Trpc2-deficient lactating mice exhibit altered brain and behavioral responses to bedding stimuli

Abstract

The trpc2 gene encodes an ion channel involved in pheromonal detection and is found in the vomeronasal organ. In tprc2(-/-) knockout (KO) mice, maternal aggression (offspring protection) is impaired and brain Fos expression in females in response to a male are reduced. Here we examine in lactating wild-type (WT) and KO mice behavioral and brain responses to different olfactory/pheromonal cues. Consistent with previous studies, KO dams exhibited decreased maternal aggression and nest building, but we also identified deficits in nighttime nursing and increases in pup weight. When exposed to the bedding tests, WT dams typically ignored clean bedding, but buried male-soiled bedding from unfamiliar males. In contrast, KO dams buried both clean and soiled bedding. Differences in brain Fos expression were found between WT and KO mice in response to either no bedding, clean bedding, or soiled bedding. In the accessory olfactory bulb, a site of pheromonal signal processing, KO mice showed suppressed Fos activation in the anterior mitral layer relative to WT mice in response to clean and soiled bedding. However, in the medial and basolateral amygdala, KO mice showed a robust Fos response to bedding, suggesting that regions of the amygdala canonically associated with pheromonal sensing can be active in the brains of KO mice, despite compromised signaling from the vomeronasal organ. Together, these results provide further insights into the complex ways by which pheromonal signaling regulates the brain and behavior of the maternal female.

Figure 1

KO dams defensively bury both clean and soiled bedding. A) WT dams show a significantly longer latency to bury clean than soiled bedding, but KO dams begin burying both with a shorter latency, B) WT dams spend significantly more time burying soiled bedding than clean, but KO dams bury soiled and clean for longer periods. C) KO dams show a shorter latency to crouch over the nest than WT dams. KO = Trpc2^-/-, WT = Trpc2^+/+, CB = exposed to clean bedding, SB = exposed to soiled bedding. N's shown in parentheses. Bars marked with an a are significantly different from WT CB. * indicates P <0.05.

Figure 2

KO dams and pups weigh more, KO dams provide different maternal care. A) KO dams weigh more than WT dams on PPD 6, B) KO dams eat/drink more frequently, C) KO pups weigh more than WT pups on PPD 0 and PPD 6, D) KO dams nest-build less frequently, E) KO dams nurse less frequently at night, starting at PPD 3. KO = Trpc2-/-, WT = Trpc2+/+, PPD = postpartum day. Ns shown in parentheses. * p < 0.05.