title: Neurotransmission plays contrasting roles in the maturation of inhibitory synapses on axons and dendrites of retinal bipolar cells.
abstract: Neuronal output is modulated by inhibition onto both dendrites and axons. It is unknown whether inhibitory synapses at these two cellular compartments of an individual neuron are regulated coordinately or separately during in vivo development. Because neurotransmission influences synapse maturation and circuit development, we determined how loss of inhibition affects the expression of diverse types of inhibitory receptors on the axon and dendrites of mouse retinal bipolar cells. We found that axonal GABA but not glycine receptor expression depends on neurotransmission. Importantly, axonal and dendritic GABAA receptors comprise distinct subunit compositions that are regulated differentially by GABA release: Axonal GABAA receptors are down-regulated but dendritic receptors are up-regulated in the absence of inhibition. The homeostatic increase in GABAA receptors on bipolar cell dendrites is pathway-specific: Cone but not rod bipolar cell dendrites maintain an up-regulation of receptors in the transmission deficient mutants. Furthermore, the bipolar cell GABAA receptor alterations are a consequence of impaired vesicular GABA release from amacrine but not horizontal interneurons. Thus, inhibitory neurotransmission regulates in vivo postsynaptic maturation of inhibitory synapses with contrasting modes of action specific to synapse type and location.
authors.affiliation: Department of Biological Structure, University of Washington, Seattle, WA 98195; wongr2@uw.edu mhoon@uw.edu.
authors.forename: Mrinalini
authors.initials: M
authors.lastname: Hoon
authors.affiliation: Department of Physiology and Biophysics, University of Washington, Seattle, WA 98195; Howard Hughes Medical Institute, University of Washington, Seattle, WA 98195;
authors.forename: Raunak
authors.initials: R
authors.lastname: Sinha
authors.affiliation: Department of Biological Structure, University of Washington, Seattle, WA 98195;
authors.forename: Haruhisa
authors.initials: H
authors.lastname: Okawa
authors.affiliation: Department of Biological Structure, University of Washington, Seattle, WA 98195;
authors.forename: Sachihiro C
authors.initials: SC
authors.lastname: Suzuki
authors.affiliation: Department of Neurobiology, David Geffen School of Medicine at UCLA, University of California, Los Angeles, CA 90095; Veterans Administration Greater Los Angeles Healthcare System, Los Angeles, CA 90073;
authors.forename: Arlene A
authors.initials: AA
authors.lastname: Hirano
authors.affiliation: Department of Neurobiology, David Geffen School of Medicine at UCLA, University of California, Los Angeles, CA 90095; Veterans Administration Greater Los Angeles Healthcare System, Los Angeles, CA 90073; Jules Stein Eye Institute, Department of Ophthalmology, David Geffen School of Medicine at UCLA, University of California, Los Angeles, CA 90095; Department of Medicine, David Geffen School of Medicine at UCLA, University of California, Los Angeles, CA 90095.
authors.forename: Nicholas
authors.initials: N
authors.lastname: Brecha
authors.affiliation: Department of Physiology and Biophysics, University of Washington, Seattle, WA 98195; Howard Hughes Medical Institute, University of Washington, Seattle, WA 98195;
authors.forename: Fred
authors.initials: F
authors.lastname: Rieke
authors.affiliation: Department of Biological Structure, University of Washington, Seattle, WA 98195; wongr2@uw.edu mhoon@uw.edu.
authors.forename: Rachel O L
authors.initials: RO
authors.lastname: Wong
mesh_terms: D000818:Animals; D001369:Axons / Q000378:metabolism*; D003712:Dendrites / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D008822:Mice, Transgenic; D011963:Receptors, GABA-A / Q000235:genetics / Q000378:metabolism*; D018009:Receptors, Glycine / Q000235:genetics / Q000378:metabolism; D051245:Retinal Bipolar Cells / Q000378:metabolism*; D013569:Synapses / Q000235:genetics / Q000378:metabolism*; D009435:Synaptic Transmission / Q000502:physiology*
chemical_list: D011963:Receptors, GABA-A; D018009:Receptors, Glycine
keywords: GABA receptor; axon-dendrite; retina; synaptic inhibition