Variance analysis as a method to predict the locus of plasticity at populations of non-uniform synapses

Our knowledge on synaptic transmission in the central nervous system has often been obtained by evoking synaptic responses to populations of synapses. Analysis of the variance in synaptic responses can be applied as a method to predict whether a change in synaptic responses is a consequence of alter...

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Main Authors: Lucas B. Lumeij, Aile N. van Huijstee, Natalie L. M. Cappaert, Helmut W. Kessels
Format: Article
Language:English
Published: Frontiers Media S.A. 2023-07-01
Series:Frontiers in Cellular Neuroscience
Subjects:
Online Access:https://www.frontiersin.org/articles/10.3389/fncel.2023.1232541/full
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author Lucas B. Lumeij
Aile N. van Huijstee
Natalie L. M. Cappaert
Helmut W. Kessels
author_facet Lucas B. Lumeij
Aile N. van Huijstee
Natalie L. M. Cappaert
Helmut W. Kessels
author_sort Lucas B. Lumeij
collection DOAJ
description Our knowledge on synaptic transmission in the central nervous system has often been obtained by evoking synaptic responses to populations of synapses. Analysis of the variance in synaptic responses can be applied as a method to predict whether a change in synaptic responses is a consequence of altered presynaptic neurotransmitter release or postsynaptic receptors. However, variance analysis is based on binomial statistics, which assumes that synapses are uniform. In reality, synapses are far from uniform, which questions the reliability of variance analysis when applying this method to populations of synapses. To address this, we used an in silico model for evoked synaptic responses and compared variance analysis outcomes between populations of uniform versus non-uniform synapses. This simulation revealed that variance analysis produces similar results irrespectively of the grade of uniformity of synapses. We put this variance analysis to the test with an electrophysiology experiment using a model system for which the loci of plasticity are well established: the effect of amyloid-β on synapses. Variance analysis correctly predicted that postsynaptically produced amyloid-β triggered predominantly a loss of synapses and a minor reduction of postsynaptic currents in remaining synapses with little effect on presynaptic release probability. We propose that variance analysis can be reliably used to predict the locus of synaptic changes for populations of non-uniform synapses.
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spelling doaj.art-3c0a6d33a1764686ad7d746255c1000f2023-07-17T13:38:50ZengFrontiers Media S.A.Frontiers in Cellular Neuroscience1662-51022023-07-011710.3389/fncel.2023.12325411232541Variance analysis as a method to predict the locus of plasticity at populations of non-uniform synapsesLucas B. LumeijAile N. van HuijsteeNatalie L. M. CappaertHelmut W. KesselsOur knowledge on synaptic transmission in the central nervous system has often been obtained by evoking synaptic responses to populations of synapses. Analysis of the variance in synaptic responses can be applied as a method to predict whether a change in synaptic responses is a consequence of altered presynaptic neurotransmitter release or postsynaptic receptors. However, variance analysis is based on binomial statistics, which assumes that synapses are uniform. In reality, synapses are far from uniform, which questions the reliability of variance analysis when applying this method to populations of synapses. To address this, we used an in silico model for evoked synaptic responses and compared variance analysis outcomes between populations of uniform versus non-uniform synapses. This simulation revealed that variance analysis produces similar results irrespectively of the grade of uniformity of synapses. We put this variance analysis to the test with an electrophysiology experiment using a model system for which the loci of plasticity are well established: the effect of amyloid-β on synapses. Variance analysis correctly predicted that postsynaptically produced amyloid-β triggered predominantly a loss of synapses and a minor reduction of postsynaptic currents in remaining synapses with little effect on presynaptic release probability. We propose that variance analysis can be reliably used to predict the locus of synaptic changes for populations of non-uniform synapses.https://www.frontiersin.org/articles/10.3389/fncel.2023.1232541/fullsynapsehippocampusvarianceuniformityamyloid–betaexcitatory postsynaptic current (EPSC)
spellingShingle Lucas B. Lumeij
Aile N. van Huijstee
Natalie L. M. Cappaert
Helmut W. Kessels
Variance analysis as a method to predict the locus of plasticity at populations of non-uniform synapses
Frontiers in Cellular Neuroscience
synapse
hippocampus
variance
uniformity
amyloid–beta
excitatory postsynaptic current (EPSC)
title Variance analysis as a method to predict the locus of plasticity at populations of non-uniform synapses
title_full Variance analysis as a method to predict the locus of plasticity at populations of non-uniform synapses
title_fullStr Variance analysis as a method to predict the locus of plasticity at populations of non-uniform synapses
title_full_unstemmed Variance analysis as a method to predict the locus of plasticity at populations of non-uniform synapses
title_short Variance analysis as a method to predict the locus of plasticity at populations of non-uniform synapses
title_sort variance analysis as a method to predict the locus of plasticity at populations of non uniform synapses
topic synapse
hippocampus
variance
uniformity
amyloid–beta
excitatory postsynaptic current (EPSC)
url https://www.frontiersin.org/articles/10.3389/fncel.2023.1232541/full
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AT ailenvanhuijstee varianceanalysisasamethodtopredictthelocusofplasticityatpopulationsofnonuniformsynapses
AT natalielmcappaert varianceanalysisasamethodtopredictthelocusofplasticityatpopulationsofnonuniformsynapses
AT helmutwkessels varianceanalysisasamethodtopredictthelocusofplasticityatpopulationsofnonuniformsynapses