Sexually reproducing animals display differences in social behaviors such as mating, parental care, and territorial aggression. These dimorphic behaviors are a consequence of molecular, cellular and circuit level sex differences in the brain. The amygdala is a deeply conserved evolutionary structure, including in humans, that is thought to control emotions and other instinctual responses. Indeed the amygdala is thought to mediate many behaviors such as fear, stress response, predator avoidance, mating and aggression. This functional diversity is reflected in the cellular and molecular heterogeneity of the region. One component of the amygdala, the medial amygdala (MeA), is thought to be critical for mating and aggressive behavior. My mentor's lab, the Shah Lab, has identified a discrete set of neurons in the MeA that is sexually dimorphic, which suggests that these neurons may be important for dimorphic displays of mating and fighting. Consistent with this idea, these neurons (and only these neurons within the MeA) express the enzyme aromatase. Aromatase converts circulating testosterone into estrogen in the male brain, and its function is essential for male-typical displays of mating and aggression. Thus previous work has shown that the MeA is required for dimorphic social behaviors, and this subset of neurons in the MeA expresses an enzyme that is also required for these behaviors. I hypothesize that these aromatase+ MeA neurons are essential for the display of mating and aggression. To test my hypothesis I will genetically ablate these neurons in a conditional manner in both males and females and test for alterations in mating and aggression. This study will not only shed light on the function of aromatase+ neurons in the MeA in controlling sexually dimorphic behaviors, but because the MeA is a highly evolutionarily conserved region, it is very likely to be pertinent to human health as well. Pathophysiological studies demonstrate the relevance of the amygdala to many neuropsychiatric disorders: mood and anxiety disorders, autism spectrum disorders, schizophrenia, and more, all of which show sex differences. My studies will advance our understanding of basic neural circuitry and function of this important, sexually dimorphic brain region, which will be invaluable to human health and disease.

Public Health Relevance

Pathophysiological studies demonstrate the relevance of the amygdala to many neuropsychiatric disorders: mood and anxiety disorders, autism spectrum disorders, schizophrenia, and more, which all show sex differences. My studies will advance our understanding of basic neural circuitry and function of this important, sexually dimorphic brain region, which will be relevant to human health and disease.

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Predoctoral Individual National Research Service Award (F31)
Project #
5F31NS078959-03
Application #
8641736
Study Section
Special Emphasis Panel (ZRG1-F03A-N (20))
Program Officer
Gnadt, James W
Project Start
2012-04-01
Project End
2015-03-31
Budget Start
2014-04-01
Budget End
2015-03-31
Support Year
3
Fiscal Year
2014
Total Cost
$36,276
Indirect Cost
Name
University of California San Francisco
Department
Anatomy/Cell Biology
Type
Schools of Medicine
DUNS #
094878337
City
San Francisco
State
CA
Country
United States
Zip Code
94143
Unger, Elizabeth K; Burke Jr, Kenneth J; Yang, Cindy F et al. (2015) Medial amygdalar aromatase neurons regulate aggression in both sexes. Cell Rep 10:453-62
Morgan, Charles W; Julien, Olivier; Unger, Elizabeth K et al. (2014) Turning on caspases with genetics and small molecules. Methods Enzymol 544:179-213
Yang, Cindy F; Chiang, Michael C; Gray, Daniel C et al. (2013) Sexually dimorphic neurons in the ventromedial hypothalamus govern mating in both sexes and aggression in males. Cell 153:896-909