*4.1. G*α*i2*

VSNs in the apical layer of epithelium in the VNS express *G*α*i2* (Table 1), and these cells have been implicated in moderating pup-directed aggression by detecting pup odor cues, major urinary proteins (MUPs), and odor cues from the facial area, such as exocrine gland-secreted peptide 1 (*ESP1*; Table 1; [90–92]). Pup odors activate regions of the OB and AOB (Table 1) that are innervated by *G*α*i2* neurons [58], prompting aggression. However, male mice with deletion of the *G*α*i2* gene were less aggressive towards pups, and showed increased grooming and retrieval of pups (Table 1), most likely because activation in the MPOA was increased in *<sup>G</sup>*α*i2-*/*-* males [93]. It is likely that *G*α*i2* activates *Trp2* and calcium ion entry downstream of V1R activation (Table 1), moderating aggression [93]. *G*α*i2* may also interact with FPRs and ORs in the VNO [83,94] to mediate pup-directed aggression and paternal care (Table 1).

#### *4.2. Trp2 (or Trpc2)*

In the VNO, activation of vomeronasal GPCRs causes a phospholipase C-dependent cascade [81], which regulates the *Trp2* cation channel [81,95]. Consequently, *Trp2* plays an important role in signal transduction in both V1R and V2R-expressing neurons [75,95]. Furthermore, *Trp2* plays a role in the expression of aggression in males (Table 1), with male *Trp2*-/- mice showing deficiency in social recognition of conspecifics [81], and a reduction in aggression in resident-intruder style tests [95,96]. These studies indicate that aggression requires a functional VNO. While commonly associated with sexual behaviors, *Trp2* could mediate paternal care by reducing aggression in males that might otherwise be directed towards their own pups. Inactivation of the *Trp2* channel does not impair detection of MHC peptides [30], most likely because MCH genes are expressed in a subpopulation of basilar VNS neurons, with M10 in particular being related to the expression of V2Rs [81]. This suggests that males could still identify their own pups via an MHC signature, as sensory neurons respond to MHC peptides in both the VNO and the MOE [97]. If *Trp2* in biparental males is deactivated while cohabiting with a female during the gestation period, or by olfactory cues from the pups themselves, this could cause males to respond paternally rather than aggressively towards their young [22]. Female *Trp2*-/- mice show impaired nest building behavior and time spent with pups [98,99], further suggesting that *Trp2* could also be important for regulating some direct paternal care behaviors as well (Table 1).
