Oxytocin Neurons Enable Social Transmission of Maternal Behavior

Abstract

Maternal care is profoundly important for mammalian survival, and maternal behaviors can also be expressed by non-biological parents after experience with infants. One critical molecular signal for maternal behavior is oxytocin, a hormone released in the brain by hypothalamic paraventricular nucleus (PVN). Oxytocin enables plasticity within the auditory cortex, a necessary step for responding to infant vocalizations. To determine how this change occurs during natural experience, we continuously monitored homecage behavior of female virgin mice co-housed for days with an experienced mother and litter, synchronized with in vivo recordings from virgin PVN cells, including from identified oxytocin neurons. Mothers engaged virgins in maternal care by ensuring that virgins were in the nest, and demonstrated maternal behavior in self-generated pup retrieval episodes. These social interactions activated virgin PVN and gated behaviorally-relevant cortical plasticity for pup distress calls. Thus rodent maternal behavior can be learned by social transmission, and our results describe a mechanism for adapting the brains of adult caregivers to infant needs via endogenous oxytocin. One Sentence Summary:Mother mice help co-housed virgins become maternal by enacting specific behaviors that activate virgin oxytocin neurons.Main Text: Social interactions, such as pair bond formation and child rearing, are fundamental aspects of animal and human behavior (1-4). Parental care is especially important in mammals, and new parents must rapidly and reliably express a number of behaviors required for survival of offspring. Some parental behavior is therefore believed to be at least in part innate and hard-wired, or gated by neurochemical changes after mating. However, maternal behavior can also be acquired from experience. In humans and other primates, individuals other than the biological parents can learn to successfully care for children after instruction or observation of experienced caretakers and infants (1-8). It is unclear how expression of such alloparenting behaviors in rodents or other species can also be learned from experience, and if so, what mechanisms of neuromodulation and plasticity underlie learning of maternal behaviors.One of the most important molecular modulators of neural circuit function for social interactions and maternal physiology is the evolutionarily-ancient peptide hormone oxytocin (1,2, 9,10). In mammals, oxytocin is released from the hypothalamus and is critical for childbirth and lactation (10,11). Oxytocin also acts in the brain where it is believed to increase the salience of social information, enhancing pair bonding and maternal behavior (1,9,(12)(13)(14)(15), and enabling onset of alloparenting in mice. Specifically, pup-naïve virgin female mice initially ignore neonates and cues related to infant need, e.g., ultrasonic distress calls emitted by pups isolated from the nest (15). However, after several days of co-housing with experienced mothers ('dams') and litters, most virgin females become mate...

Neural circuitry for maternal oxytocin release induced by infant cries

“…Oxytocin neurons were identified by reliable spiking responses to brief pulses of blue light ( Figures 1C and S1 ), elicited by short blue light pulses (50 ms; Figures S1A and B ) or long pulses (200 ms; Figures S1C-G ) at various laser powers. Recordings from ChR2+ (OT+) and ChR2− (OT−) neurons were made at similar depths from the pial surface, and had baseline firing rates ( Figure 1D ) comparable to those previously reported for extracellular recordings of PVN neurons in rodents (Wakerley and Lincoln, 1973; Summerlee and Lincoln, 1981; Belin and Moos, 1986; Brown and Moos, 1997) including recent studies of optically-identified oxytocin cells (Carcea et al, 2019; Tang et al, 2020).…”

“…These studies suggested that oxytocin neurons exhibit bursts of high-frequency action potentials in response to suckling or during the expulsive phase of labor (Wakerley and Lincoln, 1973; Summerlee, 1981; Summerlee and Lincoln, 1981; Belin and Moos, 1986; Brown and Moos, 1997). More recently, recordings in awake female mice and rats revealed that identified oxytocin neurons display lower frequency firing during social interactions with conspecifics (Carcea et al, 2019; Tang et al, 2020). We found that oxytocin neurons in awake animals exhibited sustained increases in firing lasting for hundreds of seconds after exposure to pup calls.…”

“…Our results show that pup calls can act as a natural signal for relieving synaptic inhibition and enabling the activation of oxytocin neurons in dams. Both putative and identified oxytocin cells are relatively silent in vivo, having very low spontaneous firing rates (Wakerley and Lincoln, 1973; Summerlee, 1981; Summerlee and Lincoln, 1981; Belin and Moos, 1986; Brown and Moos, 1997; Carcea et al, 2019; Tang et al, 2020). This implies that oxytocin neurons are not easily activated by spontaneous synaptic events but require strong and synchronous synaptic drive to reach action potential threshold.…”

“…It has therefore been historically challenging to make recordings from unambiguously identified oxytocin neurons. Recent studies using optogenetic phototagging or Ca 2+ imaging methods have successfully recorded from identified PVN oxytocin neurons in non-parental female and male rodents in vivo (Hung et al, 2017; Carcea et al, 2019; Resendez et al, 2020; Tang et al, 2020), showing that these cells can be activated during social interactions. Other hypothalamic cell types possibly receive information about non-somatic sensory input as well, such as activation of CRH neurons by visual stimuli (Daviu et al, 2020).…”

Systematic analysis of goal-related movement sequences during maternal behavior in a female mouse model for Rett syndrome

“…Particularly, detailed characterization of different aspects of maternal behavior have shown that at least three, one-hour exposures to pups are needed to induce full and/or partial maternal behavior in adult mice (Alsina-Llanes et al, 2015;Stolzenberg and Rissman, 2011). For pup retrieval specifically, cohousing with pups and dam contributes significantly to efficient retrieval in nulliparous mice (Cohen et al, 2011;Marlin et al, 2015;Krishnan et al, 2017;Carcea et al, 2020). Thus, mice still require a sensitization period for efficient expression of maternal behavior, but on a shorter time scale (Alsina-Llanes et al, 2015;Calamandrei and Keverne, 1994;Lonstein and De Vries, 2000;Krishnan et al, 2017).…”