Mapping of excitatory and inhibitory postsynaptic potentials of neuronal populations in hippocampal slices using the GEVI, ArcLight

To understand the circuitry of the brain, it is essential to clarify the functional connectivity among distinct neuronal populations. For this purpose, neuronal activity imaging using genetically-encoded calcium sensors such as GCaMP has been a powerful approach due to its cell-type specificity. However, calcium (Ca 2+ ) is an indirect measure of neuronal activity. A more direct approach would be to use genetically encoded voltage indicators (GEVIs) to observe subthreshold, synaptic activities. The GEVI, ArcLight, which exhibits large fluorescence transients in response to voltage, was expressed in excitatory neurons of the mouse CA1 hippocampus. Fluorescent signals in response to the electrical stimulation of the Schaffer collateral axons were observed in brain slice preparations. ArcLight was able to map both excitatory and inhibitory inputs projected to excitatory neurons. In contrast, the Ca 2+ signal detected by GCaMP6f, was only associated with excitatory inputs. ArcLight and similar voltage sensing probes are also becoming powerful paradigms for functional connectivity mapping of brain circuitry.