Real Time NEURON Simulation for Experimental Applications

The goal of this Phase II proposal is to combine the power of the NEURON mathematical modeling software with the Cybercyte “plug and play” dynamic clamp system. The end product will be a user-friendly, powerful and reliable way for a typical patch-clamp electrophysiologist to combine theoretical predictions and living cells directly, in real-time, during an experiment. The NEURON-Cybercyte package will be a turn-key system which enables 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. Its ease of use and simplicity is in automating the processes that ensure the stability and reliability needed for the large array of ion channels, cell types, and neural circuits found in the nervous system. In Phase I, we demonstrated proof of concept and built a prototype interface to enable NEURON models to interact through the Cybercyte dynamic clamp system, with live experiments, in real time. In Phase II we will build on this work to optimize the hardware, software, and databases in this package so that the user has a seamless, user-friendly experience. The challenges we will overcome are combining cutting edge computational abilities from two different systems, with an offline compendium of neuroscience knowledge. In the same way that AI creates presents a comfortable interface for people to get answers to complex questions without any need for understanding the sophisticated systems and databases underlying the interaction, we are creating a comfortable interface enabling users to have computers converse with cells, without any need for any programming, engineering, or searching databases. The four aims of this project are: Aim 1: Expand and optimize the major applications of the NEURON-Cybercyte package: In this aim, we will optimize the prototype to be able to work with the major applications of dynamic clamp, namely: A) electronic expression of modeled currents into experimental cells; B) insertion of experimental currents into synthetic cells; and C) cell to cell coupling with modeled synaptic transmission linking experimental cells. Aim 2: Develop a library of tested models. This follows from the strong demand from our users and interviews for a library of tested cellular models that are ready-to-use in one or more of the three modes described in the first aim. Aim 3: Develop a user toolkit. This user toolkit will enable rapid adaptation and testing of new and existing NEURON models for integration into the Cybercyte system for experimental use. We will develop user safeguards to allow relatively computationally naïve users to produce high quality data. Completion of these aims will result in a commercial advanced dynamic clamp system with an interface to NEURON, which is powerful, versatile, reliable, but plug and play to install, and simple to use.