# Investigating the response of CNS neurons to electric and magnetic stimulation

> **NIH NIH R01** · MASSACHUSETTS GENERAL HOSPITAL · 2022 · $901,162

## Abstract

Our long-term goals are to better understand the response of neurons to artificial stimulation, and, to use this
knowledge to develop new and more effective strategies for stimulating non- or improperly-functioning neurons
of the CNS. The development of models that comprehensively and accurately predict the response of neural
populations to electric stimulation has proven challenging, in part because of the significant morphological
differences that can exist even between nearby cells, and, a lack of understanding as to how such differences
shape each cell’s response to stimulation. A comprehensive understanding of the activation process would not
only allow the development of models that would more accurately predict population responses but would also
support the development of more effective stimulation strategies. In the retina for example, cells that respond
to increases in luminance (ON cells) typically lie adjacent to cells that respond to luminance decreases (OFF
cells); the two do not typically fire action potentials in response to the same stimulus and therefore, a
prosthesis that activates both simultaneously creates a pattern of neural activity that is non-physiological. Mis-
match between natural and artificial signals limits the quality of vision that can be obtained by a retinal
prosthesis and similarly limits the effectiveness of other CNS-based prostheses as well. Here, we propose to
comprehensively study how individual cellular properties each influence the response to artificial stimulation.
Our approach will be to map sensitivity across a cell, and then compare physiological maps to cellular
morphology, including the expression of voltage-gated ion channels; this will allow us to identify the specific
cellular regions that have the strongest influence on responsivity. Computational models based on our precise
anatomical measurements can be calibrated from the physiological maps to optimize the accuracy of the
models; they will also help to unequivocally identify the relative sensitivity of individual features. Comparison of
multiple cells within the same cell type will help to further identify the features that have the strongest influence
on threshold and repeating the process across multiple cell types, different CNS regions and multiple species
will lead to a comprehensive understanding of the activation process, along with the concurrent development of
models that accurately predict the response of large populations of neurons to many different forms of
stimulation. The inclusion of non-human primate tissue in the study will enhance the translation value of our
findings. Validated models will be used to study responses to more advanced stimulating strategies, e.g. the
high-rate stimulus trains that produce selective activation in ON vs. OFF cell types of the retina, and, the use of
magnetic stimulation from implantable micro-coils to selectively target pyramidal neurons in the cortex while
avoiding nearby passing axons fro...

## Key facts

- **NIH application ID:** 10168669
- **Project number:** 5R01NS110575-03
- **Recipient organization:** MASSACHUSETTS GENERAL HOSPITAL
- **Principal Investigator:** Shelley Fried
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $901,162
- **Award type:** 5
- **Project period:** 2019-06-15 → 2024-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10168669

## Citation

> US National Institutes of Health, RePORTER application 10168669, Investigating the response of CNS neurons to electric and magnetic stimulation (5R01NS110575-03). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10168669. Licensed CC0.

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