PROJECT SUMMARY/ABSTRACT Traumatic brain injury (TBI) can lead to cognitive disabilities and epilepsy, but circuit mechanisms remain unknown. I hypothesize that the death of inhibitory interneurons and subsequent reorganization of neural circuitry in hippocampus leads to post-traumatic deficits in spatial coding and memory. To test this, I propose studies to systematically and comprehensively map the progressive structural and functional breakdown of hippocampal neurons in a widely used mouse model of TBI. In Aim 1, I will use advanced whole-brain circuit mapping technologies to visualize the inputs and outputs of hippocampal CA1 neurons in control and brain injured animals. In Aims 2 and 3, I will use calcium imaging with miniature microscopes to determine how spatial coding in hippocampus is altered by TBI and after interneuron transplantation. My long term goal is to build an independent academic career dedicated to developing novel circuit-based therapeutics for brain and spinal cord injury. Achieving this goal will require extensive training in the principles of neurotrauma, physiology and behavior. UCI is an outstanding institution for training in these areas, primarily due to the rich community of prominent neuroscientists and clinicians performing neurotrauma research and the pioneering role of UCI in the neurobiology of learning and memory, epilepsy and behavior. To help me achieve my goals, I have assembled a world-class team of internationally recognized scientists who will provide me with hands-on technical training, formal coursework and career guidance during the award and beyond.

PROJECT NARRATIVE Traumatic brain injury is a debilitating disorder that affects 70 million people worldwide every year but has no treatment. The goal of this proposal is to systematically map the input-output connections to excitatory hippocampal neurons after brain injury and track the progressive in vivo functional changes in neuron activity over time.