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Genetic and Structural Analysis of the Basolateral Amygdala Complex in BXD Recombinant Inbred Mice

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Abstract

The amygdala integrates and coordinates emotional and autonomic responses. The genetics that underlie variation in amygdala structure may be coupled to variation in levels of aggression, fear, anxiety, and affiliated behaviors. We systematically quantified the volume and cell populations of the basolateral amygdala complex (BLAc) across 35 BXD recombinant inbred (RI) lines, the parental strains—C57BL/6J (B6) and DBA/2J (D2)—and F1 hybrids (n cases = 199, bilateral analysis). Neuron number and volume vary 1.7- to 2-fold among strains (e.g., neuron number ranged from 88,000 to 170,000). Glial and endothelial populations ranged more widely (5- to 8-fold), in part because of higher technical error. A quantitative trait locus (QTL) for the BLAc size is located on chromosome (Chr) 8 near the Large gene. This locus may also influence volume of other regions including hippocampus and cerebellum. Cell populations in the BLAc appear to be modulated more weakly by loci on Chrs 11 and 13. Candidate genes were selected on the basis of correlation with BLAc traits, chromosomal location, single nucleotide polymorphism (SNP) density, and expression patterns in the Allen Brain Atlas. Neurod2, a gene shown to be significant for the formation of the BLAc by knockout studies, is among the candidates genes. Other candidates include Large, and Thra. Responses to drugs of abuse and locomotor activity were the most notable behavioral correlates of the BLAc traits.

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Acknowledgments

The authors would like to thank Arthur G. Centeno and Dave J. Seecharan for technical assistance. We thank Dr. Glenn D. Rosen and colleagues for building the Mouse Brain Library. We thank Dr. Kenneth J. Manly, Jintao Wang, and Dr. Elissa J. Chesler for their many contributions to GeneNetwork. This study was supported by NIAAA-INIA (grants U01AA13499 and U24AA13513). GN is supported by NIDA, NIMH and NIAAA (grant P20-DA 21131), the NCRR BIRN (U01NR 105417), and the NCI MMHCC (U01CA105417).

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Authors and Affiliations

  1. Department of Anatomy and Neurobiology, University of Tennessee Health Science Center, 855 Monroe Avenue, Memphis, TN, 38163, USA

    Khyobeni Mozhui, Kristin M. Hamre, Lu Lu & Robert W. Williams

  2. Section on Behavioral Science and Genetics, Laboratory for Integrative Sciences, NIAAA, Rockville, MD, USA

    Andrew Holmes

  3. Key Laboratory of Nerve Regeneration, Nantong University, Nantong, Jiangsu Province, China

    Lu Lu

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  1. Khyobeni Mozhui
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  2. Kristin M. Hamre
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  3. Andrew Holmes
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  4. Lu Lu
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  5. Robert W. Williams
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Correspondence to Lu Lu or Robert W. Williams.

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Mozhui, K., Hamre, K.M., Holmes, A. et al. Genetic and Structural Analysis of the Basolateral Amygdala Complex in BXD Recombinant Inbred Mice. Behav Genet 37, 223–243 (2007). https://doi.org/10.1007/s10519-006-9122-3

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