# Behavioral and neural mechanisms mediating social motivation in a rat model for ASD

> **NIH NIH R01** · UNIVERSITY OF MARYLAND BALTIMORE · 2024 · $442,962

## Abstract

Project Summary
Autism spectrum disorder (ASD) is characterized by impaired social communication, often attributed to
misreading of emotional cues. Despite progress toward understanding ASD, treatment options remain limited.
This is partly due to limitations of animal models of ASD that fail to capture an essential aspect of the ASD
condition – people with ASD have impairments in the motivation to engage in social interactions. We recently
developed an operant model of choice between addictive drugs and social interaction, showing that operant
social reward prevents drug self-administration and drug relapse. Our model highlights the importance of
incorporating social factors into addiction neuroscience to mimic the human condition more closely. Our model
allows us to directly assess both social reward and motivation to engage socially and the ethology of
consequent naturalistic volitional social interactions using machine learning approaches for complex social
behavior. The combination of a novel operant social model and advanced computational neuroethological
analytical pipelines provides a unique toolkit to study the neurobiological mechanisms underlying social reward
and potential disruption of social motivation in rodent model for ASD. The overarching aim of this proposal is to
study the neural mechanisms mediating social motivation and the impact of Shank3 mutation (a rat model for
ASD). In Aim 1, we will use open-source Python packages with graphical interface and intuitive workflow that
uses pose-estimation, to create supervised and unsupervised machine learning-based predictive classifiers of
social behavior. We hypothesize that Shank3-deficient rat model, but not wild-type rats will show aberrant
social behaviors. In Aim 2, we will investigate the potential autism-like-induced shifts in social motivation using
different behavioral approaches: social seeking, social progressive ratio, and social self-administration despite
negative consequences. By combining our social self-administration model with a rat model of ASD, we will
test the hypothesis that Shank3-deficient rats will show a disruption in social motivation behaviors, relative to
wild-type rats. In Aim 3, we will use single-unit electrophysiological recording into the Medial Amygdala (MeA –
a brain region critical for social behaviors) to identify units encoding rats’ social motivation or potential deficit in
social motivation using a translational relevant social choice procedure. Additionally, we will use optogenetic
approaches to reverse potential Shank3-dependent social motivation deficit in awake-behaving rats. These
approaches will provide new frameworks on our understanding of the role of MeA for predicting aspects of
future social-related events and for using these predictions to guide behavior within a rat model for ASD. Our
proposal will provide new insights into behavioral and neural mechanisms mediating the motivation for social
interaction in rat model for ASD.

## Key facts

- **NIH application ID:** 10754891
- **Project number:** 5R01MH129310-02
- **Recipient organization:** UNIVERSITY OF MARYLAND BALTIMORE
- **Principal Investigator:** Marco Venniro
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $442,962
- **Award type:** 5
- **Project period:** 2022-12-16 → 2027-10-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10754891

## Citation

> US National Institutes of Health, RePORTER application 10754891, Behavioral and neural mechanisms mediating social motivation in a rat model for ASD (5R01MH129310-02). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/10754891. Licensed CC0.

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