Chronic experiments performed on 32 Sprague-Dawley rats using a movement-feeding operant reflex (Skinner box) model showed that microinjection of scopolamine into the neostriatum had effects on this reflex which depended on the stage of learning. In animals with weakly fixed reflexes (prior to reaching the stage of memory consolidation), bilateral microinjection of 0.3 microgram of scopolamine into the caudate nucleus completely inhibited the reflex for a prolonged period of time. When the operant habit was well fixed, bilateral microinjection of the same doses of scopolamine into the neostriatum had no effect on the reflex. These results suggest that the neostriatum cholinergic system is critically involved in forming the motor engram. The cholinergic system of the caudate nucleus either takes no part in realizing the well-fixed conditioned reflex movement response and/or other forebrain structures are involved in the reflex, compensating for the disturbance in neostriatal cholinergic function.
A discrimination conditioned active avoidance reflex (CAAR) model in a T maze was used in 18 rats to study the effects of bilateral microinjections of the selective muscarinic M1 receptor blocker pirenzepine into the neostriatum on the acquisition of the CAAR and behavior in an open field test. There was sharp degradation of learning of the CAAR and a significant improvement in motor activity both in the open field test and in the maze itself in rats given bilateral microinjections (pirenzepine, 0.004 mg) into the neostriatum as compared with intact controls. This suggests that changes in motor behavior (a sharp increase in locomotor activity) may be among the reasons for difficulty in learning the CAAR in rats after pirenzepine microinjections. Another reason for difficulty in learning the CAAR in these animals may be impairment of the perception of the conditioned signals (a flashing light) and poor differentiation. This is particularly indicated by the delay in the start chamber (double that seen in intact animals) on presentation of conditioned signals despite the high level of motor activity. These results and published data provide evidence for the complex nature of changes induced by blockade of muscarinic M1 receptors in the neostriatum.
Data have been obtained in chronic experiments on 34 dogs, based on an instrumental defense reflex model associated with the maintenance of a specific posture, which suggest that activation of the cholinergic system of the neostriatum leads to a large number of changes in both the sensory and the motor spheres. The influences on motor behavior, observed mainly through effects on the cholinergic system of the contralateral caudate nucleus, reside in the intensification of the tonic constituent of movement, in inhibition of the phasic component of movement, and restriction of locomotor activity, all the way up to complete shutdown. The influences on sensory mechanisms, observed both through ipsi- and contralateral effects on the cholinergic system of the neostriatum, reside in an improvement of the differentiation of significant signals and are evidently through inhibition of the nonspecific afferent stream. Data are presented on the important role of the cholinoreactive systems of the CM-Pf complex of the thalamus in the intensification of the cholinergic activity of the neostriatum.
Studies were carried out into the role of the parafascicular (Pf) nuclei of the rat thalamus in learning a conditioned active escape reflex (CAER) in a T-maze, a reflex associated with discrimination of visual stimuli, and into the regulatory effect on this learning process of activation of the neostriatal cholinergic system. The following results were obtained using 57 Sprague-Dawley rats divided into a number of experimental groups: 1) bilateral microinjection of carbacholine (0.03 microgram) into the neostriatum on days 4, 5, and 6 of training produced significant (p < 0.01) increases in the proportion of correct discriminant CAER performances; 2) bilateral lesioning of the Pf nuclei led to irreversible disruption of the previously learned CAER. Rats with initially bilaterally lesioned Pf nuclei did not learn the discriminant CAER at all after 10 days of training (16 combinations), and microinjection of carbacholine into the neostriatum of these animals was ineffective. It is concluded that the integrity of the afferent input into the Pf nuclei of the thalamus is an important factor for activation of the neuronal background of the neostriatum, and is required for cholinergic activation of the neostriatum to be effective.
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