Lesion-Induced Dendritic Remodeling as a New Mechanism of Homeostatic Structural Plasticity in the Adult Brain

Neurons display structural plasticity in the form of dynamic remodeling of spines and axons. These structural changes are also observed upon synaptic rewiring of a lesioned circuit and contribute to homeostatic maintenance of network activity. In contrast to structural plasticity of spines and axons, the functional significance of dendritic plasticity of denervated neurons is much less understood. Denervation-induced dendritic retraction is considered atrophic and functionally detrimental for neurons. We are suggesting a different interpretation and propose that limited denervation-induced changes of dendritic morphology lead to a homeostatic increase of neuronal excitability. Thus, dendritic remodeling may be functionally restorative. We have used a classical denervation model (entorhinal cortex lesion) for morphological and compartmental computer simulations. These indicate that plastic remodeling of dendrites following loss of entorhinal inputs to dentate granule cells boosts their responsiveness to synaptic activation and thereby maintains their firing rate. Simulations in both reconstructed as well as synthetic morphologies show that dendrite retraction precisely compensates for the denervation-evoked loss of synapses. We suggest that in addition to remodeling of spines and axons, a novel form of homeostatic structural plasticity based on dendritic remodeling is operating in a partially denervated circuit.