title: Neural circuits via which single prolonged stress exposure leads to fear extinction retention deficits.
abstract: Single prolonged stress (SPS) has been used to examine mechanisms via which stress exposure leads to post-traumatic stress disorder symptoms. SPS induces fear extinction retention deficits, but neural circuits critical for mediating these deficits are unknown. To address this gap, we examined the effect of SPS on neural activity in brain regions critical for extinction retention (i.e., fear extinction circuit). These were the ventral hippocampus (vHipp), dorsal hippocampus (dHipp), basolateral amygdala (BLA), prelimbic cortex (PL), and infralimbic cortex (IL). SPS or control rats were fear conditioned then subjected to extinction training and testing. Subsets of rats were euthanized after extinction training, extinction testing, or immediate removal from the housing colony (baseline condition) to assay c-Fos levels (measure of neural activity) in respective brain region. SPS induced extinction retention deficits. During extinction training SPS disrupted enhanced IL neural activity and inhibited BLA neural activity. SPS also disrupted inhibited BLA and vHipp neural activity during extinction testing. Statistical analyses suggested that SPS disrupted functional connectivity within the dHipp during extinction training and increased functional connectivity between the BLA and vHipp during extinction testing. Our findings suggest that SPS induces extinction retention deficits by disrupting both excitatory and inhibitory changes in neural activity within the fear extinction circuit and inducing changes in functional connectivity within the Hipp and BLA.
authors.affiliation: Department of Psychological and Brain Sciences, University of Delaware, Newark, Delaware 19716, USA dknox@psych.udel.edu.
authors.forename: Dayan
authors.initials: D
authors.lastname: Knox
authors.affiliation: Center for Molecular and Behavioral Neuroscience, Rutgers University, Newark, New Jersey 07102, USA.
authors.forename: Briana R
authors.initials: BR
authors.lastname: Stanfield
authors.affiliation: Department of Psychological and Brain Sciences, University of Delaware, Newark, Delaware 19716, USA.
authors.forename: Jennifer M
authors.initials: JM
authors.lastname: Staib
authors.affiliation: School of Public Policy and Administration, University of Delaware, Newark, Delaware 19716, USA.
authors.forename: Nina P
authors.initials: NP
authors.lastname: David
authors.affiliation: Department of Psychological and Brain Sciences, University of Delaware, Newark, Delaware 19716, USA.
authors.forename: Samantha M
authors.initials: SM
authors.lastname: Keller
authors.affiliation: Department of Psychological and Brain Sciences, University of Delaware, Newark, Delaware 19716, USA.
authors.forename: Thomas
authors.initials: T
authors.lastname: DePietro
mesh_terms: D000679:Amygdala / Q000378:metabolism* / Q000473:pathology; D000818:Animals; D002540:Cerebral Cortex / Q000378:metabolism* / Q000473:pathology; D004597:Electroshock; D005108:Extinction, Psychological / Q000502:physiology*; D005163:Factor Analysis, Statistical; D005239:Fear / Q000502:physiology*; D046352:Freezing Reaction, Cataleptic; D006624:Hippocampus / Q000378:metabolism* / Q000473:pathology; D007150:Immunohistochemistry; D008297:Male; D008569:Memory Disorders / Q000378:metabolism / Q000473:pathology; D009434:Neural Pathways / Q000378:metabolism / Q000473:pathology; D009474:Neurons / Q000378:metabolism / Q000473:pathology; D016760:Proto-Oncogene Proteins c-fos / Q000378:metabolism; D017207:Rats, Sprague-Dawley; D013315:Stress, Psychological / Q000378:metabolism* / Q000473:pathology
chemical_list: D016760:Proto-Oncogene Proteins c-fos