Language
English
Publication Date
12-5-2022
Journal
eLife
DOI
10.7554/eLife.83813
PMID
36468693
PMCID
PMC9873254
PubMedCentral® Posted Date
12-5-2022
PubMedCentral® Full Text Version
Post-print
Abstract
Neurodegenerative diseases are characterized by selective vulnerability of distinct cell populations; however, the cause for this specificity remains elusive. Here, we show that entorhinal cortex layer 2 (EC2) neurons are unusually vulnerable to prolonged neuronal inactivity compared with neighboring regions of the temporal lobe, and that reelin + stellate cells connecting EC with the hippocampus are preferentially susceptible within the EC2 population. We demonstrate that neuronal death after silencing can be elicited through multiple independent means of activity inhibition, and that preventing synaptic release, either alone or in combination with electrical shunting, is sufficient to elicit silencing-induced degeneration. Finally, we discovered that degeneration following synaptic silencing is governed by competition between active and inactive cells, which is a circuit refinement process traditionally thought to end early in postnatal life. Our data suggests that the developmental window for wholesale circuit plasticity may extend into adulthood for specific brain regions. We speculate that this sustained potential for remodeling by entorhinal neurons may support lifelong memory but renders them vulnerable to prolonged activity changes in disease.
Keywords
Mice, Animals, Alzheimer Disease, Neurons, Hippocampus, Entorhinal Cortex
Published Open-Access
yes
Recommended Citation
Zhao, Rong; Grunke, Stacy D; Wood, Caleb A; et al., "Activity Disruption Causes Degeneration of Entorhinal Neurons in a Mouse Model of Alzheimer’s Circuit Dysfunction" (2022). Faculty and Staff Publications. 4926.
https://digitalcommons.library.tmc.edu/baylor_docs/4926
Included in
Health Services Research Commons, Medical Cell Biology Commons, Medical Molecular Biology Commons, Medical Specialties Commons, Microbiology Commons