View in EDS

Translational Research Approach to Social Orienting Deficits in Autism: The Role of Superior Colliculus-Ventral Tegmental Pathway

Saved in:
Bibliographic Details
Title: Translational Research Approach to Social Orienting Deficits in Autism: The Role of Superior Colliculus-Ventral Tegmental Pathway
Authors: Alessandro Contestabile, Nada Kojovic, Giulia Casarotto, Farnaz Delavari, Patric Hagmann, Marie Schaer, Camilla Bellone
Source: Mol Psychiatry
Molecular psychiatry, vol. 30, no. 8, pp. 3729-3739
Publisher Information: Springer Science and Business Media LLC, 2024.
Publication Year: 2024
Subject Terms: Animals, Ventral Tegmental Area/metabolism, Ventral Tegmental Area/physiopathology, Mice, Mice, Knockout, Autism Spectrum Disorder/physiopathology, Autism Spectrum Disorder/metabolism, Male, Humans, Female, Superior Colliculi/metabolism, Superior Colliculi/physiopathology, Magnetic Resonance Imaging/methods, Translational Research, Biomedical/methods, Nerve Tissue Proteins/genetics, Nerve Tissue Proteins/metabolism, Neural Pathways/physiopathology, Child, Social Behavior, Autistic Disorder/physiopathology, Autistic Disorder/metabolism, Disease Models, Animal, Neurons/metabolism, Mice, Inbred C57BL, Microfilament Proteins/genetics, Microfilament Proteins/metabolism, Child, Preschool, Social Interaction, Article
Description: Autism Spectrum Disorder (ASD) is characterized by impairments in social interaction and repetitive behaviors. A key characteristic of ASD is a decreased interest in social interactions, which affects individuals' ability to engage with their social environment. This study explores the neurobiological basis of these social deficits, focusing on the pathway between the Superior Colliculus (SC) and the Ventral Tegmental Area (VTA). Adopting a translational approach, our research used Shank3 knockout mice (Shank3-/-), which parallel a clinical cohort of young children with ASD, to investigate these mechanisms. We observed consistent deficits in social orienting across species. In children with ASD, fMRI analyses revealed a significant decrease in connectivity between the SC and VTA. Additionally, using miniscopes in mice, we identified a reduction in the frequency of calcium transients in SC neurons projecting to the VTA, accompanied by changes in neuronal correlation and intrinsic cellular properties. Notably, the interneural correlation in Shank3-/- mice and the functional connectivity of the SC to VTA pathway in children with ASD correlated with the severity of social deficits. Our findings underscore the potential of the SC-VTA pathway as a biomarker for ASD and open new avenues for therapeutic interventions, highlighting the importance of early detection and targeted treatment strategies.
Document Type: Article
Other literature type
File Description: application/pdf
ISSN: 1476-5578
1359-4184
DOI: 10.21203/rs.3.rs-4017167/v1
DOI: 10.1038/s41380-025-02962-w
Access URL: https://pubmed.ncbi.nlm.nih.gov/40188311
http://nbn-resolving.org/urn/resolver.pl?urn=urn:nbn:ch:serval-BIB_ED7B5D9E01276
https://serval.unil.ch/resource/serval:BIB_ED7B5D9E0127.P001/REF.pdf
https://serval.unil.ch/notice/serval:BIB_ED7B5D9E0127
Rights: CC BY
Accession Number: edsair.doi.dedup.....1c6987546aa197efd3f4473f2a55cde6
Database: OpenAIRE
Description
Abstract:Autism Spectrum Disorder (ASD) is characterized by impairments in social interaction and repetitive behaviors. A key characteristic of ASD is a decreased interest in social interactions, which affects individuals' ability to engage with their social environment. This study explores the neurobiological basis of these social deficits, focusing on the pathway between the Superior Colliculus (SC) and the Ventral Tegmental Area (VTA). Adopting a translational approach, our research used Shank3 knockout mice (Shank3-/-), which parallel a clinical cohort of young children with ASD, to investigate these mechanisms. We observed consistent deficits in social orienting across species. In children with ASD, fMRI analyses revealed a significant decrease in connectivity between the SC and VTA. Additionally, using miniscopes in mice, we identified a reduction in the frequency of calcium transients in SC neurons projecting to the VTA, accompanied by changes in neuronal correlation and intrinsic cellular properties. Notably, the interneural correlation in Shank3-/- mice and the functional connectivity of the SC to VTA pathway in children with ASD correlated with the severity of social deficits. Our findings underscore the potential of the SC-VTA pathway as a biomarker for ASD and open new avenues for therapeutic interventions, highlighting the importance of early detection and targeted treatment strategies.
ISSN:14765578
13594184
DOI:10.21203/rs.3.rs-4017167/v1