Motor dysfunction is common in autism. The primary motor cortex (area M1) has been implicated in the manifestation of these symptoms. Stelios Smirnakis proposes to study M1 circuit function, particularly during motor skill learning, to elucidate mechanisms that underlie motor deficits in autism.
Autism spectrum disorder (ASD) is diagnosed in boys 4-5 times more frequently than in girls. Many factors contribute to this gender bias, but the origins of the biological factors remain largely unknown. Sex differences in the expression of candidate risk genes may underlie at least some of this bias, but these differences have not been explored.
Individuals with autism spectrum disorder (ASD) have structural and functional deficits of the temporoparietal junction (TPJ), as well as problems with social and executive functions, which are associated with the TPJ. Michael Graziano and his colleagues recently showed that the TPJ is a convergence point for two major brain networks with implications in ASD: the frontoparietal control network (FPN) and the default mode network (DMN)[ref]Ingelström K.M. et al. J. Neurosci. 35, 9432-9445 (2015) PubMed[/ref]. To isolate these network nodes, they used a data-driven parcellation technique that allows spatial separation of partially overlapping functional processes.
Autism spectrum disorders (ASDs) are heterogeneous neurodevelopmental syndromes characterized by repetitive behaviors and deficits in the core domains of language development and social interactions. Although the clinical criteria used to define ASDs are entirely behavioral, a wealth of research suggests that mechanisms underlying sensory processing and sensorimotor coupling are altered in individuals with ASDs, and that these differences significantly contribute to ASD pathology. However, the neural basis for these sensory and sensorimotor phenotypes are not completely understood.
Attentional deficits are a major cause of disability in individuals with autism. Recently, Vikaas Sohal and colleagues described a possible circuit mechanism contributing to attentional deficits in autism[ref]Luongo F.J. et al. Biol. Psychiatry 79, 667-675 (2016) PubMed[/ref]. For the current project, Sohal proposes to identify a specific cellular locus underlying these circuit abnormalities.
Research into the developmental underpinnings of autism spectrum disorder (ASD) is hampered by a lack of techniques for describing neural development at the cellular and circuit levels. Ethan Scott and his colleagues plan to use zebrafish as a platform for anatomical and functional analyses of ASD etiology at the level of individual neurons and the circuits that they form. Zebrafish larvae are transparent, allowing neural development in the intact animal to be examined with a range of microscopic and optogenetic techniques.
Single-nucleotide polymorphism genotyping and whole-exome and whole-genome sequencing studies have been key for the identification of genetic loci and mutations underlying autism spectrum disorder (ASD) susceptibility. Although none of the risk genes identified so far contribute to more than 1 percent of ASD cases, overall the search for ASD treatments can profoundly benefit from the study of rare and syndromic forms of ASDs.
Autism spectrum disorder (ASD) is diagnosed in an increasingly large proportion of the population. Changes in neurocircuitry resulting from alterations in genetic and epigenetic programming are thought to represent an underlying cause of ASD-related behavior, and alterations in the anatomical and electrophysiological properties of local neural circuits in mouse models of ASD have been described. Yet it remains unclear how changes in longer-range neural connectivity are affected in ASD. Bidirectional connections between the thalamus and cortex are one set of long-range projections that are critical for filtering, selecting and perceiving sensory stimuli and generating motor outputs. Interestingly, human imaging studies have implicated thalamocortical circuit dysfunction in ASD.
The brain abnormalities that lead to autism spectrum disorder (ASD) remain poorly understood. Convergent data from clinical and basic science research studies suggest that abnormalities in brain interneurons may contribute to the condition. These interneurons are also implicated in tics and Tourette syndrome, which are frequently comorbid with ASD.
Autism spectrum disorders (ASDs) comprise a heterogeneous set of neurodevelopmental and neuropsychiatric conditions that affect both social and nonsocial behavior. The laboratory mouse is currently the best mammalian system available for studying ‘genocopies’ of allelic variants found in humans. The use of such mouse genocopies in ASD research has come under criticism because of concerns that the behavioral assays used to phenotype these models are too crude and far removed from human behavior to be informative. These considerations have fueled a push for the use of non-human primate (NHP) models, such as the marmoset, in autism research. But such NHP models are expensive, laborious to generate, and present ethical problems. A complementary approach, therefore, is to develop more sensitive, objective and quantitative automated approaches to measuring ASD-related behavioral phenotypes in mice.