Traumatic Brain Injury (TBI) affects more than 1.5 million people in the United States each year and even mild TBI (mTBI) can lead to a vast array of neurological symptoms, chief among them persistent memory impairment. TBI predominantly causes damage to the frontal and temporal lobes of cerebral cortex, regions known to be critical for a wide range of higher cognitive functions, including memory. Neural oscillations are functionally implicated in a variety of cognitive tasks and present a mechanism for coordinating activity across multiple brain regions. Gamma oscillations (30-200 Hz), measured by electroencephalogram recording in humans, change after TBI across multiple brain regions including the frontal lobes. The generation and maintenance of neural oscillations represent the coherent, coordinated activity of groups of many neurons and depends on the balance of excitatory and inhibitory synaptic transmission. Results from our laboratory and others have shown that mTBI disrupts the necessary balance between excitatory and inhibitory synaptic transmission in the hippocampus and restoring this balance reinstates normal hippocampal function as assayed by both physiology and behavior. The investigations proposed herein will provide behavioral and electrophysiological data which in turn will shed light on potential biological correlates of cognitive and memory dysfunction following mTBI.
In Aim 1 I will test the hypothesis that gamma oscillations are disrupted in the medial prefrontal cortex (mPFC) following a mouse model of experimental mTBI and oscillatory alterations correlate with behavioral dysfunction.
In Aim 2 I will test the hypothesis that mTBI-induced alterations to the balance between excitatory and inhibitory synaptic transmission in the mPFC also correlate with post-mTBI behavioral dysfunction. This work will provide a potential biological correlate of cognitive deficits that are the hallmark symptom of mTBI, as well as a physiological correlate, disrupted gamma oscillations, that can be measured in both mTBI patients and rodent models of mTBI.
By completing this work; I hope to gain insight into alterations in neural oscillations after mild traumatic brain injury. Additionally; I will determie the alterations in synaptic physiology in the medial prefrontal cortex following mild traumatic brain injury. Finally; I will demonstrate the cognitive and behavioral relevance of alterations toboth oscillations and measures of synaptic physiology by correlating these changes with behavioral deficits in a behavioral task probing working memory function.