Cell Biology of the Retina

Harvard University (Medical School), Boston MA

Investigators

Linked publications & trials

Abstract

DESCRIPTION (provided by applicant): The objective of our research is to understand how the retina of mammals analyzes the visual world and encodes its spatial, temporal and chromatic contrast into a message of action potentials which is sent to the brain. In the retina, dopamine is the modulator responsible for many of the events that lead to neural adaptation to light. To identify the mechanisms and neural networks that control the release of dopamine, we labeled genetically dopaminergic amacrine cells (DA cells) in the mouse and could therefore investigate their physiology in vitro after dissociation of the retina. We also developed a technique to study global gene expression in single neurons. The present application has the following aims: (i) we will test the hypothesis that DA cells, in addition to dopamine, release GABA by exocytosis both over their entire surface and at their synapses with AII amacrine cells, the neuron that transfer rod signals to cone bipolar cells. (ii) We will investigate the light responses of DA cells by intracellular recordings in the intact mouse retina. (iii) By profiling gene expression on high-density arrays of oligonucleotide probes covering the transcribed mouse genome, we will compile a comprehensive list of the transcripts contained in DA cells. Knowledge of the repertory of ion channels, transmitter receptors, components of G-protein-coupled second messenger pathways and secreted neuroactive molecules that are contained in DA cells will allow us to formulate meaningful hypotheses about novel functions that can be tested experimentally. Finally, we will compare the transcriptome of DA cells with that of two other types of retinal neurons, type 2 catecholaminergic amacrines and rod bipolars. In addition to the presence of novel molecules, we will be searching for answers to questions that are at the very heart of the concept neuronal cell type: we want to uncover cell-type specific molecules and identify a "molecular signature" for the unique functions that are carried out by the three types of neurons in the processing of light signals. (iv) We will identify by electron microscopy the neurons that control the activity of DA cells in light and darkness. These studies are crucial to the understanding of the mechanism of vision in the retina.