SFARI | Award Type: Pilot

Role of autism risk genes in frontal-sensory cognitive control circuits in mice

Cognitive control deficits are one of the frequent challenges accompanying ASD. However, very little is known about the link between ASD risk genes and neural circuit mechanisms in control of cognitive control behavior. In the current project, Hirofumi Morishita plans to use mouse models to test the hypothesis that frontal-sensory projection neurons are convergingly vulnerable to multiple ASD risk gene manipulations and are also responsible for cognitive control behaviors. Findings from these studies are expected to establish pre-clinical strategies for ameliorating cognitive deficits in ASD.

Assessing the functions of autism risk genes in deep layer cortical neurons during primate midfetal development

Recent technological advances have identified many ASD risk genes, but how these genes affect brain development and function remains unknown, especially in primates. In the current project, Xinyu Zhao, Qiang Chang, André Sousa and Daifeng Wang plan to genetically manipulate three ASD risk genes in marmoset brain slices followed by multimodal integrative analysis of electrical activities, gene expression and chromatin accessibility of single neurons in the prefrontal cortex. The results will provide new and in-depth knowledge of the neuronal functions of these genes in primate brains.

Using human innervated intestinal organoids to study enteric glial dysfunction in autism

Gut disturbances are unusually common in individuals with ASD, but the pathogenesis of these issues is unknown. In the current project, Paul Tesar aims to use human innervated intestinal organoids derived from individuals with ASD to identify molecular changes in cells in the enteric nervous system that may underly these symptoms.

Neural basis for observational learning in autism mouse models

Core characteristics of ASD are dominated by problems with social engagement that have been proposed, in part, to emanate from an inability to interpret others’ intentions. Observational social learning is also utilized by many animals, including rodents, however it has yet to be assessed in ASD models. Anis Contractor’s lab is developing methods to assess whether observational learning is disrupted in mouse models of ASD, and in parallel, determine the underlying neural circuit mechanisms.

The role of the superior colliculus in tactile sensory processing in mouse models of autism

Somatosensory hyper- or hyposensitivity is commonly associated with ASD and early tactile challenges can contribute to certain aspects of ASD-related social phenotypes. Kate Hong’s lab aims to uncover mechanisms that control tactile sensitivity and adaptation in the superior colliculus by performing simultaneous behavioral and electrophysiological recordings in mouse models of ASD.

Zebrafish functional analysis of autism risk genes

Understanding the neurobiological functions of genes that increase risk for ASD is a critical step in therapy development. In the current project, Summer Thyme and colleagues aim to define how such genes impact zebrafish brain development, brain activity, and behavior. These studies also set the stage for drug screening using zebrafish mutants.

Cortico-cerebellar communication during flexible motor control in mouse models of autism

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.

Understanding insomnia in the autism spectrum using mouse models

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.

Enhancing reciprocal cooperation through prefrontal microstimulation

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.

Tracking sensory signals across multiple cortical areas during impaired sensory perception in Cntnap2 knockout mice

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.