Learning and memory impairments are a common complaint in the elderly and are very severe in patients with Alzheimer's disease. A brain area that shows age-related degeneration is the medial septum-diagonal band of Broca complex (MSDB), and consistent degeneration of the MSDB occurs in Alzheimer's disease. The MSDB provides a major subcortical input to the hippocampus, a brain structure well known to be critical for memory. To date, most studies have focused on cholinergic MSDB neurons because agents have been available to damage these neurons selectively. Less is known about the function of noncholinergic MSDB neurons, even though their projection to the hippocampus can be as large as the cholinergic neurons. The proposed studies hypothesize that noncholinergic MSDB neurons are important for spatial memory because they modulate hippocampal physiology. Administration of kainic acid into the MSDB can damage noncholinergic MSDB neurons and spare the cholinergic neurons. The studies in this proposal do the following: 1) provide more information regarding the damaging effects of kainic acid administration on noncholinergic MSDB neurons, 2) examine the effects of intraseptal kainic acid administration on spatial memory, 3) investigate whether changes in spatial memory caused by intraseptal kainic acid is due to alterations of hippocampal place cells, 4) determine the effects of intraseptal kainic acid administration on rhythmic activity patterns (theta rhythm) in the hippocampus and entorhinal cortex. The proposed studies focus on a population of neurons that has not received much previous study, and therefore, the results of this proposal will greatly advance our knowledge of the role of noncholinergic MSDB neurons in memory. Additionally, much will be learned of the interaction between the medial septum-diagonal band complex and the hippocampus. Because these brain areas are so important in memory, the results from this proposal will have important broad implications in the treatment and prevention of memory impairments.
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