Identification of the cell-type specific mRNA translational control in learning and memory formation

In response to cellular stress, protein translation is regulated via the phosphorylation state of the α-subunit of eukaryotic translation initiation factor 2 (eIF2α). When phosphorylated, eIF2α reduces general protein synthesis while upregulating specific mRNA translation. De novo protein synthesis is critical for long-term memory consolidation and synaptic plasticity, particularly long-term potentiation and long-term depression (LTD). Translational control by p-eIF2α is implicated in these processes in a way that is cell-type specific; however, in relation to LTD, this cell-type specificity remains largely uncharacterized. The goal of the study is to address the current gap in memory research by examining the cell-type specific role of eIF2α in LTD and long-term memory. Wild-type mice undergo a memory task that requires them to identify a familiar object in a novel location to behaviourally induce LTD. Immunohistochemistry and fluorescence microscopy are used to probe for relative p-eIF2α expression and cell-type specific markers, which is expected to allow for the identification of the brain regions and cell types implicated in LTD through increased p-eIF2α expression. The present study provides the foundation for future work understanding the necessity and sufficiency of a given cell-type in the translational regulation of LTD and long-term memory, which may be targeted by the cell-type specific genetic ablation of p-eIF2α. Ultimately, this will allow for a more comprehensive understanding of memory processes. With a thorough understanding of the pathways and cell types involved in memory processes, effective and targeted treatments can be developed for neurological disorders and diseases affecting memory.