On neurotransmitter mechanisms of reinforcement and internal inhibition

Experiments reported in this study have been performed in order to investigate cholinergic and GABA-ergic neurotransmitter systems and substance P in the realization of internal inhibition and pain reinforcement. This was accomplished during the elaboration of inhibitory and defensive conditioned reflexes to light flashes in alert, nonimmobilized rabbits. Present results together with a review of past research indicate that the cholinergic system is directly involved in transmitting the effects of pain reinforcement to neocortical neurons. Substance P, a neuropeptide, reduces the background activity of neocortical and hippocampol neurons and the response of cortical neurons to pain and positive conditioned stimuli. The cholinergic system and substance P exert a modulating effect on the elaboration of internal inhibition. Phenybut, a GABA derivative capable of penetrating the blood-brain barrier, enhances inhibitory hyperpolarization in the cerebral cortex and improves discrimination between the inhibitory and reinforcing light flashes. It appears, therefore, that the GABA-ergic system plays a leading part in the elaboration of internal inhibition. Neuronal activity and slow potential changes in response to positive conditioned and pain stimuli occur in the same direction after administering the preparations, and the dynamics of these changes is different from that in responses to inhibitory stimuli. It may be supposed on these grounds that the neurotransmitter and neuromodulator systems studied possess a considerable degree of plasticity.     

The neurophysiological validation of the hyperpolarization theory of internal inhibition

The experiments in conscious non-immobilized rabbits showed that cessation of the reactions without reinforcement (elaboration of the internal inhibition) is accompanied by an enhanced phasic state, by alternation of activation and inhibition of neuron firing, and by the corresponding slow potential oscillation (SPO). These changes can be either localized, predominantly in the structures of conditioned stimulus, or, under enhancement of the inhibitory state, generalized in the brain structures. On the basis of our experience and published data, it is concluded that the above event results from relative enhancement of the inhibitory hyperpolarizing processes due to increase in reactivity of the inhibitory systems to stimulus, which acquires inhibitory properties during learning. Changes in the excitability and reactivity of neuron populations appearing during enhancement of the hyperpolarizing inhibition, and differing in the various brain structures, play an active role in the execution of the main function of the internal inhibition: limitation of excitation transmission to the effectors. An inhibitory mediator gamma aminobutyric acid (GABA) is of great importance in inhibiting the excitation in response to the stimulus which lost its biological significance. These experimental data and their interpretation in the light of published data give the basis for the development of the hyperpolarization theory of internal inhibition.     

Increased regularity of activity of cortical neurons in learning due to disinhibitory effect of reinforcement

This paper reviews the author’s studies on neurophysiologic mechanisms of conditioned reflex learning. Electroencephalograms, evoked potentials, activity of neocortical and hippocampal neurons and the rabbits’ behavior in the course of elaboration of defensive and inhibitory conditioned reflexes to light flashes have been recorded. Electric shock (ECS) applied to the paw served as reinforcement. The study demonstrated three types of reinforcement effect on the activity of cortical neurons: activating, disinhibitory, and inhibitory. EEG activation due to reinforcement is accompanied by a change in phasic cortical neuronal activity from chaotic or irregular, typical of rest or inhibition, to regular tonic discharges (in neocortex and hippocampus) and group discharges in the stress rhythm, 5–7 Hz in the hippocampus. Following a number of conditioning trials, the effect of reinforcement is simulated by the effect of a conditioned stimulus. With EEG activation and increased regularity in impulses, facilitation of motor reactions is observed.     

Neurophysiologic mechanisms of internal inhibition

The experimental results obtained in the authors’ laboratory as a result of multiple recording of slow biopotentials, the recording of neuronal activity and of mathematical modeling, are reviewed. The authors conclude that the elaboration of internal inhibition is followed, and determined to a great extent, by the restriction in conduction of excitations due to the increase of inhibitory hyperpolarization and discordance in the periodicity of slow potentials, reflecting oscillations in excitability of neuronal populations in the cortex and other brain structures.