Rose Lab

How experience changes neurons...

 

Investigation of Activity-Dependent Intracellular Signaling Mechanisms of Neurons. In their typical environment, neurons are constantly receiving a multitude of inputs and the intensity and pattern of this incoming stimulation determines the ongoing shape, structure and signaling organization of the neuron. The general research focus in my laboratory is to uncover cellular mechanisms in neurons that are engaged following depolarizing stimulation with the broader goal of understanding how neurons process and store information. My laboratory employs several approaches to gain insight into how neurons are uniquely adapted to modify themselves following a change in stimulus input.  At the single-cell level, my laboratory employs dissociated hippocampal neuron cultures to directly observe protein redistribution and aggregation following induced activity: This is accomplished using fluorescence microscopy of either live cells expressing reporter constructs or employing immunocytochemistry with fixed preparations. From this work, students have the opportunity to be involved in the design of DNA constructs, DNA cloning, expression of DNA plasmids and epifluorescence microscopy. In addition to examining dissociated neurons, my laboratory also utilizes the C. elegans model system to investigate processes at the single-neuron level within an intact animal model. These microscopic worms are transparent allowing direct observation of reporter transgenes in the whole animal. In addition, C. elegans  is a well-characterized genetic model for which a library of mutant strains are available; thus, this system allows for visualizing how modifying expression and/or function of identified neuronal proteins influences and sometimes determines intracellular protein organization and ultimately, the final behavioral output. From these experiments, students can gain experience in further DNA cloning as well as microinjection, confocal microscopy of transgenic C. elegans strains and whole animal behavioral assays. Taken together, these two research directions converge to reveal how ongoing signaling can change a single neuron and how these changes can be reflected in the whole, behaving animal.