Optical methods for monitoring neuron activity.

A method for monitoring neuron activity that does not require electrodes might be useful in situations where the use of electrodes is difficult because of neuron size, geometry, or number. A neuron will interact with electromagnetic or ultrasonic radiation in many different ways. If any one of these interactions changes during neuron activity, then its measurement could be used as a noninvasive method for monitoring that activity. The use of an optical method was suggested by the discovery of changes in light scattering, birefringence, and fluorescence that accompany the action potential (Co­ hen, Keynes & Hille 1968, Tasaki et al 1968). However, because the signal-to-noise ratios of these signals were too small to be used to monitor activity in individual neurons, a search for larger signals was initiated (Davila, Cohen & Waggoner 1 972, Cohen, 1973). At present, the largest signals are changes in absorption of light by axons stained with the merocyanine dyes (Ross et al 1977, Salzberg et al 1977), whose structures are shown in Figure 1. These absorption signals are about 100 times larger than the largest signal available in 1 971. The first part of this article presents evidence that the absorption changes of these dyes somehow result from the changes in membrane potential rather than from the ionic currents or the increases in membrane permeability that occur during an action potential. This is followed by a review of our efforts to find larger signals. The use of a dye may lead to pharmacologic effects or to photodynamic damage, and both possible problems are discussed briefly. Because the light from many different parts of a preparation can be measured simultaneously, it should, in principle, be possible to monitor activity in many neurons at once. It is this application that has inspired our interest in optical