Frontiers in Systems Neuroscience (Mar 2014)
Denervation-induced homeostatic dendritic plasticity in morphological granule cell models
Abstract
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.
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