Novel Approaches for Monitoring Electrical and Ionic Activity from Identified Cell Types in Intact Mouse Brain and Spinal Cord

Genetically-encoded calcium indicators (GECIs), such as GCaMP6s, are widely used for monitoring neuronal activity due to their cell-type specificity and high signal-to-noise ratio. However, calcium indicators do not capture the primary information-carrying events, that are action potentials or spikes. The relationship between calcium transients and action potentials is often complex, with non-linear and variable characteristics, which complicates the interpretation of calcium imaging data. Current algorithms for inferring spikes from calcium signals are limited by the scarcity of ground truth datasets, particularly from diverse neuronal subtypes and recording contexts, including the spinal cord and deep brain areas. This project addresses this gap by characterizing the relationship between spiking and calcium dynamics in different neuronal populations. Using a micro-optrode, a specialized tool developed in the De Koninck lab that enables simultaneous in vivo optical and electrical recordings from single neurons in the spinal cord and cortex, we investigated how calcium transients correlate with spiking across diverse firing patterns and response amplitudes under both spontaneous and stimulus-evoked conditions. Previous studies have shown marked differences in calcium signaling between excitatory and inhibitory neurons, as well as among inhibitory subtypes, likely due to variations in endogenous calcium buffering mechanisms. Establishing these benchmarks aims to improve algorithms for inferring action potentials from calcium imaging, enhancing both the accuracy and interpretability of this technique. Additionally, we plan to evaluate the performance of next-generation microoptrodes to gain new insights into neuronal dynamics, ultimately advancing the comparability between studies using electrophysiology and those using calcium imaging.

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