Kainate receptors mediate signaling in both transient and sustained OFF bipolar cell pathways in mouse retina.
A fundamental question in sensory neuroscience is how parallel processing is implemented at the level of molecular and circuit mechanisms. In the retina, it has been proposed that distinct OFF cone bipolar cell types generate fast/transient and slow/sustained pathways by the differential expression of AMPA- and kainate-type glutamate receptors, respectively. However, the functional significance of these receptors in the intact circuit during light stimulation remains unclear. Here, we measured glutamate release from mouse bipolar cells by two-photon imaging of a glutamate sensor (iGluSnFR) expressed on postsynaptic amacrine and ganglion cell dendrites. In both transient and sustained OFF layers, cone-driven glutamate release from bipolar cells was blocked by antagonists to kainate receptors but not AMPA receptors. Electrophysiological recordings from bipolar and ganglion cells confirmed the essential role of kainate receptors for signaling in both transient and sustained OFF pathways. Kainate receptors mediated responses to contrast modulation up to 20 Hz. Light-evoked responses in all mouse OFF bipolar pathways depend on kainate, not AMPA, receptors.
Department of Ophthalmology and Visual Science, Department of Cellular and Molecular Physiology, and Program in Cellular Neuroscience, Neurodegeneration and Repair, Yale University School of Medicine, New Haven, Connecticut 06511, Department of Anatomical Sciences and Neurobiology, University of Louisville, School of Medicine, Louisville, Kentucky 40202, and Howard Hughes Medical Institute, Janelia Farm Research Campus, Ashburn, Virginia 20147.
Bart G
BG
Borghuis
Loren L
LL
Looger
Susumu
S
Tomita
Jonathan B
JB
Demb
D000200:Action Potentials / Q000187:drug effects / Q000502:physiology; D000818:Animals; D004347:Drug Interactions; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D005260:Female; D018698:Glutamic Acid / Q000378:metabolism; D018738:Hexamethonium / Q000494:pharmacology; D066298:In Vitro Techniques; D008027:Light; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018733:Nicotinic Antagonists / Q000494:pharmacology; D018408:Patch-Clamp Techniques; D010775:Photic Stimulation; D011422:Propionates / Q000494:pharmacology; D018092:Kainic Acid Receptors / Q000819:agonists / Q000037:antagonists & inhibitors / Q000502:physiology*; D012160:Retina / Q000166:cytology*; D051245:Retinal Bipolar Cells / Q000187:drug effects / Q000502:physiology*; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology*; D014795:Visual Pathways / Q000187:drug effects / Q000502:physiology*
D018691:Excitatory Amino Acid Antagonists; D018698:Glutamic Acid; D018738:Hexamethonium; D018733:Nicotinic Antagonists; D011422:Propionates; D018092:Kainic Acid Receptors; C114785:2-amino-4-phosphono-propinate
OFF bipolar cell; glutamate sensor; kainate receptor; mouse; retinal circuitry; two-photon imaging