Functional Imaging of Nervous Systems Using Voltage‐Sensitive Dyes

Abstract

Abstract Voltage‐sensitive dyes are small molecules that bind to cell membranes and change their optical properties, absorption or fluorescence, in response to changes in membrane potential, the voltage across the membrane. These optical changes are extremely rapid and tend to be linear reporters of local electrical events. Thus, these ‘potentiometric probes’ behave as molecular voltmeters and can be used, with a high‐speed camera or other image dissector, for functional imaging of electrical activity including action potentials, synaptic potentials, and passive (electrotonic) signals. No physical contact with the object is required and spatial and temporal resolution is limited primarily by signal‐to‐noise considerations. Such millisecond time‐resolved functional imaging can be of single cells, of regions of cells or of nervous systems, of cardiac muscle or of any other electrically active tissue. In the nervous system, functional imaging of electrical activity can lead to an understanding of the spatio‐temporal relationships between neurons and of their functional connectivity. Key Concepts: In electrically excitable cells, the membrane potential can change extremely rapidly. Some coloured molecules (dyes) change their optical properties in response to changes in the local electric field. Changes in the optical properties of the molecules that stain‐cell membranes can be used to follow rapid changes in membrane potential. A high‐speed camera, usually with a microscope, can be used together with these dyes to monitor the electrical activity at hundreds or even thousands of sites, virtually simultaneously. Functional imaging of electrical activity can lead to an understanding of the spatio‐temporal relationships in nervous systems, and to the functional connectivity among neurons.