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Loss of mGluR5 Receptors from Key Inhibitory Brain Neurons (Parvalbumin-Positive Interneurons) May Be at Root of Many Neurodevelopmental Disorders, Including Autism and Schizophrenia; Receptor Loss May Be Reversible
The loss of a critical receptor in a special class of inhibitory neurons in the brain may be responsible for neurodevelopmental disorders including autism and schizophrenia, according to new research by researchers from the Salk Institute for Biological Sciences and the University of California, San Diego (UCSD). The importance of the receptor, called mGluR5, in other areas of the brain had been previously established. Until now, however, no one had studied the receptor’s specific role in a cell type known as parvalbumin-positive interneurons, thought to be important in general cognition and generating certain types of oscillatory wave patterns in the brain. "We found that without this receptor in the parvalbumin cells, mice have many serious behavioral deficits," says Dr. Terrence Sejnowski, head of Salk's Computational Neurobiology Laboratory, which led the research published online in Molecular Psychiatry on August 11, 2015. "And a lot of them really mimic closely what we see in schizophrenia." The article is titled “Disruption of mGluR5 in Parvalbumin-Positive Interneurons Induces Core Features of Neurodevelopmental Disorders.” Scientists had previously discovered that when molecular signaling was disrupted in these cells during development, the brain's networks did not form correctly. Separate studies have revealed that mGluR5 receptors, which transmit glutamate signaling in the brain, are linked to addiction disorders, anxiety, and fragile X syndrome. But, in those cases, mGluR5 is affected in excitatory cells, not inhibitory cells like the parvalbumin-positive interneurons. The Salk team wondered what the role of mGluR5 was in the parvalbumin cells because these cells are deemed so important in brain development. The scientists partnered with Dr.