Abstract
Extracellular electrophysiology and two-photon calcium imaging are widely used methods for measuring physiological activity with single-cell resolution across large populations of cortical neurons. While each of these two modalities has distinct advantages and disadvantages, neither provides complete, unbiased information about the underlying neural population. Here, we compare evoked responses in visual cortex recorded in awake mice under highly standardized conditions using either imaging of genetically expressed GCaMP6f or electrophysiology with silicon probes. Across all stimulus conditions tested, we observe a larger fraction of responsive neurons in electrophysiology and higher stimulus selectivity in calcium imaging, which was partially reconciled by applying a spikes-to-calcium forward model to the electrophysiology data. However, the forward model could only reconcile differences in responsiveness when restricted to neurons with low contamination and an event rate above a minimum threshold. This work established how the biases of these two modalities impact functional metrics that are fundamental for characterizing sensory-evoked responses.
Highlights
Systems neuroscience aims to explain how complex adaptive behaviors can arise from the interactions of many individual neurons
For selectivity metrics, applying the forward model played the biggest role in improving cross-modal similarity, there was a greater discrepancy between the resulting distributions for static gratings, natural scenes, and natural movies than there was for drifting gratings
Our study shows that population-level functional metrics computed from imaging and electrophysiology experiments can display systematic biases
Summary
Systems neuroscience aims to explain how complex adaptive behaviors can arise from the interactions of many individual neurons. Population recordings—which capture the activity of multiple neurons simultaneously—have become the foundational method for progress in this domain. Extracellular electrophysiology and calcium-dependent two-photon optical physiology are by far the most prevalent population recording techniques, due to their single-neuron resolution, ease of use, and scalability. Recent advances have made it possible to record simultaneously from thousands of neurons with electrophysiology (Jun et al, 2017; Siegle et al, 2021; Stringer et al, 2019a) or tens of thousands of neurons with calcium imaging (Sofroniew et al, 2016; Stringer et al, 2019b; Weisenburger et al, 2019). While insights gained from both methods have been invaluable to the field, it is clear that neither technique provides a completely faithful picture of the underlying neural activity. Our goal is to better understand the inherent biases of each recording modality, and how to appropriately compare results obtained with one method to those obtained with the other
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