Authors:	Kirischuk, Sergei
Title:	Keeping excitation–inhibition ratio in balance
Online publication date:	13-Jan-2023
Year of first publication:	2022
Language:	english
Abstract:	Unrelated genetic mutations can lead to convergent manifestations of neurological disorders with similar behavioral phenotypes. Experimental data frequently show a lack of dramatic changes in neuroanatomy, indicating that the key cause of symptoms might arise from impairment in the communication between neurons. A transient imbalance between excitatory (glutamatergic) and inhibitory (GABAergic) synaptic transmission (the E/I balance) during early development is generally considered to underlie the development of several neurological disorders in adults. However, the E/I ratio is a multidimensional variable. Synaptic contacts are highly dynamic and the actual strength of synaptic projections is determined from the balance between synaptogenesis and synaptic elimination. During development, relatively slow postsynaptic receptors are replaced by fast ones that allow for fast stimulus-locked excitation/inhibition. Using the binomial model of synaptic transmission allows for the reassessing of experimental data from different mouse models, showing that a transient E/I shift is frequently counterbalanced by additional pre- and/or postsynaptic changes. Such changes—for instance, the slowing down of postsynaptic currents by means of immature postsynaptic receptors—stabilize the average synaptic strength, but impair the timing of information flow. Compensatory processes and/or astrocytic signaling may represent possible targets for medical treatments of different disorders directed to rescue the proper information processing. Keywords: neurological disorders; genetic mouse models; binomial model of synaptic transmission; readily releasable pool; release probability; quantal size
DDC:	610 Medizin 610 Medical sciences
Institution:	Johannes Gutenberg-Universität Mainz
Department:	FB 04 Medizin
Place:	Mainz
ROR:	https://ror.org/023b0x485
DOI:	http://doi.org/10.25358/openscience-8565
Version:	Published version
Publication type:	Zeitschriftenaufsatz
Document type specification:	Scientific article
License:	CC BY
Information on rights of use:	https://creativecommons.org/licenses/by/4.0/
Journal:	International journal of molecular sciences 23 10
Pages or article number:	5746
Publisher:	MDPI
Publisher place:	Basel
Issue date:	2022
ISSN:	1422-0067
Publisher DOI:	10.3390/ijms23105746
Appears in collections:	DFG-491381577-G