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.
The loss of inhibitory interneurons is associated with cognitive and behavioral deficits in neurological disorders including epilepsy and traumatic brain injury. Interneuron transplantation has been demonstrated to be therapeutic, but it is currently unknown where transplanted cells receive input from. The goal of this proposal is to map the brain regions and cells types that input onto transplanted interneurons in the healthy and injured brain.
