Modeling the effects of neuronal morphology on dendritic chloride diffusion and GABAergic inhibition

Gamma-aminobutyric acid receptors (GABA_ARs) are ligand-gated chloride (Cl⁻) channels which mediate the majority of inhibitory neurotransmission in the CNS. Spatiotemporal changes of intracellular Cl⁻ concentration alter the concentration gradient for Cl⁻ across the neuronal membrane and thus affect the current flow through GABA_ARs and the efficacy of GABAergic inhibition. However, the impact of complex neuronal morphology on Cl⁻ diffusion and the redistribution of intracellular Cl⁻ is not well understood. Recently, computational models for Cl⁻ diffusion and GABA_AR-mediated inhibition in realistic neuronal morphologies became available [1–3]. Here we have used computational models of morphologically complex dendrites to test the effects of spines on Cl⁻ diffusion. In all dendritic morphologies tested, spines slowed down longitudinal Cl⁻ diffusion along dendrites and decreased the amount and spatial spread of synaptically evoked Cl⁻ changes. Spine densities of 2-10 spines/µm decreased the longitudinal diffusion coefficient of Cl⁻ to 80-30% of its value in smooth dendrites, respectively. These results suggest that spines are able to limit short-term ionic plasticity [4] at dendritic GABAergic synapses.