title: Diminished amygdala activation and behavioral threat response following traumatic brain injury.
abstract: Each year, approximately 3.8 million people suffer mild to moderate traumatic brain injuries (mTBI) that result in an array of neuropsychological symptoms and disorders. Despite these alarming statistics, the neurological bases of these persistent, debilitating neuropsychological symptoms are currently poorly understood. In this study we examined the effects of mTBI on the amygdala, a brain structure known to be critically involved in the processing of emotional stimuli. Seven days after lateral fluid percussion injury (LFPI), mice underwent a series of physiological and behavioral experiments to assess amygdala function. Brain-injured mice exhibited a decreased threat response in a cued fear conditioning paradigm, congruent with a decrease in amygdala excitability determined with basolateral amygdala (BLA) field excitatory post-synaptic potentials together with voltage-sensitive dye imaging (VSD). Furthermore, beyond exposing a general decrease in the excitability of the primary input of the amygdala, the lateral amygdala (LA), VSD also revealed a decrease in the relative strength or activation of internuclear amygdala circuit projections after LFPI. Thus, not only does activation of the LA require increased stimulation, but the proportion of this activation that is propagated to the primary output of the amygdala, the central amygdala, is also diminished following LFPI. Intracellular recordings revealed no changes in the intrinsic properties of BLA pyramidal neurons after LFPI. This data suggests that mild to moderate TBI has prominent effects on amygdala function and provides a potential neurological substrate for many of the neuropsychological symptoms suffered by TBI patients.
authors.affiliation: Neuroscience Graduate Group, Perelman School of Medicine, University of Pennsylvania, 3451 Walnut Street, Philadelphia, PA 19104, United States.
authors.forename: Christopher P
authors.initials: CP
authors.lastname: Palmer
authors.affiliation: Critical Care Medicine, Department of Anesthesiology, The Children's Hospital of Philadelphia, 3401 Civic Center Blvd, Philadelphia, PA 19104, United States.
authors.forename: Hannah E
authors.initials: HE
authors.lastname: Metheny
authors.affiliation: Critical Care Medicine, Department of Anesthesiology, The Children's Hospital of Philadelphia, 3401 Civic Center Blvd, Philadelphia, PA 19104, United States.
authors.forename: Jaclynn A
authors.initials: JA
authors.lastname: Elkind
authors.affiliation: Critical Care Medicine, Department of Anesthesiology, The Children's Hospital of Philadelphia, 3401 Civic Center Blvd, Philadelphia, PA 19104, United States; Department of Anesthesiology & Critical Care Medicine, Perelman School of Medicine, University of Pennsylvania, 3451 Walnut Street, Philadelphia, PA 19104, United States. Electronic address: cohena@email.chop.edu.
authors.forename: Akiva S
authors.initials: AS
authors.lastname: Cohen
mesh_terms: D015763:2-Amino-5-phosphonovalerate / Q000031:analogs & derivatives / Q000494:pharmacology; D018750:6-Cyano-7-nitroquinoxaline-2,3-dione / Q000494:pharmacology; D000679:Amygdala / Q000473:pathology / Q000503:physiopathology*; D000818:Animals; D001930:Brain Injuries / Q000473:pathology* / Q000503:physiopathology*; D001931:Brain Mapping; D003213:Conditioning, Psychological / Q000502:physiology; D003463:Cues; D004195:Disease Models, Animal; D004558:Electric Stimulation; D004924:Escape Reaction / Q000502:physiology*; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D019706:Excitatory Postsynaptic Potentials / Q000187:drug effects / Q000502:physiology; D005239:Fear / Q000523:psychology / Q000528:radiation effects; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D026941:Sodium Channel Blockers / Q000494:pharmacology; D013779:Tetrodotoxin / Q000494:pharmacology; D056969:Voltage-Sensitive Dye Imaging
chemical_list: D018691:Excitatory Amino Acid Antagonists; D026941:Sodium Channel Blockers; C096637:2-amino-5-phosphono-3-pentenoic acid; D013779:Tetrodotoxin; D018750:6-Cyano-7-nitroquinoxaline-2,3-dione; D015763:2-Amino-5-phosphonovalerate
keywords: Amygdala; Cued fear; LFPI; Lateral fluid percussion; Threat response; Traumatic brain injury; Voltage-sensitive dye; mTBI