Understanding the Instinctive Drive for Social Interactions

Neurodevelopmental disorders that cause cognitive, behavioural or motor impairments affect around 15% of children and adolescents worldwide¹, with diagnoses of profound autism and attention deficit hyperactivity disorder increasing in the USA and contributing to a major economic burden^2,3. Yet the origins and mechanisms of these conditions remain poorly understood, limiting progress in therapies. Comprehensive cell atlases of the developing human brain, alongside those of model organisms such as mice and non-human primates, are now providing high-resolution measures of gene expression, cell-type abundance and spatial distribution. In this Perspective, we highlight recent studies that have identified novel developmental cell populations, revealed conserved and divergent patterns of cell genesis, migration and maturation across species, and begun testing hypotheses that link them to processes ranging from transcriptional control of cell fate specification to the emergence of complex behaviours. We present remaining conceptual and technical challenges and provide an outlook on how further studies of human and mammalian brain development can empower a deeper understanding of neurodevelopmental and neuropsychiatric disorders. Future efforts expanding to additional developmental stages, including adolescence, as well as whole-brain, multimodal and cross-species integration, will yield new insights into how development shapes the brain. These atlases promise to serve as essential references for unravelling mechanisms of brain function and disease vulnerability, and for advancing precision medicine.

Mammalian behaviour and physiology undergo major changes in early life. Young animals rely on conspecifics to meet their needs and start showing nutritional independence and sex-specific social interactions at weaning and puberty, respectively. How neuronal populations regulating homeostatic functions and social behaviours develop during these transitions remains unclear. We used paired transcriptomic and chromatin accessibility profiling to examine the developmental trajectories of neuronal populations in the hypothalamic preoptic region, where cell types with key roles in physiological and behavioural control have been identified^1,2,3,4,5,6. These data show a marked diversity of developmental trajectories shaped by the sex of the animal, and the location and behavioural or physiological function of the corresponding cell types. We identify key stages of preoptic development, including early diversification, perinatal emergence of sex differences, postnatal maturation and refinement of signalling networks, and nonlinear transcriptional changes accelerating at the time of weaning and puberty. We assessed preoptic development in various sensory mutants and find a major role for vomeronasal sensing in the timing of preoptic cell type maturation. These results provide new insights into the development of neurons controlling homeostatic functions and social behaviours and lay ground for examining the dynamics of these functions in early life.

Social grouping increases survival in many species, including humans^1,2. By contrast, social isolation generates an aversive state (‘loneliness’) that motivates social seeking and heightens social interaction upon reunion^3,4,5. The observed rebound in social interaction triggered by isolation suggests a homeostatic process underlying the control of social need, similar to physiological drives such as hunger, thirst or sleep^3,6. In this study, we assessed social responses in several mouse strains, among which FVB/NJ mice emerged as highly, and C57BL/6J mice as moderately, sensitive to social isolation. Using both strains, we uncovered two previously uncharacterized neuronal populations in the hypothalamic preoptic nucleus that are activated during either social isolation or social rebound and orchestrate the behaviour display of social need and social satiety, respectively. We identified direct connectivity between these two populations and with brain areas associated with social behaviour, emotional state, reward and physiological needs and showed that mice require touch to assess the presence of others and fulfil their social need. These data show a brain-wide neural system underlying social homeostasis and provide significant mechanistic insights into the nature and function of circuits controlling instinctive social need and for the understanding of healthy and diseased brain states associated with social context.