Impaired social processes are a common feature in diverse psychiatric disorders such as communication disorders, autism-spectrum disorder, depression, and schizophrenia. Despite extensive studies using mouse models and human brain imaging, the mechanisms underlying deficiencies in social processes are obscure. Experiments with ArpC3 or Shank3 mice reveal that homozygous mutants from both strains are deficient in social behavior. We have developed a system where selected genes can be disrupted within a specific neural circuit and have some preliminary results that a prefrontal cortex (PFC) to basolateral amygdala (BLA) circuit can modulate social behavior. The Overall Goal of this proposal is to use this novel circuit-based gene manipulation approach to identify neural circuits in the ArpC3 and Shank3 mutant mice that may regulate social behaviors. Our Central Hypothesis is that disturbances in a PFC-BLA neural circuit produce abnormal social behaviors.
In Aim #1 we will determine whether the PFC-BLA circuit is a common neural pathway controlling abnormal social behavior in ArpC3 and Shank3 mice.
Aim #2 will analyze the collateral circuit projecting from the PFC to both BLA and VTA, and test the distinctive responses of recipient neurons in the BLA and VTA during social interaction.
Aim #3 will focus on identifying additional neural circuits downstream of the PFC-BLA circuit that can modulate social processes.

Public Health Relevance

In the RDoC matrix, social processes represent an important behavioral domain in humans. We have found that a PFC-BLA neural circuit may regulate social behaviors in ArpC3 mice and this work will be extended further in this strain and examined in Shank3 mice. Identification of a common neural circuit for social behavior may provide a foundation for therapeutic intervention in humans.

Agency
National Institute of Health (NIH)
Institute
National Institute of Mental Health (NIMH)
Type
Research Project (R01)
Project #
1R01MH117429-01A1
Application #
9739624
Study Section
Biobehavioral Regulation, Learning and Ethology Study Section (BRLE)
Program Officer
Simmons, Janine M
Project Start
2019-06-18
Project End
2023-04-30
Budget Start
2019-06-18
Budget End
2020-04-30
Support Year
1
Fiscal Year
2019
Total Cost
Indirect Cost
Name
University of Tennessee Health Science Center
Department
Anatomy/Cell Biology
Type
Schools of Medicine
DUNS #
941884009
City
Memphis
State
TN
Country
United States
Zip Code
38103