Vasopressin eliminates the expression of familiar odor bias in neonatal female mice through V1aR

Abstract

Summary V1aR has a well established role in the neural regulation of adult mammalian social behavior. The role of V1aR in developmentally emerging social behavior is less well understood. We mapped V1aR at post-natal day 8 (P8) and demonstrate developmentally-specific expression in the neocortex and hippocampus. We tested the ability of male and female C57BL/6J mice to show orienting bias to a familiar odor at this age. We demonstrate that females, but not males, show an orienting bias for odors previously paired with the mother, which is eliminated by V1aR signaling. Arginine-vasopressin (AVP) and the vasopressin V1a receptor (V1aR) acting within the forebrain are involved in social behavior in adult animals. Much less is known about the function of V1aR in neurobehavioral development. In the present study, at post-natal day 8 (P8) in neonatal C57BL/6J mice, we map V1aR and use an olfactory exposure paradigm to assess a role for V1aR on olfactory preferences. In addition to V1aR in the lateral septum and ventral tegmental area, we observe V1aR in the neocortex and hippocampus, not typically observed in adult mice, implicating a developmental sensitive period for V1aR to modulate these brain areas in an experience-dependent manner. Males and females were tested on P8 for orienting preferences after exposure to a non-social odor, presented either when the mother was in the home cage (contingent) or when the mother had been removed from the home cage (not contingent). Wild-type female mice show a selective orienting bias toward the exposed odor, but only in the contingent condition. Males did not show orienting bias after either training condition. Female Avpr1a-/- mice showed strong familiar odor bias, regardless of the training condition. This finding led us to test the ability of AVP to diminish odor bias in females. Central application of AVP eliminated odor bias in Avpr1a+/+, but not Avpr1a-/- female mice. Together, these data indicate that AVP acting at V1aR eliminates the expression of familiar odor bias in neonatal mice. This suggests a developmental role for AVP on familiarity bias, which has implications for species-typical life history trajectories of social learning and natal dispersal.

Developmental effects of vasotocin and nonapeptide receptors on early social attachment and affiliative behavior in the zebra finch

“…The production of AVP mRNA in the meAMY and BSTm begins later in development (between postnatal day 3 and day 14) and is highly sexually dimorphic, with production of AVP starting later in females and taking longer to reach adult levels (Szot and Dorsa, 1993). Additionally, binding sites were found in the developing rodent brain in both the amygdala and septum between postnatal day 0 and 8, as well as several brain regions where nonapeptide receptors are not expressed in adulthood, including the hippocampus, dentate gyrus, and caudate nucleus (mice: Hammock et al, 2013; rat: Petracca et al, 1986; multiple vole species: Wang et al, 1997). AVT is produced in the brain at least as early as 4 weeks of age in male canaries, though earlier ages were not assessed (Voorhuis et al, 1991).…”

“…In rodents, the beginning of production of AVP/OT from the extrahypothalamic sources and central nonapeptide receptor expression is coincident with important milestones in early social attachment and learning (Blass, 1987; Buijs et al, 1980; Hammock et al, 2013; Petracca et al, 1986; Szot and Dorsa, 1993; Wang & Young, 1997). A limited number of experimental manipulations of nonapeptides during development in rodents provide further evidence for the organizational hypothesis.…”

Post-weaning infant-to-mother bonding in nutritionally independent female mice

“…The neural pathways involved in attachment in infants are unclear, but vasopressin and oxytocin could also play a role here since they are also present in the developing brain. Neonatal social behavior is influenced by the activity levels of both neuropeptides [54][55]. Activation of the infant oxytocin system is provoked by the sensory experiences of maternal engagement [56], which could control reciprocal bonding behaviors between mother and infant [22].…”

Effects of alcohol and psychostimulants on the vasopressin system: Behavioural implications

“…For example, the V1a is involved in initial olfactory learning to allow the pup to detect the food and protection from the mother. Using the V1a KO mice tool, Hammock et al . showed that the normal strong preference for the odour of the mother is unspecific in these animals.…”