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Maternal Brain Circuit Activated by Pups’ Cries Boosts Oxytocin

    PVN neurons, maternal brain, oxytocin, baby, mother, paraventricular nucleus, milk production

    Written by: Alla Katsnelson, Ph.D | Issue # 118 | 2024

    • Infants’ cries drive an increase in brain levels of oxytocin, a hormone that induces contractions during labor and regulates maternal behaviors and milk production.
    • Oxytocin is produced by neurons in a brain area called the hypothalamus, but researchers did not know how infants’ distress sounds could increase its levels.  
    • A new mouse study has identified a circuit, present only in the maternal brain, that responds to the sound of infant cries and that regulates maternal behaviors such as taking care of pups.

    A crying infant might pull on the heartstrings of any passerby, but those tears have a well-known physiological effect on the baby’s mother. By somehow increasing levels of the hormone oxytocin, the sound of a baby wailing compels a new mom to provide care for the baby and sometimes to release breast milk

    Researchers have now identified the mechanism underlying the link between infants’ cries and oxytocin increase  (1). In mice, they discovered a neuronal circuit that exists exclusively in the brains of mothers and activates oxytocin-releasing neurons in a brain region called the hypothalamus. They found that this circuit engages the auditory system and was activated by the sounds of a pup’s distress call. The findings show how sensory cues produced by an infant can spark a neural chain of events in the maternal brain to directly increase oxytocin levels.

    “We found that infant cries could stimulate oxytocin neurons and lead to oxytocin release,” says Robert Froemke, a neuroscientist at New York University who co-led the study. “However, this required seconds to minutes of hearing the cries, as the oxytocin neurons are slow to respond, only firing after hearing quite a few cries over and over again, and when ‘they are sure’ there’s really a needy baby nearby.”

    Oxytocin is a peptide hormone that is produced mainly in a specific nucleus of the hypothalamus, called the paraventricular nucleus (PVN). Its main functions include inducing contractions during labor, stimulating the release of breast milk, and promoting parental care (2). To investigate how exactly a baby’s cries act as a signal for neurons in the PVN to release oxytocin, the researchers began by recording the activity of those neurons in mouse dams while playing auditory recordings of pups’ distress calls. The neurons got activated, the researchers found but only after pup distress calls had been broadcast for about 30 minutes. Those neurons didn’t get activated when the researchers played other sounds—and they also did not get activated in mice that had never had babies.  

    Next, the researchers injected the PVN neurons with a virus-based tracer molecule to identify what other parts of the brain they connected with. The tracer revealed that the neurons projecting from the PVN come from a lower brain area called the thalamus—and specifically, a part of the thalamus that processes auditory input. Recording showed that the extended thalamic stimulation spurred oxytocin production by lifting the inhibition on PVN neurons. Other studies have hinted that the thalamic region involved plays a role in perceiving unconscious sounds, especially ones that carry emotional value. 

    To demonstrate this circuit’s involvement in parental behaviors relating to caring for infants, Froemke and his colleagues used a technique called chemogenetic suppression to prevent the thalamic neurons from signaling to the PVN. Those dams eventually stopped retrieving crying pups that had been moved away from them by researchers. But when the chemical block was removed, their commitment to pup retrieval returned. Finally, by labeling oxytocin molecules with sensors, the researchers also showed that activation of the PVN neurons upon hearing pups’ distress cries resulted in oxytocin being released specifically in a brain area that has been linked to maternal behaviors (3). That brain area, called the ventral tegmental area, is thought to regulate behavior related to reward and motivation. 

    According to a commentary accompanying the study, one of its limitations was the unnatural conditions of the experiment, with mice hearing recordings of pup calls (4). The circuitry may be different if the dams hear their own pups’ cries, say the commentary’s authors, Flavia Ricciardi and Cristina Márquez from the University of Coimbra in Portugal. One question the research raises is whether this circuitry is affected in people with conditions such as postpartum depression, they write.  

    Froemke says a future direction is to study how this circuit affects oxytocin’s role in lactation and nursing. “We’re hopeful that new technical developments will let us start working on bona fide milk delivery in years ahead,” he says. 

    References

      1. Valtcheva S, Issa HA, Bair-Marshall CJ, Martin KA, Jung K, Zhang Y, Kwon HB, Froemke RC. Neural circuitry for maternal oxytocin release induced by infant cries. Nature. 2023: 621(7980):788-795.
      2. Valtcheva S, Froemke RC. Neuromodulation of maternal circuits by oxytocin. Cell Tissue Res. 2019: 375(1):57-68. 
      3. Pedersen CA, Caldwell JD, Walker C, Ayers G, Mason GA. Oxytocin activates the postpartum onset of rat maternal behavior in the ventral tegmental and medial preoptic areas. Behav Neurosci. 1994: 108(6):1163-1171. 
      4. Ricciardi F, Márquez C. The neural circuit that makes maternal mice respond to pups’ cries. Nature. 2023: 621(7980):693-694.