title: Spines slow down dendritic chloride diffusion and affect short-term ionic plasticity of GABAergic inhibition.
abstract: Cl(-) plays a crucial role in neuronal function and synaptic inhibition. However, the impact of neuronal morphology on the diffusion and redistribution of intracellular Cl(-) is not well understood. The role of spines in Cl(-) diffusion along dendritic trees has not been addressed so far. Because measuring fast and spatially restricted Cl(-) changes within dendrites is not yet technically possible, we used computational approaches to predict the effects of spines on Cl(-) dynamics in morphologically complex dendrites. In all morphologies tested, including dendrites imaged by super-resolution STED microscopy in live brain tissue, spines slowed down longitudinal Cl(-) diffusion along dendrites. This effect was robust and could be observed in both deterministic as well as stochastic simulations. Cl(-) extrusion altered Cl(-) diffusion to a much lesser extent than the presence of spines. The spine-dependent slowing of Cl(-) diffusion affected the amount and spatial spread of changes in the GABA reversal potential thereby altering homosynaptic as well as heterosynaptic short-term ionic plasticity at GABAergic synapses in dendrites. Altogether, our results suggest a fundamental role of dendritic spines in shaping Cl(-) diffusion, which could be of relevance in the context of pathological conditions where spine densities and neural excitability are perturbed.
authors.affiliation: Institute of Clinical Neuroanatomy, Neuroscience Center, Goethe University Frankfurt, Frankfurt/Main, Germany.
authors.forename: Namrata
authors.initials: N
authors.lastname: Mohapatra
authors.affiliation: Interdisciplinary Institute for Neuroscience, CNRS UMR 5297, Bordeaux, France.|Interdisciplinary Institute for Neuroscience, University of Bordeaux, France.
authors.forename: Jan
authors.initials: J
authors.lastname: Tønnesen
authors.affiliation: Institute of Clinical Neuroanatomy, Neuroscience Center, Goethe University Frankfurt, Frankfurt/Main, Germany.
authors.forename: Andreas
authors.initials: A
authors.lastname: Vlachos
authors.affiliation: Institute of Anatomy and Cell Biology, Heidelberg University, Heidelberg, Germany.
authors.forename: Thomas
authors.initials: T
authors.lastname: Kuner
authors.affiliation: Institute of Clinical Neuroanatomy, Neuroscience Center, Goethe University Frankfurt, Frankfurt/Main, Germany.
authors.forename: Thomas
authors.initials: T
authors.lastname: Deller
authors.affiliation: Interdisciplinary Institute for Neuroscience, CNRS UMR 5297, Bordeaux, France.|Interdisciplinary Institute for Neuroscience, University of Bordeaux, France.
authors.forename: U Valentin
authors.initials: UV
authors.lastname: Nägerl
authors.affiliation: Biology Department and Neurosciences Institute, The University of Texas at San Antonio, San Antonio, USA.
authors.forename: Fidel
authors.initials: F
authors.lastname: Santamaria
authors.affiliation: Institute of Clinical Neuroanatomy, Neuroscience Center, Goethe University Frankfurt, Frankfurt/Main, Germany.
authors.forename: Peter
authors.initials: P
authors.lastname: Jedlicka
mesh_terms: D000818:Animals; D001921:Brain / Q000502:physiology; D002712:Chlorides / Q000378:metabolism*; D019295:Computational Biology / Q000379:methods; D003712:Dendrites / Q000378:metabolism*; D049229:Dendritic Spines / Q000502:physiology*; D006801:Humans; D008959:Models, Neurological; D009435:Synaptic Transmission; D005680:gamma-Aminobutyric Acid / Q000378:metabolism
chemical_list: D002712:Chlorides; D005680:gamma-Aminobutyric Acid