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Genes 'light-up' depressive illness

Clinical depression, irritability, lower motivation, obesity, and drug and alcohol dependence could be related to problems with addiction. The brain's limbic system, the seat of basic emotions and drives, may hold the formulation for new therapies.
Genes 'light-up' depressive illness
Dysfunction of the limbic system can result in reduced ability to experience pleasure – which leads to reward dysfunction and possible addiction to food, alcohol and other drugs. The EU-funded OPTO-REW (Optogenetic investigation of GABAergic interneurons in the limbic system during reward and addiction) project looked into how nerve cells are wired and communicate in this area. Knowing the biochemical basis of reward-related behaviour could lead to the development of new therapies to tackle neuropsychiatric disorders.

The study used optogenetics and mouse genetics with a focus on the local inhibitory interneurons that express parvalbumin and somatostatin. Parvalbumin neurons are 'fast-spiking' to achieve quick firing of a neuron as well as rapid response and neuronal recovery. Somatostatin nerve cells on the other hand are low threshold-spiking.

Using labelling in genetically modified mice, researchers could work out the function of each type of neuron coupled with the mouse's behaviour when it is awake. Optogenetic techniques caused light-sensitive proteins such as channelrhodopsin – opened by a blue light pulse and closed by a green or yellow light – to light up every millisecond when the neurons were activated.

Manipulation of GABAergic interneurons in the limbic system enabled the study of connections between reward and addiction. Based on genetic models and also in these neurons, researchers looked at the roles of dopamine and serotonin, the reward and well-being chemicals, during nerve transmission.

Using optogenetics and electrophysiology, OPTO-REW studies identified the targets of the inhibitory actions of parvalbumin-expressing (PV+) cells. They found that these cells inhibit most of the neuronal population but avoid the somatostatin-expressing (SOM+) interneurons. These results have been published in the Journal of Neuroscience (January 2013).

Due to OPTO-REW research, scientists can now activate as well as silence PV+ and SOM+ interneurons of the striatum, a critical part of the reward system. Results could reveal their functional role during encoding of reward-associated cues and the learning of new habits.

Outcomes of the project's research stand to literally shed light on the function of discrete neuronal classes and their specific receptors. This will provide a foundation for the rational design of new pharmaceutical therapies targeting the limbic system.

Related information


Addiction, limbic system, optogenetics, parvalbumin, somatostatin
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