Functional Alterations in the Amygdala Following Traumatic Brain injury

Traumatic brain injury (TBI) afflicts approximately 3.8 million people each year, in the United States alone. In addition to the largely acute physical and cognitive symptoms of TBI, patients exhibit a heightened risk of developing persistent neuropsychological symptoms including anxiety, aggression, rage, depression/anhedonia and apathy in the months to years after TBI. Despite the deleterious impact of these neuropsychological symptoms, very little is known of their neurological bases and there is currently no treatment targeting the underlying neuropathology giving rise to these symptoms. Employing a murine model of mild to moderate traumatic brain injury (mTBI), known as lateral fluid percussion injury (LFPI), we examined the effects mTBI on the physiology and function of the amygdala; a brain structure critical in processing emotional responses to sensory stimuli in humans. Behavioral experiments using a cued-fear conditioning paradigm, revealed significant deficits in the behavioral threat response of brain injured animals. We then utilized a combination of intracellular, extracellular, and voltage sensitive dye imaging (VSD) recording techniques to determine electrophysiological alterations in the amygdala following LFPI. These experiments revealed that LPFI causes a robust decrease in network excitability and circuit propagation strength in the basolateral and central amygdalae (BLA & CeA), without affecting the intrinsic excitability of BLA pyramidal neurons. Further experiments demonstrated that the injury-induced decrease in BLA network excitability is due in part to a decrease in glutamatergic excitation and preservation or augmentation of GABAergic inhibition; which increases the ratio inhibition to excitation in the amygdala of brain injured animals. This work demonstrates that mTBI has robust effects on amygdalar physiology that ultimately disrupt its normal function. The brain injury induced alterations in amygdalar function described herein, provide a potential neurological substrate for the neuropsychological symptoms suffered by TBI patients