title: Light-evoked lateral GABAergic inhibition at single bipolar cell synaptic terminals is driven by distinct retinal microcircuits.
abstract: Inhibitory amacrine cells (ACs) filter visual signals crossing the retina by modulating the excitatory, glutamatergic output of bipolar cells (BCs) on multiple temporal and spatial scales. Reciprocal feedback from ACs provides focal inhibition that is temporally locked to the activity of presynaptic BC activity, whereas lateral feedback originates from ACs excited by distant BCs. These distinct feedback mechanisms permit temporal and spatial computation at BC terminals. Here, we used a unique preparation to study light-evoked IPSCs recorded from axotomized terminals of ON-type mixed rod/cone BCs (Mb) in goldfish retinal slices. In this preparation, light-evoked IPSCs could only reach axotomized BC terminals via the lateral feedback pathway, allowing us to study lateral feedback in the absence of overlapping reciprocal feedback components. We found that light evokes ON and OFF lateral IPSCs (L-IPSCs) in Mb terminals having different temporal patterns and conveyed via distinct retinal pathways. The relative contribution of rods versus cones to ON and OFF L-IPSCs was light intensity dependent. ACs presynaptic to Mb BC terminals received inputs via AMPA/KA- and NMDA-type receptors in both the ON and OFF pathways, and used TTX-sensitive sodium channels to boost signal transfer along their processes. ON and OFF L-IPSCs, like reciprocal feedback IPSCs, were mediated by both GABA(A) and GABA(C) receptors. However, our results suggest that lateral and reciprocal feedback do not cross-depress each other, and are therefore mediated by distinct populations of ACs. These findings demonstrate that retinal inhibitory circuits are highly specialized to modulate BC output at different light intensities.
authors: Department of Biomedical Sciences, Colorado State University, Ft Collins, Colorado 80523, USA. jozsef.vigh@colostate.edu
authors: Jozsef
authors: J
authors: Vigh
authors: Evan
authors: E
authors: Vickers
authors: Henrique
authors: H
authors: von Gersdorff
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D002264:Carboxylic Acids / Q000494:pharmacology; D003521:Cyclopropanes / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D004558:Electric Stimulation; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D025461:Feedback, Physiological / Q000502:physiology; D005260:Female; D018756:GABA Antagonists / Q000494:pharmacology; D006054:Goldfish; D066298:In Vitro Techniques; D053444:Inhibitory Postsynaptic Potentials / Q000187:drug effects / Q000502:physiology; D008027:Light; D008297:Male; D009433:Neural Inhibition / Q000187:drug effects / Q000502:physiology*; D018408:Patch-Clamp Techniques; D037342:Pertussis Toxin / Q000494:pharmacology; D010775:Photic Stimulation / Q000379:methods; D010786:Photoreceptor Cells / Q000502:physiology; D017729:Presynaptic Terminals / Q000187:drug effects / Q000502:physiology*; D011422:Propionates / Q000494:pharmacology; D011724:Pyridazines / Q000494:pharmacology; D011810:Quinoxalines / Q000494:pharmacology; D012160:Retina / Q000166:cytology*; D051245:Retinal Bipolar Cells / Q000145:classification / Q000166:cytology* / Q000502:physiology; D015398:Signal Transduction / Q000187:drug effects; D026941:Sodium Channel Blockers / Q000494:pharmacology; D018709:Statistics, Nonparametric; D013779:Tetrodotoxin / Q000494:pharmacology; D005680:gamma-Aminobutyric Acid / Q000378:metabolism*
chemical_list: C114785:2-amino-4-phosphono-propinate; C469433:2-aminomethylcyclopropanecarboxylic acid; D002264:Carboxylic Acids; D003521:Cyclopropanes; D018691:Excitatory Amino Acid Antagonists; D018756:GABA Antagonists; D011422:Propionates; D011724:Pyridazines; D011810:Quinoxalines; D026941:Sodium Channel Blockers; C062865:2,3-dioxo-6-nitro-7-sulfamoylbenzo(f)quinoxaline; D013779:Tetrodotoxin; D005680:gamma-Aminobutyric Acid; C049853:gabazine; D037342:Pertussis Toxin