Retinal ganglion cell responses to extracellular stimulation for high-fidelity vision restoration
Abstract/Contents
- Abstract
- Future high-fidelity, large-scale electrical brain-machine interfaces will have the ability to restore population-level neural function to treat debilitating sensorimotor conditions. Achieving this will require fine, simultaneous, targeted closed-loop extracellular control of many individual neurons, carefully taking into account their natural physiological properties. Reconstitution of naturalistic neuronal activity in vivo necessitates advances in the engineering of bio-interfacing electrodes, understanding of population-level functional physiology, and mapping of biophysical responses to artificial external current. However, until recently, the electrophysiological exploration of neuronal responses to pulses of extracellular electrical current has been limited to either mostly non-primate cells, aggregated signals from hundreds or thousands of neurons, or peripheral nerve-fiber bundles. Additionally, most detailed explorations of single neuron biophysics have been conducted on cultured neurons with unnatural morphologies and extracellular environments. Using intact pieces of excised retinal tissue as a model system for ease of access, correlatability to therapeutic interventions for patients, and similarity to the cortex, our lab has previously independently characterized the recording and extracellular stimulus response properties of four macaque retinal ganglion cell (RGC) types: ON and OFF parasol and midget cells at a large scale using a densely spaced 512-electrode MEA. My graduate work builds on these initial studies by 1) systematically relating the recorded features of spontaneous activity of four RGC types at different eccentricities to their electrical response properties across dozens of different retinal preparations and thousands of individual cells, exploring the mechanism of this relationship using simulated neural models, and investigating the practical utility of such a characterization for future retinal implant engineering, and 2) generalizing the insights derived from the extracellular probing of macaque RGCs to human RGCs, which demonstrate very similar recording and electrical response properties. This work reveals that RGCs across different macaque and human eyes have near a uniform relationship between activity recording and electrical response properties that depend on broad cellular characteristics such as membrane morphology and ion channel density. It also demonstrates that these properties can be leveraged to aid in retinal implant design--specifically calibration of electrical stimuli--for use in treating acquired blindness. Finally, it implies that similar analyses are possible in various CNS circuits, making high-resolution artificial electrode access to these systems possible.
Description
| Type of resource | text |
|---|---|
| Form | electronic resource; remote; computer; online resource |
| Extent | 1 online resource. |
| Place | California |
| Place | [Stanford, California] |
| Publisher | [Stanford University] |
| Copyright date | 2023; ©2023 |
| Publication date | 2023; 2023 |
| Issuance | monographic |
| Language | English |
Creators/Contributors
| Author | Madugula, Sasidhar Sathya |
|---|---|
| Degree supervisor | Chichilnisky, E.J |
| Thesis advisor | Chichilnisky, E.J |
| Thesis advisor | Baccus, Stephen A |
| Thesis advisor | Huguenard, John |
| Thesis advisor | Mitra, Subhasish |
| Thesis advisor | Palanker, Daniel |
| Degree committee member | Baccus, Stephen A |
| Degree committee member | Huguenard, John |
| Degree committee member | Mitra, Subhasish |
| Degree committee member | Palanker, Daniel |
| Associated with | Stanford University, School of Medicine |
| Associated with | Stanford University, Neurosciences Program |
Subjects
| Genre | Theses |
|---|---|
| Genre | Text |
Bibliographic information
| Statement of responsibility | Sasidhar Madugula. |
|---|---|
| Note | Submitted to the Neurosciences Program. |
| Thesis | Thesis Ph.D. Stanford University 2023. |
| Location | https://purl.stanford.edu/ky669ry3652 |
Access conditions
- Copyright
- © 2023 by Sasidhar Sathya Madugula
- License
- This work is licensed under a Creative Commons Attribution Non Commercial 3.0 Unported license (CC BY-NC).
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