Light-activated proteins help show how dopamine neurons form

Using light-sensitive proteins, Ruhr University Bochum (RUB) scientists, in collaboration with Bonn University (both in Germany), have identified how neurons that produce dopamine are generated and the networks in which they form in the course of brain development. In the process, the researchers discovered that the neurons use not only dopamine for signal transmission, but also the much-faster glutamate.

Neurons that produce dopamine for the purpose of transmitting signals to other cells affect numerous crucial brain functions. This becomes evident in diseases such as Parkinson's and schizophrenia, where dopamine transmission in the brain is impaired. As the brain develops, these neurons mature into several specialized subtypes, which generate synapses to other important brain regions. They affect, for example, motor control, reward behavior, motivation, and impulse control.

Using genetic-engineering methods, the researchers coupled the dopamine-producing neurons of mice with light-sensitive proteins, enabling them to excite individual dopamine neurons with light stimuli and track the signaling pathways. With the aid of glutamate, locally inhibiting neurons were activated in the prefrontal cortex, a control center in the brain. These, in turn, are responsible for the regulation of signal transmission in the prefrontal cortex: they are involved, for example, in deciding if a signal should be forwarded. To identify in what way different subtypes of dopamine-producing neurons are generated, the researchers muted one gene in mice, thereby suppressing the formation of dopamine neurons in the prefrontal cortex.

Together with the RUB team headed by Prof. Dr. Magdalena Sauvage, the Bonn researchers tested this in attention experiments. Mice were rewarded with food if they nudged a rapidly blinking light as quickly as possible.

"The results have shown that animals in which the dopamine-producing cells had been genetically switched off didn't demonstrate any apparent changes to their attention and impulse control, but they pursued acquired behavior patterns much more persistently," says Prof. Sauvage.

A pathological clinging to certain notions or repeating words and movements in an unsuitable context does also occur in mental disorders such as obsessive-compulsive disorder or schizophrenia, where the function of the prefrontal cortex is disturbed. Accordingly, the results of the research cooperation contribute to an improved understanding of the development and function of dopamine-producing neurons and possibly related diseases.

Full details of the work appear in the journal Nature Neuroscience; for more information, please visit http://dx.doi.org/10.1038/nn.4020.

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