Modulating behavior deficits in Alzheimer’s disease models by targeting interneurons
OA Version
Citation
Abstract
Alzheimer’s Disease (AD) is the most common form of dementia and a multifaceted challenge. AD is represented by cognitive decline, memory deficits, and diversification in behavior. The hallmark pathological characteristics of AD include amyloid-beta plaques and phosphorylated tau tangles; however, recent studies have explored the dysregulation of neuronal networks and its effect on behavior and memory deficits in AD mouse models (APP/PS1 mice). Here we investigate the role of amyloid pathology on interneurons using chemogenetics, behavioral testing, calcium imaging, and multiphoton and confocal microscopy. We show that APP/PS1 mouse models are more hyperactive than Wild-type (WT) mice and found that caffeine administered in WT mice mimic phenotypic behavior of APP/PS1 mice. Based on these findings, we use chemogenetics to target inhibitory somatostatin-expressing (SOM) interneurons to establish a comparison between spontaneity of excitatory and inhibitory interneurons in APP/PS1 mice. We found that hyperactive SOM interneurons were accompanied by decreased excitatory neuron activity in APP/PS1 mice, hypothesizing that inhibiting SOM restores brain-wide network dysfunction in mouse models.
Description
2024