New fluorescent proteins report electrical signals of brain cells

The protein was engineered by researchers at RIKEN to help analyze rapid electrical signals in populations of nerve cells and provides a unique window onto cellular-dynamics of neuronal webs. Further work with this protein is expected to dramatically extend the scope of research into brain function.

One of the key challenges in analyzing neural network dynamics is to monitor the activity of multiple neurons simultaneously. Voltage-sensitive fluorescent proteins (VSFP) make such analysis possible by encoding voltage sensors at the genetic level, enabling researchers to non-invasively target and visualize the activity of specific cell populations. VSFPs have, until now, suffered from interference with tissue background fluorescence and poor long-term expression in nerve cells.

A new series of red-shifted VSFPs, designed by a research team at the RIKEN Brain Science Institute, has overcome these limitations. By fusing the voltage-sensitive domain of a voltage-sensing phosphatase (Ci-VSP) to red-shifted fluorescent proteins, the researchers generated a series of VSFPs emitting different spectral colors. In a paper in the journal Chemistry & Biology, the researchers use these proteins to uncover details of the voltage-sensing mechanism in Ci-VSP, while also demonstrating the effectiveness of one variant (VSFP3.1_mOrange2) for analysis of electrical signals in hippocampal neurons.

The glimpse of the cellular-level dynamics of neuronal networks provided by VSFPs will vastly expand our understanding of information processing in the brain. By extending and clarifying the mechanisms of existing VSFPs, the new family of red-shifted proteins brings this potential one step closer to reality, enabling groundbreaking advances in understanding brain function.

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For more information, please contact:

Dr. Thomas Knöpfel
Laboratory for Neuronal Circuit Dynamics RIKEN Brain Science Institute
Tel: +81-(0)48-467-9740 / Fax: +81-(0)48-467-9739
Email: tknopfel@brain.riken.jp
Ms. Saeko Okada (PI officer)
Global Relations Office
RIKEN
Tel: +81-(0)48-462-1225 / Fax: +81-(0)48-467-9443
Email: koho@riken.jp