Cell-Type-Specific Regulation of the eIF2α Pathway in Long-Term Memory

Daniella Jezdic, Department of Biomedical Sciences, University of Windsor
Bromleigh Dobson, Department of Biomedical Sciences, University of Windsor
Vijendra Sharma, Department of Biomedical Sciences, University of Windsor
Maria Badalova, Department of Biomedical Sciences, University of Windsor

Description

Long-term memory consolidation results from synaptic plasticity dependent on mRNA translation. One of the translation mechanisms is regulated by eukaryotic translation initiation factor 2 alpha (eIF2α). The phosphorylation of eIF2α leads to a decrease in general translation while inducing the translation of specific mRNA transcripts. While the regulation of protein synthesis through the eIF2α pathway has been shown to influence long-term potentiation, its role in long-term depression (LTD) remains much less explored. Research suggests that phosphorylated eIF2α (p-eIF2α) regulation is cell-type-specific, however this research has focused primarily on long-term potentiation, not LTD. We hypothesize that p-eIF2α levels are differentially regulated across specific cell types during LTD. To investigate this, we will use novel object recognition, a long-term memory task, to induce LTD in mice. Immunohistochemistry will be performed to visualize p-eIF2α and total eIF2α expression across various hippocampal cell types, including excitatory neurons, inhibitory neurons, parvalbumin-expressing interneurons, somatostatin interneurons, astrocytes, vasoactive intestinal peptide-expressing interneurons, and microglia. The kinases regulating p-eIF2α expression (PKR, PERK, GCN2, and MARK) will then be assessed to determine which are upregulated. We expect to identify specific cell types expressing increased p-eIF2α levels following LTD induction, providing insight into cell-type-specific regulation of the eIF2α pathway. Proper regulation of the eIF2α signalling pathway is crucial for synaptic plasticity and memory. Consequently, chronic activation of p-eIF2α is linked to various neurological disorders, highlighting its potential as a therapeutic target and the significance of our research for future health advancements.

 
Mar 22nd, 11:00 AM Mar 22nd, 5:30 PM

Cell-Type-Specific Regulation of the eIF2α Pathway in Long-Term Memory

Long-term memory consolidation results from synaptic plasticity dependent on mRNA translation. One of the translation mechanisms is regulated by eukaryotic translation initiation factor 2 alpha (eIF2α). The phosphorylation of eIF2α leads to a decrease in general translation while inducing the translation of specific mRNA transcripts. While the regulation of protein synthesis through the eIF2α pathway has been shown to influence long-term potentiation, its role in long-term depression (LTD) remains much less explored. Research suggests that phosphorylated eIF2α (p-eIF2α) regulation is cell-type-specific, however this research has focused primarily on long-term potentiation, not LTD. We hypothesize that p-eIF2α levels are differentially regulated across specific cell types during LTD. To investigate this, we will use novel object recognition, a long-term memory task, to induce LTD in mice. Immunohistochemistry will be performed to visualize p-eIF2α and total eIF2α expression across various hippocampal cell types, including excitatory neurons, inhibitory neurons, parvalbumin-expressing interneurons, somatostatin interneurons, astrocytes, vasoactive intestinal peptide-expressing interneurons, and microglia. The kinases regulating p-eIF2α expression (PKR, PERK, GCN2, and MARK) will then be assessed to determine which are upregulated. We expect to identify specific cell types expressing increased p-eIF2α levels following LTD induction, providing insight into cell-type-specific regulation of the eIF2α pathway. Proper regulation of the eIF2α signalling pathway is crucial for synaptic plasticity and memory. Consequently, chronic activation of p-eIF2α is linked to various neurological disorders, highlighting its potential as a therapeutic target and the significance of our research for future health advancements.

https://scholar.uwindsor.ca/we-spark-conference/2025/postersessions/32