The Synapse Diversity Dilemma: Molecular Heterogeneity Confounds Studies of Synapse Function.

Grant SGN, Fransén E

Front Synaptic Neurosci 12 (-) 590403 [2020-10-02; online 2020-10-02]

Recent studies have shown an unexpectedly high degree of synapse diversity arising from molecular and morphological differences among individual synapses. Diverse synapse types are spatially distributed within individual dendrites, between different neurons, and across and between brain regions, producing the synaptome architecture of the brain. The spatial organization of synapse heterogeneity is important because the physiological activation of heterogeneous excitatory synapses produces a non-uniform spatial output of synaptic potentials, which confounds the interpretation of measurements obtained from population-averaging electrodes, optrodes and biochemical methods that lack single-synapse resolution. Population-averaging measurements cannot distinguish between changes in the composition of populations of synapses and changing synaptic physiology. Here we consider the implications of synapse diversity and its organization into synaptome architecture for studies of synapse physiology, plasticity, development and behavior, and for the interpretation of phenotypes arising from pharmacological and genetic perturbations. We conclude that prevailing models based on population-averaging measurements need reconsideration and that single-synapse resolution physiological recording methods are required to confirm or refute the major synaptic models of behavior.

PubMed 33132891

DOI 10.3389/fnsyn.2020.590403

Crossref 10.3389/fnsyn.2020.590403

pmc: PMC7561708


Publications 9.5.1