Ethanol‐Induced Suppression of Hippocampal Long‐Term Potentiation Is Blocked by Lesions of the Septohippocampal Nucleus

Systemic ethanol increases synaptic inhibition and suppresses long-term potentiation (LTP) in the dentate gyrus of the rat hippocampus. Local application of ethanol directly into the dentate gyrus of anesthetized rats increased the perforant path to dentate feed-forward inhibition, but had no effect on LTP. Local application of ethanol to the medial septum, a subcortical structure with major input to the dentate, increased recurrent inhibition. Selective disruption of septodentate input produced by lesions of the septohippocampal nucleus blocked the effects of systemic ethanol on LTP. These findings are the first to demonstrate that septodentate input is necessary for ethanol to increase recurrent inhibition and suppress LTP in the dentate gyrus and suggest an important role for extrahippocampal modulation of both short- and long-term plasticity in the hippocampus.