9514557 Walsh An exciting, unresolved question in neuroscience is how animals acquire and store memories. For mammals there is an identified site, the hippocampus, at which memory processing appears to occur. The structure and function of this site is known in some detail, however the nature of the inputs that control the functioning of hippocampal neurons is largely unknown. One of the input brain regions, the medial septum, contains neurons that project to and control the hippocampus. The medial septum appears to integrate subcortical information about the 'biological significance' of episodes or events and in turn modulate the responsiveness of the hippocampus to its primary, cortical input. Septal neurons release two types of neurotransmitter molecules, acetylcholine and GABA, which modulate the physiology of hippocampal neurons and hence the memory- related functions of the hippocampus. Studies conducted through funding by this award examine the neurotransmitters and brain circuits involved in a specific type of learning related to remembering a position in space. One set of experiments is designed to examine whether site-specific manipulations of different molecular receptors (benzodiazepine receptors), in the medial septum, will alter the activity of septal neurons and of memory processes. In other experiments, tests are conducted to determine the physiological mechanisms through which intraseptal injection of a receptor blocker drug (flumazenil) enhances the activity of neurons that project to the hippocampus and increases working memory. These studies should provide a better understanding of specific brain circuits and neurochemical mechanisms that control memory in mammals. The expectation is that such a detailed understanding of a specific type of learning at a specific site will contribute importantly to a general understanding of how animals learn, and remember what they learn.
