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

Abstract

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 [Glu(11,16)]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.

Corticotropin-Releasing Factor and Acute Stress Prolongs Serotonergic Regulation of GABA Transmission in Prefrontal Cortical Pyramidal Neurons

“…CRF-induced alteration of the effect of 5-HT on sIPSC in rat PFC neurons, similar to the signaling involved in CRF potentiation of NMDARs in dopamine neurons (Ungless et al, 2003) and CRF facilitation of LTP in hippocampal neurons (Blank et al, 2002). How CRF/PKC prolongs the regulation of sIPSC by 5-HT is unclear.…”

“…3A,B), suggesting the lack of involvement of PKA. In contrast, the phospholipase C (PLC)/PKC pathway has been shown to be involved in CRF potentiation of NMDARs in dopamine neurons (Ungless et al, 2003) and CRF priming of long-term potentiation (LTP) in hippocampal neurons (Blank et al, 2002). Therefore, we tested whether inhibition of this pathway could interfere with the CRF-induced prolongation of the effect of 5-HT on sIPSC.…”

Correlated memory defects and hippocampal dendritic spine loss after acute stress involve corticotropin-releasing hormone signaling

“…The spine loss was associated with the attenuation of LTP selectively in the C/A pathway and required CRH-CRFR 1 signaling. CRH is released in hippocampus during stress and at modest levels contributes to priming of LTP (80). At higher levels the peptide may injure hippocampal neurons directly (81, 82) via CRFR 1 (54).…”

Anxiogenic and aversive effects of corticotropin-releasing factor (CRF) in the bed nucleus of the stria terminalis in the rat: role of CRF receptor subtypes

“…For example, CRF has been shown to increase hippocampal long-term potentiation (Blank et al 2002;Wang et al 1998Wang et al , 2000 and facilitate learning of certain behavioral tasks, including aversive learning (Blank et al 2002;Garcia-Lecumberri and Ambrosio 2000;Heinrichs et al 1997b;Hung et al 1992;Lee 1995;Lee and Sung 1989;Liang et al 2001;Liang and Lee 1988;Ma et al 1999;Radulovic et al 1999;Zorrilla et al 2002), while disruption of CRF receptor function can attenuate certain forms of learning (Contarino et al 1999;Heinrichs 2003). Thus, the apparent blockade of intra-BNST CRF-induced conditioned place aversion by both CRF 1 and CRF 2 antagonist could be a result of an attenuated ability of the animal to associate the aversive effects of CRF in the BNST with the environment in which CRF is administered, rather than an attenuation of the actual aversive effects of CRF itself.…”