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Publications of the Week

A Photoswitchable GPCR-Based Opsin for Presynaptic Inhibition

By May 26, 2021May 27th, 2021No Comments

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This week, we profile a recent publication in Neuron from Dr. Michael Bruchas (pictured top row, second from left) at UW.

Can you provide a brief overview of your lab’s current research focus?  
We focus on neuromodulatory processing in the brain, as it relates to effective behavior.  We focus on a particular type of receptor called G-protein coupled receptors, which govern numerous brain responses and facilitate the communication of chemical transmission in the brain across a host of biological processes.  These include reward, motivation, pain, homeostasis, stress, among others.  These receptors represent one of our largest possible places for which to develop new therapies for a variety of neurological and psychiatric diseases.  Our efforts to understand them at a systems and cell biology level will facilitate the development of new pharmacological approaches

What is the significance of the findings in this publication?  
This new GPCR-based opsin from lamprey affords us the ability to turn on inhibitory G-protein signaling with rapid, spatially focused precision.  This provides us the means to test various connectivity in circuits in the brain, while also manipulating neuromodulation as very discrete epochs.  We hope to use this opsin as a new scaffold to design new opsin proteins with other characteristics for neuroscientists to use as tools, and for us to better understand neuromodulatory signaling in the brain.

What are the next steps for this research?  
We plan to use these tools to better understand effective behavior at the systems and cell biology level.  We also plan to develop new versions and to continue to explore biology to find new opsins like these to open new doors within neuroscience research.  The use of basic biological discovery, with no immediate medical impact, gave us the gift of this tool, and we are excited to continue looking to other fields of biology to identify other unique proteins which can be used for their light sensitivity and cellular signaling.

This work was funded by:
This work was funded by the National Institutes of Health Brain Initiative, National Institute of Mental Health, and National Institute of Drug Abuse. Grant numbers: R01 MH111520; NIH R21 DA049569, K01 DA042219, K01 DK115634, T32DA007278, P30DA048736, and R35 GM122577.

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