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.     

Participation of frontal lobe neurons in the organization of successive inhibition and disinhibition of conditioned reflexes in the dog

Neuronal activity in g. proreus was studied during classical secretory conditioning and its differentiation in dogs. Three types of changes in neuronal reaction pattern were identified during differential conditioned stimulus compared to the pattern observed during positive conditioned stimulus. It has been shown that signal significance of the conditioned stimulus may be coded by specific distribution of interspike intervals in response to different conditioned stimuli. In situation of successive inhibition or disinhibition of the differentiation some neurones displayed simultaneous appearance of interspike intervals specific for responses to current and previously presented conditioned stimuli.     

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.     

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.     

Neurons of the rabbit midbrain reticular formation during a defensive conditioned reflex]

Analysis of unit activity of the midbrain reticular formation was carried out on alert rabbits during defensive conditioning. Most of the examined neurones exhibited phasic responses corresponding in time to the components of the evoked potential (EP) recorded in the cortical visual area in response to the "indifferent" stimulus, and to the conditioned stimulus and electric cutaneous reinforcement. The data obtained are considered from the standpoint of the Anokhin functional systems theory. A conclusion has been made regarding the participation of reticular units in providing all the basic mechanisms of the functional system of the behavioral act. Discharges of one and the same neurone may correspond to different components of the EPs to conditioned and unconditioned stimuli. In different behavioral acts a neurone may apparently participate in different systemic mechanisms.     

Changes in the configuration of conditioned reactions of visual cortex neurons during changes in reinforcement parameters]

In order to study the influences of controlled changes of defensive integration on the activity of visual cortical units their responses to a conditioned light flash and electric cutaneous stimulation with a 600 msec interval between them were recorded in experiments on alert rabbits. It has been shown that in a third of the neurones the types of reaction to light flashes and electric stimuli coincide. The changes in parameters of the reinforcing shock led to a changed response of most cells to the conditioned photic stimulus and electric stimulation. The changes may have affected units which produce any activation phase, including cells with activity characteristic of detectory ("simple" and "complex") visual neurones. The data obtained suggest that the special function of the visual cortex is used in different ways in systemic mechanisms of conditioned and unconditioned defensive acts and that the integrated system of a behavioral act exerts control both on the use of the unit in a certain systemic process and on its receptive field.     

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.     

Activity of neurons of the motor zone of the cortex during elaboration of a local instrumental defensive reflex in the rabbit

During instrumental defensive reaction of wrist extension in response to a sound (conditioned) stimulus, two types of neuronal responses in the rabbit motor cortex were discovered. The first type was recorded in cells with activity not connected with electromyographic activity of wrist extensors. The reaction consisted in the appearance of inhibitory response at the place of the cancelled electrocutaneous stimulation at animal's performance of conditioned reaction to sound. The second type of responses was shown for a neurone with the activity significantly related to electromyographic activity. In this case the conditioned motor response was accompanied by enhancement of the cellular activation reaction to sound and the increase of spike activity in interstimuli intervals.     

Hippocampal State-Dependent Behavioral Reflex to an Identical Sensory Input in Rats

We examined the local field potential of the hippocampus to monitor brain states during a conditional discrimination task, in order to elucidate the relationship between ongoing brain states and a conditioned motor reflex. Five 10-week-old Wistar/ST male rats underwent a serial feature positive conditional discrimination task in eyeblink conditioning using a preceding light stimulus as a conditional cue for reinforced trials. In this task, a 2-s light stimulus signaled that the following 350-ms tone (conditioned stimulus) was reinforced with a co-terminating 100-ms periorbital electrical shock. The interval between the end of conditional cue and the onset of the conditioned stimulus was 4±1 s. The conditioned stimulus was not reinforced when the light was not presented. Animals successfully utilized the light stimulus as a conditional cue to drive differential responses to the identical conditioned stimulus. We found that presentation of the conditional cue elicited hippocampal theta oscillations, which persisted during the interval of conditional cue and the conditioned stimulus. Moreover, expression of the conditioned response to the tone (conditioned stimulus) was correlated with the appearance of theta oscillations immediately before the conditioned stimulus. These data support hippocampal involvement in the network underlying a conditional discrimination task in eyeblink conditioning. They also suggest that the preceding hippocampal activity can determine information processing of the tone stimulus in the cerebellum and its associated circuits.     

Activity of neurons in the pedunculopontine nucleus in conditioned instrumental appetitive reflex

Activity of 91 neurons in the compact and diffuse parts of the pedunculopontine tegmental nucleus (PPTg) was recorded in freely moving rabbits during execution of instrumental appetitive conditioning. Of the recorded neurons, 37.4% changed their activity in response to a conditioned stimulus, which is the evidence for the PPTg involvement in instrumental conditioning. Excitatory conditioned neuronal responses to the conditioned stimulus and food reinforcement significantly prevailed over inhibitory reactions. Neuronal responses to the conditioned stimulus were classified in several basic patterns reflecting stimulus effects, structure of the behavioral act, and reinforcement properties. These reactions indicate the involvement of the PPTg in attention, motor learning, and reinforcement. The revealed differences in associative reactive properties of the compact and diffuse parts of the PPTg to the conditioned stimulus and reinforcement point to the functional heterogeneity of this structure and suggest the leading role of the cholinergic part of the PPTg in instrumental appetitive conditioning and reinforcement as well as the essential contribution of the diffuse part into classical appetitive conditioning.     

Directional Theta Coherence in Prefrontal Cortical to Amygdalo-Hippocampal Pathways Signals Fear Extinction

Theta oscillations are considered crucial mechanisms in neuronal communication across brain areas, required for consolidation and retrieval of fear memories. One form of inhibitory learning allowing adaptive control of fear memory is extinction, a deficit of which leads to maladaptive fear expression potentially leading to anxiety disorders. Behavioral responses after extinction training are thought to reflect a balance of recall from extinction memory and initial fear memory traces. Therefore, we hypothesized that the initial fear memory circuits impact behavioral fear after extinction, and more specifically, that the dynamics of theta synchrony in these pathways signal the individual fear response. Simultaneous multi-channel local field and unit recordings were obtained from the infralimbic prefrontal cortex, the hippocampal CA1 and the lateral amygdala in mice. Data revealed that the pattern of theta coherence and directionality within and across regions correlated with individual behavioral responses. Upon conditioned freezing, units were phase-locked to synchronized theta oscillations in these pathways, characterizing states of fear memory retrieval. When the conditioned stimulus evoked no fear during extinction recall, theta interactions were directional with prefrontal cortical spike firing leading hippocampal and amygdalar theta oscillations. These results indicate that the directional dynamics of theta-entrained activity across these areas guide changes in appraisal of threatening stimuli during fear memory and extinction retrieval. Given that exposure therapy involves procedures and pathways similar to those during extinction of conditioned fear, one therapeutical extension might be useful that imposes artificial theta activity to prefrontal cortical-amygdalo-hippocampal pathways that mimics the directionality signaling successful extinction recall.     

Reversal of signal significance of stimuli in the avoidance reflex]

The course of reversal learning in go -- no go avoidance reflex differentiation in both cats and dogs was analysed in terms of interrelations between drive and instrumental reflex activity. When signalling properties of the conditioned stimuli were reversed, marked changes in the drive state of experimental animals occurred. The increase of the fear drive influenced both the transfer of the instrumental response to the new positive conditioned stimulus and the extinction of the response to the previously positive stimulus. The quality of the conditioned stimuli and their reflexogenic strength exerted clear effects on the fear drive and on the course of reversal learning. Prefrontal lesions affected the drive state and the conditioned reflex activity of the animals during the reversal learning.     

Neuronal activity of the cerebral cortex in cats with conditioned inhibition

Unit activity of the somatosensory cortex was studied in chronic experiments on cats during alimentary instrumental conditioned reflex performance and elaboration of conditioned inhibition (CI). First presentations of the CI signal at the beginning of CI formation caused, due to orienting reaction to a new stimulus, a levelling of the response of the neurones to the positive conditioned signal included into the CI complex. At the stage of consolidated CI, this depression proceeded gradually during the development of conditioned inhibition caused by consecutive presentations of the nonreinforced CI combination. Two groups of neurones were involved in the process of the CI performance: one of them being the same which was activated also in response to positive stimulation during performance of the conditioned response, and the second one being areactive to the positive conditioned stimulus but reducing the frequency of the background activity.     

Role of conditioned reinforcers in the initiation, maintenance and extinction of drug-seeking behavior.

The development of a secondary reinforcer as a result of associating a neutral stimulus (buzzer) with intravenous (IV) doses of morpine was studied in rats. Secondary reinforcement developed in the absence of physical dependence and followed the association of the stimulus with either response-contingent or non-contingent injections of morphine. Strength of the conditioned reinforcer, measured in terms of responding on a lever for the stimulus plus infusion of saline solution, was proportional to the unit dosage of morphine employed in pairings of buzzer and drug. When extinction of the lever-press response for IV morphine was conducted (by substituting saline for morphine solution) in the absence of the conditioned reinforcing stimulus, it was seen later that the stimulus could still elicit lever responses, until it too had been present for a sufficient interval of non-reinforced responding. Similarly, extinction of the response for morphine by blocking its action with naloxone in the absence of the stimulus did not eliminate the conditioned reinforcement. Another study showed that a passive, subcutaneous (SC) dose of morphine served to maintain lever-pressing on a contingency of buzzer plus saline infusion. Furthermore, the stimuli resulting from the presence of morphine (after a SC injection) were able to reinstate the lever-responding with only the buzzer-saline contingency when such responses had previously been extinguished. Moreover, it was shown that d-amphetamine could restore responding under the same conditions, and that morphine could also do so for rats in which the primary reinforcer had been d-amphetamine. It is suggested that animal data such as these show that procedures designed for the elimination of human drug-taking behavior must take into account secondary reinforcers as well as the primary reinforcer(s).     

Efferent activity in theOctopus statocyst nerves

Summary Single unit electrophysiological recordings were obtained from efferent fibres in the statocyst nerves ofOctopus vulgaris. A preparation comprising the CNS and a single statocyst was employed. 42% of the efferents displayed a level of resting activity; transient changes in this activity occurred at irregular intervals.The responses of the efferent units were examined during sinusoidal oscillations of the statocyst at stimulus frequencies between 0.01–1 Hz, and amplitudes up to 35°. 84% of the units showed activity synchronised with the imposed oscillations; the time taken to establish this response varied for different units (Fig. 1).The lowest stimulus frequency at which a unit could be entrained varied for different units, with those units with a resting level of activity having the lowest thresholds. The peak firing frequency of the efferents was found to increase with increasing stimulus frequency or amplitude (Fig. 3). However, the change in firing frequency was much smaller than that reported for the statocyst afferents to similar stimuli.The efferent units of the posterior crista nerve were found to respond to clockwise or anticlockwise rotations (Fig. 4), with the individual units having unipolar responses. The phase response of the units changed little with increasing stimulus amplitude but an increase in phase lag occurred with an increase in the stimulus frequency (Fig. 5). The form of this relationship (Fig. 6) was similar to that reported for the statocyst crista afferents.The principal source of the input to the efferents in these experiments was shown to be afferents from the contralateral statocyst. These results are discussed and compared with data from the vertebrate semicircular canal system.     

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.     

Dynamics of the spectral composition of the hippocampal theta-rhythm in the dog during switching-over of heterogeneous instrumental reflexes

In two dogs with electrodes chronically implanted in the hippocampus, hippocampal electrical activity and the heart rate were recorded in the process of elaboration of a conditioned switch-over of operant alimentary and defensive responses. Averaged computerized spectral characteristics of hippocampal theta-rhythm were essentially different between the alimentary and defensive situations in intersignal period as well as during the action of triggering conditioned stimulus. Individual differences in the dominant frequency of bioelectrical activity were observed. The animal with a higher theta-rhythm frequency elaborated conditioned switch-over of heterogeneous operant responses sooner and more successfully.     

A glimpse of the brain transforming a sensory signal into a motor response

Averages were made of neuronal spike activity recorded successively from eight relay regions along the auditorimotor pathway of naive cats and cats conditioned to blink in response to a 70 dB click conditioned stimulus (CS). It was hypothesized that the patterns of activity could be distinguished as sensory or motor by differences in their relationship to the pattern of the acoustic CS vs that of the conditioned response (CR). If so, it was also hypothesized that the acoustic stimulus would be better expressed at early auditorimotor relays and the motor response at later relays along the pathway. To test these hypotheses, Pearson correlation coefficients were calculated between the mean patterns of unit activity at each of the auditorimotor relays and (1) the rectified sound pattern of the CS and (2) the averaged, rectified electromyographic (EMG) activity of the muscles (orbicularis oculis) that produced the CR. In both naive and conditioned cats, there were significant positive correlations between the patterns of spike activity and the sound at early relays along the auditorimotor pathway such as the cochlear nucleus and inferior colliculus. In the conditioned animals, the spike activity of later nuclei in the auditorimotor pathway, such as the rostral thalamus and the motor cortex, had the highest positive correlations with the motor response. These correlations were low in the naive animals. Thus, the mean patterns of spike activity along the auditorimotor pathway appeared to distinguish the sound from the motor response and provided a glimpse of the process supporting transformation of the CS into the incipient CR.     

A glimpse of the brain transforming a sensory signal into a motor response

Averages were made of neuronal spike activity recorded successively from eight relay regions along the auditorimotor pathway of naive cats and cats conditioned to blink in response to a 70 dB click conditioned stimulus (CS). It was hypothesized that the patterns of activity could be distinguished as sensory or motor by differences in their relationship to the pattern of the acoustic CS vs that of the conditioned response (CR). If so, it was also hypothesized that the acoustic stimulus would be better expressed at early auditorimotor relays and the motor response at later relays along the pathway. To test these hypotheses, Pearson correlation coefficients were calculated between the mean patterns of unit activity at each of the auditorimotor relays and (1) the rectified sound pattern of the CS and (2) the averaged, rectified electromyographic (EMG) activity of the muscles (orbicularis oculis) that produced the CR. In both naive and conditioned cats, there were significant positive correlations between the patterns of spike activity and the sound at early relays along the auditorimotor pathway such as the cochlear nucleus and inferior colliculus. In the conditioned animals, the spike activity of later nuclei in the auditorimotor pathway, such as the rostral thalamus and the motor cortex, had the highest positive correlations with the motor response. These correlations were low in the naive animals. Thus, the mean patterns of spike activity along the auditorimotor pathway appeared to distinguish the sound from the motor response and provided a glimpse of the process supporting transformation of the CS into the incipient CR.     

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.