It’s likely that improper development and/or function of neurons throughout different regions of the brain contributes to many of the characteristics of PWS, including hyperphagia, anxiety, OCD behaviors, sleep disturbances, and temper outbursts. However, it’s very difficult to develop effective therapeutics without first understanding which of the various types of brain neurons are specifically involved in any given behavior. The goal is to target specific neuron/areas that are at the root of a problem instead of using broad acting medications that affect the whole brain and therefore have a higher risk of unwanted side effects. Over the past 10 years, an exciting new neurobiological technique, called optogenetics, is allowing researchers to more specifically define which neurons contribute to which behaviors. They can then focus on the biological activity of those neurons to dissect out how those neurons impact behavior.
The optogenetics technique uses a gene that encodes a light-sensitive protein from algae. Lab mice are bred to express this protein in specific subtypes of brain neurons. Using fiber optics, the protein can be activated by a particular wavelength of light, which then triggers nerve activity. Thus the researcher is effectively able to control which neuron fires and when.
A recent article in Nature highlights how optogenetics is being used by many labs to map out the circuitry of neurons that control feeding behaviors. These studies have shown that activating small populations of specific neurons in mice can significantly impact food seeking behavior, specifically AgRP neurons promote eating, and both POMC and CGRP neurons suppress eating.
FPWR is excited to be funding research in the area of optogenetics. Dr. Ralph DiLeone at Yale University is currently working on a project using optogenetics to explore the effects of stimulating and inhibiting one particular type of neurons (dopamine receptor type 1 neurons) in the prefrontal cortex on hyperphagia in a mouse model of PWS. His group also recently published a paper outlining a modification to the optogenetics technique that will allow researchers to ask more complex questions.
Beyond better understanding appetite and feeding behaviors, optogenetics can be used to elucidate the neural circuits that are involved in numerous other behaviors that impact people with PWS, including those involved in breathing and respiration, sleep disordered breathing, circadian rhythm and sleep disruption, and anxiety and mood. It is important to note that optogenetics itself is not being developed into a therapeutic tool for use in humans. More so, it is a powerful research tool for mapping neural circuitry, and identifying specific targets within the brain. Drugs can then be developed that impact and modify neuronal activity in similar way.
For more information on optogenetics, please see the recent review article from Jennings and Stuber, “Tools for Resolving Functional Activity and Connectivity within Intact Neural Circuits”.
Click here for a video link of optogenetics in use.