title: Vesicular neurotransmitter transporter expression in developing postnatal rodent retina: GABA and glycine precede glutamate.
abstract: Vesicular transporters regulate the amount and type of neurotransmitter sequestered into synaptic vesicles and, hence, the kind of signal transmitted to postsynaptic neurons. Glutamate is the prominent excitatory neurotransmitter in retina; GABA and glycine are the main inhibitory neurotransmitters. Little is known about the ontogeny of vesicular neurotransmission in retina. We investigated expression of glutamatergic [vesicular glutamate transporter 1 (VGLUT1)] and GABA/glycinergic [vesicular GABA/glycine transporter (VGAT)] vesicular transporters in postnatal retina. VGLUT1 labels glutamatergic synapses. VGLUT1 and synaptic vesicle 2 colocalized to photoreceptor terminals. VGLUT1 colocalized with PKC to rod bipolar terminals and to ON bipolar terminals in metabotropic glutamate receptor 6+/- mice. Developmentally, VGAT expression precedes VGLUT1. In rat and mouse retina, VGAT occurred in the inner retina by postnatal day 1 (P1). In rat retina, VGLUT1 was in the outer retina by P5-P7 and the inner retina by P7. In the mouse retina, VGLUT1 expression was in the outer retina by P3 and the inner retina by P5. Both rat and mouse retina had an adult pattern of VGLUT1 expression by P14. VGLUT1 expression precedes ribbon synapses, which are first observed in the inner retina at P11 (Fisher, 1979) in mouse and P13 (Horsburgh and Sefton, 1987) in rat. The ribbon synapse marker RIBEYE was not detected in inner retina of P5 or P7 rat. Spontaneous EPSCs in mouse ganglion cells were recorded as early as P7. Together, these findings indicate that vesicular GABA and glycine transmission precedes vesicular glutamate transmission in developing rodent retina. Furthermore, vesicular glutamate transmission likely occurs before ribbon synapse formation in the inner retina.
authors.affiliation: Department of Ophthalmology, University of California School of Medicine, San Francisco, California 94143-0730, USA. cjj@itsa.ucsf.edu
authors.forename: Juliette
authors.initials: J
authors.lastname: Johnson
authors.forename: Ning
authors.initials: N
authors.lastname: Tian
authors.forename: Matthew S
authors.initials: MS
authors.lastname: Caywood
authors.forename: Richard J
authors.initials: RJ
authors.lastname: Reimer
authors.forename: Robert H
authors.initials: RH
authors.lastname: Edwards
authors.forename: David R
authors.initials: DR
authors.lastname: Copenhagen
mesh_terms: D000367:Age Factors; D000818:Animals; D002352:Carrier Proteins / Q000096:biosynthesis*; D019706:Excitatory Postsynaptic Potentials / Q000502:physiology; D050485:GABA Plasma Membrane Transport Proteins; D018698:Glutamic Acid / Q000378:metabolism*; D005998:Glycine / Q000378:metabolism*; D006579:Heterozygote; D066298:In Vitro Techniques; D008562:Membrane Glycoproteins / Q000096:biosynthesis; D008565:Membrane Proteins / Q000096:biosynthesis*; D026901:Membrane Transport Proteins; D051379:Mice; D008810:Mice, Inbred C57BL; D008817:Mice, Mutant Strains; D009419:Nerve Tissue Proteins / Q000096:biosynthesis; D009474:Neurons / Q000166:cytology / Q000378:metabolism; D027361:Organic Anion Transporters; D018408:Patch-Clamp Techniques; D020419:Photoreceptor Cells, Vertebrate / Q000378:metabolism / Q000648:ultrastructure; D017729:Presynaptic Terminals / Q000378:metabolism; D051381:Rats; D020318:Rats, Long-Evans; D012160:Retina / Q000166:cytology / Q000254:growth & development / Q000378:metabolism*; D012165:Retinal Ganglion Cells / Q000166:cytology / Q000378:metabolism; D050598:Vesicular Glutamate Transport Protein 1; D033921:Vesicular Transport Proteins; D005680:gamma-Aminobutyric Acid / Q000378:metabolism*
chemical_list: D002352:Carrier Proteins; D050485:GABA Plasma Membrane Transport Proteins; D008562:Membrane Glycoproteins; D008565:Membrane Proteins; D026901:Membrane Transport Proteins; D009419:Nerve Tissue Proteins; D027361:Organic Anion Transporters; C493465:Slc17a7 protein, mouse; C493466:Slc17a7 protein, rat; C489614:Sv2a protein, mouse; C489618:Sv2a protein, rat; D050598:Vesicular Glutamate Transport Protein 1; D033921:Vesicular Transport Proteins; D018698:Glutamic Acid; D005680:gamma-Aminobutyric Acid; D005998:Glycine