A stochastic model of hippocampal synaptic plasticity with geometrical readout of enzyme dynamics

Rodrigues, Yuri Elias, Tigaret, Cezar Mugurel ORCID: https://orcid.org/0000-0001-5848-6697, Marie, Hélène, O'Donnell, Cian and Veltz, Romain 2023. A stochastic model of hippocampal synaptic plasticity with geometrical readout of enzyme dynamics. eLife 12 , e80152. 10.7554/eLife.80152

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Abstract

Discovering the rules of synaptic plasticity is an important step for understanding brain learning. Existing plasticity models are either (1) top-­down and interpretable, but not flex- ible enough to account for experimental data, or (2) bottom-­up and biologically realistic, but too intricate to interpret and hard to fit to data. To avoid the shortcomings of these approaches, we present a new plasticity rule based on a geometrical readout mechanism that flexibly maps synaptic enzyme dynamics to predict plasticity outcomes. We apply this readout to a multi-­timescale model of hippocampal synaptic plasticity induction that includes electrical dynamics, calcium, CaMKII and calcineurin, and accurate representation of intrinsic noise sources. Using a single set of model parameters, we demonstrate the robustness of this plasticity rule by reproducing nine published ex vivo experiments covering various spike-­timing and frequency-­dependent plasticity induction proto- cols, animal ages, and experimental conditions. Our model also predicts that in vivo-­like spike timing irregularity strongly shapes plasticity outcome. This geometrical readout modelling approach can be readily applied to other excitatory or inhibitory synapses to discover their synaptic plasticity rules.

Item Type:	Article
Date Type:	Publication
Status:	Published
Schools:	MRC Centre for Neuropsychiatric Genetics and Genomics (CNGG) Medicine Neuroscience and Mental Health Research Institute (NMHRI)
Subjects:	Q Science > QA Mathematics > QA76 Computer software Q Science > QP Physiology
Publisher:	eLife Sciences Publications
ISSN:	2050-084X
Funders:	Medical Research Council (MR/V034111/1), ComputaBrain Idex UCA Jedi, ComputaBrain Idex UCA Jedi, Medical Research Council (MR/V034111/1), Leverhulme Trust (RPG-2019-229)
Date of First Compliant Deposit:	18 August 2023
Date of Acceptance:	22 March 2023
Last Modified:	27 Feb 2024 12:37
URI:	https://orca.cardiff.ac.uk/id/eprint/161930

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