barriers to diffusion in dendrites and estimation of calcium spread following synaptic inputs壁垒扩散在树突和估计的钙传播后突触输入.pdfVIP

Barriers to Diffusion in Dendrites and Estimation of Calcium Spread Following Synaptic Inputs 1,2 3 4 Armin Biess *, Eduard Korkotian , David Holcman * ¨ ¨ 1 Bernstein Center for Computational Neuroscience, Gottingen, Germany, 2 Max-Planck-Institute for Dynamics and Self-Organization, Gottingen, Germany, 3 Department ´ of Neurobiology, Weizmann Institute of Science, Rehovot, Israel, 4 Department of Computational Biology, Ecole Normale Superieure, Paris, France Abstract The motion of ions, molecules or proteins in dendrites is restricted by cytoplasmic obstacles such as organelles, microtubules and actin network. To account for molecular crowding, we study the effect of diffusion barriers on local calcium spread in a dendrite. We first present a model based on a dimension reduction approach to approximate a three dimensional diffusion in a cylindrical dendrite by a one-dimensional effective diffusion process. By comparing uncaging experiments of an inert dye in a spiny dendrite and in a thin glass tube, we quantify the change in diffusion constants due to molecular crowding as Dcyto/D water = 1/20. We validate our approach by reconstructing the uncaging experiments using Brownian simulations in a realistic 3D model dendrite. Finally, we construct a reduced reaction-diffusion equation to model calcium spread in a dendrite under the presence of additional buffers, pumps and synaptic input. We find that for moderate crowding, calcium dynamics is mainly regulated by the buffer concent