The dosage of the neuroD2 transcription factor regulates amygdala development and emotional learning.
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, alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor, and GABA(A) receptor. Thus, neuroD2 is essential for amygdala development and genes involved in amygdala function are altered in neuroD2-deficient mice.
Lin
Chin-Hsing
CH
Division of Clinical Research, Fred Hutchinson Cancer Research Center, Seattle, WA 98109, USA.
Hansen
Stacey
S
Wang
Zhenshan
Z
Storm
Daniel R
DR
Tapscott
Stephen J
SJ
Olson
James M
JM
D000679:Amygdala / Q000254:growth & development* / Q000378:metabolism; D000818:Animals; D017209:Apoptosis / Q000502:physiology; D051792:Basic Helix-Loop-Helix Proteins / Q000235:genetics / Q000378:metabolism*; D001526:Behavioral Symptoms; D015153:Blotting, Western; D047369:Chromatin Immunoprecipitation; D004644:Emotions / Q000502:physiology*; D006579:Heterozygote; D007150:Immunohistochemistry; D020287:In Situ Nick-End Labeling; D007858:Learning / Q000502:physiology*; D051379:Mice; D009419:Nerve Tissue Proteins / Q000378:metabolism; D009479:Neuropeptides / Q000235:genetics / Q000378:metabolism*
D051792:Basic Helix-Loop-Helix Proteins; D009419:Nerve Tissue Proteins; D009479:Neuropeptides; C098995:Neurod2 protein, mouse