Global Ca2+ signaling drives ribbon-independent synaptic transmission at rod bipolar cell synapses.
Ribbon-type presynaptic active zones are a hallmark of excitatory retinal synapses, and the ribbon organelle is thought to serve as the organizing point of the presynaptic active zone. Imaging of exocytosis from isolated retinal neurons, however, has revealed ectopic release (i.e., release away from ribbons) in significant quantities. Here, we demonstrate in an in vitro mouse retinal slice preparation that ribbon-independent release from rod bipolar cells activates postsynaptic AMPARs on AII amacrine cells. This form of release appears to draw on a unique, ribbon-independent, vesicle pool. Experimental, anatomical, and computational analyses indicate that it is elicited by a significant, global elevation of intraterminal [Ca(2+)] arising following local buffer saturation. Our observations support the conclusion that ribbon-independent release provides a read-out of the average behavior of all of the active zones in a rod bipolar cell's terminal.
Departments of Cellular and Molecular Physiology and Ophthalmology and Visual Science, Yale University, New Haven, Connecticut 06520, Department of Biology, University of Maryland, College Park, Maryland 20742, and Circuit Dynamics and Connectivity Unit, National Institutes of Health (NIH)/National Institute of Neurological Disorders and Stroke (NINDS), Bethesda, Maryland 20892.
Bhupesh
B
Mehta
Jiang-Bin
JB
Ke
Lei
L
Zhang
Alexander D
AD
Baden
Alexander L
AL
Markowitz
Subhashree
S
Nayak
Kevin L
KL
Briggman
David
D
Zenisek
Joshua H
JH
Singer
D000818:Animals; D002118:Calcium / Q000378:metabolism*; D020013:Calcium Signaling / Q000187:drug effects / Q000502:physiology*; D002614:Chelating Agents / Q000494:pharmacology; D004533:Egtazic Acid / Q000031:analogs & derivatives / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D019706:Excitatory Postsynaptic Potentials / Q000187:drug effects / Q000502:physiology; D005260:Female; D066298:In Vitro Techniques; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008954:Models, Biological; D012160:Retina / Q000166:cytology; D051245:Retinal Bipolar Cells / Q000187:drug effects / Q000502:physiology* / Q000648:ultrastructure; D013569:Synapses / Q000187:drug effects / Q000502:physiology* / Q000648:ultrastructure; D009435:Synaptic Transmission / Q000187:drug effects / Q000502:physiology*; D013572:Synaptic Vesicles / Q000648:ultrastructure
D002614:Chelating Agents; D004791:Enzyme Inhibitors; D004533:Egtazic Acid; C025603:1,2-bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid; D002118:Calcium
exocytosis; retina; ribbon; vesicle