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

• DOI: 10.1016/j.neuron.2016.04.041
• Publication Date: 2016-05-28T03:06:16Z
• Authors: Santhosh Sethuram...; Amanda J. McLaughlin; Geoffery deRosenroll; Alex Hoggarth; David J. Schwab; Gautam B. Awatramani
• Keywords: Neural coding

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.