Graduate Program for Neuroscience, Boston University, Boston, MA, USA; Department of Psychological and Brain Sciences, The Center for Systems Neuroscience, Neurophotonics Center, and Photonics Center, Boston University, Boston, MA, USA.
Department of Psychological and Brain Sciences, The Center for Systems Neuroscience, Neurophotonics Center, and Photonics Center, Boston University, Boston, MA, USA.
Neurobiol Aging. 2023 May;125:9-31. doi: 10.1016/j.neurobiolaging.2023.01.007. Epub 2023 Jan 31.
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.
网络功能障碍与许多疾病和精神障碍有关，而海马体则是这些异常的共同起源。为了验证慢性调节神经元和星形胶质细胞会导致认知障碍的假设，我们在腹侧海马体中激活了 CaMKII+神经元或 GFAP+星形胶质细胞中的 hM3D(Gq)通路，持续 3、6 和 9 个月。CaMKII-hM3Dq 的激活在 3 个月时损害了恐惧的消退，在 9 个月时损害了获得。CaMKII-hM3Dq 的操作和衰老对焦虑和社交互动有不同的影响。GFAP-hM3Dq 的激活在 6 个月和 9 个月时影响了恐惧记忆。GFAP-hM3Dq 的激活仅在最早的时间点影响了开放场中的焦虑。CaMKII-hM3Dq 的激活改变了小胶质细胞的数量，而 GFAP-hM3Dq 的激活影响了小胶质细胞的形态特征，但对星形胶质细胞中的这些指标均没有影响。总的来说，我们的研究阐明了不同的细胞类型如何通过网络功能障碍来改变行为，同时也增加了胶质细胞在调节行为方面的更直接作用。
