November 7, 2025

@michaelokun

We desperately need new research tools to move the ball forward in Parkinson's. How about seeing dopamine in a new light? Enter 'far-red sensors' that unlock multiplex brain signals. Neuromodulation refers to how brain chemicals, like dopamine, fine tune and adjust communication in neural circuits in order to shape behavior and physiology. A new paper in Science by Zheng and colleagues describes a far-red dopamine sensor that opens the door to simultaneously watching multiple brain chemicals 'in action' during real behaviors. Key Points: - Enables simultaneous tracking of chemicals (dopamine, acetylcholine and cAMP) in living mouse brain circuits w/ minimal spectral overlap. - Uses a chemigenetic strategy that pairs a GRAB-based sensor core w/ far-red fluorescent dyes to overcome brightness and overlap issues. - Reveals coordinated and behavior-linked neuromodulator dynamics that may become disrupted by cocaine exposure. My take: When we interviewed Ed Boyden at MIT for the book, he stressed to us that we need to develop new tools to get us upstream in understanding Parkinson's. This will be a key to navigating new therapies. Here are 5 points that resonated w/ me: 1- New tools are allowing us to see dopamine and other brain chemicals working together in real time. 2- This technology lets researchers study more than one brain signal at once which is a major step for understanding complex circuits. 3- Far-red chemistry improves clarity, so signals do not blur together during experiments. 4- Insights from these multiplex recordings may lead to smarter targets for brain therapies in conditions like Parkinsons or addiction. 5- Continued collaboration between chemistry and neuroscience will hopefully bring us even better sensors and deeper views into brain function. https://www.nature.com/articles/s41583-025-00972-9 https://pubmed.ncbi.nlm.nih.gov/39763912/ www.pdplan.org #michaelokun #fixelinstitute #parkinson