Variation in mouse basolateral amygdala volume is associated with differences in stress reactivity and fear learning

Rebecca J. Yang, Khyobeni Mozhui, Rose Marie Karlsson, Heather A. Cameron, Robert W. Williams, Andrew Holmes

Research output: Contribution to journalArticle

81 Citations (Scopus)

Abstract

A wealth of research identifies the amygdala as a key brain region mediating negative affect, and implicates amygdala dysfunction in the pathophysiology of anxiety disorders. Although there is a strong genetic component to anxiety disorders such as posttraumatic stress disorder (PTSD) there remains debate about whether abnormalities in amygdala function predispose to these disorders. In the present study, groups of C57BL/6 x DBA/2 (B x D) recombinant inbred strains of mice were selected for differences in volume of the basolateral amygdala complex (BLA). Strains with relatively small, medium, or large BLA volumes were compared for Pavlovian fear learning and memory, anxiety-related behaviors, depression-related behavior, and glucocorticoid responses to stress. Strains with relatively small BLA exhibited stronger conditioned fear responses to both auditory tone and contextual stimuli, as compared to groups with larger BLA. The small BLA group also showed significantly greater corticosterone responses to stress than the larger BLA groups. BLA volume did not predict clear differences in measures of anxiety-like behavior or depression-related behavior, other than greater locomotor inhibition to novelty in strains with smaller BLA. Neither striatal, hippocampal nor cerebellar volumes correlated significantly with any behavioral measure. The present data demonstrate a phenotype of enhanced fear conditioning and exaggerated glucocorticoid responses to stress associated with small BLA volume. This profile is reminiscent of the increased fear processing and stress reactivity that is associated with amygdala excitability and reduced amygdala volume in humans carrying loss of function polymorphisms in the serotonin transporter and monoamine oxidase A genes. Our study provides a unique example of how natural variation in amygdala volume associates with specific fear- and stress-related phenotypes in rodents, and further supports the role of amygdala dysfunction in anxiety disorders such as PTSD.

Original languageEnglish (US)
Pages (from-to)2595-2604
Number of pages10
JournalNeuropsychopharmacology
Volume33
Issue number11
DOIs
StatePublished - Oct 1 2008

Fingerprint

Fear
Amygdala
Learning
Anxiety Disorders
Post-Traumatic Stress Disorders
Glucocorticoids
Anxiety
vif Genes
Depression
Phenotype
Basolateral Nuclear Complex
Corpus Striatum
Serotonin Plasma Membrane Transport Proteins
Inbred Strains Mice
Monoamine Oxidase
Corticosterone
Rodentia
Brain
Research

All Science Journal Classification (ASJC) codes

  • Pharmacology
  • Psychiatry and Mental health

Cite this

Variation in mouse basolateral amygdala volume is associated with differences in stress reactivity and fear learning. / Yang, Rebecca J.; Mozhui, Khyobeni; Karlsson, Rose Marie; Cameron, Heather A.; Williams, Robert W.; Holmes, Andrew.

In: Neuropsychopharmacology, Vol. 33, No. 11, 01.10.2008, p. 2595-2604.

Research output: Contribution to journalArticle

Yang, Rebecca J. ; Mozhui, Khyobeni ; Karlsson, Rose Marie ; Cameron, Heather A. ; Williams, Robert W. ; Holmes, Andrew. / Variation in mouse basolateral amygdala volume is associated with differences in stress reactivity and fear learning. In: Neuropsychopharmacology. 2008 ; Vol. 33, No. 11. pp. 2595-2604.
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