Losing a critical receptor in a special class of inhibitory neurons in the brain may cause neurodevelopmental disorders, such as autism and schizophrenia, according to new research by Salk Institute's Computational Neurobiology Laboratory scientists. While the importance of the receptor, mGluR5, in other areas of the brain had been established, no one had studied its specific role in a cell type known as parvalbumin-positive interneurons. The neurons are considered important in developing general cognition and generating certain types of oscillatory wave patterns in the brain, according to research published in Molecular Psychiatry on August 11, 2015, and reported in Bioscience Technology (http://www.biosciencetechnology.com/news/2015/08/receptors-brain-linked-schizophrenia-autism?et_cid=4736557&et_rid=45505806&type=cta).
As Terrence Sejnowski, head of Salk's Computational Neurobiology Laboratory, explained, "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."
Scientists had previously discovered 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.
In 2014 researchers at Washington University in St. Louis concluded that the problems people with autism have with memory formation, higher-level thinking and social interactions may be partially attributable to the activity of receptors inside brain cells. They discovered that the mGlu5 receptor becomes activated when it binds to the neurotransmitter glutamate, which is associated with learning and memory. This leads to chain reactions that convert the glutamate's signal into messages traveling inside the cell (http://www.sciencedaily.com/releases/2014/03/140326141654.htm).
The Salk team questioned the role of mGluR5 in the parvalbumin cells, because the cells were considered so important in brain development. They worked with Athina Markou's team from the Department of Psychiatry at the University of California, San Diego, to examine what occurred when the receptor was "selectively deleted from these cells after the brain's initial formation." They discovered that without the receptor in these cells, mice had numerous developmental problems, including "obsessive, repetitive grooming behavior and anti-social tendencies." Additionally, the patterns of activity in the animals' brains resembled patterns observed in humans suffering from schizophrenia.
"This discovery implies that changes after birth, not just before birth, are affecting the way the network is set up," said Margarita Behrens, corresponding author and Salk staff scientist.
According to Sejnowski, the findings indicate that an alteration in mGluR5 receptors in these brain cells could lead to the formation of some neurodevelopmental disorders. He believes that the molecular change is potentially reversible.
He concluded, "The cells are still alive, and if we can figure out how to go in and change some of these molecular switches, we might actually be able to put the cells back into healthy, functioning states."
