Cell-specific modeling of retinal ganglion cell electrical activity

Guo, Tianruo; Tsai, David; Morley, John W.; Suaning, Gregg J.; Lovell, Nigel H.; Dokos, Socrates

doi:10.1109/embc.2013.6611053

Cited by 8 publications

(1 citation statement)

References 16 publications

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“…We used membrane dynamics from Fohlmeister (Fohlmeister et al, 2010) and ion channel densities for the five different sections along the neuron [dendrites, soma, axon hillock (soma to AIS), AIS, axon] can be found in Supplementary Table S1. Consistent with previous work in the retina (Jeng et al, 2011; Guo et al, 2013), the levels of voltage-gated sodium and potassium ion channels in the proximal axon were approximately 7x greater than those in the soma. Intracellular (axial) resistivity was set to 143.2 Ω⋅cm (Fohlmeister et al, 2010), specific membrane capacitance 1 μF/cm 2 and model temperature was set to 35°C similar to experimental conditions.…”

Section: Methodssupporting

confidence: 90%

Scaling of the AIS and Somatodendritic Compartments in α S RGCs

Raghuram

Werginz

Fried

2019

Front. Cell. Neurosci.

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The anatomical properties of the axon initial segment (AIS) are tailored in certain types of CNS neurons to help optimize different aspects of neuronal function. Here, we questioned whether the AISs of retinal ganglion cells (RGC) were similarly customized, and if so, whether they supported specific RGC functions. To explore this, we measured the AIS properties in alpha sustained RGCs (α S RGCs) of mouse; α S RGCs sizes vary systematically along the nasal temporal axis of the retina, making these cells an attractive population with which to study potential correlations between AIS properties and cell size. Measurements of AIS length as well as distance from the soma revealed that both were scaled to cell size, i.e., cells with large dendritic fields had long AISs that were relatively far from the soma. Within the AIS, the percentage of Nav1.6 voltage-gated sodium channels remained highly consistent, regardless of cell size or other AIS properties. Although ON RGCs were slightly larger than OFF cells at any given location of the retina, the level of scaling and relative distribution of voltage-gated sodium channels were highly similar. Computational modeling revealed that AIS scaling influenced spiking thresholds, spike rate as well as the kinetics of individual action potentials, Interestingly, the effect of individual features of the AIS varied for different neuronal functions, e.g., AIS length had a larger effect on the efficacy by which the AIS initiated spike triggered the somatic spike than it did on repetitive spiking. The polarity of the effect varied for different properties, i.e., increases to soma size increased spike threshold while increases to AIS length decreased threshold. Thus, variations in the relative level of scaling for individual components could fine tune threshold or other neuronal functions. Light responses were highly consistent across the full range of cell sizes suggesting that scaling may post-synaptically shape response stability, e.g., in addition to several well-known pre-synaptic contributors.

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Section: Methodssupporting

confidence: 90%

Scaling of the AIS and Somatodendritic Compartments in α S RGCs

Raghuram

Werginz

Fried

2019

Front. Cell. Neurosci.

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A spectral element method with adaptive segmentation for accurately simulating extracellular electrical stimulation of neurons

Eiber

Dokos

Lovell

et al. 2016

Med Biol Eng Comput

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The capacity to quickly and accurately simulate extracellular stimulation of neurons is essential to the design of next-generation neural prostheses. Existing platforms for simulating neurons are largely based on finite-difference techniques; due to the complex geometries involved, the more powerful spectral or differential quadrature techniques cannot be applied directly. This paper presents a mathematical basis for the application of a spectral element method to the problem of simulating the extracellular stimulation of retinal neurons, which is readily extensible to neural fibers of any kind. The activating function formalism is extended to arbitrary neuron geometries, and a segmentation method to guarantee an appropriate choice of collocation points is presented. Differential quadrature may then be applied to efficiently solve the resulting cable equations. The capacity for this model to simulate action potentials propagating through branching structures and to predict minimum extracellular stimulation thresholds for individual neurons is demonstrated. The presented model is validated against published values for extracellular stimulation threshold and conduction velocity for realistic physiological parameter values. This model suggests that convoluted axon geometries are more readily activated by extracellular stimulation than linear axon geometries, which may have ramifications for the design of neural prostheses.

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Influence of cell morphology in a computational model of ON and OFF retinal ganglion cells

Guo

Tsai

Morley

et al. 2013

2013 35th Annual International Conference of the IEEE Engineering in Medicine and Biology Society (EMBC)

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We developed anatomically and biophysically detailed ionic models to understand how cell morphology contributes to the unique firing patterns of ON and OFF retinal ganglion cells (RGCs). With identical voltage-gated channel kinetics and distribution, cell morphology alone is sufficient to generate quantitatively distinct electrophysiological responses. Notably, recent experimental observations from ON and OFF RGCs can be closely reproduced by the variations in their cell morphologies alone. Our results suggest that RGC morphology in conjunction with biophysical properties and network connectivity are able to produce the diverse response repertoire of RGCs.

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Cell-specific modeling of retinal ganglion cell electrical activity

Cited by 8 publications

References 16 publications

Scaling of the AIS and Somatodendritic Compartments in α S RGCs

Scaling of the AIS and Somatodendritic Compartments in α S RGCs

A spectral element method with adaptive segmentation for accurately simulating extracellular electrical stimulation of neurons

Influence of cell morphology in a computational model of ON and OFF retinal ganglion cells

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