Persistent inhibition of hippocampal long-term potentiation in vivo by learned helplessness stress.
The persistent cognitive disruptive effects of stress have been strongly implicated in the pathophysiology of depression and post-traumatic stress disorder. Here we examined factors influencing the time course of recovery from the inhibitory effect of acute inescapable stressors on the ability to induce long-term potentiation (LTP) in the dorsal hippocampus in vivo. We tested different forms of LTP, different stressors and different inbred strains of rats. Acute elevated platform stress completely, but transiently (<3 h), inhibited induction of both NMDA receptor-dependent LTP induced by a standard high frequency (200 Hz) conditioning stimulus and an additional LTP that required voltage-dependent Ca(2+) channel activation triggered by strong (400 Hz) conditioning stimulation. In contrast, acute inescapable footshock stress, used to study learned helplessness, inhibited LTP for at least 4 weeks. Contrary to expectations, there was no clear relationship between the ability of the footshock to trigger helpless behavior, a model of stress-induced depression, and the magnitude of LTP inhibition. Moreover, LTP did not appear to be affected by genetic susceptibility to learned helplessness, a model of genetic vulnerability to depression. This long-lasting synaptic plasticity disruption may underlie persistent impairment of hippocampus-dependent cognition by excessive acute inescapable stress.
Ryan
Benedict K
BK
Department of Pharmacology and Therapeutics, Trinity College Dublin, Ireland.
Vollmayr
Barbara
B
Klyubin
Igor
I
Gass
Peter
P
Rowan
Michael J
MJ
D000818:Animals; D004594:Electrophysiology; D019706:Excitatory Postsynaptic Potentials; D006380:Helplessness, Learned; D006624:Hippocampus / Q000503:physiopathology*; D017774:Long-Term Potentiation / Q000502:physiology*; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D016194:Receptors, N-Methyl-D-Aspartate / Q000378:metabolism; D013315:Stress, Psychological / Q000503:physiopathology*
D016194:Receptors, N-Methyl-D-Aspartate