The genetic control of neuronal number and behavior

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Project Summary/Abstract The genetic control of neuron number is an important mechanism by which genes can encode for behavior. Expansions of specific neuronal populations have been associated with behavioral innovations such as increased olfactory abilities, while deficiencies of particular neuronal types in humans have been associated with disorders including autism spectrum disorder. However, the genes and molecular pathways that specify neuron number to govern behavior are largely unknown. The proposed research investigates two ways in which innate behaviors are controlled by population sizes of specific neurons in the hypothalamus of Peromyscus deer mice. In the first aim, I will investigate how variation in parental nesting behavior is controlled by numbers of neuron expressing vasopressin, a neuropeptide with important roles in sociosexual behavior. In the second aim, I will investigate how variation in sex-specific parental behaviors are controlled by sex-specific neuronal numbers. This research takes advantage of two closely-related species of Peromyscus deer mice which have evolved large, heritable differences in parental care, but have minimal genetic differences between them. First, I will use comparative genomic sequencing and neurogenetics approaches, such as the detection of immediate- early genes, to implicate candidate cell types whose neuron numbers are co-evolving with and responsible for behavioral differences across Peromyscus species. Then, by combining genetic mapping with single-nuclei sequencing, I will determine the causal genetic loci controlling neuronal population sizes and test candidate genes for their effect on neuron number and downstream behavior. This research will implicate important neurodevelopmental pathways regulating innate behavior and contribute to our ability to diagnose and treat neurodevelopmental diseases. The proposed research will be conducted under the mentorship of Dr. Hopi Hoekstra, an expert in Peromyscus behavioral genetics, and Dr. Sean Eddy, an expert in comparative genomic data analysis. Additionally, I will be mentored by an advisory committee composed of Dr. Catherine Dulac, an expert in neurogenetics of social behaviors, Dr. Steve McCarroll, an expert in neuronal single-cell genomics, and Drs. Francesca Dominici and David Parkes, co-directors of the Harvard Data Science Initiative. Under this mentorship, I will develop research skills in molecular biology, mouse behavioral experiments, and neuronal single-cell data analysis. I will also use my training and participation in the MOSAIC program to develop leadership skills including lab management, inclusive mentoring, and scientific presentation skills. Together, my research training and career development activities will launch my successful transition to an independent research scientist.