Abstract
Purpose :
The factors influencing the sensitivity of cortical neurons to artificial stimulation are not fully understood. While advances in computational modeling improve the ability to estimate the fields arising from a given set of stimulating conditions, the factors governing the neuronal sensitivity to such fields have not been completely elucidated. This understanding is essential to the development of cortical prostheses that strive to restore vision to the blind.
Methods :
The sensitivity of individual cortical neurons to different forms of stimulation were studied in mouse brain slices. The small micro-coils used here confined the induced fields to a narrow region within targeted cells; this enabled the sensitivity of individual regions to be compared. Responses were captured using cell-attached patch clamp electrodes. Stratification levels and anatomical features were used to classify cells into known types so that responses across individual types could be compared.
Results :
In naïve (unstimulated) L5 pyramidal neurons (PNs), the proximal axon had the highest sensitivity to stimulation. Interestingly however, after a brief period of stimulation, the sensitivity of the apical dendrite increased beyond that of the axon; the number of stimuli required to induce the switch was comparable to that delivered during commonly-used clinical paradigms of repetitive transcranial magnetic stimulation (rTMS). Once the change in sensitivity occurred, it persisted for the duration of an experiments (~1 hour). Consistent repetitive stimulation induced the change with fewer pulses than trains in which stimulation was intermittent. Many aspects of the response (peak firing rate, duration, etc.) were different for different types of PNs. Rotation of the micro-coil revealed that fields oriented along the long axis of PNs were highly effective but those oriented orthogonally did not induce spiking, even for delivery of several thousand stimuli.
Conclusions :
Spatially-narrow fields can activate neurons at thresholds much lower than those previously thought possible. This suggests that activation in response to certain forms of stimulation may be more widespread than previously thought. In addition, the lack of effectiveness for certain field orientations suggests that activation can be narrowly confined for well-designed coils or electrodes. This has the potential to greatly improve the acuity of artificial vision.
This is an abstract that was submitted for the 2017 ARVO Annual Meeting, held in Baltimore, MD, May 7-11, 2017.