title: Sex-specific neuroanatomical correlates of fear expression in prefrontal-amygdala circuits.
abstract: BACKGROUND
  The neural projections from the infralimbic region of the prefrontal cortex to the amygdala are important for the maintenance of conditioned fear extinction. Neurons in this pathway exhibit a unique pattern of structural plasticity that is sex-dependent, but the relationship between the morphologic characteristics of these neurons and successful extinction in male and female subjects is unknown.
  
  
  METHODS
  Using classic cued fear conditioning and an extinction paradigm in large cohorts of male and female rats, we identified subpopulations of both sexes that exhibited high (HF) or low (LF) levels of freezing on an extinction retrieval test, representing failed or successful extinction maintenance, respectively. We combined retrograde tracing with fluorescent intracellular microinjections to perform three-dimensional reconstructions of infralimbic neurons that project to the basolateral amygdala in these groups.
  
  
  RESULTS
  The HF and LF male rats exhibited neuroanatomical distinctions that were not observed in HF or LF female rats. A retrospective analysis of behavior during fear conditioning and extinction revealed that despite no overall sex differences in freezing behavior, HF and LF phenotypes emerged in male rats during extinction and in female rats during fear conditioning, which does not involve infralimbic-basolateral amygdala neurons.
  
  
  CONCLUSIONS
  Our results suggest that the neural processes underlying successful or failed extinction maintenance may be sex-specific. These findings are relevant not only to future basic research on sex differences in fear conditioning and extinction but also to exposure-based clinical therapies, which are similar in premise to fear extinction and which are primarily used to treat disorders that are more common in women than in men.
authors.affiliation: Department of Psychology, Northeastern University, Boston, Massachusetts.
authors.forename: Tina M
authors.initials: TM
authors.lastname: Gruene
authors.affiliation: Department of Psychology, Northeastern University, Boston, Massachusetts.
authors.forename: Elian
authors.initials: E
authors.lastname: Roberts
authors.affiliation: Department of Psychology, Northeastern University, Boston, Massachusetts.
authors.forename: Virginia
authors.initials: V
authors.lastname: Thomas
authors.affiliation: Department of Psychology, Northeastern University, Boston, Massachusetts.
authors.forename: Ashley
authors.initials: A
authors.lastname: Ronzio
authors.affiliation: Department of Psychology, Northeastern University, Boston, Massachusetts. Electronic address: r.shansky@neu.edu.
authors.forename: Rebecca M
authors.initials: RM
authors.lastname: Shansky
mesh_terms: D000679:Amygdala / Q000502:physiology*; D000818:Animals; D005108:Extinction, Psychological / Q000502:physiology*; D005239:Fear / Q000502:physiology*; D005260:Female; D008297:Male; D009445:Neuroanatomy; D009474:Neurons / Q000502:physiology*; D017397:Prefrontal Cortex / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012727:Sex Characteristics
keywords: Basolateral Amygdala; Dendritic Morphology; Fear Extinction; Individual Differences; Infralimbic Cortex; Sex Differences