The mechanism of action of a reinforcing stimulus]

Experiments on alert non-immobilized rabbits revealed that electrical cutaneous stimulation of a limb, used as a reinforcing agent in elaboration of a conditioned reflex to photic flashes, weakened slow polyrhythmic oscillations of background EEG and late components of evoked potentials in the visual cortex to photic flashes. Against this background, the connection between slow potentials and spike activity in both the visual and sensorimotor cortical areas considerably diminished. During EEG activation, induced by the reinforcing stimulus, inhibitory pauses and post-inhibitory activation in the firing of the neocortical units weakened and protracted, ordered spike activity appeared. The data obtained are in agreement with the hypothesis that weakening of the recurrent inhibition system is one of the basic mechanisms in the action of the reinforcing stimulus in conditioning.     

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.     

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.     

Evoked potentials during the elaboration of a conditioned reflex to hippocampal stimulation in rats

In experiments on 9 rats, the study of evoked potentials (EPs) of the CA1 field of the dorsal hippocampus to stimulation of its symmetrical part serving as a signal of drinking conditioned reflex (CR) showed that during reflex elaboration, the amplitude of the main EP components significantly decreased; CR did not appear when the population spike (PS) was absent in the hippocampal response. PS always accompanying CR was not specific only of it, it was also recorded at other behavioural reactions. Changes of fascia dentata EPs in the process of CR elaboration to stimulation of its symmetrical part consisted in decrease of the initial negative wave and increase of the positive one. The obtained data point to a significant reconstruction of excitatory and inhibitory inputs to the hippocampus and fascia dentata under the influence of conditioned activity.     

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.     

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.     

Effect of the enkephalin derivative DAGO on neuronal behavior and activity in the neocortex and hippocampus of rabbits during the acquisition of conditioned defense and inhibitory reflexes

After subcutaneous injection of 25 mkg/kg morphine-like opiate--DAGO a decrease was observed of probabilities of rabbits movements at light flashes--defensive reflex signal. The level of the background neuronal impulse activity became gradually lower in the sensorimotor cortex and the hippocampus and did not change in the visual cortex. Decrease and restoration of responses to the reinforcing stimulus (electrocutaneous limb stimulation) in all studied cortical zones proceeded in one direction while there were significant differences in dynamics of responses to inhibitory and reinforced light flashes depending on the studied cortical zone and biological significance of the stimulus. Appearance is discussed of particular characteristics of neurones systemic organization during learning at change of reinforcement properties under the influence of the studied substance, as well as similarity of some features of mechanisms of internal inhibition elaboration in a defensive situation and of properties of positive reinforcement.     

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.     

The dependence of the neuronal reactions of the sensorimotor cortex to a simultaneous complex stimulus on the level of the differentiation of its components]

On alert animals the change was studied of the neuronal activity of the sensorimotor cortical area of cats brain in dependence on the level of differentiation of the components of simultaneous heteromodal complex stimulus. According to the character of this dependence and a number of other parameters two groups of neurones were singled out in the sensorimotor cortex. It was shown that parameters of reactions of all recorded neurones of the sensorimotor cortex to the positive conditioned signal were the first established after consolidation of the animal conditioned motor activity. In the course of elaboration following parameters changed: expressiveness, intensity, duration and value of latency. Reactions of neurones of both groups to the inhibitory stimuli were stabilized only after consolidation of the habit of differentiation. Responses of the first group neurones changed only by the pattern of discharge, while the responses of the second group neurones could change by expressiveness of response, its sign, duration and value of latency. Oscillations of the differentiation level after finishing of the elaboration of inhibitory conditioned reactions affected only the responses of the second group neurones to complex components.     

Effects of selective blockade of synaptic transmission in the parafascicular complex on activity of sensorimotor cortex neurons

Neuronal firing activity pattern in the sensorimotor complex and conditioned reflexes produced by blockade of noradrenergic and serotoninergic input to the parafascicular complex (CM-PF) were investigated during chronic experiments on cats in which lever-pressing reflex had previously been set up. Micro-injection of obsidan, a beta-adrenergic blocker and lysergide, a serotonin blocker, were found to produce intensification and inhibition, respectively, of neuronal spontaneous firing activity in the sensorimotor cortex, with both blockers having a similar (inhibitory) effect on neuronal response induced by conditioned acoustic stimuli. Blockade of monoaminergic inputs to the CM-PF temporarily suppressed execution of the conditioned reflex and the non-conditioned reflex of lever-pressing (for 30–60 min). The study concludes that the pattern of effect produced by the monoaminergic system on the sensorimotor cortex is largely determined by indirect as well as direct agents and that such effects are mediated by neurons belonging to the CM-PF complex of the thalamic nuclei.A. A. Bogomolets Institute of Physiology, Academy of Sciences of the Ukrainian SSR, Kiev. Translated from Neirofiziologiya, Vol. 22, No. 3, pp. 327–336, May–June, 1990.     

Dynamics of caudate nucleus involvement in the process of internal inhibition of the food-getting reflex]

Changes of slow spindle electrical activity (12 to 14 cps) and evoked potentials in the cat caudate nuclei and the motor cortex were studied at different stages of elaboration of differentiation inhibition of a conditioned food-procuring reflex to acoustic stimuli. It has been shown that participation of the caudate nuclei in the inhibitory process begins at the stage of enhancement of food-procuring activity (second stage) and is apparently due to the animal's strong alimentary motivational excitation. At the third stage the inhibitory influence of caudate nuclei on the animal's motor activity in general, and the activity of the motor cortex in particular, develops to the full.     

Effects of food motivation on spike activity of cat somatic cortex neurons

Spike response to unconditioned electrocutaneous stimulation was investigated in cortical neurons of areas 3 and 4 in untrained hungry cats during heightened excitation motivated by food presentation and when at rest. This reinforcement led to changed background activity level, reduced intensity of the initial stages of spike response, and disappearance of late neuronal response. Neuronal response of the same cortical area to a conditioned stimulus (a clicking sound) during reduced food motivation (the animals being sated during the course of the experiment) was also studied under the effects of instrumental feeding reflex. Coordination between the timing of neuronal response and their corresponding movements was discovered from comparing response pattern accompanying the execution of paw-placing (conditioned reflex and intersignal) movements and those recorded at different levels of food-induced excitation, as well as a similarity between these reactions. It was found that the initial stages of neuronal response to a conditioned signal only occurred during contraction of the brachial biceps muscle, while coordination between their timing and that of EMG changes was dependent on the animal's degree of satiation. Findings indicate the possibility of food-induced excitation substantially influencing spike response pattern in somatic cortex neurons.A. A. Bogomolets Institute of Physiology, Academy of Sciences of the Ukrainian SSR, Kiev. Translated from Neirofiziologiya, Vol. 19, No. 6, pp. 725–735, November–December, 1987.     

Effect of substance P on behavior in the rabbit and the activity of cortical neurons during training

Subcutaneous injection of substance P to rabbits in a dose of 250 mcg/kg elicited a transitory disappearance of motor reactions to painful reinforcing stimuli and a reduction of their probability to reinforced and inhibitory light flashes, as well as a protracted heart rate increase and decrease of respiration rate. One third of the neurones recorded decreased their background firing level and or excitatory components of the reactions to reinforcement and conditioned light flashes. The decrease was most distinctly seen in the sensorimotor cortex and less pronounced in the visual cortical area and hippocampus. The influence of the substance P on different types of cortical inhibition was not the same. Tonic inhibition of neuronal activity in response to reinforcement was enhanced. Bioelectrical parameters which reflect an enhancement of inhibitory hyperpolarization during elaboration of internal inhibition (i.e. inhibitory firing delays and corresponding background and evoked slow potentials oscillations) were not changed.     

Characteristics of cortical responses to electrostimulation of the internal geniculate body during formation of a defensive conditioned reflex]

During elaboration of a classical defensive conditioned reflex the dogs exhibited a dependence of the changes in amplitude and configuration of evoked potentials (EP) to electrical stimulation of the medial geniculate body (MGB), a conditioned stimulus, on the nature of effector manifestation of the conditioned reflex: the late components were the most depressed at multiple phasic reactions and not infrequently increased and became complicated at single and short motor reactions as well as at their incidental absence. The primary oscillations, while mostly remaining unchanged, were depressed in the case of conditioned reactions attended with a general motor restlessness. A difference has been revealed during conditioning in the EP changes to electrical stimulation of MGB and to an adequate peripheral stimulation. It has been assumed that EP changes during conditioned activity are determined by the relationship between the levels of tonic and phasic cortical activation.     

Effect of GABA on a temporary connection in a neuronal population of the sensorimotor cortex in rabbits

Evoked activity of sensorimotor cortical neurones in response to stimulation of the pyramidal tract, medial lemniscus and reticular nucleus of the midbrain tegmentum; driving reaction of cortical neurones at stimulation of these brain structures of growing frequency, and conditioned reflexes elaborated by combination of direct stimulation of the sensorimotor cortex and electrocutaneous stimulation were studied in awake nonimmobilized rabbits. Application to the cortex of GABA solutions of low concentration (less than or equal to 1%) emphasizes the evoked neuronal responses, facilitates the appearance of driving reaction and contributes to the manifestation of the temporary connection. Application of GABA solutions of higher concentration (greater than 2%) leads to opposite effects. Positive correlation is found between electrical and behavioural phenomena. The described experimental approach may be used for analysis of various types of influences on temporary connection formation.     

The modulation of the pulse activity of neocortical neurons during a conditioned reflex]

Spontaneous and evoked activity of neurons in the sensorimotor cortex was recorded in cats with learned conditioned placing reaction before, during, and after the iontophoretic application of synaptically active substances. It was shown that apart from direct excitatory effect on the cortical neurons during its application, glutamate (Glu) exerted some modulatory influence on unit activity in subsequent 20 min. Noradrenaline suppressed the background and evoked activity through beta 1 adrenoreceptors. Activation of beta 2 adrenoreceptors by metaproterenol was accompanied by facilitation of the background and evoked activity during application and 10-20 min after. The joint application of Glu and metaproterenol improved facilitation of neuronal responses evoked by conditioned stimuli. Application of levodopa, like Glu, increased the background and evoked activity of many sensorimotor cortical neurons. The joint effect of Glu and levodopa was not substantially more intensive than the changes produced by the isolated application of any of these substances. A nonselective blocker of DA1 and DA2 receptors haloperidol either increased or did not change the background and evoked activity of some cortical neurons. In contrast to isolated application of Glu, simultaneous application of Glu and haloperidol to neocortex suppressed the neuronal responses associated with conditioned movements. The results suggest that the Glu-induced potentiation is substantially realized through molecular mechanisms common for Glu and dopamine, probably, through Gi-proteins. The conclusion is drawn that the adrenergic and dopaminergic inputs to neocortical neurons are involved in the Glu-mediated plastic changes in the cortex during conditioning.     

Neurophysiological analysis of efferent-afferent interaction of neurons of the parietal associate cortex in cats

Neuronal responses of the parietal associate cortex (field 5) was recorded in waking cat during electrical stimulation of the pyramidal tract axons and afferent stimulation. The electrical stimulation of the pyramid evoked marked responses in 39% of neurons. 87% of these neurons increased spike activity during sematic nociceptive stimulation, 61% of test neurons were activated by light or tonal stimulation. Neuronal activity was recorded during defensive conditioning to the pyramidal tract axons stimulation. It has been shown that conditioned stimulation of the pyramidal tract evoked plastic changes of responses in 66% of neurons of the parietal cortex. These data are discussed relative to the possible functional role of the efferent-afferent interaction to field 5.     

Electroencephalographic studies on classically conditioned defensive reflex and avoidance lever-pressing in the dog (author's transl)]

Six dogs with implanted cortical and subcortical electrodes were trained to press a lever to avoid electroshock to a hind leg. Intracerebral stimulation at low frequency was delivered as an "indifferent" or a "CD" tracer. Changes of EEG responses to the tracers prior to the voluntary lever-pressing or the conditioned avoidance lever-pressing were prior to the voluntary lever-pressing or the conditioned avoidance lever-pressing were examined by continuous frequency analysis. (1) Evoked potentials to the tracer stimulation were changed just before the conditioned defensive reflex, the voluntary lever-pressing and the conditioned avoidance lever-pressing, regardless of the site of the tracer stimulation. (2) The cortical and subcortical structures (Hippo, RF) seemed to be involved in the neural circuit responsible for the avoidance lever-pressing, whereas the sensorimotor cortex may be essential in the circuit for the alimentary lever-pressing. (3) The avoidance lever-pressing and the EEG response to the "CS" tracer were influenced by the internal inhibition (experimental extinction, inhibitory mechanism was discussed.     

The disinhibitory influence of the activating system when artificially excited from different points in the brain]

EEG activation can be produced by electrical stimulation of some cortical points with the same threshold current strength as by the midbrain RF and thalamic CM stimulation. Near-threshold stimulation of all these points acting simultaneously with inhibitory conditioned signals does not disturb the effector inhibition but displays an EEG difference between negative signals: the fine differentiation sound evokes considerable EEG desynchronization, while the rough one does not change the background rhythms. The same stimulation combined with a positive signal which has been made ineffective by successive inhibition or extinction, reestablishes the intensive EEG activation in response to this signal and the effector conditioned reflex. Therefore a mode-rate additional stimulation of the activating points in the cortex, RF and CM has a disinhibitory influence. When initiated in the cortex this influence may be transmitted from the cortical point to other parts of the brain along transcortical and corticofugal connections.     

Dynamics of the activity of rabbit visual cortex neurons during elaboration of elementary conditioned reflexes to time and association

Elaboration of a reflex to time (with omissions of stimuli) and of association; light--light + electrocutaneous stimulation of the paw was studied on neurones of the rabbit visual cortex. It was shown that by similarity of patterns of the discharge to a conditioned stimulus and to reinforcement, 83% of neurones reveal the formation of a reflex to time, and 57%--elaboration of association. Three ways of coding plastic reorganizations of the neuronal discharges are suggested; by the total number of spikes in the response, by the total sum of inhibitory periods, and by the pattern of the response. It has been found that in the reflex to time the early components of the response to the stimulus are reproduced during omissions; in elaboration of the association the late components of the discharge reaction to reinforcement are mainly repeated. Most cells with plastic reorganizations possessed polysensority and revealed discharge sensitization during habituation.