Hippocampal Role in Cognitive Functions and Memory, and Effects of a Novel Cognitive Enhancer on Learning Deficits Due to Hippocampal Lesions

Abstract

Abstract: In the 21st century, advances in basic research on higher brain functions in both system and molecular levels will proceed therapeutics to alleviate senile dementia, including Alzheimer's disease. In this review, we present our recent experimental results in the hippocampal formation (HF) in reference to human amnesia and a role of the HF in episodic memory and learning. First, we analyzed the activity of the HF neurons in both monkeys and rats. Neural activity in the monkey HF was analyzed during a spatial moving task in which the monkey could control a motorized, movable device (cab) and its route to a target location by pressing the bars. Some HF neurons responded to the occurrence of significant events (or episodes) in the place field where neuronal activity increased. This indicates that HF gating of incoming information may depend on where the monkey is located. These responses suggest representation related to episodic memory, and linkage among diverse information including both spatial and non‐spatial cues. Rats were also trained to explore a circular open‐field to obtain rewards [intracranial self‐stimulation (ICSS)]. When ICSS delivery place was changed, about 20% of the place neurons shifted place fields to locations newly associated with ICSS rewards. These neurophysiological results suggest that the HF is crucial to represent associative relations among multiple cues or factors and to learn such relations. Second, we investigated effects of the newly developed compound (T‐588), on learning and memory in rats. Treatment with the compound ameliorated deficits in learning the spatial tasks due to selective lesions of the CA1 subfield.