Intrinsic excitability mechanisms of neuronal ensemble formation
- Columbia University, United States
Abstract
Neuronal ensembles are coactive groups of cortical neurons, found in spontaneous and evoked activity, that can mediate perception and behavior. To understand the mechanisms that lead to the formation of ensembles, we co-activated layer 2/3 pyramidal neurons in brain slices from mouse visual cortex, in animals of both sexes, replicating in vitro an optogenetic protocol to generate ensembles in vivo. Using whole-cell and perforated patch-clamp pair recordings we find that, after optogenetic or electrical stimulation, coactivated neurons increase their correlated activity, a hallmark of ensemble formation. Coactivated neurons showed small biphasic changes in presynaptic plasticity, with an initial depression followed by a potentiation after a recovery period. Optogenetic and electrical stimulation also induced significant increases in frequency and amplitude of spontaneous EPSPs, even after single-cell stimulation. In addition, we observed unexpected strong and persistent increases in neuronal excitability after stimulation, with increases in membrane resistance and reductions in spike threshold. A pharmacological agent that blocks changes in membrane resistance can revert this effect. These significant increases in excitability may partly generate the observed biphasic synaptic plasticity. We propose that cell-intrinsic changes in excitability are involved in the formation of neuronal ensembles. We propose an 'iceberg' model, by which increased neuronal excitability makes subthreshold connections suprathreshold, enhancing the effect of already existing synapses, and generating a new neuronal ensemble.
Data availability
Data have been deposited with Dryad (doi:10.5061/dryad.j6q573ngc)
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Intrinsic excitability mechanisms of neuronal ensemble formationDryad Digital Repository, doi:10.5061/dryad.j6q573ngc.
Article and author information
Author details
Tzitzitlini Alejandre-García
Jesús Pérez-Ortega
Funding
National Institute of Mental Health (R01EY011787)
- Rafael Yuste
National Institute of Mental Health (R01MH115900)
- Rafael Yuste
Consejo Nacional de Ciencia y Tecnología (287725)
- Tzitzitlini Alejandre-García
Consejo Nacional de Ciencia y Tecnología
- Jesús Pérez-Ortega
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 were performed by following the U.S. National Institutes of Health and Columbia University Institutional Animal Care and Use Committee guidelines (IACUC, Protocol #AC-AAAV3464).
Copyright
© 2022, Alejandre-García 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.
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Intrinsic excitability mechanisms of neuronal ensemble formation
eLife 11:e77470.
https://doi.org/10.7554/eLife.77470
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