# Real Time NEURON Simulation for Experimental Applications

> **NIH NIH R43** · CYTOCYBERNETICS, INC. · 2022 · $256,581

## Abstract

The goal of this proposal is to combine the power of the NEURON mathematical modeling software with the
Cybercyte “plug and play” dynamic clamp system. Our product will enable all neuronal electrophysiologists to be
able to perform sophisticated NEURON model based dynamic clamp experiments, without any requirement for
programming, engineering, or mathematical modeling skills. Our product is an integrated package of hardware
and software specifically for neuroscience applications, focusing on the specific stability and reliability needed
for routine neuronal electrophysiology and the large array of ion channels found in the nervous system. The four
aims of this project are:
Aim 1. Implement and Test Electronic Expression Mode. In this aim, the patch clamp amplifier is used in
current clamp mode to run cell-based action potentials from live cells, augmented with computer models of
specific channels. Artificial ion channels generated by computer models are used to inject an equivalent current
to mimic the effects of channel mutations, gain of function, state dependent drug binding etc., to reveal their
mechanisms of action on the excitability of real neurons. This can be thought of as an inexpensive “short cut” to
the painstaking process of generating genetic models of ion channels and other electrophysiological models.
Aim 2. Implement and Test Synthetic Cell Mode. In synthetic cell mode, all of the component currents, except
for the one of interest, are modelled, along with membrane action potentials. The current of interest is then
generated in, for example, an HEK cell expressing the channel of interest and controlled by a voltage-clamp
amplifier. The command input to the voltage clamp is the simulated action potential from the dynamic clamp
system with the synthetic cell. For example, real drugs can be added to the cloned channel of interest or the
consequences of a real kinetic mutation can be analyzed.
Aim 3. Implement and Demonstrate Cell Coupling Mode. Cell coupling mode was arguably the first form of
dynamic clamp invented. Originally it used analog circuitry to mimic gap junctional resistance between cells.
With NEURON, we can implement complex forms of cell to cell coupling, including synaptic transmission and
interneurons.
Aim 4. Implement and Test Diagnostics and Experimental Safeguards. A major limitation of dynamic clamp
applications in research & development, particularly in commercial applications, is the difficulty in maintaining
quality control. This aim helps automate the process of quality control to make the system accessible to non-
specialist users.
 Completion of these aims will result in a commercial advanced dynamic clamp system with an interface to
NEURON, which is powerful, reliable, but plug and play to install, and simple to use.

## Key facts

- **NIH application ID:** 10384810
- **Project number:** 1R43NS125749-01
- **Recipient organization:** CYTOCYBERNETICS, INC.
- **Principal Investigator:** Mark W Nowak
- **Activity code:** R43 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $256,581
- **Award type:** 1
- **Project period:** 2022-07-15 → 2024-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10384810

## Citation

> US National Institutes of Health, RePORTER application 10384810, Real Time NEURON Simulation for Experimental Applications (1R43NS125749-01). Retrieved via AI Analytics 2026-05-27 from https://api.ai-analytics.org/grant/nih/10384810. Licensed CC0.

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