Predicting neuronal firing from calcium imaging using a control theoretic approach.

Calcium imaging techniques, such as two-photon imaging, have become a powerful tool to explore the functions of neurons and the connectivity of their circuitry. Frequently, fluorescent calcium indicators are taken as a direct measure of neuronal activity. These indicators, however, are slow relative to behavior, obscuring functional relationships between an animal's movements and the true neuronal activity. As a consequence, the firing rate of a neuron is a more meaningful metric. Converting calcium imaging data to the firing of a neuron is nontrivial. Most state-of-the-art methods depend largely on non-mechanistic modeling frameworks such as neural networks, which do not illuminate the underlying chemical exchanges within the neuron, require significant data to be trained on, and cannot be implemented in real-time. Leveraging modeling frameworks from chemical reaction networks (CRN) coupled with a control theoretic approach, a new algorithm is presented leveraging a fully deterministic ordinary differential equation (ODE) model. This framework utilizes model predictive control (MPC) to challenge state-of-the-art correlation scores while retaining interpretability. Furthermore, these computations can be done in real time, thus, enabling online experimentation informed by neuronal firing rates. To demonstrate the use cases of this architecture, it is tested on ground truth datasets courtesy of the spikefinder challenge. Finally, we propose potential applications of the model for guiding experimental design.