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.

Olfaction is the main sensory system used by rodents to interact with their environment, and perturbations of the olfactory system cause defects in many of the behaviors affected in mouse models of ASDs, including maternal-pup interactions, social interactions and mating behaviors. Sandeep Robert Datta and his colleagues therefore hypothesize that social behavioral deficits expressed in rodent models of disease reflect lesions within the olfactory system and within sensorimotor systems tasked with converting olfactory information into context-appropriate action.

The Datta lab will explore this hypothesis in four distinct mouse ASD models — SHANK3, CNTNAP2, NLGN3 and 16p11.2 deletion mice — each of which exhibit various social behavioral deficits. The researchers plan to precisely quantify the performance of ASD model mice in a variety of learned and innate odor-related tasks, going beyond previous (largely qualitative) assessments to enable detailed comparisons of olfactory function in six distinct paradigms. In addition, by taking advantage of their recently developed next-generation behavioral profiling technique¹, Datta’s team will define the underlying structure of behavior exhibited by ASD mice and control mice as they freely interact with odors and conspecifics.

Taken together, these quantitative experiments will identify deficits in olfactory perception that may underlie social behavioral deficits in ASD model mice, will highlight differences and core similarities in odor-related behaviors in ASD model mice and will provide insight into approaches for potentially ameliorating social deficits in individuals with ASD.