Chemogenetic Activation of Prefrontal Cortex Rescues Synaptic and Behavioral Deficits in a Mouse Model of 16p11.2 Deletion Syndrome

The Journal of Neuroscience : the Official Journal of the Society for Neuroscience
Wei WangZhen Yan

Abstract

Microdeletion of the human 16p11.2 gene locus has been linked to autism spectrum disorder (ASD) and intellectual disability and confers risk for a number of other neurodevelopmental deficits. Transgenic mice carrying 16p11.2 deletion (16p11+/-) display phenotypes reminiscent of those in human patients with 16p11.2 deletion syndrome, but the molecular mechanisms and treatment strategies for these phenotypes remain unknown. In this study, we have found that both male and female 16p11+/- mice exhibit deficient NMDA receptor (NMDAR) function in the medial prefrontal cortex (mPFC), a brain region critical for high-level "executive" functions. Elevating the activity of mPFC pyramidal neurons with a CaMKII-driven Gq-DREADD (Gq-coupled designer receptors exclusively activated by designer drugs) led to the significant increase of NR2B subunit phosphorylation and the restoration of NMDAR function, as well as the amelioration of cognitive and social impairments in 16p11+/- mice. These results suggest that NMDAR hypofunction in PFC may contribute to the pathophysiology of 16p11.2 deletion syndrome and that restoring PFC activity is sufficient to rescue the behavioral deficits.SIGNIFICANCE STATEMENT The 16p11.2 deletion syndrome is strongly...Continue Reading

Citations

Aug 1, 2019·Brain : a Journal of Neurology·Julia B KahnDouglas A Coulter
Jul 23, 2020·Journal of Neurophysiology·Alexandria B MarcianteJ Thomas Cunningham
Mar 28, 2021·Nature Reviews. Neuroscience·Xin TangMriganka Sur
May 20, 2021·Neuropsychopharmacology : Official Publication of the American College of Neuropsychopharmacology·Zi-Jun WangZhen Yan

❮ Previous
Next ❯

Related Concepts

Related Feeds

Autism

Autism spectrum disorder is associated with challenges with social skills, repetitive behaviors, and often accompanied by sensory sensitivities and medical issues. Here is the latest research on autism.

Related Papers

Journal of Developmental and Behavioral Pediatrics : JDBP
Ellen Hanson16p11.2 Study Group Clinicians
Neuropsychopharmacology : Official Publication of the American College of Neuropsychopharmacology
Jennifer J DoneganDaniel J Lodge
Neuropsychopharmacology : Official Publication of the American College of Neuropsychopharmacology
Laura J StoppelMark F Bear
© 2022 Meta ULC. All rights reserved