Spines slow down dendritic chloride diffusion and affect short-term ionic plasticity of GABAergic inhibition.

Namrata Mohapatra,U Valentin Nägerl,Peter Jedlicka,Fidel Santamaria,Andreas Vlachos,Thomas Kuner,Jan Tønnesen,Thomas Deller

doi:10.1038/srep23196

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.

Highlights

Inhibitory synapses exhibit a unique form of plasticity, which depends on short- or long-term shifts in ionic concentration
We have tested the hypothesis that inhibitory synaptic activation results in a local rise in the concentration of dendritic Cl− and the spread of this concentration gradient is controlled by transmembrane Cl− transport but strongly affected by the diffusion rate of Cl−, which depends on dendritic morphology, i.e. presence of dendritic spines
We simulated Cl− diffusion following a focal increase of intracellular Cl− concentration ([Cl−]i) in the middle of the dendrite (Fig. 1)

Summary

Introduction

Inhibitory synapses exhibit a unique form of plasticity, which depends on short- or long-term shifts in ionic concentration. This phenomenon has been referred to as ionic plasticity[3,4]. Neurons, when exposed to intense inhibitory activity, accumulate intracellular Cl−, which substantially modifies the GABAergic reversal potential (EGABA)[19,20,21,22,23]. Such activity-dependent shifts in Cl− concentration and EGABA underlie short-term ionic plasticity at GABAergic synapses[24,25,26]. Our numerical simulations predict that spines influence short-term ionic plasticity by retarding dendritic spread of Cl− ions, yielding a decrease in the apparent diffusion coefficient for Cl−

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