Gephyrin phosphorylation facilitates sexually dimorphic development and function of parvalbumin interneurons in the mouse hippocampus.

The precise function of specialized GABAergic interneuron subtypes is required to provide appropriate synaptic inhibition for regulating principal neuron excitability and synchronization within brain circuits. Of these, parvalbumin-type (PV neuron) dysfunction is a feature of several sex-biased psychiatric and brain disorders, although, the underlying developmental mechanisms are unclear. While the transcriptional action of sex hormones generates sexual dimorphism during brain development, whether kinase signaling contributes to sex differences in PV neuron function remains unexplored.

Shank3 deficits in the anteromedial bed nucleus of the stria terminalis trigger an anxiety phenotype in mice.

Anxiety disorders are the most prevalent co-morbidity factor associated with the core domains of autism spectrum disorders (ASD). Investigations on potential common neuronal mechanisms that may explain the co-occurrence of ASD and anxiety disorders are still poorly explored. One of the key questions that remained unsolved is the role of Shank3 protein in anxiety behaviours.

A neural substrate for negative affect dictates female parental behavior.

Parental behaviors secure the well-being of newborns and concomitantly limit negative affective states in adults, which emerge when coping with neonatal distress becomes challenging. Whether negative-affect-related neuronal circuits orchestrate parental actions is unknown. Here, we identify parental signatures in lateral habenula neurons receiving bed nucleus of stria terminalis innervation (LHb).

The exciting side of unconventional glycine receptors.

In this issue of Neuron, Bossi, Dhanasobhon, and colleagues uncover the functional relevance of GluN1/GluN3A excitatory glycine receptors (eGlyRs) in the neocortex and amygdala. This study provides exciting new insights into the role of unconventional eGlyRs in brain function.

Oxytocin neurons mediate the effect of social isolation via the VTA circuits.

Social interaction during adolescence strongly influences brain function and behavior, and the recent pandemic has emphasized the devastating effect of social distancing on mental health. While accumulating evidence has shown the importance of the reward system in encoding specific aspects of social interaction, the consequences of social isolation on the reward system and the development of social skills later in adulthood are still largely unknown. Here, we found that 1 week of social isolation during adolescence in male mice increased social interaction at the expense of social habituation and social novelty preference.

Heterogeneous fates of simultaneously-born neurons in the cortical ventricular zone.

Neocortical excitatory neurons belong to diverse cell types, which can be distinguished by their dates of birth, laminar location, connectivity, and molecular identities. During embryogenesis, apical progenitors (APs) located in the ventricular zone first give birth to deep-layer neurons, and next to superficial-layer neurons. While the overall sequential construction of neocortical layers is well-established, whether APs produce multiple neuron types at single time points of corticogenesis is unknown.

Reflections on a specialist HIV menopause service: Experiences of managing menopause in women living with HIV: Experiences of managing menopause in women living with HIV.

Objectives: We describe here characteristics and clinical outcomes of women living with HIV attending an HIV menopause service.

Methods: This was a retrospective case note review of women attending the monthly HIV menopause clinic from January 2015 to July 2018.

Results: In all, 55 women attended the service.

Downregulation of the schizophrenia risk-gene Dgcr2 alters early microcircuit development in the mouse medial prefrontal cortex.

Alterations in the generation, migration and integration of different subtypes of neurons in the medial prefrontal cortex (mPFC) microcircuit could play an important role in vulnerability to schizophrenia. Using in vivo cell-type specific manipulation of pyramidal neurons (PNs) progenitors, we aim to investigate the role of the schizophrenia risk-gene DiGeorge Critical Region 2 (Dgcr2) on cortical circuit formation in the mPFC of developing mice. This report describes how Dgcr2 knock down in upper-layer PNs impacts the functional maturation of PNs and interneurons (INs) in the mPFC.

Superior Colliculus to VTA pathway controls orienting response and influences social interaction in mice.

Social behaviours characterize cooperative, mutualistic, aggressive or parental interactions that occur among conspecifics. Although the Ventral Tegmental Area (VTA) has been identified as a key substrate for social behaviours, the input and output pathways dedicated to specific aspects of conspecific interaction remain understudied. Here, in male mice, we investigated the activity and function of two distinct VTA inputs from superior colliculus (SC-VTA) and medial prefrontal cortex (mPFC-VTA).

Inhibition of Trpv4 rescues circuit and social deficits unmasked by acute inflammatory response in a Shank3 mouse model of Autism.

Mutations in the SHANK3 gene have been recognized as a genetic risk factor for Autism Spectrum Disorder (ASD), a neurodevelopmental disease characterized by social deficits and repetitive behaviors. While heterozygous SHANK3 mutations are usually the types of mutations associated with idiopathic autism in patients, heterozygous deletion of Shank3 gene in mice does not commonly induce ASD-related behavioral deficit. Here, we used in-vivo and ex-vivo approaches to demonstrate that region-specific neonatal downregulation of Shank3 in the Nucleus Accumbens promotes D1R-medium spiny neurons (D1R-MSNs) hyperexcitability and upregulates Transient Receptor Potential Vanilloid 4 (Trpv4) to impair social behavior.

VTA dopamine neuron activity encodes social interaction and promotes reinforcement learning through social prediction error.

Social interactions are motivated behaviors that, in many species, facilitate learning. However, how the brain encodes the reinforcing properties of social interactions remains unclear. In this study, using in vivo recording in freely moving mice, we show that dopamine (DA) neurons of the ventral tegmental area (VTA) increase their activity during interactions with an unfamiliar conspecific and display heterogeneous responses.

RAB39B-mediated trafficking of the GluA2-AMPAR subunit controls dendritic spine maturation and intellectual disability-related behaviour.

Mutations in the RAB39B gene cause X-linked intellectual disability (XLID), comorbid with autism spectrum disorders or early Parkinson's disease. One of the functions of the neuronal small GTPase RAB39B is to drive GluA2/GluA3 α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPAR) maturation and trafficking, determining AMPAR subunit composition at glutamatergic postsynaptic neuronal terminals. Taking advantage of the Rab39b knockout murine model, we show that a lack of RAB39B affects neuronal dendritic spine refinement, prompting a more Ca-permeable and excitable synaptic network, which correlates with an immature spine arrangement and behavioural and cognitive alterations in adult mice.

Bugs R Us: Restoring sociability with microbiota in autism.

In a recent publication in , Buffington et al. provide a fascinating example of hologenomic behavioral regulation in an autism mouse model. The authors report that gut bacteria from wild-type mice rescue the social deficit of Cntnap2 knockout mice.

Deconstructing the contribution of sensory cues in social approach.

Social interaction is a complex and highly conserved behavior that safeguards survival and reproductive success. Although considerable progress has been made regarding our understanding of same-sex conspecific and non-aggressive interactions, questions regarding the precise contribution of sensory cues in social approach and their specific neurobiological correlates remain open. Here, by designing a series of experiments with diverse social and object stimuli manipulations in custom-made enclosures, we first sought to deconstruct key elements of social preference as assessed by the three-chamber task.

Drug-Evoked Synaptic Plasticity of Excitatory Transmission in the Ventral Tegmental Area.

Cocaine leads to a strong euphoria, which is at the origin of its recreational use. Past the acute effects, the drug leaves traces in the brain that persist long after it has been cleared from the body. These traces eventually shape behavior such that drug use may become compulsive, and addiction develops.

Deficit in Motor Skill Consolidation-Dependent Synaptic Plasticity at Motor Cortex to Dorsolateral Striatum Synapses in a Mouse Model of Huntington's Disease.

Huntington's disease (HD) is a neurodegenerative disease notably characterized by progressive motor symptoms. Although the loss of medium spiny neurons (MSNs) in the striatum has been associated with motor deficits, premanifest patients already present cognitive deficiencies and show early signs of motor disabilities. Here, in a YAC128 HD mouse model, we identified impairment in motor skill consolidation at the age of 11-14 weeks.

Oral immunotherapy tolerizes mice to enzyme replacement therapy for Morquio A syndrome.

Immune response to therapeutic enzymes poses a detriment to patient safety and treatment outcome. Enzyme replacement therapy (ERT) is a standard therapeutic option for some types of mucopolysaccharidoses, including Morquio A syndrome caused by N-acetylgalactosamine-6-sulfate sulfatase (GALNS) deficiency. Current protocols tolerize patients using cytotoxic immunosuppressives, which can cause adverse effects.

Linking NMDA Receptor Synaptic Retention to Synaptic Plasticity and Cognition.

NMDA receptor (NMDAR) subunit composition plays a pivotal role in synaptic plasticity at excitatory synapses. Still, the mechanisms responsible for the synaptic retention of NMDARs following induction of plasticity need to be fully elucidated. Rabphilin3A (Rph3A) is involved in the stabilization of NMDARs at synapses through the formation of a complex with GluN2A and PSD-95.

Morphine withdrawal recruits lateral habenula cytokine signaling to reduce synaptic excitation and sociability.

The lateral habenula encodes aversive stimuli contributing to negative emotional states during drug withdrawal. Here we report that morphine withdrawal in mice leads to microglia adaptations and diminishes glutamatergic transmission onto raphe-projecting lateral habenula neurons. Chemogenetic inhibition of this circuit promotes morphine withdrawal-like social deficits.

SHANK3 Downregulation in the Ventral Tegmental Area Accelerates the Extinction of Contextual Associations Induced by Juvenile Non-familiar Conspecific Interaction.

Haploinsufficiency of the gene, encoding for a scaffolding protein located in the postsynaptic density of glutamatergic synapse, has been linked to forms of autism spectrum disorders (ASDs). It has been shown that SHANK3 controls the maturation of social reward circuits in the ventral tegmental area (VTA). Whether the impairments in associative learning observed in ASD relate to SHANK3 insufficiency restricted to the reward system is still an open question.

What does cannabis do to the brain before birth?

Being exposed to cannabinoids in the womb has different consequences for male and female rats.