Neuromodulation plays a critical role in brain function in both health and disease, and new tools that capture neuromodulation with high spatial and temporal resolution are needed. Here, we introduce a synthetic catecholamine nanosensor with fluorescent emission in the near infrared range (1000–1300 nm), near infrared catecholamine nanosensor (nIRCat). We demonstrate that nIRCats can be used to measure electrically and optogenetically evoked dopamine release in brain tissue, revealing hotspots with a median size of 2 µm. We also demonstrated that nIRCats are compatible with dopamine pharmacology and show D2 autoreceptor modulation of evoked dopamine release, which varied as a function of initial release magnitude at different hotspots. Together, our data demonstrate that nIRCats and other nanosensors of this class can serve as versatile synthetic optical tools to monitor neuromodulatory neurotransmitter release with high spatial resolution.

Social environments experienced at different developmental stages profoundly shape adult behavioural and neural phenotypes, and may have important interactive effects. We asked if social experience before and after weaning influenced adult social cognition in male prairie voles. Animals were raised either with or without fathers and then either housed singly or in sibling pairs. Males that were socially deprived before (fatherless) and after (singly housed) weaning did not demonstrate social recognition or dissociate spatial from social information. We also examined oxytocin and vasopressin receptors (OTR and V1aR) in areas of the forebrain associated with social behaviour and memory. Pre-and post-wean experience differentially altered receptor expression in several structures. Of note, OTR in the lateral septum-an area in which oxytocin inhibits social recognition-was greatest in animals that did not clearly demonstrate social recognition. The combination of absentee fathers on V1aR in the retrosplenial cortex and single housing on OTR in the septohippocampal nucleus produced a unique phenotype previously found to be associated with poor reproductive success in nature. We demonstrate that interactive effects of early life experiences throughout development have tremendous influence over brain -behaviour phenotype and can buffer potentially negative outcomes due to social deprivation.

Social behavior is pervasive across the animal kingdom, and elucidating how the brain enables animals to respond to social contexts is of great interest and profound importance. Our understanding of 'the social brain' has been fractured as it has matured. Two drastically different conceptualizations of the social brain have emerged with relatively little awareness of each other. In this review, we briefly recount the history behind the two dominant definitions of a social brain. The divide that has emerged between these visions can, in part, be attributed to differential attention to cortical or sub-cortical regions in the brain, and differences in methodology, comparative perspectives, and emphasis on functional specificity or generality. We discuss how these factors contribute to a lack of communication between research efforts, and propose ways in which each version of the social brain can benefit from the perspectives, tools, and approaches of the other. Interface between the two characterizations of social brain networks is sure to provide essential insight into what the social brain encompasses.

Nonapeptide receptors, like oxytocin receptor (OTR) and vasopressin 1a receptor (V1aR), modulate a variety of functions across taxa, and mediate phenotypic variation within and between species. Despite the popularity of studying nonapeptides in adults, developmental perspectives on properties of OTR and V1aR expression are lacking. Study of prairie voles (Microtus ochrogaster) has facilitated an understanding of mechanisms of social behavior and provides great potential to inform how early life experiences alter phenotype. We provide the first comprehensive profiling of OTR and V1aR in male and female prairie voles across postnatal development and into adulthood. Differences in receptor densities across the forebrain were region- and sex-specific. Postnatal changes in receptor expression fell into four themes: (a) constant over time, (b) increasing with age, (c) decreasing with age, or (d) peaking during late pre-weaning (postnatal day 15-21). We also examined the influence of post-weaning social and spatial enrichment (i.e., environmental complexity) on OTR and V1aR. Environmental complexity appeared to promote expression of OTR in males and females, and reduced expression of V1aR across several brain regions in males. Our results show that nonapeptide receptor profiles are plastic over development and suggest that different patterns of expression might represent functional differences in sensitivity to nonapeptide activation over a period when social environments are dynamic. Our results on environmental complexity suggest that nonapeptide sensitivity responds flexibly to different environmental contexts during development. Understanding the developmental trajectories of nonapeptide receptors provides a better understanding of the dynamic nature of social behavior and the underlying mechanisms.

During pregnancy, females undergo several physiologically driven changes that facilitate adaptive behaviours and prepare the mother to care for her developing offspring. The nonapeptide hormone oxytocin is best recognised for its involvement in mammalian pregnancy and has been tightly associated with maternal care, in addition to its roles in pregnancy, parturition, and lactation. A closely related nonapeptide hormone, arganine vasopressin, has received considerably less attention for its role in pregnancy but has recently been implicated in modulating maternal care and aggression. Here, we examine the expression patterns of receptors for oxytocin (OTR) and vasopressin (V1aR) over the course of pregnancy, ranging from non-mated virgin to immediately postpartum female prairie voles (Microtus ochrogaster). Surprisingly, we found that OTR was highly stable in all measured structures in the forebrain. V1aR was also stable throughout most of the brain. Two exceptions to this were found in the ventral pallidum (VPall) and the paraventricular nucleus of the hypothalamus (PVN); both significantly correlated with the length of time females were pregnant. Changes in the PVN may reflect functional feedback in vasopressin release, or preparatory changes for ensuing maternal behaviour. The results also indicate an unappreciated role for VPall V1aR in pregnancy, which may relate to the function of the VPall in hedonic ‘liking’ and motivational ‘wanting.’ Taken together, our data indicate that with a few compelling exceptions, nonapeptide dynamics during prairie vole pregnancy are largely limited to changes in the synthesis and release of oxytocin and vasopressin, not the receptors to which they bind.