title: A Central Role for Mixed Acetylcholine/GABA Transmission in Direction Coding in the Retina.
abstract: A surprisingly large number of neurons throughout the brain are endowed with the ability to co-release both a fast excitatory and inhibitory transmitter. The computational benefits of dual transmitter release, however, remain poorly understood. Here, we address the role of co-transmission of acetylcholine (ACh) and GABA from starburst amacrine cells (SACs) to direction-selective ganglion cells (DSGCs). Using a combination of pharmacology, optogenetics, and linear regression methods, we estimated the spatiotemporal profiles of GABA, ACh, and glutamate receptor-mediated synaptic activity in DSGCs evoked by motion. We found that ACh initiates responses to motion in natural scenes or under low-contrast conditions. In contrast, classical glutamatergic pathways play a secondary role, amplifying cholinergic responses via NMDA receptor activation. Furthermore, under these conditions, the network of SACs differentially transmits ACh and GABA to DSGCs in a directional manner. Thus, mixed transmission plays a central role in shaping directional responses of DSGCs.
authors.affiliation: Department of Biology, University of Victoria, Victoria, BC V8W 3N5, Canada.
authors.forename: Santhosh
authors.initials: S
authors.lastname: Sethuramanujam
authors.affiliation: Department of Biology, University of Victoria, Victoria, BC V8W 3N5, Canada.
authors.forename: Amanda J
authors.initials: AJ
authors.lastname: McLaughlin
authors.affiliation: Department of Biology, University of Victoria, Victoria, BC V8W 3N5, Canada.
authors.forename: Geoffery
authors.initials: G
authors.lastname: deRosenroll
authors.affiliation: Department of Biology, University of Victoria, Victoria, BC V8W 3N5, Canada.
authors.forename: Alex
authors.initials: A
authors.lastname: Hoggarth
authors.affiliation: Department of Physics and Astronomy, Northwestern University, Evanston, IL 60208, USA.
authors.forename: David J
authors.initials: DJ
authors.lastname: Schwab
authors.affiliation: Department of Biology, University of Victoria, Victoria, BC V8W 3N5, Canada. Electronic address: gautam@uvic.ca.
authors.forename: Gautam B
authors.initials: GB
authors.lastname: Awatramani
mesh_terms: D000109:Acetylcholine / Q000502:physiology*; D025042:Amacrine Cells / Q000502:physiology*; D000818:Animals; D018698:Glutamic Acid / Q000502:physiology; D051379:Mice; D009038:Motion; D009433:Neural Inhibition / Q000502:physiology; D012165:Retinal Ganglion Cells / Q000502:physiology*; D009435:Synaptic Transmission / Q000502:physiology*; D005680:gamma-Aminobutyric Acid / Q000502:physiology*
chemical_list: D018698:Glutamic Acid; D005680:gamma-Aminobutyric Acid; D000109:Acetylcholine