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Variation in mouse basolateral amygdala volume is associated with differences in stress reactivity and fear learning.
Neuropsychopharmacology 2008; 33(11):2595-604N

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.

Authors+Show Affiliations

Section on Behavioral Science and Genetics, Laboratory for Integrative Neuroscience, National Institute on Alcohol Abuse and Alcoholism, NIH, Rockville, MD 20852-9411, USA.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Comparative Study
Journal Article
Research Support, N.I.H., Extramural
Research Support, N.I.H., Intramural

Language

eng

PubMed ID

18185497

Citation

Yang, Rebecca J., et al. "Variation in Mouse Basolateral Amygdala Volume Is Associated With Differences in Stress Reactivity and Fear Learning." Neuropsychopharmacology : Official Publication of the American College of Neuropsychopharmacology, vol. 33, no. 11, 2008, pp. 2595-604.
Yang RJ, Mozhui K, Karlsson RM, et al. Variation in mouse basolateral amygdala volume is associated with differences in stress reactivity and fear learning. Neuropsychopharmacology. 2008;33(11):2595-604.
Yang, R. J., Mozhui, K., Karlsson, R. M., Cameron, H. A., Williams, R. W., & Holmes, A. (2008). Variation in mouse basolateral amygdala volume is associated with differences in stress reactivity and fear learning. Neuropsychopharmacology : Official Publication of the American College of Neuropsychopharmacology, 33(11), pp. 2595-604. doi:10.1038/sj.npp.1301665.
Yang RJ, et al. Variation in Mouse Basolateral Amygdala Volume Is Associated With Differences in Stress Reactivity and Fear Learning. Neuropsychopharmacology. 2008;33(11):2595-604. PubMed PMID: 18185497.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Variation in mouse basolateral amygdala volume is associated with differences in stress reactivity and fear learning. AU - Yang,Rebecca J, AU - Mozhui,Khyobeni, AU - Karlsson,Rose-Marie, AU - Cameron,Heather A, AU - Williams,Robert W, AU - Holmes,Andrew, Y1 - 2008/01/09/ PY - 2008/1/11/pubmed PY - 2009/4/23/medline PY - 2008/1/11/entrez SP - 2595 EP - 604 JF - Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology JO - Neuropsychopharmacology VL - 33 IS - 11 N2 - 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. SN - 1740-634X UR - https://www.unboundmedicine.com/medline/citation/18185497/Variation_in_mouse_basolateral_amygdala_volume_is_associated_with_differences_in_stress_reactivity_and_fear_learning_ L2 - http://dx.doi.org/10.1038/sj.npp.1301665 DB - PRIME DP - Unbound Medicine ER -