A Role for Vasoactive Intestinal Peptide Interneurons in Neurodevelopmental Disorders

Area of Science:

• Neuroscience
• Developmental Biology
• Genetics

Background:

• GABAergic inhibitory interneurons expressing vasoactive intestinal peptide (VIP-INs) are crucial for cerebral cortical network dynamics and development.
• VIP-IN dysfunction is increasingly implicated in neurodevelopmental disorders (NDDs).

Purpose of the Study:

• To review the circuit functions of VIP-INs and their role in NDD pathogenesis.
• To identify disease-associated genes highly expressed in VIP-INs using single-cell RNA sequencing data.
• To explore the broad implication of VIP-INs in autism spectrum disorder and intellectual disability.

Main Methods:

• Literature review of VIP-IN circuit functions and NDD mechanisms.
• Analysis of publicly available single-cell RNA sequencing data (Allen Institute).
• Survey of disease-associated genes and their phenotypes in VIP-INs.

Main Results:

• VIP-INs exhibit recurring circuit motifs across cortical areas, shaping sensory input, development, and behavior.
• Several underexplored disease-associated genes are highly expressed in VIP-INs.
• VIP-IN involvement appears more pronounced in autism spectrum disorder and intellectual disability than epileptic encephalopathy.

Conclusions:

• VIP-INs are critical regulators of neural circuits and their dysfunction contributes to NDDs.
• Cell type-specific investigations are vital for understanding NDD pathogenesis and developing targeted therapeutics.
• Genomic data analysis reveals novel VIP-IN-associated genes relevant to NDDs.