Contribution of mGluR5 to pathophysiology in a mouse model of human chromosome 16p11.2 microdeletion

Abstract

Microdeletions of chromosome 16p11.2 can cause autism, but the pathogenic mechanisms remain unclear. Here the authors show that in a 16p11.2 mouse model, mGluR5 synaptic plasticity and protein synthesis are altered and that a modulator of mGluR5 reverses the cognitive deficits. Human chromosome 16p11.2 microdeletion is the most common gene copy number variation in autism, but the synaptic pathophysiology caused by this mutation is largely unknown. Using a mouse with the same genetic deficiency, we found that metabotropic glutamate receptor 5 (mGluR5)-dependent synaptic plasticity and protein synthesis was altered in the hippocampus and that hippocampus-dependent memory was impaired. Notably, chronic treatment with a negative allosteric modulator of mGluR5 reversed the cognitive deficit.