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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.

Abstract
Age-related memory impairments may be due to dysfunction of the septohippocampal system. The medial septal area (MSA) provides the major cholinergic projection to the hippocampus and is critical for memory. Knowledge of the neurobiological mechanisms by which the cholinergic system can attenuate age-related memory loss can facilitate the development of effective cognitive enhancers. At present, one of the best neurobiological models of memory formation is long-term potentiation/long-term depression (LTP/LTD). In previous studies, intraseptal infusion of the muscarinic agonist oxotremorine, which excites MSA neurons, improved memory in aged rats. The present study examined LTP and LTD in aged Fisher 344 rats following intraseptal infusion of oxotremorine. LTP and LTD were assessed using the slope of the EPSP recorded from the hilar region of the dentate gyrus. Induction of LTP was blocked in the lateral 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 pharmacological activation of the MSA can modulate LTP and LTD in the hippocampus of aged rats. The implications of these results with respect to memory and synaptic plasticity in the hippocampus are discussed.
AuthorsK Pang, M J Williams, D S Olton
JournalBrain research (Brain Res) Vol. 632 Issue 1-2 Pg. 150-60 (Dec 31 1993) ISSN: 0006-8993 [Print] Netherlands
PMID8149224 (Publication Type: Journal Article, Research Support, U.S. Gov't, P.H.S.)
Chemical References
  • Oxotremorine
Topics
  • Aging (physiology)
  • Animals
  • Electric Stimulation
  • Evoked Potentials (physiology)
  • Female
  • Frontal Lobe (drug effects, growth & development, physiology)
  • Hippocampus (drug effects, growth & development, physiology)
  • Infusions, Parenteral
  • Long-Term Potentiation (physiology)
  • Male
  • Memory (physiology)
  • Neuronal Plasticity (physiology)
  • Neurons (drug effects, physiology)
  • Oxotremorine (administration & dosage, pharmacology)
  • Rats
  • Rats, Inbred F344
  • Synaptic Transmission (physiology)

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