This proposal will support investigation of pre- and postsynaptic mechanisms contributing to the reproducibility, timing, and dynamic range of signaling at the rod bipolar-All amacrine cell synapse in the rod pathway of the mammalian retina. The long-term goal of this research is to understand how visual information is encoded by synaptic interactions between retinal neurons.
Three specific aims will be addressed using electrophysiological recordings from synaptically coupled neurons in a retinal slice preparation.
Specific aim 1 investigates the presynaptic basis of reproducibility. The hypothesis that the kinetic properties of the presynaptic calcium channel, the retina-specific Cav1.4, and its placement relative to release sites in the active zone allow changes in presynaptic membrane potential to be transmitted reliably by the synapse will be tested.
Specific aim 2 will examine presynaptic mechanisms that control the timing of neurotransmitter release from rod bipolar cell terminals and investigate the hypothesis that activity-dependent modulation of the proteins composing the release machinery alters the kinetics of exocytosis.
Specific aim 3 will examine postsynaptic mechanisms controlling the dynamic range of the synapse. The hypothesis that voltage-gated sodium and potassium channels in the All membrane act to amplify small synaptic conductances and limit changes in the dynamic range of the synapse during activity-dependent synaptic depression will be addressed. Together, these specific aims will serve to elucidate the mechanisms that permit the normal function of retinal synapses during visual processing. This is a necessary first step in understanding altered retinal function in pathological states affecting vision. In particular, as mutations in Cav1.4 are responsible for X-linked incomplete congenital stationary night blindness, understanding the role that these channels play normally in synaptic transmission may provide insight into this disease.

Agency
National Institute of Health (NIH)
Institute
National Eye Institute (NEI)
Type
Research Project (R01)
Project #
5R01EY017836-04
Application #
7797383
Study Section
Biology and Diseases of the Posterior Eye Study Section (BDPE)
Program Officer
Greenwell, Thomas
Project Start
2007-04-01
Project End
2012-03-31
Budget Start
2010-04-01
Budget End
2011-03-31
Support Year
4
Fiscal Year
2010
Total Cost
$336,353
Indirect Cost
Name
Northwestern University at Chicago
Department
Ophthalmology
Type
Schools of Medicine
DUNS #
005436803
City
Chicago
State
IL
Country
United States
Zip Code
60611
Demb, Jonathan B; Singer, Joshua H (2016) Mind the Gap Junctions: The Importance of Electrical Synapses to Visual Processing. Neuron 90:207-9
Mortensen, Lena S; Park, Silvia J H; Ke, Jiang-Bin et al. (2016) Complexin 3 Increases the Fidelity of Signaling in a Retinal Circuit by Regulating Exocytosis at Ribbon Synapses. Cell Rep 15:2239-2250
Pallotto, Marta; Watkins, Paul V; Fubara, Boma et al. (2015) Extracellular space preservation aids the connectomic analysis of neural circuits. Elife 4:
Firl, Alana; Ke, Jiang-Bin; Zhang, Lei et al. (2015) Elucidating the role of AII amacrine cells in glutamatergic retinal waves. J Neurosci 35:1675-86
Demb, Jonathan B; Singer, Joshua H (2015) Functional Circuitry of the Retina. Annu Rev Vis Sci 1:263-289
Choi, Hannah; Zhang, Lei; Cembrowski, Mark S et al. (2014) Intrinsic bursting of AII amacrine cells underlies oscillations in the rd1 mouse retina. J Neurophysiol 112:1491-504
Margolis, David J; Gartland, Andrew J; Singer, Joshua H et al. (2014) Network oscillations drive correlated spiking of ON and OFF ganglion cells in the rd1 mouse model of retinal degeneration. PLoS One 9:e86253
Stafford, Benjamin K; Manookin, Michael B; Singer, Joshua H et al. (2014) NMDA and AMPA receptors contribute similarly to temporal processing in mammalian retinal ganglion cells. J Physiol 592:4877-89
Mehta, Bhupesh; Ke, Jiang-Bin; Zhang, Lei et al. (2014) Global Ca2+ signaling drives ribbon-independent synaptic transmission at rod bipolar cell synapses. J Neurosci 34:6233-44
Ke, Jiang-Bin; Wang, Yanbin V; Borghuis, Bart G et al. (2014) Adaptation to background light enables contrast coding at rod bipolar cell synapses. Neuron 81:388-401

Showing the most recent 10 out of 17 publications