MEMORY PROCESSING BY THE LIMBIC SYSTEM - ROLE OF SPECIFIC NEUROTRANSMITTER SYSTEMS

Experiments using localized infusions into selected brain structures o f 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 activ ated in that sequence. Cholinergic muscarinic receptors are activated concurrently with the former. GABA(A) receptors modulated by brain ben zodiazepines and by beta-noradrenergic receptors inhibit the process. (2) The sequential involvement of NMDA and AMPA receptors suggests tha t long-term potentiation (LTP) of the synapses activated by the learni ng experiences in the hippocampus and/or amygdala and medial septum is the crucial event. Expression of this LTP at the time of testing is n ecessary 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 differ ent components of memories. The entorhinal cortex, through mechanisms that require intact NMDA receptors and are inhibited by GABA(A) recept ors, intervenes in post-training memory processing 90-180 min after th e other limbic regions. The entorhinal cortex integrates consecutively acquired memories; this role could be maintained by the LTP that is g enerated after training in the amygdala, hippocampus and medial septum . Post-training intervention of the entorhinal cortex does not occur i f this region is inhibited at the time of training.