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The Journal of Neuroscience, May 1, 2002, 22(9):3788-3794

Priming of Long-Term Potentiation in Mouse Hippocampus by Corticotropin-Releasing Factor and Acute Stress: Implications for Hippocampus-Dependent Learning

Thomas Blank*, Ingrid Nijholt*, Klaus Eckart, and Joachim Spiess

Department of Molecular Neuroendocrinology, Max-Planck Institute for Experimental Medicine, D-37075 Goettingen, Germany

In the present experiments, we characterized the action of human/rat corticotropin-releasing factor (h/rCRF) and acute stress (1 hr of immobilization) on hippocampus-dependent learning and on synaptic plasticity in the mouse hippocampus. We first showed that h/rCRF application and acute stress facilitated (primed) long-term potentiation of population spikes (PS-LTP) in the mouse hippocampus and enhanced context-dependent fear conditioning. Both the priming of PS-LTP and the improvement of context-dependent fear conditioning were prevented by the CRF receptor antagonist [Glu11,16]astressin. PS-LTP priming and improved learning were also reduced by the protein kinase C inhibitor bisindolylmaleimide I. Acute stress induced the activation of Ca2+/calmodulin-dependent kinase II (CaMKII) 2 hr after the end of the stress session. The CaMKII inhibitor KN-62 antagonized the stress-mediated learning enhancement, however, with no effect on PS-LTP persistence. Thus, long-lasting increased neuronal excitability as reflected in PS-LTP priming appeared to be essential for the enhancement of learning in view of the observation that inhibition of PS-LTP priming was associated with impaired learning. Conversely, it was demonstrated that inhibition of CaMKII activity reduced contextual fear conditioning without affecting PS-LTP priming. This observation suggests that priming of PS-LTP and activation of CaMKII represent two essential mechanisms that may contribute independently to long-term memory.

Key words: priming; neuronal excitability; h/rCRF; CaMKII; LTP; PKC; classical fear conditioning

* T.B. and I.N. contributed equally to this work.

Copyright © 2002 Society for Neuroscience  0270-6474/02/2293788-07$05.00/0


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