title: Genetic targeting and physiological features of VGLUT3+ amacrine cells.
abstract: Amacrine cells constitute a diverse class of interneurons that contribute to visual signal processing in the inner retina, but surprisingly, little is known about the physiology of most amacrine cell subtypes. Here, we have taken advantage of the sparse expression of vesicular glutamate transporter 3 (VGLUT3) in the mammalian retina to target the expression of yellow fluorescent protein (YFP) to a unique population of amacrine cells using a new transgenic mouse line. Electrophysiological recordings made from YFP-positive (VGLUT3+) amacrine cells provide the first functional data regarding the active membrane properties and synaptic connections of this recently identified cell type. We found that VGLUT3+ amacrine cells receive direct synaptic input from bipolar cells via both N-methyl-d-aspartate receptors (NMDARs) and non-NMDARs. Voltage-gated sodium channels amplified these excitatory inputs but repetitive spiking was never observed. VGLUT3+ amacrine cells responded transiently to both light increments (ON response) and decrements (OFF response); ON responses consisted exclusively of inhibitory inputs, while OFF responses comprised both excitatory and inhibitory components, although the inhibitory conductance was larger in amplitude and longer in time course. The physiological properties and anatomical features of the VGLUT3+ amacrine cells suggest that this bistratified interneuron may play a role in disinhibitory signaling and/or crossover inhibition between parallel pathways in the retina.
authors.affiliation: Synaptic Physiology Section, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, Maryland 20892-3701, USA.
authors.forename: William N
authors.initials: WN
authors.lastname: Grimes
authors.forename: Rebecca P
authors.initials: RP
authors.lastname: Seal
authors.forename: Nicholas
authors.initials: N
authors.lastname: Oesch
authors.forename: Robert H
authors.initials: RH
authors.lastname: Edwards
authors.forename: Jeffrey S
authors.initials: JS
authors.lastname: Diamond
mesh_terms: D025042:Amacrine Cells / Q000145:classification / Q000187:drug effects / Q000502:physiology*; D026922:Amino Acid Transport Systems, Acidic / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D000831:Animals, Newborn; D001703:Biophysics; D019256:Cadmium Chloride / Q000494:pharmacology; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D019706:Excitatory Postsynaptic Potentials / Q000187:drug effects / Q000235:genetics; D049452:Green Fluorescent Proteins / Q000235:genetics; D066298:In Vitro Techniques; D008027:Light; D008564:Membrane Potentials / Q000187:drug effects / Q000235:genetics*; D051379:Mice; D008822:Mice, Transgenic; D010455:Peptides / Q000494:pharmacology; D012160:Retina / Q000166:cytology*; D051245:Retinal Bipolar Cells / Q000187:drug effects / Q000502:physiology; D026941:Sodium Channel Blockers / Q000494:pharmacology; D013569:Synapses / Q000235:genetics / Q000502:physiology; D013779:Tetrodotoxin / Q000494:pharmacology; D014914:Whole Blood Coagulation Time
chemical_list: D026922:Amino Acid Transport Systems, Acidic; D019256:Cadmium Chloride; D018691:Excitatory Amino Acid Antagonists; D049452:Green Fluorescent Proteins; D010455:Peptides; D026941:Sodium Channel Blockers; D013779:Tetrodotoxin; C504941:Slc17a8 protein, mouse; C064719:iberiotoxin