Optical neural action potential detection

Currently methods to measure action potentials in nerves require the measurement of electric potentials with electrodes, making these methods invasive. Voltage sensitive dyes allow for non-contact optical detection of action potentials, however these dyes are toxic. Small volume change due to stimulation of unmyelinated axons in cuttlefish[1], and crab or lobster leg nerves[2] has been observed. In a previous OCT based method, a dual channel phase sensitive 2 point TD-OCT system was used to optically detect action potentials [3]. SD-OCT has the sensitivity to measure fast (millisecond) and small (nanometer scale) changes in optical path length that occur during action potential propagation over the full depth profile. Figure 1 demonstrates the nanoscale displacement measured during action potential propagation in a cray fish nerve recently obtained in our lab. This opens the possibility for non-invasive methods to monitor action potentials in neurobiology. Based on this observation we hypothesize that similar swelling on the millisecond time scale takes place in the human nerve fiber layer. In SD-OCT a full depth profile is acquired in a single shot in less than 50 microseconds. The SD-OCT method can use retinal surfaces as phase reference with respect to the retinal nerve fiber layer to measure relative swelling, thus eliminating patient motion as a major phase noise source. The long term objective is to develop a method that can test In-vivo the local functionality of the human nerve fiber layer. No such method currently exists. To achieve this goal, suitable models, such as the salamander retina, will be selected to investigate action potential propagation in vitro.

Figure 1: Experimental configuration

 

Figure 2: Optical detection of nerve action potential in a cray fish nerve. The nerve was electrically stimulated. The Electrical Signal shows the recorded electrical response to the stimulation, demonstrating an action potential travelling through the nerve. The Optical Signal shows swelling of the nerve by 2-3 nanometer on a time scale of 1-2 milliseconds, coinciding with the presence and the duration of the action potential.

Figure 3 shows the result for a lobster leg stimulated at 3.7 Hz by 300 μA. To the left, the cross-sectional image of the nerve is shown. The arrow indicates the location where the beam was positioned for action potential recording. The circle at the base of the arrow indicates the location where the displacement was measured. The nerve bundle was approximately 50 μm in diameter. To the right, the optically detected displacement and the corresponding electrical response are shown as a function of time. A transient change in axon bundle thickness is evident, and the matching measured electrical signal more closely resembles the potential difference measured across two electrodes for simple action potential propagation. The onset and duration of electrical response and transient displacement show a clear correlation.

Figure 3: Optical detection of a ction potentials in a lobster leg nerve bundle. Data was averaged over 100 stimuli Left: Cross-sectional image of the nerve. The base of the arrow indicates the location of the displacement measurement. Right: Optically detected displacement and the corresponding electrical response as a function of time. The nerve was stimulated at 2 msec.