A Central Role for Mixed Acetylcholine/GABA Transmission in Direction Coding in the Retina

Neuron. 2016 Jun 15;90(6):1243-1256. doi: 10.1016/j.neuron.2016.04.041. Epub 2016 May 26.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acetylcholine / physiology*
  • Amacrine Cells / physiology*
  • Animals
  • Glutamic Acid / physiology
  • Mice
  • Motion
  • Neural Inhibition / physiology
  • Retinal Ganglion Cells / physiology*
  • Synaptic Transmission / physiology*
  • gamma-Aminobutyric Acid / physiology*


  • Glutamic Acid
  • gamma-Aminobutyric Acid
  • Acetylcholine

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