Year: 2024
Type: article
Abstract: 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 brain for example, fast synaptic inhibition is mediated by chloride permeable GABAA receptors, and single-cell intracellular recordings have been the only method for estimating driving forces across these receptors (DFGABAA). Here we present a new 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 DFGABAA from genetically targeted cell types over multiple timescales. ORCHID confirms theoretical predictions about the biophysical mechanisms that establish DFGABAA, reveals novel differences in DFGABAA between neurons and astrocytes, and affords the first in vivo measurements of intact DFGABAA. This work extends our understanding of inhibitory synaptic transmission and establishes a precedent for all-optical methods to assess ionic driving forces.
Source: Nature Communications
Institutions: University of Cape Town, Johns Hopkins University, Johns Hopkins Medicine, Johns Hopkins Hospital, University of Oxford, Gatsby Computational Neuroscience Unit, University College London, Brown University, Howard Hughes Medical Institute, Janelia Research Campus, Wellcome Centre for Infectious Diseases Research in Africa, Institute of Infectious Disease and Molecular Medicine
Language: English
Subfield: Cellular and Molecular Neuroscience
Field: Neuroscience
Domain: Life Sciences
Open Access status: gold
Estimated APC paid: $6,790
Awards: High resolution profiling of neuronal lineages by functional characterisation and sequencing of barcoded RNA, G148749436, G3620007234, Cestode modulation of host networks in the human brain., Ionic dynamics and plasticity in developing neuronal networks, Human cell-type specific ion dynamics in neuroinflammation and seizures
OpenAlex ID: W4403463891