UC Irvine

Traumatic brain injury produces a range of long-lasting cognitive deficits. The underlying causes of these deficits could be in part due to reorganization of normal neural connectivity within brain regions critically important for cognition. Inhibitory interneurons play critical roles in normal circuit function, are known to be vulnerable in disease states, and are highly plastic in response to injury. The overall goal of my thesis work is to understand how traumatic brain injury affects brain circuitry from the microscopic to the mesoscopic scale with a particular focus on somatostatin-expressing (SST+) neurons. First, I show that SST+ neurons are the most vulnerable population of neuron to traumatic brain injury. Second, I use rabies virus tracing and novel brain clearing techniques to create whole-brain maps of the sources of input onto SST+ neurons both in hippocampus and prefrontal cortex, two brain regions involved in cognition. Analysis of brain-wide connectivity changes after trauma reveal profound changes both in long-range and local patterns of connectivity, even in regions distal from the site of injury. Finally, I use interneuron progenitor transplantation and the same mapping approach to identify the sources of input onto grafted interneurons in the injured brain. My results provide the first comprehensive characterization of brain-wide circuit reorganization of a single a well-defined neuronal subtype after traumatic brain injury, and reveal that new SST neurons introduced into the injured brain environment maintain the capacity to rewire in the correct ways.