Lateralized Decrease of Parvalbumin+ Cells in the Somatosensory Cortex of ASD Models Is Correlated with Unilateral...

Area of Science:

• Neuroscience
• Developmental Neuroscience
• Autism Spectrum Disorder Research

Background:

• Cortical functions rely on inhibitory control of excitatory networks.
• Parvalbumin (PV+)-expressing basket cells (BCs) are crucial for maintaining excitation/inhibition (E/I) balance.
• Disrupted E/I balance is a key feature of autism spectrum disorder (ASD).

Purpose of the Study:

• To investigate the role of PV+ BCs in the somatosensory cortex of mouse models of ASD.
• To explore the relationship between E/I balance, sensory processing, and ASD.
• To identify potential neural underpinnings of sensory hypersensitivity in ASD.

Main Methods:

• Utilized Shank3-/- and Cntnap2-/- mouse models of ASD.
• Identified the dominant hemisphere using a forepaw reaching task.
• Employed double labeling with anti-PV antibody and Vicia villosa lectin (VVA) to quantify BCs.
• Assessed mechanical sensitivity in hindpaws.

Main Results:

• A lateralized decrease in PV+ BCs was observed in the dominant somatosensory cortex of ASD models.
• The total number of BCs remained unchanged, but a subset of BCs lacked PV expression (PV-).
• Dominant hindpaws exhibited increased mechanical sensitivity, correlating with reduced PV+ interneurons and PV expression in the dominant cortex.

Conclusions:

• Decreased inhibitory input from PV+ interneurons in the dominant somatosensory cortex may contribute to sensory hypersensitivity in ASD.
• Lateralized alterations in inhibitory circuits could underlie asymmetric sensory processing in ASD.
• These findings highlight a potential mechanism for sensory abnormalities in autism spectrum disorder.