Poster presentation | Open | Published:
Modeling the effects of neuronal morphology on dendritic chloride diffusion and GABAergic inhibition
BMC Neurosciencevolume 15, Article number: P138 (2014)
Gamma-aminobutyric acid receptors (GABAARs) 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 GABAARs 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 GABAAR-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  at dendritic GABAergic synapses.
Jedlicka P, Deller T, Gutkin BS, Backus KH: Activity-dependent intracellular chloride accumulation and diffusion controls GABAA receptor-mediated synaptic transmission. Hippocampus. 2011, 21: 885-898.
Doyon N, Prescott SA, Castonguay A, Godin AG, Kröger H, Koninck YD: Efficacy of synaptic inhibition depends on multiple, dynamically interacting mechanisms implicated in chloride homeostasis. PLoS Comput Biol. 2011, 7 (9): e1002149-10.1371/journal.pcbi.1002149.
Lewin N, Aksay E, Clancy CE: Computational modeling reveals dendritic origins of GABAA-mediated excitation in CA1 pyramidal neurons. PLoS One. 2012, 7 (10): e47250-10.1371/journal.pone.0047250.
Raimondo JV, Markram H, Akerman CJ: Short-term ionic plasticity at GABAergic synapses. Front Syn Neurosci. 2012, 4: 5-10.3389/fnsyn.2012.00005.
Supported by the NSF/BMBF (US-German Collaboration in Computational Neuroscience, No. 01GQ1203A).