Optogenetic techniques incorporate light-sensitive proteins into the membranes of targeted cells and enable researchers to alter cell behavior by stimulating the proteins with light. Many studies have used optogenetics to create neurons that can be activated in vivo and on demand by exposure to light from nearby light-emitting diodes (LEDs). This field is still growing, and scientists are finding new ways to employ optogenetic methods to manipulate biological systems in living models.

Researchers lead by Michael Bruchas at the Washington University School of Medicine (St. Louis, MO) recently developed a protein called opto-MOR that combines parts of an opioid receptor protein with light-sensitive protein sequences (Neuron 86, 923–935; 2015). In artificial and in vitro settings, opto-MOR is highly sensitive to light and initiates cascading intracellular effects that are typical of opioid receptors.

With this tool in hand, Bruchas and his team prepared a mouse model to test opto-MOR in vivo. They developed a viral construct that induces cells to express opto-MOR and infused the construct into parts of the brain that are associated with dopamine release and corresponding behavioral responses. They also embedded LEDs in the brains of the mice, near the sites of viral infusion. By activating the LEDs, the researchers could presumably mimic opiate exposure. “Rather than a drug such as morphine activating an opioid receptor, the light provides the reward,” Bruchas summarized in a press release.

To verify this presumption, Bruchas et al. designed a conditioning experiment wherein mice received LED stimulation upon entering a specific chamber. Control mice were indifferent to this chamber, but mice with opto-MOR showed either a preference or aversion toward the chamber, depending on which region of the brain had been infused with opto-MOR. These behavioral phenotypes are corroborated by similar behavioral responses that accompany administration of opioid agonists in the same regions of the brain.

The behavioral results suggests that LED stimulation can affect neurons though opto-MOR in much the same way that drugs affect neurons through opiate receptors. In practice, though, drug administration is a very coarse manipulation, and neuroactive compounds can interact with a wide range of non-specific cell types in exposed areas, eliciting undesired side effects. The scientists note that, with more research, technologies like opto-MOR might present a precise alternative for studying neural circuits and perhaps even treating pain with fewer unintended side effects.