Research

Examining the Social Brain

Circuits underlying sex-specific behaviors

Our genetic manipulation of pheromone signaling led to a novel assessment of the respective roles of the vomeronasal organ (VNO) and the main olfactory epithelium (MOE) in pheromone-mediated behaviors. We discovered that, in contrast to previous thinking, VNO activity is not required for the initiation of male-female mating behavior in the mouse, and instead, ensures sex discrimination among conspecifics. In contrast, MOE signaling appears essential to trigger mating in the mouse. In a follow-up study, we showed that female mice lacking TRPC2, an ion channel specifically expressed in the VNO and essential for vomeronasal signal transduction, display unique characteristics of male sexual behaviors and show defects in female-typical behaviors. These data led us to propose that functional neuronal circuits underlying both male-and female-specific behaviors exist in the mouse female brain, and that, in normal females, the vomeronasal system controls the sex-specificity of social behaviors by activating female-specific effector circuits, while repressing male-specific circuits.

Imaged right: TRPC2 labeling (green) in the VNO

Circuits underlying parental behavior

The sexual dimorphism of male and female behavior towards pups offers a unique opportunity to explore the nature and function of the underlying neural circuits. Using c-fos induction as readout of neuronal activity, we identified Galanin-expressing neurons in the Medial Preoptic Area (MPOA) as specifically activated during parental behavior of both males and females and showed that their ablation results in dramatic impairment of parental responses in males and females, while optogenetic activation in virgin males suppresses pup-directed aggression and induces pup grooming. These data provide significant insights into the control of opposing social behaviors: parenting versus pup-directed aggression, and opens new avenues to dissect circuits underlying parental behaviors and their modulation by social experience.

Left: In situ staining of galanin and cfos identifying MPOA neurons critical for parental behavior

Social representation in the medial amygdala

 

The medial amygdala (MeA) plays a critical role in processing species- and sex-specific signals that trigger social and defensive behaviors.  We used a micro-endoscope to perform long-term Ca2+ imaging in MeA across different social contexts. We found that sexual experience triggers lasting and sex-specific changes in MeA activity, which, in males, involve signaling by oxytocin. Further, we found that exposure to pups, a male, or a female activated distinct groups of cells in a salt and pepper distribution without any clear spatial organization.

Imaged right: experimental paradigm (left), spatial distribution of male and female responsive neurons in MeA

 

Genomic Imprinting

 

Utilizing RNA-sequencing and a powerful statistical model, we were able to map 41 novel imprinted genes in the developing and adult mouse cerebellum, adding to the known list of 74. Notably, we were able to demonstrate that many of these imprinted genes are parentally biased specifically in the brain and not in other organs. We also showed that parentally biased genes vary in the degree of their bias depending on age and brain region. As mice age, the bias tends to level out.

Imaged left: hierarchical clustering of imprinted genes expressed differentially depending on the brain/body region

 

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