Chronic Gq activation of ventral hippocampal neurons and astrocytes differentially affects memory and behavior.
Neurobiology of aging（2023）
Network dysfunction is implicated in numerous diseases and psychiatric disorders, and the hippocampus serves as a common origin for these abnormalities. To test the hypothesis that chronic modulation of neurons and astrocytes induces impairments in cognition, we activated the hM3D(Gq) pathway in CaMKII+ neurons or GFAP+ astrocytes within the ventral hippocampus across 3, 6, and 9 months. CaMKII-hM3Dq activation impaired fear extinction at 3 months and acquisition at 9 months. Both CaMKII-hM3Dq manipulation and aging had differential effects on anxiety and social interaction. GFAP-hM3Dq activation impacted fear memory at 6 and 9 months. GFAP-hM3Dq activation impacted anxiety in the open field only at the earliest time point. CaMKII-hM3Dq activation modified the number of microglia, while GFAP-hM3Dq activation impacted microglial morphological characteristics, but neither affected these measures in astrocytes. Overall, our study elucidates how distinct cell types can modify behavior through network dysfunction, while adding a more direct role for glia in modulating behavior.更多