Hippocampal dendritic spines express the RyR3 but not the RyR2 ryanodine receptor isoform

Abstract

The hippocampus is a brain region implicated in synaptic plasticity and memory formation; both processes require neuronal Ca²⁺ signals generated by Ca²⁺ entry via plasma membrane Ca²⁺ channels and Ca²⁺ release from the endoplasmic reticulum (ER). Through Ca²⁺-induced Ca²⁺ release, the ER-resident ryanodine receptor (RyR) Ca²⁺ channels amplify and propagate Ca²⁺ entry signals, leading to activation of cytoplasmic and nuclear Ca²⁺-dependent signaling pathways required for synaptic plasticity and memory processes. Earlier reports have shown that mice and rat hippocampus expresses mainly the RyR2 isoform, with lower expression levels of the RyR3 isoform and almost undetectable levels of the RyR1 isoform; both the RyR2 and RyR3 isoforms have central roles in synaptic plasticity and hippocampal-dependent memory processes. Here, we describe that dendritic spines of rat primary hippocampal neurons express the RyR3 channel isoform, which is also expressed in the neuronal body and neurites. In contrast, the RyR2 isoform, which is widely expressed in the neuronal body and neurites of primary hippocampal neurons, is absent from the dendritic spines. We propose that this asymmetric distribution is of relevance for hippocampal neuronal function. We suggest that the RyR3 isoform amplifies activity-generated Ca²⁺ entry signals at postsynaptic dendritic spines, from where they propagate to the dendrite and activate primarily RyR2-mediated Ca²⁺ release, leading to Ca²⁺ signal propagation into the soma and the nucleus where they activate the expression of genes that mediate synaptic plasticity and memory.

Keywords: Calcium release channels; Expansion microscopy; Immunofluorescence; Primary hippocampal cultures; Protein colocalization.