Graduate Studies Faculty
Catherine W. Morgans, PhD
Programs:Neuroscience Graduate Program
Physiology & Pharmacology
Program in Molecular & Cellular Biosciences
Research Interests:neuroscience, synapse, retina, melanoma » PubMed Listing
Preceptor RotationsAcademic Term Available Summer 2016 Yes Fall 2016 Yes Winter 2016 Yes Spring 2016 Yes Summer 2017 Yes Fall 2017 Yes Winter 2017 Yes Spring 2017 Yes
Faculty MentorshipDr. Morgans is available as a mentor for 2016-2017.
We are interested in how synaptic transmission is influenced by the structural organization and biochemical properties of the synapse, and how these can be perturbed in neurological diseases. Our research is focused on the retina, specifically, the synapses between photoreceptors and bipolar cells, which represent the first stage of image processing in the visual system. At this synapse, visual information is split into ON and OFF pathways that signal increases and decreases in light intensity, respectively. This split occurs because of the opposing responses of ON- and OFF-bipolar cells to glutamate released from the photoreceptors. Photoreceptors release glutamate in darkness and respond to light by decreasing glutamate release. OFF-bipolar cells are depolarized by glutamate (resulting in a hyperpolarizing response to light), while ON-bipolar cells are hyperpolarized by glutamate (causing a depolarizing response to light). Photoreceptor synapses have unique structural and biochemical features that directly relate to their physiology, both pre-synaptically at the photoreceptor active zone, and post-synaptically in the ON-bipolar cell dendrites. Mutations in genes exclusively expressed at these sites cause congenital visual diseases, and we are using several mouse models of these diseases in our research. Our experimental approach combines immunohistochemistry, biochemistry, molecular biology and electrophysiology.
Presynaptic: Spatial Organization of the Photoreceptor Ribbon Synapse
The synaptic ribbon is a specialized organelle present at the active zone of photoreceptor synapses that maintains a release-ready pool of synaptic vesicles in close proximity to the presynaptic calcium channels. Of particular interest is the question of how the synaptic ribbons, which are synthesized in the cytoplasm, and the calcium channels, which are processed via the secretory pathway, come together to form a functional active zone. To address this, we are investigating physical interactions between the calcium channels and synaptic ribbon/active zone components. We have shown that mutations that disrupt these interactions result in a spatially disorganized synapse, in which the synaptic ribbons are not tethered to the plasma membrane and neurotransmitter release is inefficient. We are also investigating how sites of calcium entry and extrusion across the plasma membrane, and internal sites of calcium release and storage are organized within the photoreceptor synaptic terminal.
Postsynaptic: The mGluR6 Signal Transduction Pathway in ON-Bipolar Cells
Glutamate is typically an excitatory neurotransmitter, but glutamate hyperpolarizes (depresses) ON-bipolar cells. They respond to glutamate via a metabotropic receptor, mGluR6 that is exclusively expressed in ON-bipolar cell dendrites. Binding of glutamate by mGluR6 initiates a G protein-mediated signal transduction pathway that closes a cation channel and hyperpolarizes the cell. We have identified essential components of this pathway including the RGS proteins required to terminate G-protein activation, and the mGluR6-coupled cation channel, TRPM1. Now we are addressing the following questions: How is TRPM1 gated, and modulated, and what are the properties of the current? How is the mGluR6 signal transduction pathway modulated and how does this affect the ability of the ON-bipolar cell to adapt to different levels of background light? How does the mGluR6 pathway intersect with other signaling pathways in the ON-bipolar cell dendrites to generate the complete light response of the cell?
TRPM1: A Target of Autoantibodies in Melanoma-Associated Retinopathy.
Some patients with cutaneous metastatic melanoma develop night blindness caused by autoantibodies directed against metastasizing melanocytes cross-reacting with proteins in ON-bipolar cells. This paraneoplastic syndrome is known as melanoma-associated retinopathy (MAR). We have shown that TRPM1, which is expressed by bipolar cells in the retina and melanocytes in the skin, is a key MAR antigen. We are currently identifying other retinal proteins targeted by melanoma-associated autoantibodies and are investigating the application of these antigens in the development of prognostic/diagnostic tests for melanoma metastasis.