The dosage of the neuroD2 transcription factor regulates amygdala development and emotional learning
- Chin-Hsing Lin*,†,
- Stacey Hansen*,
- Zhenshan Wang‡,
- Daniel R. Storm‡,
- Stephen J. Tapscott†,§,¶,∥, and
- James M. Olson*,¶,∥,**,††
- Divisions of *Clinical Research and †Human Biology, Fred Hutchinson Cancer Research Center, Seattle, WA 98109; and Departments of ‡Pharmacology, §Neurology, ¶Pathology, and **Pediatrics, and ∥Program in Neurobiology and Behavior, University of Washington, Seattle, WA 98105
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Communicated by Robert N. Eisenman, Fred Hutchinson Cancer Research Center, Seattle, WA, August 22, 2005 (received for review June 28, 2005)
Abstract
The amygdala is centrally involved in formation of emotional memory and response to fear or risk. We have demonstrated that the lateral and basolateral amygdala nuclei fail to form in neuroD2 null mice and neuroD2 heterozygotes have fewer neurons in this region. NeuroD2 heterozygous mice show profound deficits in emotional learning as assessed by fear conditioning. Unconditioned fear was also diminished in neuroD2 heterozygotes compared to wild-type controls. Several key molecular regulators of emotional learning were diminished in the brains of neuroD2 heterozygotes including Ulip1, α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor, and GABAA receptor. Thus, neuroD2 is essential for amygdala development and genes involved in amygdala function are altered in neuroD2-deficient mice.
Footnotes
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↵ †† To whom correspondence should be addressed. E-mail: jolson{at}fhcrc.org.
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Abbreviations: CS, conditioned stimulus; US, unconditioned stimulus; bHLH, basic helix-loop-helix; ChIP, chromatin immunoprecipitation; LA, lateral amygdala; BLA, basolateral amygdala; AMPA, α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid; En, embryonic day n; Pn, postnatal day n.
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Freely available online through the PNAS open access option.
- Copyright © 2005, The National Academy of Sciences
