Rats were bilaterally implanted with cannulae in the entorhinal cortex, amygdala, and hippocampus; after recovery, they were trained in a step-down inhibitory avoidance task and tested for retention 24 h later. Muscimol (0.03 microgram) or D-amino-5-phosphonovalerate (5.0 micrograms) infused in the entorhinal cortex 20 min prior to training inhibited the amnestic effect of the same dose of muscimol infused into this area 100 min after training. Thus, memory-relevant information must be processed by the entorhinal cortex at the time of training in order that this cortex may play a late post-training role in memory processing. Pretraining intraentorhinal muscimol administration did not affect the amnestic effect of the post-training infusion of muscimol into the amygdala and hippocampus, or the inhibition of memory expression induced by a pretest infusion of CNQX into the amygdala and hippocampus or into the entorhinal cortex. Pretest intraentorhinal muscimol also did not influence the effect of pretest intra-amygdala and intrahippocampal CNQX administration. These data indicate that the cells of the entorhinal cortex that are sensitive to pretraining muscimol are not part of the inputs that lead to post-training processing by the amygdala and hippocampus, or to the intervention of the amygdala, hippocampus, and entorhinal cortex in memory expression. The present findings are compatible with the possibility that, instead, the entorhinal cortex may be an output of the amygdala and hippocampus at the time of memory expression.

Bilateral infusion of CNQX (0.5 microgram) into the amygdala and the dorsal hippocampus prior to a retention test blocked the expression of step-down inhibitory avoidance in rats 6, 13, or 20 days after training. Retention test performance recovered 90 min after the infusions. Pretest intrahippocampal CNQX (0.5 microgram) blocked the expression of habituation to a novel environment measured 20 days after training. The data suggest that memory expression depends on non-NMDA receptor-mediated mechanisms, perhaps the expression of LTP, up to at least 20 days after acquisition. These mechanisms operate in the hippocampus in both tasks and in the amygdala in the avoidance task.

The bilateral infusion of CNQX (0.5 or 1.25 micrograms) into the amygdala or dorsal hippocampus 10 min prior to a retention test partially blocked the expression of stepdown inhibitory avoidance in rats 24 h after training. When infused into both the amygdala and the hippocampus at a dose of 0.5 microgram. CNQX caused a complete blockade of the expression of that task. Retention test performance recovered 2 h after the infusions. In rats trained for habituation to a novel environment and tested 24 h later, pretest intrahippocampal CNQX (0.5 microgram) blocked the expression of retention at a dose of 0.5 microgram, and intra-amygdala CNQX (0.5 or 1.25 micrograms) had no effect. The data suggest that, up to at least 1 day after training, memory of the avoidance task depends on glutamate acting on non-NMDA receptors in both the hippocampus and the amygdala, whereas memory of the habituation task depends on non-NMDA receptor activity in the hippocampus but not the amygdala.

Experiments using localized infusions into selected brain structures of agonists and antagonists of various synaptic receptors, given before or after behavioral training, have led to the following conclusions: (1) Memory is processed shortly after training in the amygdala, medial septum and hippocampus by glutamatergic NMDA and AMPA receptors activated in that sequence. Cholinergic muscarinic receptors are activated concurrently with the former. GABA(A) receptors modulated by brain benzodiazepines and by beta-noradrenergic receptors inhibit the process. (2) The sequential involvement of NMDA and AMPA receptors suggests that long-term potentiation (LTP) of the synapses activated by the learning experiences in the hippocampus and/or amygdala and medial septum is the crucial event. Expression of this LTP at the time of testing is necessary for retrieval: AMPA receptor blockade in the hippocampus and amygdala at the time of testing hinders retrieval. This suggests that the LTP underlies the memory process itself. (3) The amygdala, medial septum and hippocampus mediate different types of memory and/or different components of memories. The entorhinal cortex, through mechanisms that require intact NMDA receptors and are inhibited by GABA(A) receptors, intervenes in post-training memory processing 90-180 min after the other limbic regions. The entorhinal cortex integrates consecutively acquired memories; this role could be maintained by the LTP that is generated after training in the amygdala, hippocampus and medial septum. Post-training intervention of the entorhinal cortex does not occur if this region is inhibited at the time of training.

414 IMPEDE A EXPRESSÃO DA MEMÔRIA DE DUAS DIFERENTES TA REFAS. R.Walz, M.Biarichin, A.Ruschel, R.C.da Silva, M.Bueno e Silva, M.Zanatta, N.Paczko, P.P.K.Schmitz & I.Izquierdo. (Dep. Bioquímica UFRGS). O Potencial de Longa,duração (LTP) é um modelo celular para processos de memória. A indução de LTP pós-treino, mediada por receptores NMDA, sensível ao antagonista AP5, na amígdala, septo e hipocampo é necessária para a retenção das ta refas de esquiva inibitória (EI) e habituação (H). Da mesma forma, a expressão da LTP, nestas estruturas, durante a fase de manutenção, mediada por receptores AMPA e sensível ao antagonista CNQX, é necessária ate 3h após o treino das tarefas citadas. Caso inibida a expressão do LTP, ela pode ser reestabelecida com a reapresentação do estimulo que a gerou inicialmente (semelhante à memória). Se a expressão da LTP nestas estruturas também ocorresse durante o teste e fosse necessária para a evocação da tarefa, o blocueio dessa expressão com CNQX no momento do teste impediria a expressão da memória para a tarefa. Para testar esta hipótese, CNQX foi injetado pré-teste (24h após o treino) atra vés de microsseringa (coordenadas obtidas por atlas e revi. sadas histologicamente) na amígdala e/ou hipocampo de rato Wistar (250 gr). CNQX foi parcialmente amnesico quando administrado na amígdala ou hipocampo em EI, e totalmente amnésico quando administrado em ambos. No caso da H, somente o CNQX intra-hipocampal foi amnésico. (CNPq)