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Neuroscience Graduate Program at UCSF

Faculty - David Copenhagen, Ph.D.

Synaptic Interactions in the Retina: Pathways and Mechanisms

Research Description

The retina extracts and encodes specific features of the visual scene such as local contrast, color information and movement. As a sensory tissue, the retina displays an extraordinary ability to adapt to ambient light conditions that range over 10 orders of magnitude. Fundamental questions remain as to how the individual neurons are synaptically "wired" to one another via excitatory,glutamatergic and inhibitory, GABAergic and glycinergic, synaptic pathways. One of our principal areas of interest is to identify and characterize the synaptic pathways in the retina. We investigate not only the biophysical attributes of quantal synaptic transmission but also the relationships between function, connectivity, ligand-gated-channels and transporters. We utilize single cell recording, multi-electrode array, CCD imaging and confocal microscopy in these studies. A second principal area we have recently begun investigating is the development of function in the rodent retina. We have shown that dark rearing affects the anatomical and functional development of the retina. We seek to identify how this developmental retinal plasticity is controlled and what molecules are involved. A third area of ongoing research focuses on the regulation of calcium, chloride and pH in retinal neurons. We are particularly interested in the role of calcium, glutamine and glutamate transporters and the roles they play in homeostasis and regulation of synaptic transmission. In these studies we rely primarily on optical imaging using intracellular dyes, but we also use immunological and patch pipette techniques and have been able to understand function more clearly using transgenic mice lines.

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Current Projects

1. The effects of visual deprivation on the formation of retinal circuits.
We are investigating what environmental cues control maturation of the ON and OFF pathways. We are also investigating the role of various signaling molecules, such as BDNF and NMDA receptors, in regulating this maturation. We are using molecular and transgenic approaches to answer these questions.

2. Roles of vesicular glutamate transporters in retinal function.
In collaboration with Rob Edwards' lab , we are localizing and characterizing the roles for VGLUT1, VGLUT2 and VGLUT3 in mammalian retina.

3. Calcium regulation and synaptic transmission in retina.
We are investigating how calcium levels are controlled by inhibitory inputs to glutamatergic retinal neurons and the roles of plasma-membrane calcium ATPases and SERCAs in regulating intracellular calcium.

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Lab Members

Maria Fernanda Albarracin, Administrative Assistant
Christina Chun, Staff Research Associate
Michael Donovan, Postdoctoral Fellow
Sriparna Majumdar, Postdoctoral Fellow
Charlotte Oelerich, Graphics Analyst
Katalin Rabi, Postdoctoral Fellow

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Selected Publications

Link to Publications via PubMed

Selected publications from the last five years:

Krizaj D, Copenhagen DR (1998) Compartmentalization of calcium extrusion mechanisms in the outer and inner segments of photoreceptors. Neuron 21:249-256

Tian N, Copenhagen DR (1998) Characterization of spontaneous synaptic events in ganlglion cells of mouse retina Journal of Neurophysiology 80:1327-40.

Hwang TN, Copenhagen DR. (1999) Automatic detection, characterization, and discrimination of kinetically distinct spontaneous synaptic events J Neurosci Methods 92:65-73.

Krizaj D, Bao JX, Schmitz Y, Witkovsky P, Copenhagen DR. (1999) Caffeine-sensitive calcium stores regulate synaptic transmission from retinal rod photoreceptors. J Neurosci 19:7249-61.

Bieda MC, Copenhagen DR. (1999) Sodium action potentials are not required for light-evoked release of GABA or glycine from retinal amacrine cells. J Neurophysiol 81:3092-5

Tian N, Petersen C, Kash S, Baekkeskov S, Copenhagen D, Nicoll R (1999) The role of the synthetic enzyme GAD65 in the control of neuronal gamma-aminobutyric acid release. Proc Natl Acad Sci U S A 96:12911-6.

Chaudhry FA, Reimer RJ, Krizaj D, Barber D, Storm-Mathisen J, Copenhagen DR, Edwards RH (1999) Molecular analysis of system N suggests novel physiological roles in nitrogen metabolism and synaptic transmission Cell 99:769-80.

Vu TQ, Payne JA, Copenhagen DR. (2000) Localization and developmental expression patterns of the neuronal K-Cl cotransporter (KCC2) in the rat retina. J Neurosci 20:1414-1423.

Bieda, MC Copenhagen DR (2000) Inhibition is not required for the production of transient responses from retinal ganglion cells. Visual Neuroscience. 17:243-254.

Kleiman RJ, Tian N, Krizaj D, Hwang TN, Copenhagen DR, Reichardt LF. (2000) BDNF-Induced potentiation of spontaneous twitching in innervated myocytes requires calcium release from intracellular stores J Neurophysiol 84:472-83.

Tian N, Copenhagen DR. (2001) Visual deprivation alters development of synaptic function in inner retina after eye opening. Neuron 32(3):439-49.

Chaudhry FA, Krizaj D, Larsson P, Reimer RJ, Wreden C Storm-Mathisen J, Copenhagen D, Kavanaugh M, and Edwards RH. (2001) Coupled and uncoupled proton movement by amino acid transport system N. EMBO J ;20:7041-51.

Krizaj D, Copenhagen DR. Calcium regulation in photoreceptors. Front Biosci 2002 Sep 1;7:D2023-44.

Krizaj D, Demarco SJ, Johnson J, Strehler EE, Copenhagen DR (2002) Cell-specific expression of plasma membrane calcium ATPase isoforms in retinal neurons. J. Comp Neurol. 451:1-21.

Fremeau RT Jr, Burman J, Qureshi T, Tran CH, Proctor J, Johnson J, Zhang H, Sulzer D, Copenhagen DR, Storm-Mathisen J, Reimer RJ, Chaudhry FA, Edwards RH. (2002) The identification of vesicular glutamate transporter 3 suggests novel modes of signaling by glutamate. Proc Natl Acad Sci U S A. 99:14488-93.

Johnson J, Tian N, Caywood MS, Reimer RJ, Edwards RH, Copenhagen DR.(2003) Vesicular neurotransmitter transporter expression in developing postnatal rodent retina: GABA and glycine precede glutamate. J Neurosci. 23:518-29.

Krizaj D, Lai FA, Copenhagen DR. (2003) Ryanodine stores and calcium regulation in the inner segments of salamander rods and cones. J Physiol. ;547:761-74.

Wreden CC, Johnson J, Tran C, Seal RP, Copenhagen DR, Reimer RJ, Edwards RH. (2003) The H+-coupled electrogenic lysosomal amino acid transporter LYAAT1 localizes to the axon and plasma membrane of hippocampal neurons. J Neurosci. 23:1265-75.

Tian N, Copenhagen DR. (2003) Visual stimulation is required for refinement of ON and OFF pathways in postnatal retina. Neuron. 39:85-96.

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David Copenhagen, Ph.D.





Office Address

UCSF MC 0444
675 Nelson Rising Lane, Room 415A
San Francisco, CA 94158

Other Websites

Center for Integrative Neuroscience

Biomedical SciencesGraduate Program

Lab Website