Development and Function of Central Neuron Dendrites

点击翻译按钮获取中文摘要

Central neuron dendrites are stunningly complex three-dimensional structures and form the compartment of a neuron for receiving synaptic input. Consequently, dendritic architecture affects two fundamental aspects of brain function: First, it dictates which presynaptic neurons can contact the postsynaptic dendritic arbor, thus impacting neural circuit development and design. Second, it affects the summation and computation of postsynaptic signals. Consequently, healthy brain function relies on correct dendritic structure development, and dendritic defects are pathophysiological hallmarks of numerous neurological diseases. Therefore, identifying the molecular mechanisms underlying dendritic architecture development and synapse placement on dendritic arbors is imperative to understanding neural circuit development and function in the healthy and in the diseased brain. This project will combine genetic tools with quantitative dendritic structure analysis and opto- and electrophysiological recordings in the Drosophila genetic model system to unravel molecular mechanisms by which dendrites take on their correct gestalt, with specific focus on the mechanisms underlying dendritic self-avoidance and spacing of central neurons (aim 1). In the next step we will address the interplay of local synaptic activity and self-avoidance for correct dendritic architecture development (aim 2). Since we have recently uncovered a novel and unexpected function of the cell recognition molecule, Dscam1, in promoting dendrite growth and branching, we will now address the underlying molecular mechanisms (aim 3). Building on these developmental studies, we will then manipulate dendritic structure in different types of neurons with distinctly different functions and employ electro- and optophysiological approaches as well as behavioral testing to test the functional consequences that result from dendritic defects (aim 4). Therefore, we expect novel insight into the regulation of dendritic structure development and into the specific roles of distinct dendritic architecture features for neuronal function.