Whole brain circuit mapping of transplanted interneurons following traumatic brain injury

项目摘要/摘要 创伤性脑损伤后抑制性中间神经元的丢失与脑损伤的发生有关。 癫痫和其他认知缺陷。我们的实验室之前已经证明了胚胎中间神经元 移植到大脑中的祖细胞迁移、分化并在功能上整合到宿主-大脑网络中， 并能抑制自发性癫痫发作，改善小鼠学习记忆障碍。 癫痫。移植的中间神经元表现出成熟的形态和电生理特性 具有内源性中间神经元的特点。然而，神经的细胞类型和大脑区域 移植的中间神经元目前还不清楚。这项提案的目标是使用狂犬病病毒追踪 策略、全脑清除和完整脑成像将细胞类型的特定单突触输入映射到 中间神经元被移植到健康和受损的海马区。

PROJECT SUMMARY/ABSTRACT The loss of inhibitory interneurons after traumatic brain injury has been associated with the development of epilepsy and other deficits in cognition. Our lab has previously demonstrated that embryonic interneuron progenitors transplanted into the brain migrate, differentiate, and functionally integrate into host-brain networks, and can suppress spontaneous seizures and ameliorate learning and memory deficits in a mouse model of epilepsy. Transplanted interneurons exhibit mature morphologies and electrophysiological properties characteristic of endogenous interneurons. However, the cell types and brain regions that innervate transplanted interneurons are currently unknown. The goal of this proposal is to use a rabies virus tracing strategy, whole-brain clearing, and intact-brain imaging to map cell-type specific monosynaptic inputs onto interneurons grafted into the healthy and injured hippocampus.