The complex behavior of advanced nervous systems mainly originates from the elaborate branching structure of neuronal dendrites and the presence of spines. Such a structure enables the neurons to interact simultaneously with several neighbors and construct a complex network of signaling pathways. The functions of the nervous system rely on electro-chemical signaling. The transmission of chemical signals strongly depends on the transport and diffusion of ions and molecules which is governed by the dendrite structure. Understanding how signal transmission is influenced by the structure is becoming more important because pervasive changes of dendritic structure due to aging or neurodegenerative disorders have been reported. By developing a stochastic model for the transport of particles inside neuronal dendrites, we discover how the mean travel time of signals from synapses to soma depends on the key structural factors affected by neurodegenerative disorders or aging. These factors are the extent of the tree, the topological bias induced by segmental decrease of dendrite diameter, and the trapping probabilities in biochemical cages such as spines.
The cover image for the November 20 issue of the Biophysical Journal is an artistic rendering of the branching morphology of healthy and degenerate dendrites. The image in the background depicts the elaborate branching pattern of dendrites, which results in a complex network of signaling pathways. The main images are 2D projections of a healthy (left) dendritic tree and a degenerate (right) dendritic tree. The structure evolves during the course of aging or the progression of neurodegenerative disease. The population and spatial extent of branches, the density, shape, and spatial distribution of spines, and the thickness, length, and even curvature of dendritic channels can be affected. For example, the density of spines and the extent of the tree are reduced in Alzheimer's disease. As a result, chemical signal transmission and, thus, neural functions can be affected to a large extent.
The color coding in the neurons represents the particle density patterns. In this cover image, we highlight how the smooth concentration gradients in healthy cells differ from the heterogeneous concentration patterns in degenerate neurons. The color coding in the schematic represents the particle density patterns, with yellow denoting low density regions and cyan denoting high density regions. Through this cover image, we highlight the difference between the smooth concentration gradients in healthy cells and the heterogeneous concentration patterns in degenerate neurons. The pathological changes may induce local structural irregularities (e.g. the local abnormalities associated with fibrillar amyloid deposits in Alzheimer's disease), which lead to the formation of heterogeneous density patterns in the system. Such uneven distributions of signaling molecules and ions may have dramatic consequences on neural activities such as neuronal firing and the ability to maintain chemical concentrations and gradients.
- Robin Jose, Ludger Santen, M Reza Shaebani