Year-end Sale % OFF 
Abstract
Electric micro-stimulation of the nervous system is a means to restore various body functions. The stimulus amplitude necessary to generate action potentials, the lower threshold (LT), is well characterized for many neuronal populations. However, electric overstimulation above an upper threshold (UT) prevents action potential generation and therefore hinders optimal neuro-rehabilitation. Previous studies demonstrated the impact of the UT in micro-stimulation of retinal ganglion cells (RGCs). The observed phenomenon is mostly explained by (i) reversed sodium ion flow in the soma membrane, and (ii) anodal surround block that hinders spike conduction in strongly hyperpolarized regions of the axon at high stimulus intensities. However, up to now, no detailed study of the nature of these phenomena has been presented, particularly for different cell types. Here, we present computational analyses of LT and UT for layer 5 pyramidal cells (PCs) as well as alpha RGCs. Model neurons were stimulated in close vicinity to the cell body and LTs and UTs as well as the ratio UT/LT were compared. Aside from a simple point source electrode and monophasic stimuli also realistic electrode and pulse configurations were examined. The analysis showed: (i) in RGCs, the soma contributed to action potential initiation and block for small electrode distances, whereas in PCs the soma played no role in LTs or UTs. (ii) In both cell types, action potential always initiated within the axon initial segment at LT. (iii) In contrast to a complete block of spike conductance at UT that occurred in RGCs, an incomplete block of spiking appeared in PC axon collaterals. (iv) PC axon collateral arrangement influenced UTs but had small impact on LTs. (v) Population responses of RGCs change from circular regions of activation to ring-shaped patterns for increasing stimulus amplitude. A better understanding of the stimulation window that can reliably activate target neurons will benefit the future development of neuroprostheses.
Highlights
Selective micro-stimulation of single neurons and, even more provoking, their subcellular structures such as the axon initial segment (AIS), soma or axon terminals are challenging for modern neuroprostheses
Our analysis aimed to identify the somatic contribution to action potential (AP) generation at lower threshold (LT) as well as blockage of spikes at upper threshold (UT) during micro-stimulation close to the cell body
To examine the contribution of the soma to LT and UT, model neurons were either equipped with a soma consisting of a single sphere or of 41 truncated cone compartments (Figures 1C, 2A left)
Summary
Selective micro-stimulation of single neurons and, even more provoking, their subcellular structures such as the axon initial segment (AIS), soma or axon terminals are challenging for modern neuroprostheses. For cathodic stimulation there is an intensity window with a lower threshold (LT) and an upper threshold (UT) for spike initiation and propagation. High-intensity cathodic stimulation of a nerve fiber causes strongly hyperpolarized regions on both sides of the electrode, blocking the propagation of an action potential (AP) generated in the central region close to the electrode. This phenomenon is called the anodal surround block or cathodic block (Katz and Miledi, 1965; Jankowska and Roberts, 1972; Roberts and Smith, 1973; Rattay and Aberham, 1993)
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
