Optogenetics is proving to be highly promising in the treatment of obsessive-compulsive disorders

By applying light stimulation to highly specific neurons in the brain, the researchers managed to re-establish normal behaviour in mice that had beforehand presented pathological repetitive behaviour similar to that observed in human patients suffering from obsessive-compulsive disorders.

These results are published in the journal Science of June 7th 2013.

Repetitive behaviour is characterised by a certain number of neuro-psychiatric disorders, in particular obsessive-compulsive disorders, that develop to such an extent that they become a real handicap to daily life (for example, washing hands up to 30 times a day; or checking excessively that a door is locked, etc.). Obsessive-compulsive disorders affect 2 to 3% of the population and in France, it is estimated that over one million persons are affected by this disorder.

The usual treatment for obsessive-compulsive disorders is to use pharmacological treatments (anti-depressants, neuroleptics) and/or behavioural psychotherapy. However, in spite of these therapeutic combinations, severe symptoms persist in around one third of patients. So it is necessary to gain better understanding of the cerebral mechanisms that cause these repetitive behaviour patterns in order to provide better treatment.

Previous neuroimaging studies allowed us to identify dysfunctioning in neuron circuits located between the front of the brain (the orbitofrontal cortex) and more deep-seated cerebral structures (the ganglions at the base on the brain), in certain persons suffering from obsessive-compulsive disorders.

In this new study, Eric Burguière and his co-workers (in the laboratory of Pr. Ann Graybiel in the MIT) concentrated their research on this neuron circuit in order to both examine its function in detail and also to develop an approach to treating obsessive-compulsive disorders in a mutant mouse model.

In these mutant mice, the obsessive behaviour was expressed by repeated grooming all day long, to such an extent that it caused cutaneous lesions. From a physiological point of view, these animals are failing to express a protein (caused by the absence of a gene Sapap3) that is normally present in the stratial neuron synapses, a structure that is part of the ganglions at the base of the brain and is involved in functions such as learning sequences, developing habits, or decision-making.

Thanks to these mouse models, initial observations allowed the researchers to show that the emergence of compulsive behaviour in mutant mice was caused by a deficiency in behavioural inhibition. The mice are unable to stop the act of grooming, even when it is no longer necessary. The researchers then used recordings of the neuron activity to show that the dysfunction of communication in the brain between the neocortex and the striatum leads to hyperactivity of stratial neurons in mice.

The use of light