Effects of the cholinergic system of the rat neostriatum on learning active escape in normal animals and in animals with lesions to the intralaminar thalamic nuclei.

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.

Role of the cholinergic system of the neostriatum in regulating several forms of defensive behavior.

Studies were carried out on the effects of microinjection of carbacholine, a choline receptor agonist, into the dorsal striatum on the discrimination of sensory signals in chronic experiments on dogs with an operant defensive reflex involving maintenance of a flexor pose and in rats trained to a conditioned active escape reflex (CAER) in a T-maze; the sensory signals involved were important in the behavioral situations used. Carbacholine microinjection improved the process of discrimination, with an increase in the number of correct responses in rats in the T-maze discrimination-requiring CAER, and with improvements in responses to differentiation stimuli in the operant defensive reflex requiring maintenance of a defined pose in dogs. The efficiency of the effect depended on the level of training. There were two situations in which responses did not improve: when there was no signal discrimination in background conditions before microinjection, and in conditions of complete differentiation of the signals, i.e., complete training. It would appear that the neostriatum is not involved in the behavioral reactions in either of these situations, and this may result primarily from low levels of neuronal activity in response to these signals.

Participation cholinergic systems of the dorsal and ventral striatum in the training of rats to avoidance in a T-maze.

Influence of activation of cholinergic systems of the dorsal (Caudate- Putamen) and ventral (Accumbens) striatum on the process of the training of rats to active avoidance in a T-maze was investigated in experiments on 60 male Sprague-Dawley rats. The results, obtained on one and the same behavioral model (active avoidance in a T-maze), suggest the presence of particular features of the participation of the cholinergic systems of the dorsal and ventral striatum in the regulation of motor behavior. Thus, a one-time administration of carbacholine (Cbch, 0.03 microgram) increases the level of correct responses on the first and succeeding days of the training of the rats to active avoidance, when microinjections are made into the right Accumbens, and also induces a significant increase in the level of correct realizations on the second and third days of training when microinjections are made in the left Accumbens, and at the same time, similar influences on the Caudate-Putamen do not induce any significant changes in the behavior of the animals during training in a T-maze. The changes in the locomotor activity according to collective data in the various groups of rats exhibited a generally complex character from experiment to experiment, the level of the locomotor activity of the animals decreased in the majority of cases, but microinjections of the substances did not alter the locomotor activity of the animals in any of the groups. However, the degree of change in the level of locomotor activity in the group of rats with microinjections into the Accumbens (in this investigation, the degree of increase) very markedly depended on the localization of the cannula. The greatest effect was obtained in the lateral segment of this nucleus; this confirms the functional heterogeneity of this fairly small nuclear structure.

Sensory and motoric components of various forms of learned movement with change in the activity of the cholinergic system of the neostriatum.

The participation of the cholinergic system of the neostriatum in the regulation of sensorily-monitored movements and the differentiation of sensory signals were investigated in 12 Wistar rats, 27 Sprague-Dawley rats, and 6 mongrel dogs, using the following models: 1) the maintenance of learned extension of the forelimb for a specified time (rats); 2) prolonged conditioned reflex flexion of the hind limb (dogs); and 3) active avoidance in a T-maze (rats). It was demonstrated that the injection of carbacholine (0.03 microgram) into the dorsolateral division of the caudate nucleus of the rats does not bring about significant changes in the performance of movements associated with the maintenance of tonus of the forelimb, whereas the injection of carbacholine (0.05-0.1 microgram) into the same division of the caudate nucleus of the dogs improves the realization of movement associated with the maintenance of tonus of the hind limbs. The injection of a blocker of the cholinergic system (scopolamine in the rats and atropine in the dogs) in both the first and the second instance disturbed the performance of the movement by the animals. Bilateral microinjections of carbacholine (0.03 microgram) into the neostriatum of the rats significantly improves the development of a differentiated active avoidance conditioned reflex in a T-maze on the first three days of testing. The differentiation of acoustic signals by dogs also significantly improved against the background of the injection of carbacholine (0.05-0.1 microgram) into the caudate nucleus. Thus, the data obtained in the various behavioral models and different animals suggest that the cholinergic system of the neostriatum participates in the regulation of both motor and sensory mechanisms in connection with the realization of learned movement.

[The characteristics of the effect of the rat neostriatal cholinergic system on normal active avoidance learning and in destruction of the intralaminar thalamic nuclei]. / Osobennosti vliianiia kholinergicheskoi sistemy neostriatuma krys na obuchenie aktivnomu izbeganiiu v norme i pri razrushenii intralaminarnykh iader talamusa.

The learning of discriminative avoidance reflex in T-maze was studied on 57 Sprague-Dawley rats (divided into several experimental groups) at the normal conditions, both after carbacholine (0.03 mkg), or scopolamine (0.3 mkg) microinjections into neostriatum bilaterally, after uni- or bilateral lesions of intralaminar thalamic nucleus (Pf) and after neostriatal microinjections followed Pf lesion. It has been shown that bilateral carbacholine microinjections in neostriatum (in 4, 5 and 6 days of learning) significantly increased (p < 0.01) the level of correct realizations of discriminative avoidance reflex. Bilateral lesion of Pf resulted in irreversible destruction of preliminary learned active avoidance movement. In rats with preliminary lesion of Pf nuclei we had no possibility of learn discriminative avoidance reflex during 10 experimental days (160 trials). The neostriatal carbacholine microinjections to these animals didn't show any effect. It was concluded that intact afferent input from Pf nucleus is significant for activation of neostriatal neuronal background, necessary for cholinergic activation effect.

[The characteristics of the participation of the neostriatal cholinergic system in regulating different forms of defensive behavior]. / Osobennosti uchastiia kholinergicheskoi sistemy neostriatuma v reguliatsii raznykh form oboronitel'nogo povedeniia.

The effects of microinjections of the cholinergic agonist (carbacholine) into the dorsal part of the neostriatum on discrimination processing of sensory signals were studied in chronic experiments in dogs (instrumental defensive reflex connected with maintenance of flexion posture) and in rats (active avoidance learning in T-maze). It was found that an improvement of discrimination process after carbacholine injections was manifested as an increase in the number of correct responses during acquisition of discriminative avoidance reflex in T-maze (rats) and during differentiation of sound signals in instrumental defensive reaction (dogs). The efficacy of this influences was suggested to be depend on the level of animal learning. We did not shown an improvement of the responses in two cases: 1. When before the microinjections the responses on the defensive and on the discriminative signals did not distinguish; 2. Under total differentiation of signals (e. g. under total learning). In both cases the neostriatum seems to be not involved in behavioral reaction what could be accompanied by low neuronal activity during the these signals action.

[The participation of the cholinergic systems of the dorsal and ventral striatum in the active avoidance learning of rats in a T maze]. / Uchastie kholinergicheskikh sistem dorzal'nogo i ventral'nogo striatuma v obuchenii krys aktivnomu izbeganiiu v T-obraznom labirinte.

Influence of cholinergic activation of dorsal (caudo-putamen) and ventral (accumbens) striatum on active avoidance learning was studied in chronic experiments in Sprague-Dawley male rats. The results obtained on the same behavioural model testify to specific roles of dorsal and ventral cholinergic systems in the control of motor behaviour. Single carbacholine microinjection into the right Accumbens increased the level of correct responses on the first and subsequent learning days. Similar microinjection into the left accumbens on the first training day improved the level of correct responses on the second and the third learning days. Microinjections into the dorsal striatum did not change active avoidance learning in T maze. Changes in locomotor activity of the animals of different experimental groups were principally of the same nature, i.e., the level of locomotor activity in the open field decreased from trial to trial in all the groups. Carbacholine microinjection did not change spontaneous locomotion in rats. However, there were variations in modifications of locomotor activity induced by microinjections into accumbens depending on localization of the cannula. Injection into the lateral accumbens induced the most pronounced changes. This fact testifies to the functional heterogeneity of this small nucleus.

[The sensory and motor components of different forms of learned movement during a change in the activity of the neostriatal cholinergic system]. / Sensornye i motornye komponenty raznykh form vyuchennogo dvizheniia pri izmenenii aktivnosti kholinergicheskoi sistemy neostriatuma.

The role of the neostriatal cholinergic system in the regulation of sensory controlled movements were studied using two behavioral models: 1) maintenance acquired extension of forelimb during proper time (rats) and 2) prolonged conditional flexion of hindlimb (dogs). It was found that injections of carbacholine (Car, 0.03 mkg) into the dorsolateral part of nucleus caudatus (NCd) of rats did not considerable change the movement connected with maintenance of forelimb tonus, while injections of Car (0.05-0.1 mkg) into the same area of the NCd of dogs were accompanied by improved performance of movement connected with maintenance of hindlimb tonus. It is possible to suggest the follows: 1. The neostriatal mechanisms of regulation of fore- and hindlimb tonus maintenance are different. 2. The neostriatal mediator of mechanisms of tonus regulation and regulation of somesthetic control of maintenance of this tonus are probably different too. Bilateral Car microinjections (0.03 mkg) into NCd of rats improved the discriminative active avoidance learning in T-maze. The discrimination of sound signals in dogs were also significantly improved after Car injections (0.05-0.1 mkg) into the NCd. Thus, data obtained at the different behavioral models and different animals suggest that cholinergic system of Neostriatum takes part in the regulation of both motor and sensory components of learned movements realization. The possible mechanisms of this regulation are discussed.

The features of the participation of the cholinergic mechanisms of the accumbens and caudate nuclei in the regulation of an instrumental defense reflex in dogs.

The influence of microinjections of carbacholine (0.1, 0.05, and 1.0 microgram) into the dorsal striatum (head of the caudate nucleus) and the ventral striatum (nucleus accumbens) on the motor components of the instrumental response and the criteria of execution of an instrumental task was studied in chronic experiments in eight dogs, based on a model of an instrumental defense reflex associated with the maintenance of a specific posture. The varied participation of the cholinoreactive structures of the caudate and accumbens nuclei in the regulation of the instrumental defense reflex was demonstrated in the dogs. Data were obtained indicating that the cholinoreactive system of the contralateral head of the caudate nucleus is structurally included in the regulation of the motor components of the instrumental response, of the main component of the reorganization of posture (the "disburdening" of the working extremity), and in the regulation of the tonic component of the voluntary movement and of its form. At the same time, the injection of carbacholine into the nucleus accumbens exerted, rather, a nonspecific activating influence on the motor systems. An improvement in attention to significant stimuli and the prolongation of the observed effects were also features of the activation of the cholinoreactive system of this nucleus. These changes took place in the case of both ipsi- and contralateral influences; this makes it possible to consider the inclusion mainly of sensory mechanisms in the realization of these influences.

The participation of cholinergic systems of the nucleus accumbens in the differentiation of acoustic signals in dogs.

The influence of microinjections of the choline agonist, (carbacholine 0.05-0.1 microgram), into the nucleus accumbens (Acc) of the right and left hemispheres on the realization of an instrumental defense reflex associated with the maintenance of a specific posture, and on the differentiation of acoustic signals in a defense situation, was studied in chronic experiments in five dogs. It was demonstrated that the injection of fairly small doses of carbacholine (CbCh) into the Acc of the left and right hemispheres improves the differentiation of acoustic signals in the defense situation. The introduction of fairly small doses of CbCh also improves the values of the criteria of the execution of the instrumental defense reaction associated with the maintenance of a specific posture. The changes observed are prolonged in character. Analysis of the motoric components of the instrumental responses made it possible to evaluate objectively the contribution of the motor and sensory mechanisms to those changes which were elicited by the microinjections of CbCh into the Acc, and to reach conclusion regarding an important role of the cholinergic system of the nucleus accumbens in sensory processes associated with the initiation and realization of instrumental responses to defense and differential signals, and especially in the regulation of attention to significant stimuli.

[The cholinoreactive system of the neostriatum and the active avoidance behavior of rats in a T maze]. / Kholinoreaktivnaia sistema neostriatuma i povedenie aktivnogo izbeganiia v T-obraznom labirinte u krys.

In experiments with 57 Sprague-Dawley male rats was studied the influence of single right- and left-side injections of different doses of choline agonist carbachol and choline blocker scopolamine into the dorsal part of the neostriatum (the head of the caudate nucleus) on active avoidance conditioning in a T-maze and on the locomotor activity. Non-adequately high carbachol doses disturbed the process of conditioning during the whole training period inducing no significant changes in locomotor activity of the rats. Microinjections of carbachol and scopolamine in small doses did not change the process of T-maze conditioning and also did not influence the dynamics and the level of locomotor activity of the experimental rats in comparison with the control ones.

[The characteristics of the cholinergic mechanisms of the nucleus accumbens and the caudate nucleus in regulating an instrumental escape reflex in dogs]. / Osobennosti uchastiia kholinergicheskikh mekhanizmov prilezhashchego i khvostatogo iader v reguliatsii instrumental'nogo oboronitel'nogo refleksa u sobak.

We perform comparative analysis of the involvement of dorsal (Neostriatum) and ventral (Nucleus Accumbens) striatal cholinergic systems in the regulation of defensive instrumental reflex, connected with the maintenance of certain flexor posture, in dogs. The data obtained show that the carbachol microinjections (0.05 mkg) into the contralateral Head of Caudate Nucleus significantly improved instrumental reflex due to increasing of a tonic movement component and inhibition of interstimulus and phasic leg raising. In was shown that the cholinergic system of Neostriatum was of great importance for the regulation of the main component of postural adjustment: the unloading of the working limb. The same microinjections into Nucleus Accumbens significantly improved (ipsi- and contralaterally) the instrumental reflex due to prolonged increasing of a phasic component of movement and its amplitude. It can be suggested that the Neostriatum cholinergic system is structurally included into the motor components realization of instrumental reflex, connected with a certain posture maintenance. The activation of cholinergic system of Nucleus Accumbens affects this form of behavior in an excitatory way, being of nonspecific and prolonged character.

[The participation of the cholinergic system of the nucleus accumbens in the differentiation of sound signals in dogs]. / Uchastie kholinergicheskoi sistemy prilezhashchego iadra v differentsirovanii zvukovykh signalov u sobak.

Chronic experiments were carried out on five dogs with a defensive instrumental reflex (IR) associated with the maintenance of the flexor posture. Was studied the influence of carbocholine bilateral microinjections (0.05-0.10 mcg) into the nucleus accumbens (NAC) on the realization of the IR and on the behavioural differentiation of acoustic signals in a defensive situation. Cholinergic system of the NAC was shown to participate in both the motor and sensory mechanisms connected with the realization of motor responses to defensive and differentiation signals. Activation of the cholinergic system of the NAC led to an "improvement" of behavioural signal differentiation probably due to an increase of attention to significant stimuli. The cholinergic system of the NAC participated in the regulation of voluntary movements. Its influence was mainly excitatory and had unspecific and prolonged character.

[The participation of the neostriatal cholinergic system in the differentiation of acoustic signals in dogs]. / Uchastie kholinergicheskoi sistemy neostriatuma v differentsirovanii zvukovykh signalov u sobak.

In chronic experiments on six dogs the influence was studied of micro-injections of choline agonist carbocholine (0.05-0.2 mkg) and of blocker of choline receptors atropine (40 mkg) in the caudate nucleus head of the left and right hemispheres on realization of instrumental defensive reflexes, connected with the maintenance of definite posture and on differentiation of signals in defensive situation. It has been shown that the cholinergic system of the neostriatum participated in realization of both the motor and sensory mechanisms in connection with the realization of motor responses to defensive and differentiation signals. Analysis of the obtained results also allowed to make a conclusion that the influence of carbocholine micro-injections into the neostriatum on differentiation depended on a number of factors: it did not take place when the signal was poorly distinguished (judging by the values of motor components to defensive and differentiation signals) or, on the other hand, against the background of stable differentiation reaction in other animals, i.e. in case of complete learning.