Dendritic diameters affect the spatial variability of intracellular calcium dynamics in computer models

Abstract

There is growing interest in understanding calcium dynamics in dendrites, both experimentally and computationally. Many processes influence these dynamics, but in dendrites there is a strong contribution of morphology because the peak calcium levels are strongly determined by the surface to volume ratio (SVR) of each branch, which is inversely related to branch diameter. In this study we explore the predicted variance of dendritic calcium concentrations due to local changes in dendrite diameter and how this is affected by the modeling approach used. We investigate this in a model of dendritic calcium spiking in different reconstructions of cerebellar Purkinje cells and in morphological analysis of neocortical and hippocampal pyramidal neurons. We report that many published models neglect diameter-dependent effects on calcium concentration and show how to implement this correctly in the NEURON simulator, both for phenomenological pool based models and for implementations using radial 1D diffusion. More detailed modeling requires simulation of 3D diffusion and we demonstrate that this does not dissipate the local concentration variance due to changes of dendritic diameter. In many cases 1D diffusion of models of calcium buffering give a good approximation provided an increased morphological resolution is implemented.

Synaptic Activation of a Detailed Purkinje Cell Model Predicts Voltage-Dependent Control of Burst-Pause Responses in Active Dendrites

“…Then we considered the activation of voltage-dependent currents in the dendrites (Anwar et al, 2014 ) by delivering the appropriate multisynaptic stimulation pattern to the PC model in pacemaking regime. The higher synaptic depolarization in sector II than in sector I resulted in a stronger voltage-dependent activation of Ca channels in the former than in the latter (Figure 7B ).…”

ShuTu: Open-Source Software for Efficient and Accurate Reconstruction of Dendritic Morphology

“…Accurate estimates of diameters of dendrites are important for computational modeling of neurons (Psarrou et al, 2014; Anwar et al, 2014). Our automated algorithm works quite well in determining the diameters, as shown in Fig.…”

The 40-year history of modeling active dendrites in cerebellar Purkinje cells: emergence of the first single cell “community model”

“…The articles by Rapp et al ( 1992 , 1994 ) and De Schutter and Bower ( 1994a , b , c ) have collectively been cited more than 500 times, with the first description of the active Purkinje cell model De Schutter and Bower ( 1994a ) responsible for almost half those citations. Importantly, the model, we now refer to as the “R-DB model”, has formed the basis for considerable subsequent work from my own students both within my laboratory (Jaeger et al, 1996 ; Baldi et al, 1998 ; Sultan and Bower, 1998 ; Jaeger and Bower, 1999 ; Mocanu et al, 2000 ; Santamaria et al, 2002 , 2007 ; Santamaria and Bower, 2004 ; Lu et al, 2005 , 2009 ; Cornelis et al, 2010 ) and within their own independent laboratories and research (Staub et al, 1994 ; De Schutter, 1998 ; Vos et al, 1999 ; Howell et al, 2000 ; Steuber and De Schutter, 2001 , 2002 ; Gauck and Jaeger, 2003 ; Solinas et al, 2003 , 2006 ; Kreiner and Jaeger, 2004 ; Koekkoek et al, 2005 ; Santamaria et al, 2006 , 2011 ; Shin and De Schutter, 2006 ; Shin et al, 2007 ; Steuber et al, 2007 ; Achard and De Schutter, 2008 ; De Schutter and Steuber, 2009 ; Anwar et al, 2012 , 2013 , 2014 ; Coop et al, 2010 ; Tahon et al, 2011 ; Cao et al, 2012 ; Couto et al, 2015 ). Perhaps more importantly the R-DB model has become a true “community model” as it is now being used by a growing number of authors as a base for further modeling work outside its laboratories of origin (Coop and Reeke, 2001 ; Mandelblat et al, 2001 ; Miyasho et al, 2001 ; Roth and Häusser, 2001 ; Chono et al, 2003 ; Khaliq et al, 2003 ; Steuber and Willshaw, 2004 ; Ogasawara et al, 2007 ; Yamazaki and Tanaka, ...…”