Denervation-induced homeostatic dendritic plasticity in morphological granule cell models

Abstract

Event Abstract Back to Event Denervation-induced homeostatic dendritic plasticity in morphological granule cell models Steffen Platschek1, Hermann Cuntz1, 2, Mario Vuksic1, 3, Thomas Deller1 and Peter Jedlicka1* 1 Goethe University, Institute of Clinical Neuroanatomy, Neuroscience Center, Germany 2 Ernst Strüngmann Institute (ESI) for Neuroscience in Cooperation with Max Planck Society, Germany 3 University of Zagreb, School of Medicine, Croatian Institute for Brain Research, Croatia Neuronal death and subsequent denervation of target areas are major consequences of several neurological conditions such asischemia or neurodegeneration (Alzheimer's disease). The denervation-induced axonal loss results in reorganization of the dendritic tree of denervated neurons. The dendritic reorganization has been previously studied using entorhinal cortex lesion (ECL). ECL leads to shortening and loss of dendritic segments in the denervated outer molecular layer of the dentate gyrus. However, the functional importance of these long-term dendritic alterations is not yet understood and their impact on neuronal electrical properties remains unclear. Here we analyzed what happens to the electrotonic structure and excitability of dentate granule cells after lesion-induced alterations of their dendritic morphology, assuming all other parameters remain equal. We performed comparative electrotonic analysis in anatomically and biophysically realistic compartmental models of 3D-reconstructed healthy and denervated granule cells. Using the method of morphological modeling based on optimization principles minimizing the amount of wiring and maximizing synaptic democracy, we built artificial granule cells which replicate morphological features of their real counterparts. Our results show that somatofugal and somatopetal voltage attenuation in the passive cable model are strongly reduced in denervated granule cells. In line with these predictions, the attenuation both of simulated backpropagating action potentials and forward propagating EPSPs was significantly reduced in dendrites of denervated neurons. Intriguingly, the enhancement of action potential backpropagation occurred specifically in the denervated dendritic layers. Furthermore, simulations of synaptic f-I curves revealed a homeostatic increase of excitability in denervated granule cells. In summary, our morphological and compartmental modeling indicates that unless modified by changes of passive and/or active membrane properties, the plastic remodeling of dendrites following lesion of entorhinal inputs to granule cells will boost the efficacy of action potential backpropagation significantly and maintain their firing rate. Our results suggest that in addition to synaptic and intrinsic plasticity, a novel form of homeostatic plasticity,structural plasticity due todendritic remodeling.is operating in denervated neurons. Acknowledgements Supported by NSF/BMBF (US-German Collaboration in Computational Neuroscience, No. 01GQ1203A), by Young Investigators Grant (Faculty of medicine, Goethe-University) and by DFG Keywords: electrotonic analysis, Computer Simulation, compartmental modeling, morphological modeling, voltage attenuation, backpropagating action potential, homeostatic plasticity, granule cell Conference: 4th NAMASEN Training Workshop - Dendrites 2014, Heraklion, Greece, 1 Jul - 4 Jul, 2014. Presentation Type: Poster presentation Topic: morphological and functional characterizations Citation: Platschek S, Cuntz H, Vuksic M, Deller T and Jedlicka P (2014). Denervation-induced homeostatic dendritic plasticity in morphological granule cell models. Front. Syst. Neurosci. Conference Abstract: 4th NAMASEN Training Workshop - Dendrites 2014. doi: 10.3389/conf.fnsys.2014.05.00028 Copyright: The abstracts in this collection have not been subject to any Frontiers peer review or checks, and are not endorsed by Frontiers. They are made available through the Frontiers publishing platform as a service to conference organizers and presenters. The copyright in the individual abstracts is owned by the author of each abstract or his/her employer unless otherwise stated. Each abstract, as well as the collection of abstracts, are published under a Creative Commons CC-BY 4.0 (attribution) licence (https://creativecommons.org/licenses/by/4.0/) and may thus be reproduced, translated, adapted and be the subject of derivative works provided the authors and Frontiers are attributed. For Frontiers’ terms and conditions please see https://www.frontiersin.org/legal/terms-and-conditions. Received: 11 Apr 2014; Published Online: 12 Jun 2014. * Correspondence: Dr. Peter Jedlicka, Goethe University, Institute of Clinical Neuroanatomy, Neuroscience Center, Frankfurt, Other, please specify, 60590, Germany, peterjedlicka@yahoo.com Login Required This action requires you to be registered with Frontiers and logged in. To register or login click here. Abstract Info Abstract The Authors in Frontiers Steffen Platschek Hermann Cuntz Mario Vuksic Thomas Deller Peter Jedlicka Google Steffen Platschek Hermann Cuntz Mario Vuksic Thomas Deller Peter Jedlicka Google Scholar Steffen Platschek Hermann Cuntz Mario Vuksic Thomas Deller Peter Jedlicka PubMed Steffen Platschek Hermann Cuntz Mario Vuksic Thomas Deller Peter Jedlicka Related Article in Frontiers Google Scholar PubMed Abstract Close Back to top Javascript is disabled. Please enable Javascript in your browser settings in order to see all the content on this page.