and responding with a spike discharge to movement in one direction and by inhibition to movement in the opposite direction. The second group included neurons insensitive to the direction of motion and responding by an equal number of discharges to movements in two opposite directions. Besides these two main groups, other neurons responding to movement in two opposite directions by discharges with different temporal distribution and also neurons which changed the character of their response from nondirectional to directional depending on the size of the moving stimulus, were found.L. A. Orbeli Institute of Physiology, Academy of Sciences of the Armenian SSR, Erevan. Translated from Neirofiziologiya, Vol. 10, No. 4, pp. 348–354, July–August, 1978.     

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     

Electrophysiological investigation of the cat ciliary ganglion

Electrical responses of some nerves of the ciliary ganglion to stimulation of its other nerves were recorded, and intracellular recordings were also made from neurons of the ganglion (in situ). The overwhelming majority of preganglionic fibers terminate synaptically on neurons of the ganglion. Postganglionic fibers leave in the lateral and medial ciliary nerves, in which the velocity of conduction of excitation ranges from 1.9 to 9.0 m/sec. A few preganglionic fibers pass through the ciliary ganglion into the lateral ciliary nerve, giving off collaterals to neurons of the ganglion, so that stimulation of the lateral ciliary nerve evokes a response in the medial ciliary nerve (preganglionic axon reflex). The resting potential of neurons of the ciliary ganglion is 57±2.8 mV, and their action potential 68±3.6 mV. Single orthodromic stimulation usually evokes a single action potential in a neuron. The amplitude of the EPSP is increased during hyperpolarization of the postsynaptic membrane, confirming the chemical nature of synaptic transmission in the ganglion. The antidromic response consists of an IS-component and spike. The spike is followed by after-hyperpolarization, with a mean amplitude equal to 31% of the spike amplitude, and the time taken for it to fall to one–third of its initial amplitude is 75–135 msec.A. A. Bogomolets' Institute of Physiology, Academy of Sciences of the Ukrainian SSR, Kiev. Translated from Neirofiziologiya, Vol. 1, No. 1, pp. 101–108, July–August, 1969.     

Activity of sensorimotor cortex neurons during a dopaminergic transmission block in cats performing conditional reflex

Activity of sensorimotor cortex neurons was recorded in chronic experements on cats trained to perform instrumental conditional reflex; records were made before, during, and after isolated iontophoretic applications of haloperidol or glutamate, or their combined application. Haloperidol was shown either to facilitate or to inhibit the background and evoked (related to acoustic stimulation and motor response) spike activity of cortical neurons. Aftereffects of haloperidol were observed too; they were still expressed 10–15 min after the cessation of the iontophoresis. Combined haloperidol and glutamate application was followed by a sharp suppression of the evoked responses potentiated earlier by glutamate. An adenylatecyclase system is supposed to mediate the facilitation evoked by glutamate application. Some modulators, including dopamine, probably activate adenylatecyclase and in this way ensure facilitation of the glutamate-induced responses.Neirofiziologiya/Neurophysiology, Vol. 26, No. 5, pp. 347–355, September–October, 1994.     

Imitation of neurophysiological effects of long-term sensitization with the action of the blockers of protein synthesis in snailsHelix lucorum

The experiments on command neurons of defensive behavior in snailsHelix lucorum have shown that the synaptic components of responses to the testing stimuli are facilitated within 65 to 75 min after the onset of the application of the protein synthesis inhibitors cycloheximide or anisomycin (30 µM during 30 min) to the central nervous system. At the same time, the parameters of the electrical properties of neuronal membrane (membrane potential level and excitability) were not affected by the blockers. The facilitatory effects were not observed when the blockers were applied for a longer period or when their concentration was raised to 300 µM. The blockade of the responses to different sensory stimuli appeared selective. The facilitation of the responses to tactile stimulation of the head, to weak quinine solution, and to carrot juice lasted for about an hour, 2–3 h and about 1.5 h, respectively. The blockers facilitated only the responses to tactile stimulation of the head, but did not change the responses to stimulation of the middle part of the foot or the mantle bolster. Some characteristics of the blocking effects are similar to those of long-term sensitization. The blocking effects observed are suggested to be due to activation of synthesis of short-living proteins functionally related, in particular, to selective regulation of synaptic transmission.Neirofiziologiya/Neurophysiology, Vol. 26, No. 1. pp. 61–67, January–February, 1994.     

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.     

Critical role of intracellular calcium in plasticity mechanisms of defense behavior command neurons LPl1 and PPl1 of Helix lucorum during nociceptive sensitization

The role of intracellular calcium in changes in excitability and responses of defense behavior command neurons LP11 and PP11 of Helix lucorum to sensory stimulation was investigated in semi-intact preparation of a snail during nociceptive sensitization. It was found that application of sensitizing stimuli onto the snail's head initiated membrane depolarization, increase in its excitability as well as depression of neural responses evoked by sensory stimuli in short-term period of sensitization and significant facilitation of neural responses in long-term period of sensitization. To elucidate the contribution of LP11 and PP11 neurons in plasticity rearrangements involved in the mechanisms of sensitization, we applied sensitizing stimuli during strong hyperpolarization of the neurons or after intracellular injection of calcium chelators. Application of sensitizing stimuli during hyperpolarization of the neurons suppressed the increase in membrane excitability and depressed the neural responses evoked by chemical stimulation of snail's head i.m. short- and long-term periods of sensitization. At the same time, synaptic facilitation of neural responses evoked by tactile stimulation of snail's head and foot was observed, which was similar to synaptic facilitation in the control sensitized snail. Intracellular injection of EGTA or BARTA (calcium chelators) before sensitization suppressed synaptic facilitation in neural responses evoked by sensory stimulation. Under these conditions, the increase in excitability was more pronounced then in the control snail neurons. The experimental results suggest the changes in neural responses evoked by sensory stimulation in sensitized snails involve postsynaptic calcium-dependent mechanisms of plasticity in LP11 and PP11 neurons.     

Neurons of the ipsilateral and contralateral sensorimotor cortices in the cat: Their responses related to a conditioned reflex movement by one extremity

The activity of sensorimotor cortex neurons related to the performance of conditioned reflex movements by one extremity, which were evoked by the application of distant stimuli, was recorded in chronic experiments on cats. In the course of an experiment, the reflex performance was transferred from one extremity to the another, and, thus, the neuronal responses were studied in two situations: in the ipsilateral or in the contralateral position of a neuron with respect to the operating extremity. According to the pattern of their responses to the conditioning stimulus (CS), the neurons were classified into three groups. The first group consisted of neurons with bilateral type of responses, generating similar responses in both positions. The cells responding to the CS only in the ipsilateral situation formed the second group. The third group consisted of neurons with reciprocal responses, in the two above positions. The results obtained in our study illustrate basic regularities in the functioning of ipsilateral and contralateral hemispheres within the behavioral model used, and show that both hemispheres actively participate in the course of a preparation for the unilateral conditioned movement performance.Neirofiziologiya/Neurophysiology, Vol. 26, No. 5, pp. 334–346, September–October, 1994.     

Participation of interoceptive afferent impulses in polymodal responses of superior collicular neurons in the cat

Experiments on immobilized, unanesthetized cats showed that interoceptive afferent impulses reaching the brain via the vagus nerves evoke marked responses in, on average, 43% of superior collicular neurons. Both excitatory and inhibitory effects were observed. The latter were found more often during single stimulation of the vagus nerve. In half of the cases the inhibitory responses were characterized by the development of initial inhibition, clearly limited in time to between 180 and 1700 msec. Changes in spike activity of 60% of units were tonic in character. The onset of phasic responses with an initial period of activation was observed in only 9–11% of neurons. The number of these cells and also the total number of responding neurons were greater than when series of stimuli were applied to the vagus nerve. In individual cells during prolonged repetitive stimulation of the nerve gradual weakening of the responses took place. Somatic stimulation evoked mainly the development of phasic responses of excitatory type. Most of the neurons tested were bimodal and often the temporal structure of their responses was determined by the modality of the stimulus applied. The functional role of the changes discovered in spontaneous activity of superior collicular neurons under interoceptive influences and the central mechanisms of realization of such influences on the activity of the neuronal system in this brain structure are discussed.Ivano-Frankovsk Medical Institute, Ministry of Health of the Ukrainian SSR. Translated from Neirofiziologiya, Vol. 10, No. 6, pp. 590–596, November–December, 1978.