Dysfunction of striatal parvalbumin interneurons drives motor stereotypies in Cntnap2-/- mouse model of autism spectrum disorders.
Mathieu ThabaultCloé Fernandes-GomesAnne-Lise HuotMaureen FrancheteauAnaïs Balbous-GautierPierre Olivier FernagutLaurie GalvanPublished in: PNAS nexus (2024)
The involvement of parvalbumin (PV) interneurons in autism spectrum disorders (ASD) pathophysiology has been widely described without clearly elucidating how their dysfunctions could lead to ASD symptoms. The Cntnap2-/- mice, an ASD mouse model deficient for a major ASD susceptibility gene, display core ASD symptoms including motor stereotypies, which are directly linked to striatal dysfunction. This study reveals that striatal PV interneurons display hyperexcitability and hyperactivity in Cntnap2-/- mice, along with a reduced response in medium spiny neurons. We also provide evidence for a crucial role of striatal PV interneurons in motor stereotypies by demonstrating that their selective inhibition rescued a wild type-like phenotype. Our study identifies how PV interneuron dysfunctions disrupt striatal circuitry and drive the motor stereotypies in ASD.
Keyphrases
- autism spectrum disorder
- wild type
- attention deficit hyperactivity disorder
- intellectual disability
- mouse model
- parkinson disease
- functional connectivity
- genome wide
- oxidative stress
- spinal cord
- high fat diet induced
- adipose tissue
- metabolic syndrome
- deep brain stimulation
- copy number
- sleep quality
- insulin resistance
- physical activity