Wednesday, December 4, 2024
12/4/2024
Project Summary / Abstract Child health stands to benefit greatly from nurturing fathers or be harmed by paternal abuse and neglect. However, little is known about the neural basis of paternal behavior in any species, and there has been no thorough mechanistic account for why some fathers are nurturing while others are abusive or neglectful. Moreover, there is little information on how these phenotypes may be shaped by environmental experience. In the proposed research, I will use a novel biparental rodent model species, the African striped mice (ASM), to elucidate the neural and social-experiential mechanisms governing differences in paternal care. Male ASM readily exhibit pup care both before and after sexual experience and display natural variation in paternal care. ASM paternal phenotypes are also influenced by peri-adolescent social experience. Thus, using ASM, it is uniquely possible and convenient to observe both naturally occurring individual differences and experientially induced phenotypes in a single rodent species. In order to elucidate the neurobiological mechanisms subserving individual differences in paternal care, I will use a combination of behavioral, circuit activity mapping, pharmacogenetic, and molecular techniques. In Aim 1, I will define a “paternal brain network” of brain-wide pup- induced neural activity using whole-brain imaging and computational analysis. I will then test the functional relevance of neural activity in key regions for paternal care behavior by chemogenetic manipulation (i.e., DREADDs). This aim will determine whether activity in specific brain regions or patterns of coordinated brain activation subserve natural variation in paternal behavior– from caring to abusive. In Aim 2 I will characterize the transcriptional basis of variation in paternal care using single-nucleus RNA sequencing in one key brain region. This aim will distinguish whether activity in specific cell types drive natural variation in paternal care, and whether specific genes or biological pathways are linked with paternal vs infanticidal behavior. Taken together, the proposed studies will enable me to gain training in a number of cutting-edge techniques while substantially advancing the collective understanding of the neural activity and molecular basis of variation in paternal care, with future applications for improving caregiving and offspring outcomes.
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