title: 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.
authors.affiliation: Department of Psychiatry and Behavioral Sciences, Duke University Medical Center, Durham, North Carolina.|VISN 6 MIRECC, Durham Veterans Affairs Medical Center, Durham, North Carolina.
authors.forename: Rebecca C
authors.initials: RC
authors.lastname: Klein
authors.affiliation: Department of Psychiatry and Behavioral Sciences, Duke University Medical Center, Durham, North Carolina.|Neurobiology Research Laboratory, Durham Veterans Affairs Medical Center, Durham, North Carolina.
authors.forename: Shawn K
authors.initials: SK
authors.lastname: Acheson
authors.affiliation: Department of Psychiatry and Behavioral Sciences, Duke University Medical Center, Durham, North Carolina.
authors.forename: Laura H
authors.initials: LH
authors.lastname: Qadri
authors.affiliation: Department of Neurology, Duke University Medical Center, Durham, North Carolina.
authors.forename: Alina A
authors.initials: AA
authors.lastname: Dawson
authors.affiliation: Department of Psychiatry and Behavioral Sciences, Duke University Medical Center, Durham, North Carolina.|Mouse Behavioral and Neuroendocrine Analysis Core Facility, Duke University Medical Center, Durham, North Carolina.
authors.forename: Ramona M
authors.initials: RM
authors.lastname: Rodriguiz
authors.affiliation: Department of Psychiatry and Behavioral Sciences, Duke University Medical Center, Durham, North Carolina.|Mouse Behavioral and Neuroendocrine Analysis Core Facility, Duke University Medical Center, Durham, North Carolina.|Departments of Neurobiology and Cell Biology, Duke University Medical Center, Durham, North Carolina.
authors.forename: William C
authors.initials: WC
authors.lastname: Wetsel
authors.affiliation: Department of Psychiatry and Behavioral Sciences, Duke University Medical Center, Durham, North Carolina.|VISN 6 MIRECC, Durham Veterans Affairs Medical Center, Durham, North Carolina.
authors.forename: Scott D
authors.initials: SD
authors.lastname: Moore
authors.affiliation: Department of Neurology, Duke University Medical Center, Durham, North Carolina.
authors.forename: Daniel T
authors.initials: DT
authors.lastname: Laskowitz
authors.affiliation: Department of Neurology, Duke University Medical Center, Durham, North Carolina.
authors.forename: Hana N
authors.initials: HN
authors.lastname: Dawson
mesh_terms: D000679:Amygdala / Q000473:pathology* / Q000503:physiopathology; D000704:Analysis of Variance; D000818:Animals; D001703:Biophysics; D000070642:Brain Injuries, Traumatic / Q000473:pathology*; D003712:Dendrites / Q000473:pathology; D004195:Disease Models, Animal; D004558:Electric Stimulation; D004597:Electroshock / Q000009:adverse effects; D019706:Excitatory Postsynaptic Potentials / Q000502:physiology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009474:Neurons / Q000473:pathology / Q000502:physiology*; D018408:Patch-Clamp Techniques; D013315:Stress, Psychological / Q000209:etiology / Q000473:pathology*
keywords: amygdala; electrophysiology; hyperexcitability; stress; traumatic brain injury