Recent evidence indicates that activation of NMDA subtype of glutamate receptor in hippocampus is necessary for induction of certain forms of synaptic plasticity thought to be involved in the learning and memory functions of this system. The proposed experiments examine the contribution of NMDA receptors in two other forebrain systems, the lateral septum and basolateral nucleus of amygdala, to forms of learning and memory mediated by those systems. Prior lesion studies have implicated the lateral septum in mediating the detrimental effects of stimulus preexposure on later conditioning (latent inhibition), while the basolateral nucleus of the amygdala appears to be a critical substrate for taste-potentiated odor aversion learning. If activation of NMDA receptors is important for learning and memory, administration of antagonists should disrupt acquisition of these two learning tasks. The proposed studies examine the effects of the competitive NMDA antagonist APV on acquisition of these two tasks. The initial set of experiments will use intracranial microinjections of APV into the lateral septum and basolateral nucleus of amygdala to establish the effects of a range of doses of this drug on acquisition of these two tasks. Subsequent studies will examine the pharmacological specificity of APV's effects on these tasks, and assess the possibility that disruptive effects of APV on latent inhibition and potentiated odor aversion are mediated by state-dependent learning. They will therefore provide basic information about the behavioral, pharmacological and anatomical specificity of APV's effects on latent inhibition and taste-potentiated odor aversion learning. These studies have the potential to provide direct evidence concerning the role of NMDA receptors in learning and memory, and will help to establish whether mechanisms underlying synaptic plasticity in hippocampus also contribute to plasticity in other brain areas.
