Social behavior is a hallmark of human biology, and dysfunction in social behavior ? such as autism-spectrum (ASD) and related disorders ? can have immeasurable impacts on the emotional and mental health of affected individuals and their families. One of the major limitations to understanding and treating conditions like ASD is that a common mechanism that unifies the broad range of behavioral differences observed in patients has not yet been identified. Our ability to find these mechanisms is hindered by the fact that many of the animal models used to study these disorders do not have behavioral variation that adequately captures the complex changes in social behavior observed in patients. Here, I propose a novel, integrative approach to overcome these limitations and uncover the factors that shape the origins and dysfunction of the `social brain'. First, I will harness the dramatic variation in social behavior found within halictid bees to make direct comparisons between social and non-social individuals to identify: (1) the core genetic mechanisms associated with the emergence and breakdown of social behavior, and (2) differences in the genes, brains, and behaviors of social and non-social bees reared in the same, experimentally manipulated social environments. Then, I will take advantage of the automated tracking and genetic manipulation tools we have developed in bumble bees to study (3) how individual social behaviors change when these core molecular mechanisms are perturbed. The novelty of this approach lies in our ability to directly compare social and non-social bees across a range of environmental and social contexts. Studies comparing differences in the developmental trajectories of the brains of social and non-social individuals are completely untapped, and promise to help identify core neurobiological and genetic mechanisms that shape the `social brain'. Because the genetic and epigenetic mechanisms underlying brain physiology and behavior are highly conserved among insects and mammals, the insights gained from this work will also be relevant to humans.

Public Health Relevance

One of the major limiting steps in identifying the core set of mechanisms that underlie psychiatric disorders like autism is that the available animal models cannot adequately capture the complex changes in social behaviors displayed by patients. Halictid bees are an exciting new model that can overcome this limitation ? many of these bees live in elaborate societies with complex communication systems used to divide and coordinate labor among group members while many others do not. We can harness this dramatic variation to directly compare the genes, brains, and behaviors of social and non-social individuals across a range of controlled experimental conditions to uncover the core set of genetic and neurobiological mechanisms that can make and break a social brain.

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
NIH Director’s New Innovator Awards (DP2)
Project #
1DP2GM137424-01
Application #
9782448
Study Section
Special Emphasis Panel (ZRG1)
Program Officer
Sesma, Michael A
Project Start
2019-09-30
Project End
2024-05-31
Budget Start
2019-09-30
Budget End
2024-05-31
Support Year
1
Fiscal Year
2019
Total Cost
Indirect Cost
Name
Princeton University
Department
Biology
Type
Schools of Arts and Sciences
DUNS #
002484665
City
Princeton
State
NJ
Country
United States
Zip Code
08543