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J Neurophysiol 100: 304-316, 2008. First published April 24, 2008; doi:10.1152/jn.90202.2008
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Development of Presynaptic Inhibition Onto Retinal Bipolar Cell Axon Terminals Is Subclass-Specific

Timm Schubert1, Daniel Kerschensteiner1, Erika D. Eggers2, Thomas Misgeld3,4, Martin Kerschensteiner3,5, Jeff W. Lichtman3, Peter D. Lukasiewicz2 and Rachel O. L. Wong1

1Department of Biological Structure, University of Washington, Seattle, Washington; 2Department of Ophthalmology, Washington University School of Medicine, St. Louis, Missouri; 3Department of Molecular and Cellular Biology, Harvard University, Cambridge, Massachusetts; 4Institute of Neuroscience, Technical University Munich, Munich, Germany; and 5Institute of Clinical Neuroimmunology, Ludwig-Maximilians University Munich, Munich, Germany

Synaptic integration is modulated by inhibition onto the dendrites of postsynaptic cells. However, presynaptic inhibition at axonal terminals also plays a critical role in the regulation of neurotransmission. In contrast to the development of inhibitory synapses onto dendrites, GABAergic/glycinergic synaptogenesis onto axon terminals has not been widely studied. Because retinal bipolar cells receive subclass-specific patterns of GABAergic and glycinergic presynaptic inhibition, they are a good model for studying the development of inhibition at axon terminals. Here, using whole cell recording methods and transgenic mice in which subclasses of retinal bipolar cells are labeled, we determined the temporal sequence and patterning of functional GABAergic and glycinergic input onto the major subclasses of bipolar cells. We found that the maturation of GABAergic and glycinergic synapses onto the axons of rod bipolar cells (RBCs), ON-cone bipolar cells (ON-CBCs) and OFF-cone bipolar cells (OFF-CBCs) were temporally distinct: spontaneous chloride-mediated currents are present in RBCs earlier in development compared with ON- and OFF-CBC, and RBCs receive GABAergic and glycinergic input simultaneously, whereas in OFF-CBCs, glycinergic transmission emerges before GABAergic transmission. Because ON-CBCs show little inhibitory activity, GABAergic and glycinergic events could not be pharmacologically distinguished for these bipolar cells. The balance of GABAergic and glycinergic input that is unique to RBCs and OFF-CBCs is established shortly after the onset of synapse formation and precedes visual experience. Our data suggest that presynaptic modulation of glutamate transmission from bipolar cells matures rapidly and is differentially coordinated for GABAergic and glycinergic synapses onto distinct bipolar cell subclasses.


Address for reprint requests and other correspondence: R.O.L. Wong, Dept. of Biological Structure, University of Washington, HSB, I-146, Box 357420, Seattle, WA 98195-7420 (E-mail: wongr2{at}u.washington.edu)







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