Opposing effects of traumatic brain injury on excitatory synaptic function in the lateral amygdala in the absence and presence of preinjury stress

Abstract

Traumatic brain injury (TBI) is a leading cause of death and disability among young adults and is highly prevalent among recently deployed military personnel. Survivors of TBI often experience cognitive and emotional deficits, suggesting that long-term effects of injury may disrupt neuronal function in critical brain regions, including the amygdala, which is involved in emotion and fear memory. Amygdala hyperexcitability has been reported in both TBI and posttraumatic stress disorder patients, yet little is known regarding the effects of combined stress and TBI on amygdala structure and function at the neuronal level. The present study seeks to determine how the long-term effects of preinjury foot-shock stress and TBI interact to influence synaptic plasticity in the lateral amygdala (LA) of adult male C57BL/6J mice by using whole-cell patch clamp electrophysiology 2-3 months postinjury. In the absence of stress, TBI resulted in a significant increase in membrane excitability and spontaneous excitatory postsynaptic currents (sEPSCs) in LA pyramidal-like neurons. Foot-shock stress in the absence of TBI also resulted in increased sEPSC activity. In contrast, when preinjury stress and TBI occurred in combination, sEPSC activity was significantly decreased compared with either condition alone. There were no significant differences in inhibitory activity or total dendritic length among any of the treatment groups. These results demonstrate that stress and TBI may be contributing to amygdala hyperexcitability via different mechanisms and that these pathways may counterbalance each other with respect to long-term pathophysiology in the LA.

A Novel Role for the Endocannabinoid System in Ameliorating Motivation for Alcohol Drinking and Negative Behavioral Affect after Traumatic Brain Injury in Rats

“…66 Another study of CCI TBI in C57BL/6J mice showed a significant increase in spontaneous excitatory post-synaptic currents and membrane excitability 3 months post-TBI in the lateral amygdala indicating a persistent change in amygdala synaptic plasticity post-TBI. 67 Several mechanisms exist by which endocannabinoids may counter hyperexcitability. For instance, recent evidence clearly demonstrates the existence of endocannabinoid-mediated depolarization-induced suppression of excitation (DSE) in cortical inputs to the lateral and central amygdala.…”

The Neurobiological Links between Stress and Traumatic Brain Injury: A Review of Research to Date

“…Using a TBI and pre-injury foot shock stress mouse model, Klein et al [ 155 ] found that TBI or foot-shock stress individually resulted in a significant increase in membrane excitability and spontaneous excitatory postsynaptic currents (sEPSCs) in lateral amygdala pyramidal-like neurons. However, pre-injury stress and TBI led to weakened sEPSC activity compared with either condition alone [ 155 ].…”

“…Using a TBI and pre-injury foot shock stress mouse model, Klein et al [ 155 ] found that TBI or foot-shock stress individually resulted in a significant increase in membrane excitability and spontaneous excitatory postsynaptic currents (sEPSCs) in lateral amygdala pyramidal-like neurons. However, pre-injury stress and TBI led to weakened sEPSC activity compared with either condition alone [ 155 ]. The authors speculated that stress and TBI may lead to the hyperexcitation of the amygdala through various mechanisms and that these pathways counterbalance each other in cases of combined injury.…”