Adam Hantman and colleagues plan to apply established behavioral training and characterization techniques, as well as neural recording and perturbation methods, to monitor neural activity across the cortico-cerebellar network in three established genetic mouse models of ASD. The central hypothesis of the project is that disrupted cortico-cerebellar communication underlies impairments in motor control and behavioral flexibility in ASD.

Problems falling and staying asleep are extremely prevalent in individuals with ASD and heavily affect quality of life, but the underlying mechanisms are poorly understood. In the current project, Lucia Peixoto plans to investigate the relationship between sleep, circadian rhythms, sleep deprivation and ASD in three human-relevant mouse models to better understand mechanisms and pave the way to targeted therapies and interventions in the future.

The ability to reciprocally cooperate with other individuals is affected in ASD. To better understand the neural basis of cooperative interaction and to discover novel ways to casually enhance them, Steve Chang, Anirvan Nandy and Monika Jadi plan to determine the neural codes used for altruistic and mutual cooperation in the orbitofrontal cortex and apply distinct brain stimulation protocols during naturalistic social interactions.

Altered sensory processing is a core and predictive feature of ASD but the underlying mechanisms remain poorly understood. By investigating neural information processing during impaired visual perception in Cntnap2 knockout mice, Bilal Haider’s team can begin building a detailed picture of how changes in neural circuits alter perception of the external sensory world.

Individuals with ASD perceive and experience the world differently compared to neurotypical individuals, but the brain mechanisms underlying these phenomena remain unknown. Adi Mizrahi plans to study the involvement of cortical feedback in these processes using behavioral, electrophysiological and anatomical studies in the 16p11.2 deletion mouse model.

Identification of genetic contributions to autism risk has the potential to greatly improve the efficacy of diagnostic methods and treatment approaches. In the current project, Charles Langley and Gary Karpen plan to take advantage of recent improvements in human genome sequencing and analysis to determine if variation in the size or composition of previously inaccessible regions enriched for repeated DNAs impact autism risk.

Autism is a neurodevelopmental condition with a strong genetic basis, but a gap in knowledge exists between genetic and behavioral phenotypes due to a lack of neurophysiological explanation. To bridge the gap, Hiroki Asari aims to characterize and rescue changes in visual processing in autism model mice using causal experimental tools in modern systems neuroscience.

De novo, recurrent mutations in a regulatory subunit of protein phosphatase 2A (PPP2R5D, a high-confidence ASD risk gene) result in Jordan’s syndrome. Stefan Strack and colleagues have generated novel mouse models that recapitulate cardinal features of this syndrome. The current project aims to define molecular signatures and evaluate potential treatments of the disorder.

Mutations in chromatin modifiers are frequently observed in individuals with ASD. In the current project, Matthias Stadtfeld and colleagues aim to understand how loss of EHMT1 – a high-confidence ASD risk gene that encodes a histone methyltransferase – perturbs molecular and cellular functions during human neurogenesis.  They also plan to evaluate the therapeutic potential of restoring physiological levels of this enzyme.