title: Vesicular glutamate transporter 1 is required for photoreceptor synaptic signaling but not for intrinsic visual functions.
abstract: Glutamatergic neurotransmission requires vesicular glutamate transporters (VGLUTs) to sequester glutamate into synaptic vesicles. Generally, VGLUT1 and VGLUT2 isoforms show complementary expression in the CNS and retina. However, little is known about whether isoform-specific expression serves distinct pathways and physiological functions. Here, by examining visual functions in VGLUT1-null mice, we demonstrate that visual signaling from photoreceptors to retinal output neurons requires VGLUT1. However, photoentrainment and pupillary light responses are preserved. We provide evidence that melanopsin-containing, intrinsically photosensitive retinal ganglion cells (RGCs), signaling via VGLUT2 pathways, support these non-image-forming functions. We conclude that VGLUT1 is essential for transmitting visual signals from photoreceptors to second- and third-order neurons, but VGLUT1 is not necessary for intrinsic visual functions. Furthermore, melanopsin and VGLUT2 expression in a subset of RGCs immediately after birth strongly supports the idea that intrinsic vision can function well before rod- and cone-mediated signaling has matured.
authors.affiliation: Department of Ophthalmology, University of California School of Medicine, San Francisco, California 94143, USA. johnsonj@vision.ucsf.edu
authors.forename: Juliette
authors.initials: J
authors.lastname: Johnson
authors.forename: Robert T
authors.initials: RT
authors.lastname: Fremeau
authors.forename: Jacque L
authors.initials: JL
authors.lastname: Duncan
authors.forename: René C
authors.initials: RC
authors.lastname: Rentería
authors.forename: Haidong
authors.initials: H
authors.lastname: Yang
authors.forename: Zhaolin
authors.initials: Z
authors.lastname: Hua
authors.forename: Xiaorong
authors.initials: X
authors.lastname: Liu
authors.forename: Matthew M
authors.initials: MM
authors.lastname: LaVail
authors.forename: Robert H
authors.initials: RH
authors.lastname: Edwards
authors.forename: David R
authors.initials: DR
authors.lastname: Copenhagen
mesh_terms: D000818:Animals; D005074:Evoked Potentials, Visual / Q000502:physiology; D051379:Mice; D018345:Mice, Knockout; D010775:Photic Stimulation / Q000379:methods; D010786:Photoreceptor Cells / Q000502:physiology*; D020033:Protein Isoforms / Q000502:physiology; D051381:Rats; D020318:Rats, Long-Evans; D012165:Retinal Ganglion Cells / Q000502:physiology; D015398:Signal Transduction / Q000502:physiology*; D013569:Synapses / Q000502:physiology*; D050598:Vesicular Glutamate Transport Protein 1 / Q000502:physiology*; D014785:Vision, Ocular / Q000502:physiology*
chemical_list: D020033:Protein Isoforms; D050598:Vesicular Glutamate Transport Protein 1