Molecular mechanisms of activity dependent survival in the adult EC

Entorhinal cortex layer II (ECII) neurons are some of the first cells to degenerate in Alzheimer's Disease. Losing this region is impactful for cognition as ECII projections form the major cortical input into the hippocampus. To dissect the behavioral impact of ECII loss on hippocampal function, the Jankowsky lab created a chemogenetic mouse model in which ECII neurons express an engineered chloride channel (GlyCl) that prevents neuronal firing upon binding a systemically-delivered ligand. Using this model, we unexpectedly discovered that ECII neurons are particularly vulnerable to silencing and may require activity for survival. This study aims to determine the transcriptional changes correlating to degenerative phenotypes observed after electrical silencing of adult entorhinal cortex neurons. Overall design: mRNA profiles of subdissected entorhinal cortex from adult (2-4 mos) Nop-tTA x TRE-GlyCl-9531 mice at subsequent days post GlyCl-activation compared to vehicle control.