The transient receptor potential cation channel 2 (TRPC2) is canonically known for carrying pheromonal information from the vomeronasal organ (VNO) to the brain in rodents. Mice with a disabled TRPC2 gene display drastic changes in sex-specific behaviors, including sexual and aggressive behavior. Specifically, male-male and maternal aggression is absent while both males and females show male-typical mounting behavior directed towards both sexes in a non-preferential manner. In short, sexual preference seems to be severely disrupted. Several groups have shown that the VNO of TRPC2 knockout (KO) mice show a markedly reduced activation of the VNO in response to pheromones, suggesting that pheromonal signaling via TRPP2 channels in the VNO shape these sex-specific behaviors. However, TRPC2 is also expressed in other tissues, including the reproductive organs, raising the possibility that disruption of TRPC2 function outside the VNO also contributes to changes in adult sex-specific behavior. My dissertation research aims to understand the underpinnings of this behavioral change, examining how the loss of TRPC2 function influences pre- and postnatal development, reproductive success and morphological sex differences in the brain. First, I found that mice lacking TRPC2 display defects in their development, with effects on pubertal timing and pup survival, along with effects on reproductive success. While maternal experience rescued pup survival in TRPC2 KO mice, it did not improve reproductive outcomes. Next, I examined two brain regions implicated in the control of mounting and aggression, the posterodorsal aspect of the medial amygdala and ventromedial hypothalamus. Ux phystilizing a Nissl stain and glial fibrillary acidic protein immunohistochemistry, I determined that TRPC2 KO mice show altered patterns of sex differences at the cellular level in both these regions, offering insight into the neural mechanisms underlying impaired sexual and aggressive behavior. Finally, I examined whether sexual experience can reverse deficits in behavior and rescue the brain's response to pheromones. I found that prolonged sexual experience did not reinstate normal sexual preference nor recover the brain response to pheromones. These experiments suggest TRPC2 function, driven by pheromones and possibly other incoming signals, participates in organizing sex-specific behavior and brain circuitry. TRPC2 function outside the VNO may also impact adult sex-specific behaviors.
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