The rapid adoption of the larval zebrafish as a systems neuroscience model has been driven largely by its small size and optical transparency, which enable the use of imaging and optogenetics techniques to record and manipulate activity throughout the brain. Unfortunately, larval fish lack the mature behavioral repertoire of adults and so a number of learning phenomena and social behaviors cannot be investigated in these animals. Here we establish the pedomorphic fish species Danionella translucida as a laboratory model that overcomes this limitation. Adult Danionella possess the size and optical transparency of late-larval zebrafish, which we exploit to image deep within the brains of a behaviorally mature animals using two-photon microscopy. The close phylogenetic relationship between Danionella and zebrafish enabled us to use existing reagents and techniques for transgenesis, and zebrafish-derived enhancer elements drove transgene expression in Danionella with their intended specificities. In a behavioral assay for socially-reinforced place preference, interactions between fish were found to be positively reinforcing and dependent on gender, demonstrating the power of this species for studies of learning and memory as well as social behavior. The establishment of Danionella’s behavioral, molecular, and optical tractability provides a unique opportunity for researchers seeking to understand the relationship between circuits and adult-onset behaviors at a whole-brain level.

/pdf/establishment-of-the-miniature-fish-species-danionella-4jtizzod02.pdf

Establishment of the miniature fish species Danionella translucida as a genetically and optically tractable neuroscience model

Detection, processing and reinforcement of social cues: regulation by the oxytocin system.

Sex is ubiquitous and variable throughout the animal kingdom. Historically, scientists have used reductionist methodologies that rely on a priori sex categorizations, in which two discrete sexes are inextricably linked with gamete type. However, this binarized operationalization does not adequately reflect the diversity of sex observed in nature. This is due, in part, to the fact that sex exists across many levels of biological analysis, including genetic, molecular, cellular, morphological, behavioral, and population levels. Furthermore, the biological mechanisms governing sex are embedded in complex networks that dynamically interact with other systems. To produce the most accurate and scientifically rigorous work examining sex in neuroendocrinology and to capture the full range of sex variability and diversity present in animal systems, we must critically assess the frameworks, experimental designs, and analytical methods used in our research. In this perspective piece, we first propose a new conceptual framework to guide the integrative study of sex. Then, we provide practical guidance on research approaches for studying sex-associated variables, including factors to consider in study design, selection of model organisms, experimental methodologies, and statistical analyses. We invite fellow scientists to conscientiously apply these modernized approaches to advance our biological understanding of sex and to encourage academically and socially responsible outcomes of our work. By expanding our conceptual frameworks and methodological approaches to the study of sex, we will gain insight into the unique ways that sex exists across levels of biological organization to produce the vast array of variability and diversity observed in nature. 

Sex diversity in the 21st century: Concepts, frameworks, and approaches for the future of neuroendocrinology

Abstract Autism spectrum disorders (ASDs) are diagnosed in 1/100 children worldwide, based on two core symptoms: deficits in social interaction and communication, and stereotyped behaviours. G protein‐coupled receptors (GPCRs) are the largest family of cell‐surface receptors that transduce extracellular signals to convergent intracellular signalling and downstream cellular responses that are commonly dysregulated in ASD. Despite hundreds of GPCRs being expressed in the brain, only 23 are genetically associated with ASD according to the Simons Foundation Autism Research Initiative (SFARI) gene database: oxytocin OTR; vasopressin V 1A and V 1B ; metabotropic glutamate mGlu 5 and mGlu 7 ; GABA B2 ; dopamine D 1 , D 2 and D 3 ; serotoninergic 5‐HT 1B ; β 2 ‐adrenoceptor; cholinergic M 3 ; adenosine A 2A and A 3 ; angiotensin AT 2 ; cannabinoid CB 1 ; chemokine CX 3 CR1; orphan GPR37 and GPR85; and olfactory OR1C1, OR2M4, OR2T10 and OR52M1. Here, we review the therapeutic potential of these 23 GPCRs, as well as 5‐HT 2A and 5‐HT 7 , for ASD. For each GPCR, we discuss its genetic association, genetic and pharmacological manipulation in animal models, pharmacopoeia for core symptoms of ASD and rank them based on these factors. Among these GPCRs, we highlight D 2 , 5‐HT 2A , CB 1 , OTR and V 1A as the more promising targets for ASD. We discuss that the dysregulation of GPCRs and their signalling is a convergent pathological mechanism of ASD. Their therapeutic potential has only begun as multiple GPCRs could mitigate ASD. 

Towards the convergent therapeutic potential of GPCRs in autism spectrum disorders.

Oxytocin, a neuropeptide hormone, is indispensable for milk ejection during nursing and is important for uterine contractions during parturition. The exact functions of oxytocin in postpartum maternal behaviors and motivations require further investigation. To this end, we characterized the role of oxytocin in components of maternal motivations during the mid-postpartum period, which has not been previously studied. To maintain suckling stimuli, postpartum oxytocin knockout (Oxt-/- ) and heterozygous (Oxt+/- ) littermates were co-housed with a wild-type lactating mother and its litter, and were examined for their ability to retrieve pups under standard or high-risk conditions, nursing behavior, maternal aggression towards an unfamiliar intruder, and motivation to regain contact with separated pups. One-third of Oxt-/- mothers exhibited prolonged parturition but were otherwise grossly healthy. Despite their inability to eject milk, Oxt-/- mothers displayed nursing behaviors for similar durations to Oxt+/- mothers during the second postpartum week. In addition, Oxt-/- mothers were essentially intact for pup retrieval under standard conditions and were motivated to stay close to pups, although they showed a mild decrease in maternal care under high-risk conditions and increased anxiety-like behaviors in pup-related contexts. The present findings indicate that oxytocin is dispensable for nursing behavior and maternal motivations, yet suggest that oxytocin may be relevant for stress resilience in the postpartum period.

Effects of oxytocin ablation on pup rescue, nursing behaviors and response to pup separation in early-to-mid postpartum mice.

/pdf/oxytocin-receptor-is-not-required-for-social-attachment-in-7tmzg0j0.pdf

Oxytocin receptor is not required for social attachment in prairie voles

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Oxytocin receptor is not required for social attachment in prairie voles