Effects of hippocampal IP3R inhibition on contextual fear memory consolidation, retrieval, reconsolidation and extinction

Abstract

Intracellular calcium stores (ICS) play a dynamic role in neuronal calcium (Ca²⁺) homeostasis both by buffering Ca²⁺ excess in the cytoplasm or providing an additional source of Ca²⁺ when concentration increase is needed. However, in spite of the large body of evidence showing Ca²⁺ as an essential second messenger in many signaling cascades underlying synaptic plasticity, the direct involvement of the intracellular Ca²⁺-release channels (ICRCs) in memory processing has been highly overlooked. Here we investigated the role of the ICRC inositol 1,4,5-trisphosphate receptor (IP₃R) activity during different memory phases using pharmacological inhibition in the dorsal hippocampus during contextual fear conditioning. We first found that post-training administration of the IP₃R antagonist 2-aminoethyl diphenylborinate (2-APB) impaired memory consolidation in a dose and time-dependent manner. Inhibiting IP₃Rs also disrupted memory retrieval. Contextual fear memory reconsolidation or extinction, however, were not sensitive to IP₃R blockade. Taken together, our results indicate that hippocampal IP₃Rs play an important role in contextual fear memory consolidation and retrieval.

Keywords: 2-APB; Calcium; Fear conditioning; Rats.