A comparison of neuronal population dynamics measured with calcium imaging and electrophysiology

Abstract

Calcium imaging with fluorescent protein sensors is widely used to record activity in neuronal populations. The transform between neural activity and calcium-related fluorescence involves nonlinearities and low-pass filtering, but the effects of the transformation on analyses of neural populations are not well understood. We compared neuronal spikes and fluorescence in matched neural populations in behaving mice. We report multiple discrepancies between analyses performed on the two types of data, including changes in single-neuron selectivity and population decoding. These were only partially resolved by spike inference algorithms applied to fluorescence. To model the relation between spiking and fluorescence we simultaneously recorded spikes and fluorescence from individual neurons. Using these recordings we developed a model transforming spike trains to synthetic-imaging data. The model recapitulated the differences in analyses. Our analysis highlights challenges in relating electrophysiology and imaging data, and suggests forward modeling as an effective way to understand differences between these data.

Anesthetics fragment hippocampal network activity, alter spine dynamics and affect memory consolidation

“…Due to the kinetics and calcium-binding properties of GCaMP6f, action potentials can only be resolved below approx. 5 Hz and are reported non-linearly [46,75]. In contrast, the electrodes on linear probes are arranged orthogonally to the strata of CA1 and parallel to the dendrites of CA1 cells.…”

“…However, we did not detect a clear peak at 1-4 Hz in the presence of Keta/Xyl, as seen in LFP and SUA, probably due to its strongly dampening effect on calcium transients. The (low-pass) filtering of neuronal activity imposed by calcium indicators might also play a role [75].…”

Database and deep learning toolbox for noise-optimized, generalized spike inference from calcium imaging

“…A transformation of calcium signals into estimates of spike rates may be desired for multiple reasons. First, the reconstruction of spike rates can recover fast temporal structure in neuronal activity patterns that is obscured by slower calcium signals 4, 5 . Second, calcium signals contain shot noise and potentially other forms of noise that are unrelated to neuronal activity.…”

“…Imaging of somatic calcium signals using organic or genetically encoded fluorescent indicators has emerged as a key method to measure the activity of many identified neurons simultaneously in the living brain 1, 2 . However, calcium signals are only an indirect, often non-linear and low pass-filtered proxy of the more fundamental variable of interest, somatic action potentials (spikes) 3–5 . The relationship between calcium signals and spike rates is ideally assessed directly by simultaneous electrophysiological recordings — preferably in the minimally disruptive juxtacellular configuration — and optical imaging of a calcium indicator signal in the same neuron.…”

Measuring stimulus-evoked neurophysiological differentiation in distinct populations of neurons in mouse visual cortex

“…It is important to keep in mind the limitations of the data we collected. Firstly, calcium imaging provides only an imperfect proxy of neuronal activity: simultaneous juxtacellular electrophysiology indicates that the fluorescence signal from Ca 2+ indicators is more sensitive to bursts of action potentials than sparse, low-frequency spiking (Chen et al, 2013; Huang et al, 2020; Ledochowitsch et al, 2019; Siegle et al, 2020; Wei et al, 2020). Such activity may contribute to ND but would not be present in this dataset.…”