Introduction
The stochastic flickering of ion channels is known to cause ongoing membrane potential fluctuations in neurons [1]. This channel noise is often considered negligible when compared to synaptic noise, yet it can shape the integrative properties of neurons [2]. Here, we show that valuable information on a neuron's intrinsic dynamics can be extracted by closely inspecting recordings of spontaneous membrane potential fluctuations in the absence of synaptic input.
Methods
We offer a reanalysis of previously published data [3] that consists of in vitro recordings from primary electrosensory pyramidal neurons in weakly electric fish under complete synaptic blockade. Raw voltage traces are segmented based on the applied holding currents, and each segment is decomposed into a fast and slow component. These components are analyzed with a suite of techniques, including wavelet transform, principal component analysis, Hilbert transform, and empirical mode decomposition.
Results
Our analyses reveal an intrinsic noise structure that is richer than what could be expected based on usual assumptions pertaining to intrinsic voltage noise: we identify rapid, small-amplitude, shot noise-like events, and we quantify how their rate and amplitude are modulated by slower, large-amplitude fluctuations. This cross-relation is evidence that, at the single-neuron level, membrane potential dynamics can exhibit a form of phase-amplitude coupling. We also investigate the appearance of fast, intermittent subthreshold oscillations and investigate whether they are manifestation of stochastic linear dynamics, possibly with time-varying parameters.
Discussion
To our knowledge, this is the first study to explore and quantify a form of cross-frequency phase-amplitude coupling within spontaneous voltage fluctuations in single neurons. Collectively, our results suggest that spontaneous voltage noise at the single-neuron level can be nontrivial and should be closely investigated to fully contextualize the arrival of synaptic input. Given the richness of the intrinsic noise structure that we uncover, we lend concrete support to the notion that “the precise impact of synaptic noise can be evaluated only once channel noise is understood and quantified” [2].
References
1. Faisal, A. A., Selen, L. P. J., & Wolpert, D. M. (2008). Noise in the nervous system. Nature Reviews Neuroscience, 9, 292–303.
2. White, J. A., Rubinstein, J. T., & Kay, A. R. (2000). Channel noise in neurons. Trends in Neurosciences, 23, 131–137.
3. Marcoux, C. M., Clarke, S. E., Nesse, W. H., Longtin, A., & Maler, L. (2016). Balanced ionotropic receptor dynamics support signal estimation via voltage-dependent membrane noise. Journal of Neurophysiology, 115, 530–545.
Acknowledgement
This work was funded by the Natural Sciences and Engineering Research Council of Canada under Grant No. RGPIN-2022-0 531 4.
