This project plans to compare the process of circuit refinement during developmental critical periods in wild type and monogenic rat models of ASD, to test the hypothesis that experience-dependent circuit refinement during postnatal development is impaired in ASD. Gina Turrigiano and colleagues will use a complex vision-dependent learning task to drive circuit refinement and will relate defects in cellular plasticity mechanisms to altered neural circuit activity and learning.

Challenges in social communication are one of the core symptoms of ASD. In order to study neural coordination mechanisms across distributed brain circuits underlying social interactions, Shantanu Jadhav plans to utilize the strengths of the rat as a model system to implement a novel social cooperation behavioral paradigm. He and his team aim to characterize social interactions in rat models of ASD and examine how changes in network coordination contribute to altered social behavior in these models.

Social situations are processed and responded to differently in ASD. Here, Bence Ölveczky and Naoshige Uchida plan to use the rat as a model for social interactions and to parse possible mechanisms underlying these differences.

Tremendous strides have been made in determining the genetic basis of ASD, but we continue to struggle to understand the links from genes to cells to circuits to behavior. Loren Frank, Kevin Bender and David Kastner plan to study a rat model of ASD, Scn2a haploinsufficiency, at the cellular, systems and behavioral levels in an effort to understand how genetically driven changes in cellular properties drive systems-level changes in activity patterns and behavioral changes in the ability to learn and to adapt to new situations.

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.