In a study published today in EMBO Reports, researchers have uncovered a microRNA cluster that regulates synaptic strength and is also involved in the control of social behavior in mammals. The discovery provides new therapeutic strategies for the treatment of social deficits in neurodevelopmental disorders such as autism spectrum disorder or schizophrenia.
MicroRNAs are short snippets of RNA that do not code for a protein. Rather, they regulate the stability or translation rate of mRNAs, thereby inhibiting the production of particular proteins. These microRNAs form a whole new layer of gene regulation that has only been uncovered in the past 15 years. Each microRNA typically targets hundreds of different mRNAs, making them ideal for coordinating complex cellular processes.
The researchers identified a cluster of 38 microRNAs, termed miR379-410, that play an important role in neural development and sociability. They first observed that mice lacking a functional miR379-410 complex were more sociable than their littermates, indicating that miR379-410 functions to restrict sociability in healthy animals. Further investigation showed that neurons in the hippocampus of the brain in mice lacking miR379-410 formed more connections and were more likely to transmit electrical signals.
"Our study indicates that miR379-410 plays an important role in the development of neural circuitries that control social behavior," explains Gerhard Schratt of the University of Marburg in Germany.
At the molecular level, the miR379-410 complex targets thousands of genes, among them many that were known to function in regulating synaptic transmission. Moreover, a small subgroup of only five microRNAs from the cluster might explain to a large extent the upregulation of key synaptic proteins. These proteins are involved in a process termed homeostatic synaptic downscaling—a feedback loop that kicks in when the brain becomes overactive because synaptic contacts are too strong.
While the current study uses mice as a model organism, there are indications that the miR379-410 complex is also involved in the regulation of social behavior in humans. For example, several miR-379-410 members are dysregulated in the blood and brain of patients with neurodevelopmental disorders that affect social behavior, such as schizophrenia or autism spectrum disorder.
"We hope that our study will contribute to the development of treatments to ameliorate social deficits in neuropsychiatric conditions in the future," says Schratt.