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