Contextual Fear Memory Formation and Destabilization Induce Hippocampal RyR2 Calcium Channel Upregulation.

Jamileth More,Paola Haeger,Gina Sánchez,Cecilia Hidalgo,María Mercedes Casas

doi:10.1155/2018/5056181

Jamileth More, Paola Haeger + Show 3 more

Open Access

https://doi.org/10.1155/2018/5056181

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Abstract

Hippocampus-dependent spatial and aversive memory processes entail Ca2+ signals generated by ryanodine receptor (RyR) Ca2+ channels residing in the endoplasmic reticulum membrane. Rodents exposed to different spatial memory tasks exhibit significant hippocampal RyR upregulation. Contextual fear conditioning generates robust hippocampal memories through an associative learning process, but the effects of contextual fear memory acquisition, consolidation, or extinction on hippocampal RyR protein levels remain unreported. Accordingly, here we investigated if exposure of male rats to contextual fear protocols, or subsequent exposure to memory destabilization protocols, modified the hippocampal content of type-2 RyR (RyR2) channels, the predominant hippocampal RyR isoforms that hold key roles in synaptic plasticity and spatial memory processes. We found that contextual memory retention caused a transient increase in hippocampal RyR2 protein levels, determined 5 h after exposure to the conditioning protocol; this increase vanished 29 h after training. Context reexposure 24 h after training, for 3, 15, or 30 min without the aversive stimulus, decreased fear memory and increased RyR2 protein levels, determined 5 h after reexposure. We propose that both fear consolidation and extinction memories induce RyR2 protein upregulation in order to generate the intracellular Ca2+ signals required for these distinct memory processes.

Highlights

Fear conditioning, an associative learning process that produces robust memories, represents a form of Pavlovian conditioning that has received considerable attention over the last years [1, 2]
Based on the results shown in this work, we suggest that our model of context-conditioned fear memory, a task dependent on the hippocampus [9, 49], effectively promoted learning and memory acquisition, which became consolidated as indicated by the high percentage of freezing in animals evaluated 5, 24, or 29 h after training
Our novel results show that a transient increase in RyR2 protein levels occurred during consolidation of fear-conditioned memory, since hippocampal RyR2 protein upregulation occurred 5 h posttraining but not 29 h after training

Summary

Introduction

An associative learning process that produces robust memories, represents a form of Pavlovian conditioning that has received considerable attention over the last years [1, 2]. Evidence that the hippocampus forms part of the neuronal pathways involved in contextual fear conditioning came first from studies showing that lesions in the dorsal hippocampus prevent both the acquisition and the expression of context-dependent fear conditioning [3,4,5]. In agreement with the procedures developed by Pavlov many years ago [10], protocols to study memory destabilization entail special procedures, whereby animals previously exposed to fear conditioning protocols are reexposed subsequently to the conditioned stimulus in the absence of the unconditioned aversive stimulus.

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