Mice lacking a set of receptors in one type of neuron in the brain developed compulsive, anti-social behaviors. 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 Terrence Sejnowski, head of Salk’s Computational Neurobiology Laboratory, “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.
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.”This discovery implies that changes after birth, not just before birth, are affecting the way the network is set up,” says Margarita Behrens, Salk staff scientist. An alteration in mGluR5 receptors in these brain cells may be a critical step in the formation of some neurodevelopmental disorders. It’s good news, he says, because the molecular change is potentially reversible.
“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,” he says. Behrens says the study also should be a signal of caution: drugs that affect mGluR5 do so throughout the whole brain. “There are a lot of clinical trials ongoing looking at modulating mGluR5 for anxiety and Fragile X Syndrome,” she says. “But our results suggest that if you affect parvalbumin neurons, you might get behavioral changes you weren’t expecting.”
http://www.salk.edu/news/pressrelease_details.php?press_id=2104
When mice are engineered to lack the mGluR5 receptor in parvalbumin cells (right), they have fewer inhibitory (red) connections controlling the activity of excitatory neurons. Credit: Salk Institute
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