A dynamic clamp protocol to artificially modify cell capacitance
Abstract
Dynamics of excitable cells and networks depend on the membrane time constant, set by membrane resistance and capacitance. Whereas pharmacological and genetic manipulations of ionic conductances of excitable membranes are routine in electrophysiology, experimental control over capacitance remains a challenge. Here, we present capacitance clamp, an approach that allows electrophysiologists to mimic a modified capacitance in biological neurons via an unconventional application of the dynamic clamp technique. We first demonstrate the feasibility to quantitatively modulate capacitance in a mathematical neuron model and then confirm the functionality of capacitance clamp in in vitro experiments in granule cells of rodent dentate gyrus with up to threefold virtual capacitance changes. Clamping of capacitance thus constitutes a novel technique to probe and decipher mechanisms of neuronal signaling in ways that were so far inaccessible to experimental electrophysiology.
Data availability
All data generated, analysis code as well as computational modelling code is uploaded on https://zenodo.org/, see article section Data and software availability.
-
Capacitance Clamp Demonstration in Rat Dentate Gyrus Granule CellsZenodo. doi:10.5281/zenodo.5552207.
Article and author information
Author details
Funding
Bundesministerium für Bildung und Forschung (01GQ1403)
- Paul Pfeiffer
- Jan-Hendrik Schleimer
- Susanne Schreiber
Deutsche Forschungsgemeinschaft (GRK 1589/2)
- Paul Pfeiffer
- Federico José Barreda Tomás
Deutsche Forschungsgemeinschaft (EXC 257)
- Federico José Barreda Tomás
- Imre Vida
Deutsche Forschungsgemeinschaft (FOR 2134)
- Federico José Barreda Tomás
- Imre Vida
H2020 European Research Council (864243)
- Paul Pfeiffer
- Jan-Hendrik Schleimer
- Susanne Schreiber
Einstein Stiftung Berlin (EZ-2014-224)
- Jiameng Wu
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Ethics
Animal experimentation: All procedures and animal maintenance were performaed in accordance with institutional guidelines, the German Animal Welfare Act, the European Council Directive 86/609/EEC regarding the protection of animals, and guidelines from local authorities (Berlin, T-0215/11).
Reviewing Editor
- Ronald L Calabrese, Emory University, United States
Publication history
- Received: November 12, 2021
- Preprint posted: November 13, 2021 (view preprint)
- Accepted: March 17, 2022
- Accepted Manuscript published: April 1, 2022 (version 1)
- Version of Record published: May 26, 2022 (version 2)
Copyright
© 2022, Pfeiffer et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
Metrics
-
- 860
- Page views
-
- 205
- Downloads
-
- 0
- Citations
Article citation count generated by polling the highest count across the following sources: Crossref, PubMed Central, Scopus.
Download links
Downloads (link to download the article as PDF)
Open citations (links to open the citations from this article in various online reference manager services)
Cite this article (links to download the citations from this article in formats compatible with various reference manager tools)
Further reading
-
- Neuroscience
The treatment of neurodegenerative diseases is hindered by lack of interventions capable of steering multimodal whole-brain dynamics towards patterns indicative of preserved brain health. To address this problem, we combined deep learning with a model capable of reproducing whole-brain functional connectivity in patients diagnosed with Alzheimer’s disease (AD) and behavioral variant frontotemporal dementia (bvFTD). These models included disease-specific atrophy maps as priors to modulate local parameters, revealing increased stability of hippocampal and insular dynamics as signatures of brain atrophy in AD and bvFTD, respectively. Using variational autoencoders, we visualized different pathologies and their severity as the evolution of trajectories in a low-dimensional latent space. Finally, we perturbed the model to reveal key AD- and bvFTD-specific regions to induce transitions from pathological to healthy brain states. Overall, we obtained novel insights on disease progression and control by means of external stimulation, while identifying dynamical mechanisms that underlie functional alterations in neurodegeneration.
-
- Neuroscience
Previous research has associated alpha-band [8–12 Hz] oscillations with inhibitory functions: for instance, several studies showed that visual attention increases alpha-band power in the hemisphere ipsilateral to the attended location. However, other studies demonstrated that alpha oscillations positively correlate with visual perception, hinting at different processes underlying their dynamics. Here, using an approach based on traveling waves, we demonstrate that there are two functionally distinct alpha-band oscillations propagating in different directions. We analyzed EEG recordings from three datasets of human participants performing a covert visual attention task (one new dataset with N = 16, two previously published datasets with N = 16 and N = 31). Participants were instructed to detect a brief target by covertly attending to the screen’s left or right side. Our analysis reveals two distinct processes: allocating attention to one hemifield increases top-down alpha-band waves propagating from frontal to occipital regions ipsilateral to the attended location, both with and without visual stimulation. These top-down oscillatory waves correlate positively with alpha-band power in frontal and occipital regions. Yet, different alpha-band waves propagate from occipital to frontal regions and contralateral to the attended location. Crucially, these forward waves were present only during visual stimulation, suggesting a separate mechanism related to visual processing. Together, these results reveal two distinct processes reflected by different propagation directions, demonstrating the importance of considering oscillations as traveling waves when characterizing their functional role.