title: Controlled cortical impact before or after fear conditioning does not affect fear extinction in mice.
abstract: Post-traumatic stress disorder (PTSD) is characterized in part by impaired extinction of conditioned fear. Traumatic brain injury (TBI) is thought to be a risk factor for development of PTSD. We tested the hypothesis that controlled cortical impact (CCI) would impair extinction of fear learned by Pavlovian conditioning, in mice. To mimic the scenarios in which TBI occurs prior to or after exposure to an aversive event, severe CCI was delivered to the left parietal cortex at one of two time points: (1) Prior to fear conditioning, or (2) after conditioning. Delay auditory conditioning was achieved by pairing a tone with a foot shock in "context A". Extinction training involved the presentation of tones in a different context (context B) in the absence of foot shock. Test for extinction memory was achieved by presentation of additional tones alone in context B over the following two days. In pre- or post-injury paradigms, CCI did not influence fear learning and extinction. Furthermore, CCI did not affect locomotor activity or elevated plus maze testing. Our results demonstrate that, within the time frame studied, CCI does not impair the acquisition and expression of conditioned fear or extinction memory.
authors.affiliation: Neuroscience Center and Department of Pediatrics, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114, United States; Department of Neurosurgery, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114, United States; Department of Anatomy & Neurobiology, University of Puerto Rico School of Medicine, San Juan, Puerto Rico, 00936. Electronic address: demetrio.sierra@upr.edu.
authors.forename: Demetrio
authors.initials: D
authors.lastname: Sierra-Mercado
authors.affiliation: Neuroscience Center and Department of Pediatrics, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114, United States. Electronic address: LMCALLISTER1@mgh.harvard.edu.
authors.forename: Lauren M
authors.initials: LM
authors.lastname: McAllister
authors.affiliation: Neuroscience Center and Department of Pediatrics, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114, United States. Electronic address: lee.chris.ch@gmail.com.
authors.forename: Christopher C H
authors.initials: CC
authors.lastname: Lee
authors.affiliation: Department of Psychiatry, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114, United States. Electronic address: milad@nmr.mgh.harvard.edu.
authors.forename: Mohammed R
authors.initials: MR
authors.lastname: Milad
authors.affiliation: Department of Neurosurgery, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114, United States. Electronic address: eeskandar@mgh.harvard.edu.
authors.forename: Emad N
authors.initials: EN
authors.lastname: Eskandar
authors.affiliation: Neuroscience Center and Department of Pediatrics, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114, United States. Electronic address: mwhalen@partners.org.
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Whalen
mesh_terms: D000818:Animals; D001930:Brain Injuries / Q000473:pathology / Q000503:physiopathology*; D003214:Conditioning, Classical / Q000502:physiology*; D004597:Electroshock; D005108:Extinction, Psychological / Q000502:physiology*; D005239:Fear / Q000502:physiology*; D046352:Freezing Reaction, Cataleptic; D051379:Mice; D009043:Motor Activity; D010296:Parietal Lobe / Q000473:pathology / Q000503:physiopathology*; D013313:Stress Disorders, Post-Traumatic / Q000503:physiopathology*
keywords: Anxiety disorder; Dorsal hippocampus; Extinction; Fear learning; Learning and memory; Rodent; Traumatic brain injury