One of the challenges in assessing rodent models of autism/intellectual disability is linking specific genetic alterations to changes in neural function and behavior. Paul Dudchenko plans to address this challenge by using the head direction cell system — comprised of neurons that encode direction — to characterize rigid and flexible neural coding in Fmr1, Grin2b and Syngap1 knockout rats. This characterization will provide rich data on both the neural systems and the behavioral capacities of these three rodent models.

Sandeep Robert Datta and colleagues seek to understand how mutations in genes implicated in ASD influence the behavior of rats. To do so, they plan to take advantage of new machine learning-based tools to quantitatively dissect the behavior of ASD genetic rat models before and after social experience. The team’s hope is that understanding how ASD risk genes impact behavior will lead to a deeper understanding of the neural basis of ASD.

Atypical visual experience affects many individuals with autism, yet its neuronal underpinnings are poorly understood. In the current project, Davide Zoccolan plans to characterize the visual functions of an Scn2a knockout rat model of autism. The overall aim is to establish the functional relationship between possible alterations of cortical processing and visual perceptual anomalies in autism.

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.