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Olfactory Valence-Processing Deficits and Aberrant Brain Network Connectivity Underlie Social Dysfunction in

Dingding Yang1,2, Qian Liu1,2, Hangjun Ran1,2,3

  • 1Department of Neurobiology, School of Basic Medicine, Fourth Military Medical University, Xi'an, 710032, China.

Neuroscience Bulletin
|June 4, 2026
PubMed
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Shank3 mutant mice, a model for autism spectrum disorder (ASD), exhibit impaired olfaction and altered brain connectivity. These olfactory deficits correlate with autism-like behaviors, suggesting the olfactory system as a therapeutic target.

Area of Science:

  • Neuroscience
  • Behavioral Science
  • Genetics

Background:

  • Olfactory dysfunction is noted in autism spectrum disorder (ASD) models.
  • The olfactory phenotype in Shank3 knockout (Shank3-/-) mice, a key ASD model, is not well understood.

Purpose of the Study:

  • To comprehensively evaluate olfactory function in Shank3-/- mice.
  • To investigate the neural and behavioral correlates of olfactory processing deficits in this ASD model.

Main Methods:

  • Utilized a modified olfactory three-chamber test and ultrasonic vocalization (USV) detection.
  • Employed resting-state functional magnetic resonance imaging (rs-fMRI), whole-brain c-Fos mapping, and 3D behavioral analysis.

Main Results:

  • Shank3-/- mice demonstrated abnormal odor preference and hyperconnectivity in olfactory brain networks.
Keywords:
Shank3ASDOlfactory preferenceSocial deficitsc-FosfMRI

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  • Exposure to various odors elicited atypical c-Fos activation, synchronized with locomotor suppression and stereotyped behaviors.

    • Conclusions:

    • Olfactory deficits are linked to autism-like behaviors in Shank3-/- mice.
    • The olfactory system represents a potential target for novel, sensory-based autism therapies.