All-optical reporting of inhibitory receptor driving force in the nervous system
Ionic driving forces provide the net electromotive force for ion movement across receptors, channels, and transporters, and are a fundamental property of all cells. In the nervous system, fast synaptic inhibition is mediated by chloride permeable GABA<sub>A</sub> and glycine receptors, and single-cell intracellular recordings have been the only method for estimating driving forces across these receptors (DF<sub>GABAA</sub>). Here we present a tool for quantifying inhibitory receptor driving force named ORCHID: all-Optical Reporting of CHloride Ion Driving force. We demonstrate ORCHID's ability to provide accurate, high-throughput measurements of resting and dynamic DF<sub>GABAA</sub> from genetically targeted cell types over multiple timescales. ORCHID confirms theoretical predictions about the biophysical mechanisms that establish DF<sub>GABAA</sub>, reveals differences in DF<sub>GABAA</sub> between neurons and astrocytes, and affords the first in vivo measurements of intact DF<sub>GABAA</sub>. This work extends our understanding of inhibitory synaptic transmission and demonstrates the potential for all-optical methods to assess ionic driving forces.
Authors
- Eric R. Schreiter (ORCID: https://orcid.org/0000-0002-2864-7469)
- Sarah E. Newey (ORCID: https://orcid.org/0000-0001-8941-4039)
- Ahmed S. Abdelfattah (ORCID: https://orcid.org/0000-0001-8131-1772)
- Teresa J. S. Steyn (ORCID: https://orcid.org/0000-0002-1303-4512)
- Colin J. Akerman (ORCID: https://orcid.org/0000-0001-6844-4984)
- Kira M. Düsterwald (ORCID: https://orcid.org/0000-0003-3217-5326)
- Joseph V. Raimondo (ORCID: https://orcid.org/0000-0002-8266-3128)
- Eran Frank Shorer (ORCID: https://orcid.org/0000-0002-2496-0108)
- Richard J. Burman (ORCID: https://orcid.org/0000-0003-3107-7871)
- Joshua S Selfe (ORCID: https://orcid.org/0000-0001-6605-0690)
- Ariel Z. Kraitzick (ORCID: https://orcid.org/0000-0002-0466-8636)
Institutions
- Allen Institute for Brain Science (US)
- Howard Hughes Medical Institute (US)
- Johns Hopkins University (US)
- University of Cape Town (ZA)
- Janelia Research Campus (US)
- Brown University (US)
- University of Oxford (GB)
- Oxford Centre for Computational Neuroscience (GB)
- Wellcome Centre for Infectious Diseases Research in Africa (ZA)
- Johns Hopkins Hospital (US)
- University College London (GB)
Publication Details
- Journal
- Nature Communications
- Published
- 2024-10-16
- DOI
- https://doi.org/10.1038/s41467-024-53074-y
- Citations
- 2
- Primary Topic
- Photoreceptor and optogenetics research
- Type
- article
- Field-Weighted Citation Impact
- 0.54
Funders
- Wellcome Trust
- Government of the United Kingdom
- African Academy of Sciences
- Biotechnology and Biological Sciences Research Council