Synapses of the reward system at stake in autistic disorders

August 9, 2018, University of Geneva
Picture of the dopamine neurons involved in social interaction. Credit: © UNIGE

Autism spectrum disorders are a heterogeneous group of neurodevelopmental disorders, one of the main characteristics of which is impaired social communication. But what happens in patients' brains that disrupts their social skills? According to a study by scientists from the Universities of Geneva (UNIGE) and Basel (UNIBAS), in Switzerland, now published in Nature Communications, a malfunction of the synaptic activity of neurons present in the reward system seems to be at stake. By establishing a link between a genetic mutation found in people suffering from autistic disorders, a disturbance of the synapses and an alteration of social interactions, they are taking one step further in the understanding of a disorder that affects more than one child in 200 today.

In all mammals, the reward system is a fundamental brain circuit that reinforces certain behaviours by providing the motivation necessary for their achievement. Search for food, learning or emotional behaviours are, for instance, strongly linked to it. Recently, several studies have shown that a dysfunction of this system could be at the root of the alteration in social behaviours typical of autistic disorders. Dopaminergic , essential to its proper functioning, would be deficient in people with these disorders, who would thus lose all motivation to interact with others. But what are the underlying neurobiological mechanisms?

Poor synapse construction

"Basing ourselves on the hypothesis of motivation, we wanted to decipher the role of dopaminergic neurons in social interactions to verify whether alterations could explain certain social deficits specific to people suffering from ," explains Camilla Bellone, professor in the Department of Basic Neurosciences at UNIGE Faculty of Medicine, who directed this work. To do this, scientists studied mice in whom a gene called Neuroligin 3 had been suppressed, or whose activity in dopaminergic neurons had been greatly reduced, in order to imitate a mutation identified in autistic people. And unlike their counterparts, these mice had a lack of interest in novelty and less motivation to interact socially, behavioural traits frequently found in some autistic individuals.

Scientists have also studied the of mice (synapses being the part of neurons that allows them to communicate with each other). Normally, exposure to social novelty generates a synaptic modification that maintains interest and social contact. In mice with neuroligin 3 deficiency, this plasticity was much less present—synaptic reinforcement did not take place, which resulted in a poorer response to a new stimulus.

"We have observed the same synaptic deficiency in animals carrying another genetic mutation—on the Shank 3 gene—also common in autism. It is therefore a matter of poor maturation of the synapse which, in the end, prevents good social development," adds Camilla Bellone. More than 100 genes have already been identified as being linked to autistic symptoms, and many of them are involved in synaptic functioning. This explains why social disorders are so common in autistic people.

Autism presents such a variety of symptoms that it is impossible to provide all patients with the same treatment. "In order to better target treatments, it is imperative to classify behavioural disorders precisely on the basis of dysfunctions in certain brain circuits and to understand their genetic origin," says Peter Scheiffele, professor at the Biozentrum of UNIBAS, who participated in this work. Thus, patients with synaptic alterations in should react positively to therapies aimed precisely at increasing their activity, while these same therapies would remain ineffective in other patients whose social would be due to another cerebral dysfunction.

Moreover, since synaptic maturation occurs early in life, the earlier the exact causes of the disorder are identified, the more effective therapeutic interventions will be. This is what scientists in Geneva and Basel are doing—decoding the fundamental mechanisms to identify the most promising therapeutic targets.

Explore further: Poorly tuned neuronal communication may underlie neurological and psychiatric disease

More information: Sebastiano Bariselli et al, Role of VTA dopamine neurons and neuroligin 3 in sociability traits related to nonfamiliar conspecific interaction, Nature Communications (2018). DOI: 10.1038/s41467-018-05382-3

Related Stories

Poorly tuned neuronal communication may underlie neurological and psychiatric disease

February 13, 2017
A number of psychiatric and neurological disorders may result from abnormal synapses, the neuron-to-neuron connection sites that enable chemical communication between brain cells. The timing, frequency, and intensity of neuronal ...

New regulator discovered for information transfer in the brain

June 20, 2013
The protein mSYD1 has a key function in transmitting information between neurons. This was recently discovered by the research group of Prof Peter Scheiffele at the Biozentrum, University of Basel. The findings of the investigations ...

Imbalances in neural pathways may contribute to repetitive behaviors in autism

April 17, 2017
Genetic studies have linked a number of risk genes to autism spectrum disorder (ASD). Although the complex genetics underlying ASD likely involve interactions between many genes, some risk genes are singular drivers of autism-like ...

Study identifies brain circuit controlling social behavior

January 11, 2018
A new study by researchers at Roche in Basel, Switzerland has identified a key brain region of the neural circuit that controls social behavior. Increasing the activity of this region, called the habenula, led to social problems ...

When kids' autistic brains can't calm down

April 5, 2018
One-third of children who have autism spectrum disorder also have epilepsy. It's related to a major autism risk gene, which is mutated in patients with autism. But scientists didn't now why the mutation, catnap2, caused seizures.

Recommended for you

Perinatal hypoxia associated with long-term cerebellar learning deficits and Purkinje cell misfiring

August 18, 2018
Oxygen deprivation associated with preterm birth leaves telltale signs on the brains of newborns in the form of alterations to cerebellar white matter at the cellular and the physiological levels. Now, an experimental model ...

People are more honest when using a foreign tongue, research finds

August 17, 2018
New UChicago-led research suggests that someone who speaks in a foreign language is probably more credible than the average native speaker.

Critical role of DHA on foetal brain development revealed

August 17, 2018
Duke-NUS researchers have found evidence that a natural form of Docosahexaenoic Acid (DHA) made by the liver called Lyso-Phosphatidyl-Choline (LPC-DHA), is critical for normal foetal and infant brain development, and that ...

Automated detection of focal epileptic seizures in a sentinel area of the human brain

August 17, 2018
Patients with focal epilepsy that does not respond to medications badly need alternative treatments.

Men and women show surprising differences in seeing motion

August 16, 2018
Researchers reporting in the journal Current Biology on August 16 have found an unexpected difference between men and women. On average, their studies show, men pick up on visual motion significantly faster than women do.

Brain response study upends thinking about why practice speeds up motor reaction times

August 16, 2018
Researchers in the Department of Physical Medicine and Rehabilitation at Johns Hopkins Medicine report that a computerized study of 36 healthy adult volunteers asked to repeat the same movement over and over became significantly ...

0 comments

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.