ZJU's research into autism may give birth to a therapeutic revolution


Autism is a developmental disorder characterized by troubles with social interaction and communication, and by restricted and repetitive behavior. It first appears during infancy or childhood, and generally follows a steady course without remission. The number of people affected is estimated at 1–2 per 1,000 people worldwide. To this day, there has been no effective therapy for autism.

A research team headed by Prof. LUO Jianhong, vice president of ZJU, published an article entitled “Gamma Oscillation Dysfunction in mPFC Leads to Social Deficits in Neuroligin 3 R451C Knockin Mice” in the March 1 issue of Neuron, a top journal in neuroscience.

Their research findings suggest that gamma oscillation dysfunction in the mPFC leads to social deficits in autism, and manipulating mPFC interneurons may reverse the deficits in adulthood. This may open up a new vehicle for the treatment of autism.

Data from Online Mendelian Inheritance in Man reveal that mutations of approximately 30 core genes may contribute to autism and that the functions of these genes are related to those of synapses. In the nervous system, a synapse is a structure that permits a neuron (or nerve cell) to pass an electrical or chemical signal to another neuron or to the target efferent cell.

“Neuroligins (NLs) are critical for synapse formation and function. NL3 R451C is an autism-associated mutation, so we embarked on our research from NL3 R451C knockin (KI) mice which exhibit autistic behavioral abnormalities,” Luo explains.

Through a series of experiments, their work demonstrates the pivotal role of gamma oscillations in the mPFC in controlling the preference for social novelty. A single mutation in neuroligin 3 causes defects in regional oscillations and information encoding, and finally in social behaviors. In addition to revealing the role of PV neuron-driven oscillations in social novelty deficits in the mouse model of autism spectrum disorder (ASD), their research indicates that manipulating the oscillations reverses the phenotype, pointing out potential treatments for the social deficits of ASD patients, even in adulthood.

It is also noted in their research that synaptic defects are likely to contribute to the oscillation dysfunctions in KI mice, although the exact mechanism may be complicated, as some synaptic changes might be compensatory.

Furthermore, their study manifests increased theta-to-high gamma phase-amplitude coupling in the mPFC of the KI mice in the social novelty context. It also suggests the importance of high gamma oscillations in social interactions, as high gamma burst stimulation of PV neurons in the mPFC impairs the social novelty behavior of the WT mice.

This work may hold a promising future for ASD patients, though more experiments should be performed to attest to these findings.