A Tmu/Nih International Collaboration Study – Translational Research on Memory Reserve against Traumatic Brain Injury

Human brain can do everything, such as quickly to separate and process different inputs (visual, sensory, motor, etc.), decide actions, and create memories. However, traumatic brain injury (TBI) may affect brain function temporarily and induce subsequent development of dementia. While the link between TBI and neurodegeneration is still controversial, a number of epidemiological studies suggest a strong association between TBI and several types of dementia. One of our long-term goal is to understand how the role of billions of nerve cells and trillions of synapses in regulating brain communication results in the formation of memories, and how TBI impacts the brain's network dynamics and memory processes. Thus, in the project, we focus on the brain connectome networks, from macro-connectome (global networks) to micro-connectome (synaptic networks), in order to unravel the mysteries of memory impairment after TBI. In subproject 1, we have incorporated the advanced technique to track axonal fiber connection in the brain of a TBI patient and also established functional connectivity in TBI animal models. In subprojects 2 to 4, we have developed several of innovative and unique reagents and animal models, permitting new insights into the regulation of synaptic plasticity not previously achievable. Based on these findings, in the project, we will further study both clinical and translational connectomes, revealing structural and functional connectivity at the macromolecule level of the brain anatomy. Furthermore, we focus on micro-connectome relations to the macro-connectome. The level of the micro-connectome includes synaptic activation mediated by neurosteroids (subproject 2) and cytokines (subproject 3), as well as neuronal survival mediated by p53 activation (subproject 4), all will be comprehensively investigated in this project. Interestingly, TBI-induced dysregulation of these synaptic events may cause neural-connection changes and memory impairment. In combination of all subprojects, connectivity information among brain regions can be used to explore the specific connectomic maps in TBI animal models with various mechanisms of memory impairment, and further verify the effects of novel reagents in the project. The changes in macro-connectomic map induced by altered micro-connectivity at synaptic levels will also be unraveled by the close collaboration among all subprojects. This project is based on the research collaboration between USA (NIH) and Taiwanese (TMU) principle investigators.