Pavlovsky_2012_Brain.Res_1472_99

Psychological stress may lead to long-lasting brain dysfunction specifically altered emotional and cognitive capabilities Previous studies have demonstrated persistent changes in the expression of key cholinergic genes in the neocortex and hippocampus following stress with muscarinic receptor-mediated enhanced excitability In the present study we examined cholinergic-mediated glutamatergic transmission in the hippocampus of mice after exposure to stress and its potential role in synaptic plasticity and altered behavior Adult male mice were tested one month after repeated forced swimming test Non-treated age-matched animals served as controls Electrophysiological recordings were performed in the acute in-vitro slice preparation CA1 pyramidal neurons were recorded using whole cell patch configuration Extracellular recordings were done in response to Shaffer collaterals SC or stratum orien SO stimulation Animal behavior in response to inhibition of acetylcholinesterase AChE was tested in open field paradigms In whole cell patch recordings the frequency of excitatory post-synaptic currents EPSCs was significantly increased in response to muscarinic activation in stress-exposed animals This enhanced cholinergic-modulated excitatory transmission is associated with facilitation of long-term potentiation LTP in response to tetanic stimulation at the SO but not at the SC Stress-related behavioral modulation via central cholinergic pathways was enhanced by the central AChE inhibitor physostigmine thus further supporting the notion that stress is associated with long lasting hypersensitivity to acetylcholine Our results revealed a pathway-specific enhancement of cholinergic-dependent glutamatergic transmission in the hippocampus after stress These changes may underlie specific hippocampal malfunction including cognitive and emotional disturbances as observed in patients with post-traumatic stress disorder PTSD).