Abstract
Purpose :
Direct electrical stimulation of primary visual cortex (V1) has been proposed as a means to restore vision to the blind. Despite some success in eliciting visual perception in human subjects as well as in non-human primates, a well-reasoned stimulation strategy has not been developed. For example, it is not known whether certain layers of V1 are more sensitive to electric stimulation than others nor are the responses of specific neuronal types to stimulation well understood. Here we measured the responses of L5 pyramidal neurons in vitro to stimulation from electrodes positioned at different cortical depths.
Methods :
Cell-attached patch clamp was used to record spikes from L5 pyramidal neurons of V1 in an in vitro mouse brain slice preparation. Single conical-shaped platinum/iridium stimulating electrodes with impedance of 1 MΩ were positioned such that the electrode tip was initially centered directly above the soma of a targeted cell. Stimulus waveforms were cathodic-first biphasic current pulses with a pulse duration of 200 µs and no interphase intervals. Stimulation was delivered at a frequency of 200 Hz for 0.1 s (20 total pulses). The amplitude of stimulation ranged from 0 to 30 μA. Measurements were repeated as the electrode tip was translated in 100 µm steps along the apical dendrite of targeted neurons as well as along the axon.
Results :
The strongest responses (highest spike counts) were elicited when the electrode tip was positioned close to the soma (layer 5 – 6); latencies for these spikes were 0.2 - 0.4 ms. Average thresholds were 14.09 µA (STDEV: 4.83 µA). Fewer spikes were elicited when the electrode was positioned over the distal apical dendrites (layer 1 – 4), even at amplitude levels of 30 µA (the maximum that could be delivered in our system). Interestingly, spikes arising from stimulation over the apical dendrite were bigger and sharper and had longer latencies (1-2 ms) than those that arose from stimulation over the axon (layers 5 – 6).
Conclusions :
Our results suggest that L5 pyramidal neurons of V1 are maximally sensitive to stimulation over deeper cortical layers (5 – 6). Moreover, the results also suggest that electrode position can alter the spike shape. Therefore, electrode depth is not only important for threshold optimization, but also, the depth of penetration may also contribute to distinct visual percepts.
This is an abstract that was submitted for the 2016 ARVO Annual Meeting, held in Seattle, Wash., May 1-5, 2016.