Liu, Y. et al. Neuron (2023) https://doi.org/10.1016/j.neuron.2023.02.010

Most mammals’ first social relationship is with their mother. This early mother-child bond is critical for survival and might influence other behaviors later in life, including adult social behavior. A new study in Neuron reveals the critical role of serotonin in maternal affiliation by infants.

More than 10 years ago, while studying sexual preference in mice, Liu et al. noticed that the loss of the neurotransmitter serotonin (5-hydroxytryptamine; 5-HT) through knockout of tryptophan hydroxylase 2 (Tph2) – a gene encoding an enzyme required for synthetizing 5-HT in the brain – induced defective behavior in mouse pups. In their new work, the researchers generated mutations for Tph2 in rodents and non-human primates, and analyzed the behavior in Tph2−/− infants through a series of behavioral assays.

Their findings show that after separation from mothers, Tph2−/− mouse pups produced less ultrasonic vocalizations (USVs) – a signal to attract maternal caring – than Tph2+/+ and Tph2+/− pups. When presented with bedding from their mothers vs. bedding from other dams or vs. clean bedding, both Tph2+/+ and Tph2+/− mouse pups spent more time on maternal bedding, whereas Tph2−/− mouse pups showed no preference. Similarly, during separation from their mothers, Tph2–/– rat pups produced less USVs than Tph2+/+ rats, and showed no preference in the bedding preference assays. Analysis of videos of daily behaviors of monkey infants and their mothers in their home cage revealed that Tph2−/− infants interacted less with their mother than Tph2+/+ infants, indicating reduced affiliation. Altogether, these results demonstrate a conserved role for 5-HT in maternal–infant bonding, from mice to monkeys. “This is the first report of a molecule shown to play a behavioral role conserved from mice, rats to monkeys by genetic targeting,” write the investigators in their report, adding that their work should stimulate further research on the role of 5-HT in human infants.

By combining, genetics, pharmacology, optical imaging, immunocytochemistry, and chemogenetics, Liu et al. also showed that oxytocinergic neurons in the paraventricular nucleus, responsible for producing oxytocin, act downstream of serotonergic neurons in the raphe nucleus to regulate maternal affiliation in pup mouse, thereby demonstrating the role of the serotonin-oxytocin relationship in the regulation of this early social behavior.