Striatal transplants prevent AF64A-induced retention deficits.

The relevance of the cholinergic system in mnemonic processes has been repeatedly demonstrated. In addition to the cholinergic systems that project to the telencephalon, there are subcortical nuclei with intrinsic cholinergic cells which appear to be involved in memory consolidation; among these is the striatum. Intrastriatal administration of anticholinergic drugs, as well as excitotoxic and electrolytic lesions have been shown to disrupt the acquisition and retention of instrumentally conditioned behaviors. In the present study male Wistar rats were used to confirm the reported detrimental effects of striatal lesions produced by the cholinotoxin AF64A on long-term retention (LTR) of inhibitory avoidance and spontaneous locomotor activity, to determine its effects on short-term retention (STR) and to investigate whether intrastriatal homotopic transplants can reverse the AF64A-induced behavioral deficits. AF64A-striatal lesions did not interfere with STR but disrupted LTR of the inhibitory avoidance task, and striatal transplants prevented this deficit. Spontaneous locomotor activity increased after the lesion but promptly returned to baseline levels. These results support previous findings showing striatal involvement in long-term but not short-term retention and indicate that homotopic transplants induce behavioral recovery of a learning task in striatal lesioned rats.

Effects of regional GABAergic blockade of the striatum on memory consolidation.

The prediction was made that blocking the action of gamma-aminobutyric acid (GABA) in different regions of the striatum, through local injection of picrotoxin, would produce differential amnestic effects. Rats were trained in an inhibitory avoidance task, and a retention test was carried out 24 h later. Posttraining injection of picrotoxin (1 microgram/1 microliter) into posteroventral and lateral regions produced strong amnesia; an intermediate degree of impairment was found when delivered at dorsomedial regions; and no retention deficit was found when given to the ventromedial aspect of the anterior striatum. In sum, the retention impairments were consistently higher in posterior and lateral striatal regions than in the anterior and medial regions. The present findings support the concept that striatal GABAergic activity is involved in memory functions and also provide further evidence of neurochemical heterogeneity within the striatum regarding memory consolidation.

High level of footshock during inhibitory avoidance training prevents amnesia induced by intranigral injection of GABA antagonists.

Disruption of synaptic activity of a number of cerebral structures (e.g., neostriatum, amygdala, and thalamus) produces marked deficits in retention of instrumentally conditioned behaviors. When animals are given a relatively high number of training trials or high intensities of footshock during learning, however, such disruption is considerably less effective. Since there is a close anatomical and functional relationship between the neostriatum and the substantia nigra, it was of interest to determine whether enhanced training with a high level of footshock would prevent the reported amnesic state induced by injections of GABA antagonists into the latter structure. Rats were trained in a one-trial inhibitory task, using 0.2 or 0.4 mA, and then injected with microgram quantities of picrotoxin or bicuculline into the substantia nigra and posterior region of the zona incerta; retention was measured 24 h later. Only those groups that had been injected into the nigra and trained with 0.2 mA showed amnesia. These results support the hypotheses that (a) the normal activity of a set of structures is essential for the development of memory consolidation and (b) after an enhanced learning experience these structures may participate in memory consolidation, but are not necessary for the occurrence of this process.

Post-training injection of GABAergic antagonists into the striatum produces retrograde amnesia.

Although it is well established that the striatum contains both local and projection GABA neurons, little is known about their possible role in memory storage. We now report that in the Wistar rat, intrastriatal post-training injection of microgram quantities of bicuculine or picrotoxin, two GABA antagonists with different modes of action, induced retrograde amnesia of inhibitory avoidance, in concordance with the effects of injections of picrotoxin into the substantia nigra. These results suggest that GABA activity of the nigrostriatal system is involved in cognitive functions.