Identifiability of a Binomial Synapse

Gontier, Camille; Pfister, Jean-Pascal (2020). Identifiability of a Binomial Synapse. Frontiers in computational neuroscience, 14 Frontiers Research Foundation 10.3389/fncom.2020.558477

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Synapses are highly stochastic transmission units. A classical model describing this stochastic transmission is called the binomial model, and its underlying parameters can be estimated from postsynaptic responses to evoked stimuli. The accuracy of parameter estimates obtained via such a model-based approach depends on the identifiability of the model. A model is said to be structurally identifiable if its parameters can be uniquely inferred from the distribution of its outputs. However, this theoretical property does not necessarily imply practical identifiability. For instance, if the number of observations is low or if the recording noise is high, the model's parameters can only be loosely estimated. Structural identifiability, which is an intrinsic property of a model, has been widely characterized; but practical identifiability, which is a property of both the model and the experimental protocol, is usually only qualitatively assessed. Here, we propose a formal definition for the practical identifiability domain of a statistical model. For a given experimental protocol, this domain corresponds to the set of parameters for which the model is correctly identified as the ground truth compared to a simpler alternative model. Considering a model selection problem instead of a parameter inference problem allows to derive a non-arbitrary criterion for practical identifiability. We apply our definition to the study of neurotransmitter release at a chemical synapse. Our contribution to the analysis of synaptic stochasticity is three-fold: firstly, we propose a quantitative criterion for the practical identifiability of a statistical model, and compute the identifiability domains of different variants of the binomial release model (uni or multi-quantal, with or without short-term plasticity); secondly, we extend the Bayesian Information Criterion (BIC), a classically used tool for model selection, to models with correlated data (which is the case for most models of chemical synapses); finally, we show that our approach allows to perform data free model selection, i.e., to verify if a model used to fit data was indeed identifiable even without access to the data, but having only access to the fitted parameters.

Item Type:

Journal Article (Original Article)

Division/Institute:

04 Faculty of Medicine > Pre-clinic Human Medicine > Institute of Physiology

Graduate School:

Graduate School for Cellular and Biomedical Sciences (GCB)

UniBE Contributor:

Gontier, Camille Michel Jean-Claude and Pfister, Jean Pascal

Subjects:

500 Science > 570 Life sciences; biology

ISSN:

1662-5188

Publisher:

Frontiers Research Foundation

Language:

English

Submitter:

Camille Michel Jean-Claude Gontier

Date Deposited:

01 Oct 2020 10:46

Last Modified:

11 Mar 2021 19:04

Publisher DOI:

10.3389/fncom.2020.558477

BORIS DOI:

10.7892/boris.146762

URI:

https://boris.unibe.ch/id/eprint/146762

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