Brain Receptors Linked To Schizophrenia, Autism

The loss of an important receptor in a special class of inhibitory neurons may be responsible for neurodevelopmental disorders such as autism and schizophrenia, according to new research. The role of the receptor, mGluR5, in other areas of the brain had been previously established.

But until now, no one had studied their 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.

Terrence Sejnowski, head of Salk institute’s Computational Neurobiology Laboratory, says:

“We found that without this receptor in the parvalbumin cells, mice have many serious behavioral deficits. And a lot of them really mimic closely what we see in schizophrenia."

Parvalbumin-positive Interneurons

Previous research had found that when molecular signaling was disrupted in these cells during development, the brain’s networks didn’t 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 these cases, mGluR5 is affected in excitatory cells, not inhibitory cells like the parvalbumin-positive interneurons.

Salk researchers collaborated with Athina Markou’s team from the Department of Psychiatry at the University of California, San Diego, to investigate what happened when the receptor was selectively deleted from these cells after the brain’s initial formation.

Without the receptor in these cells, they found, mice had a host of developmental problems, including obsessive, repetitive grooming behavior and anti-social tendencies. Moreover, the patterns of activity in the animals’ brains resembled those seen in humans suffering from schizophrenia.

Changes Following Birth

Corresponding author Margarita Behrens, Salk staff scientist, said:

“This discovery implies that changes after birth, not just before birth, are affecting the way the network is set up."

The results suggest that an alteration in mGluR5 receptors in these brain cells may be a critical step in the formation of some neurodevelopmental disorders, adds Sejnowski. It’s good news, he says, because the molecular change is potentially reversible.

More research is needed to show whether the parvalbumin cells’ mGluR5 receptors are linked to disease in humans and, if so, what causes the loss or disruption to the receptors.

S A Barnes, A Pinto-Duarte, A Kappe, A Zembrzycki, A Metzler, E A Mukamel, J Lucero, X Wang, T J Sejnowski, A Markou, M M Behrens.
Disruption of mGluR5 in parvalbumin-positive interneurons induces core features of neurodevelopmental disorders. Molecular Psychiatry, 2015; DOI: 10.1038/mp.2015.113