Pup
pup vocalizations
Social transmission of maternal behavior
Maternal care is profoundly important for mammalian survival, and in many species requires the contribution of non-biological parents, or alloparents. In the absence of partum and post-partum related hormonal changes, alloparents acquire maternal skills from experience, by yet unknown mechanisms. One critical molecular signal for maternal behavior is oxytocin, a hormone centrally released by hypothalamic paraventricular nucleus (PVN). Do experiences that induce maternal behavior act by engaging PVN oxytocin neurons? To answer this, we used virgin female mice, animals that in the wild live in colonies with experienced mothers and their pups, helping with pup care. We replicated this setup in the lab, and we continuously monitored homecage behavior of virgin mice co-housed for days with a mother and litter, synchronized with recordings from virgin PVN cells, including from oxytocin neurons. Mothers engaged virgins in maternal care in part by shepherding virgins towards the nest, ensuring their proximity to pups, and in part by self-generating pup retrieval episodes, demonstrating maternal behavior to virgins. The frequency of shepherding and of dam retrievals correlates with virgin's subsequent ability to retrieve pups, a quintessential mouse maternal skill. These social interactions activated virgin PVN and gated behaviorally-relevant cortical plasticity for pup vocalizations. Thus, rodents can acquire maternal behavior by social transmission, and our results describe a mechanism for adapting brains of adult caregivers to infant needs via endogenous oxytocin.
Plasticity in hypothalamic circuits for oxytocin release
Mammalian babies are “sensory traps” for parents. Various sensory cues from the newborn are tremendously efficient in triggering parental responses in caregivers. We recently showed that core aspects of maternal behavior such as pup retrieval in response to infant vocalizations rely on active learning of auditory cues from pups facilitated by the neurohormone oxytocin (OT). Release of OT from the hypothalamus might thus help induce recognition of different infant cues but it is unknown what sensory stimuli can activate OT neurons. I performed unprecedented in vivo whole-cell and cell-attached recordings from optically-identified OT neurons in awake dams. I found that OT neurons, but not other hypothalamic cells, increased their firing rate after playback of pup distress vocalizations. Using anatomical tracing approaches and channelrhodopsin-assisted circuit mapping, I identified the projections and brain areas (including inferior colliculus, auditory cortex, and posterior intralaminar thalamus) relaying auditory information about social sounds to OT neurons. In hypothalamic brain slices, when optogenetically stimulating thalamic afferences to mimic high-frequency thalamic discharge, observed in vivo during pup calls playback, I found that thalamic activity led to long-term depression of synaptic inhibition in OT neurons. This was mediated by postsynaptic NMDARs-induced internalization of GABAARs. Therefore, persistent activation of OT neurons following pup calls in vivo is likely mediated by disinhibition. This gain modulation of OT neurons by infant cries, may be important for sustaining motivation. Using a genetically-encoded OT sensor, I demonstrated that pup calls were efficient in triggering OT release in downstream motivational areas. When thalamus projections to hypothalamus were inhibited with chemogenetics, dams exhibited longer latencies to retrieve crying pups, suggesting that the thalamus-hypothalamus noncanonical auditory pathway may be a specific circuit for the detection of social sounds, important for disinhibiting OT neurons, gating OT release in downstream brain areas, and speeding up maternal behavior.