title: Glutamatergic Monopolar Interneurons Provide a Novel Pathway of Excitation in the Mouse Retina.
abstract: Excitatory and inhibitory neurons in the CNS are distinguished by several features, including morphology, transmitter content, and synapse architecture [1]. Such distinctions are exemplified in the vertebrate retina. Retinal bipolar cells are polarized glutamatergic neurons receiving direct photoreceptor input, whereas amacrine cells are usually monopolar inhibitory interneurons with synapses almost exclusively in the inner retina [2]. Bipolar but not amacrine cell synapses have presynaptic ribbon-like structures at their transmitter release sites. We identified a monopolar interneuron in the mouse retina that resembles amacrine cells morphologically but is glutamatergic and, unexpectedly, makes ribbon synapses. These glutamatergic monopolar interneurons (GluMIs) do not receive direct photoreceptor input, and their light responses are strongly shaped by both ON and OFF pathway-derived inhibitory input. GluMIs contact and make almost as many synapses as type 2 OFF bipolar cells onto OFF-sustained A-type (AOFF-S) retinal ganglion cells (RGCs). However, GluMIs and type 2 OFF bipolar cells possess functionally distinct light-driven responses and may therefore mediate separate components of the excitatory synaptic input to AOFF-S RGCs. The identification of GluMIs thus unveils a novel cellular component of excitatory circuits in the vertebrate retina, underscoring the complexity in defining cell types even in this well-characterized region of the CNS.
authors.affiliation: Department of Biological Structure, University of Washington, Seattle, WA 98195-7420, USA; Department of Pharmacy, University of Pisa, Pisa 56126, Italy.
authors.forename: Luca
authors.initials: L
authors.lastname: Della Santina
authors.affiliation: Department of Physiology and Biophysics, University of Washington, Seattle, WA 98195-7290, USA; Howard Hughes Medical Institute, Seattle, WA 98195-7290, USA.
authors.forename: Sidney P
authors.initials: SP
authors.lastname: Kuo
authors.affiliation: Department of Biological Structure, University of Washington, Seattle, WA 98195-7420, USA.
authors.forename: Takeshi
authors.initials: T
authors.lastname: Yoshimatsu
authors.affiliation: Department of Biological Structure, University of Washington, Seattle, WA 98195-7420, USA.
authors.forename: Haruhisa
authors.initials: H
authors.lastname: Okawa
authors.affiliation: Department of Biological Structure, University of Washington, Seattle, WA 98195-7420, USA.
authors.forename: Sachihiro C
authors.initials: SC
authors.lastname: Suzuki
authors.affiliation: Department of Biological Structure, University of Washington, Seattle, WA 98195-7420, USA.
authors.forename: Mrinalini
authors.initials: M
authors.lastname: Hoon
authors.affiliation: Department of Cellular Neurobiology, Graduate School of Medicine, University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo, Japan.
authors.forename: Kotaro
authors.initials: K
authors.lastname: Tsuboyama
authors.affiliation: Department of Physiology and Biophysics, University of Washington, Seattle, WA 98195-7290, USA; Howard Hughes Medical Institute, Seattle, WA 98195-7290, USA.
authors.forename: Fred
authors.initials: F
authors.lastname: Rieke
authors.affiliation: Department of Biological Structure, University of Washington, Seattle, WA 98195-7420, USA. Electronic address: wongr2@uw.edu.
authors.forename: Rachel O L
authors.initials: ROL
authors.lastname: Wong
mesh_terms: D025042:Amacrine Cells / Q000166:cytology* / Q000378:metabolism / Q000648:ultrastructure; D000818:Animals; D005260:Female; D059330:GABAergic Neurons / Q000166:cytology* / Q000378:metabolism / Q000648:ultrastructure; D018698:Glutamic Acid / Q000378:metabolism*; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D051245:Retinal Bipolar Cells / Q000166:cytology / Q000378:metabolism / Q000648:ultrastructure; D012165:Retinal Ganglion Cells / Q000166:cytology* / Q000378:metabolism / Q000648:ultrastructure
chemical_list: D018698:Glutamic Acid