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Astrocytes contribute to autism spectrum disorder (ASD) pathophysiology. Here, the authors show that IP3R2 conditional KO mice show ASD-like behaviours and identify astrocyte-derived ATP as a modulator of these behaviours in mice.

Cerebellar right Crus I (RCrusI) has been implicated in autism spectrum disorder (ASD). RCrusI modulation altered RCrusI–inferior parietal lobule connectivity, and this connectivity was atypical in children with ASD and in a TscI mouse model of ASD. Inhibition of RCrusI in mice led to autism-related behaviors, and RCrusI activation rescued social impairments in TscI mice.

Neural 'hyperconnections' caused by runaway protein production can be undone.

POGZ is an autism spectrum disorder risk gene. How POGZ mutations result in ASD is unclear and animal models are lacking. Here, the authors generate a brain specific Pogz deficient mouse presenting ASD-like behaviour and show the effects of Pogz deficiency in the cerebellum.

Most studies of autism spectrum disorder (ASD) have focused on neuronal mechanisms. Here, the authors describe vascular impairments in a mouse model of 16p11.2 deletion syndrome using physiological and genetic approaches to examine endothelial-dependent phenotypes.

The Wdfy3gene has been associated with autism spectrum disorders in children. Here, the authors examine two separate mutant alleles of this gene in mice and identify its role in cortical neurogenesis, reproducing pathological changes characteristic of the disorder.

GPRASP2 plays a role in trafficking of GPCRs and mutations in this gene have been linked to neurodevelopmental disorders. Here the authors study the role of Gprasp2 in the CNS and show that it regulates the surface availability of mGluR5 receptors and that knockout mice for this protein show autistic-like behavioural abnormalities.

Yin et al. show that motor learning is delayed in mice with 16p11.2 deletion, associated with abnormal ensemble activity and delayed spine remodeling in motor cortex and reduced activity of of locus coeruleus noradrenergic neurons. The motor-related abnormalities were rescued by activation of ocus coeruleus noradrenergic neurons.

Lrfn2/SALM1 is a synaptic adhesion molecule, and is known to interact with PSD-95. Here the authors show that Lrfn2 regulates excitatory synapse maturation and maintenance, and that Lrfn2 knockout mice exhibit autism-like behaviours as well as enhanced learning and memory.

The molecular underpinning of autism is unclear. Here the authors show PX-RICS deficient mice exhibit autism-like social behavioural abnormalities and impaired GABA_A receptor trafficking, and enhancing inhibitory synaptic transmission with a GABA_Areceptor agonist ameliorate the behavioural deficits.

New evidence indicates that mutations in the postsynaptic density protein SHANK3 causes defects in corticostriatal signalling and autism-like behaviours in mice.

Loss of TSC1 function in cerebellar Purkinje cells in mice induces an autism-like phenotype that can be prevented by rapamycin treatment.

Dysregulation of mTOR signaling has been implicated in autism spectrum disorders. Here authors show that hyperconnectivity and hyperactivity of the mPFC–BLA circuitry inPten^+/−mice underlies their social impairments, and that reducing mTORC1 signaling during early postnatal development rescues these deficits.

LMO4 has been linked genetically to autism spectrum disorder and intellectual disability. Here, the authors investigate a role of LMO4 in parvalbumin neurons and, specifically, the regulation of dorsal ACC inhibitory circuits.

Mutations in SHANK2 are associated with autism spectrum disorders (ASD). Here, Peter et al. show that selective loss of Shank2in Purkinje cells of the mouse cerebellum leads to deficits in plasticity, motor behaviour, and a social behaviour phenotype similar to that seen in ASD.

Rodent study supports controversial clinical trial showing beneficial effects in children with the disorder.

CNTNAP2 or AHI1 are autism-associated genes. Here the authors show using knockdown of the genes that this results in reduced excitatory synaptic transmission in layer 2/3 pyramidal neurons in the prefrontal cortex and is associated with impaired social interaction in mice.

The main cell types involved in autism spectrum disorders through elevated protein synthesis are not well identified. Here, the authors show that overexpression of translation initiation factor eIF4E in microglia results in autism-like behaviour in male, but not female, mice.

Nuak1 is an autism spectrum disorder candidate gene. Here the authors report behavioral and cortical development in mice heterozygous for Nuak1, suggesting loss of function mutations in one copy of Nuak1 may contribute to neurodevelopmental disorders.

SHANK3 mutations have been linked to autism spectrum disorders, although the underlying mechanisms remain unclear. Here, the authors generate a complete knockout Shank3 mouse model, identifying ASD-like behaviours associated with impaired mGluR5-Homer scaffolding and abnormal brain connectivity.

Studies highlight link between immune response and unusual neural wiring.

Impaired neuronal connectivity is implicated in autism spectrum disorder (ASD). In this study, the authors perform time-lapse imaging of brain neurons from different mouse models of ASD and provide evidence for enhanced turnover of excitatory synapses as a commonly occurring mechanism in ASD.

Impairments of cerebellar-dependent motor control and learning are implicated in some forms of autism spectrum disorder (ASD). In this study, the authors provide a characterization of the motor deficits and cerebellar function abnormalities in a transgenic mouse model of ASD.

Mice lacking 4E-BP2, an eIF4E repressor, display increased translation of neuroligins; the mice also show autism-related behaviours and alterations in hippocampal synaptic activity, and these are reversed by normalization of eIF4E activity or neuroligin 1 levels.

Mice lackingCntnap2show abnormal neuronal migration, asynchronous firing patterns and have an autism-like phenotype that can be partially normalized by treatment with risperidone.

Human MEF2C haploinsufficiency results in Autism Spectrum Disorder (ASD), but it is unclear if the same is true in mice. Here, the authors show that Mef2c ^+/− mice have behavioral defects and neuronal abnormalities similar to ASD, and symptoms can be ameliorated with the new drug, NitroSynapsin.

ASH1L haploinsufficiency is strongly linked to autism, despite the unknown mechanism. Here, the authors show that ASH1L deficiency in prefrontal cortex causes the downregulation of synaptic genes, leading to seizures, which is rescued by chemogenetic and pharmacological restoration of excitation/inhibition balance.

An autism-associated mutation in Nlgn3 results in impaired oxytocin signalling in dopaminergic neurons and altered social behavioural responses in mice, and treatment with an inhibitor of MAP kinase-interacting kinases rescues these phenotypes.

Autism spectrum disorder (ASD) is characterised by synaptic surplus and atypical functional connectivity. Here, the authors show that synaptic pathology in Tsc2 haploinsufficient mice is associated with autism-like behavior and cortico-striatal hyperconnectivity, and that analogous functional hyperconnectivity signatures can be linked to mTOR-pathway dysfunction in subgroups of children with idiopathic ASD.

In humans, copy-number variants of the CYFIP1 gene have been associated with autism spectrum disorders and schizophrenia. Here, the authors characterize Cyfip1-heterozygous mice, revealing that they display deficits in brain white matter structure and functional connectivity along with abnormal behaviours.

A study has found that young male mice with a mutation of the autism-associated gene Chd8 show abnormal behaviors and elevated neuronal activation in several brain areas under stressful conditions, while female mice with the same mutation have reduced baseline neuronal activity, which may protect them from developing these abnormal phenotypes.

Stimulating the release of serotonin (5-HT) in the nucleus accumbens in wild-type mice promotes sociability, and rescues deficits in social behaviours in a mouse model of autism.

Findings support idea that gut microbiome has a role in disorder.

CPEB4 binds the mRNA of genes known to be associated with autism and shows an isoform imbalance in individuals with autism, and an equivalent imbalance in mice induces an autism-like phenotype.

Increasing expression of the autism-associated gene Ube3a, either alone or in combination with seizures, not only impairs sociability in mice but also reduces expression of the synaptic organizer Cbln1 in the ventral tegmental area, thus weakening glutamatergic transmission.

Qin et al show that autism-like social deficits in Shank3-deficient mice arise from β-catenin-mediated transcriptional upregulation of histone deacetylase 2 (HDAC2) and are persistently alleviated by brief treatment with HDAC inhibitor romidepsin.

Fragile X syndrome (FXS) is a leading cause of autism and neurons lacking FMRP show aberrant mRNA translation and intracellular signalling. Here, the authors show that neurons from Fmr1 knockout mice have increased levels of ADCY1 protein, producing abnormal ERK1/2 signalling, dysregulated protein synthesis and behavioural symptoms associated with FXS.

De novo mutations significantly contribute to autism spectrum disorders (ASD). Here, the authors demonstrate that ASD-associated de novo mutations in the POGZ gene, one of a high-confidence ASD gene, lead to ASD-related impaired neuronal development and disrupted mature cortical network function.

Kelly et al. describe two cerebellum–thalamus–mPFC pathways in mice that regulate social and repetitive behavior. PC activation in Rcrus1 and posterior vermis improved social and reduced repetitive behaviors, respectively, in PC-Tsc1 mutant mice.