TITLE: Photo-control of endogenous ion channels and neurotransmitter receptors in the CNS
AUTHOR: Richard Kramer, Ph.D., University of California, Berkeley
TIME: 12:00:00 PM DATE: Monday, June 15, 2015
PLACE: Porter Neuroscience Research Center
Live NIH Videocast (archived after seminar)
Remote control of neural activity with “light-activated” ion channels
To overcome the loss of retinal photoreceptors in diseases such as retinitis pigmentosa and macular degeneration, scientists are attempting to develop electrical prosthetic devices, in which an implantable array of electrodes is used to stimulate remaining healthy neurons downstream in the visual pathway. We are taking a different approach, which involves direct optical regulation of the electrical activity of neurons without using invasive implantable devices. We have engineered the first ion channel that is directly activated with light. This channels consists of a genetically engineered ion channel protein that is covalently attached to a specially designed light-sensitive molecule, which includes a blocker of the channel’s pore. Photoisomerization of the light-sensitive molecule extends or retracts the blocker, opening or closing the flow of ions through the pore. Different wavelengths of light switch the molecule back and forth between blocking and unblocking states, so both channel opening and closing are controllable with light. Expression of these channels in neurons allows their electrical activity to be regulated with flashes of light. Hence illumination with 390 nm light silences action potentials and 500 nm light restores activity. Introduction of light-activated channels into retinal ganglion cell may provide a non-invasive means for rapid, reversible, and spatially accurate manipulation of neural activity, perhaps restoring visual sensitivity to individuals lacking functioning rods and cones.
Associate Professor of Neurobiology
Director, Kramer Lab
Kramer uses a combination of optical, electrophysiological, and molecular methods to study ion channels, the proteins that generate electrical signals, and synaptic transmission, the process that allows a neuron to communicate chemically with other cells. Many of our most recent studies utilize novel chemical reagents, designed to manipulate or monitor the function of ion channels and synapses. Current Project: Optical studies of synaptic transmission in the retina.
Phone: (510) 643-2406
Address: University of California
Department of Molecular and Cell Biology
121 Life Sciences Addition
Berkeley, CA 94720-3200
Measuring and controlling neural activity in the retina
Neurons in the retina communicate using electrical and chemical signals. We use a combination of optical, electrophysiological, and molecular methods to study ion channels, the proteins that generate electrical signals, and synaptic transmission, the process that allows a neuron to communicate chemically with other cells. Many of our most recent studies utilize novel chemical reagents, designed to manipulate or monitor the function of ion channels and synapses.
Optical studies of synaptic transmission in the retina
Rod and cone photoreceptors transmit information to other neurons through specialized structures called ribbon synapses. Insights into how these synapses work has come largely from indirect measurements from postsynaptic bipolar or horizontal neurons in the retina. We are are taking a different approach: we are directly measuring synaptic transmssion from rod presynaptic terminals of rods and cones, using a variety of optical methods. We use lipophilic fluorescence dyes, along with 2-photon, confocal, and electron microscopy, to track the life cycle of synaptic vesicles in photoreceptor terminals. This cycle starts with vesicles that are “born” by endocytosis of membrane from the plasma membrane. The vesicles become filled with neurotransmitter while they move rapidly within the cytoplasm of the terminal. They then encounter and bind to the synaptic ribbon and ultimately fuse with the plasma membrane by exocytosis, releasing their neurotransmitter to the extracellular space to act on postsynaptic cells. We are examining how illumination regulates this process. We hope to understand how the rate of synaptic vesicle release encodes information about light intensity. In addition to studying individual synapses, optical methods allow us to simultaneously image the behavior of 2-dimensional arrays of synapses while the retina is responding to visual images, providing a vivid “moving picture” of information processing in the retina.
About the NIH Neuroscience Seminars
The NIH Neuroscience Seminar Series features lectures and discussions with leading neuroscientists. Sponsored by NINDS, NIMH, NIA, NIDCD, NIDA, NICHD,NEI,NIAAA,NIDCR, NHGRI and NCCIH, this year’s series offers seminars on aspects of molecular, cellular, developmental and cognitive neuroscience as well as neuroscience related topics in disease, pain and genetics. Seminars are held on the NIH campus on Mondays at noon in the Porter Neuroscience Research Center, Room 620/630, Building 35.