ACTIVATION OF THE MEDIAL SEPTAL AREA ATTENUATES LTP OF THE LATERAL PERFORANT PATH AND ENHANCES HETEROSYNAPTIC LTD OF THE MEDIAL PERFORANT PATH IN AGED RATS

Age-related memory impairments may be due to dysfunction of the septoh ippocampal system. The medial septal area (MSA) provides the major cho linergic projection to the hippocampus and is critical for memory. Kno wledge of the neurobiological mechanisms by which the cholinergic syst em can attenuate age-related memory loss can facilitate the developmen t of effective cognitive enhancers. At present, one of the best neurob iological models of memory formation is long-term potentiation/long-te rm depression (LTP/LTD). In previous studies, intraseptal infusion of the muscarinic agonist oxotremorine, which excites MSA neurons, improv ed memory in aged rats. The present study examined LTP and LTD in aged Fisher 344 rats following intraseptal infusion of oxotremorine. LTP a nd LTD were assessed using the slope of the EPSP recorded from the hil ar region of the dentate gyrus. Induction of LTP was blocked in the la teral perforant path, but not in the medial perforant path, following intraseptal infusions of oxotremorine. The generation and amplitude of heterosynaptic LTD was enhanced in the medial perforant path, but not in the lateral perforant path. The results provide evidence that phar macological activation of the MSA can modulate LTP and LTD in the hipp ocampus of aged rats. The implications of these results with respect t o memory and synaptic plasticity in the hippocampus are discussed.