Receptoral Mechanisms for Fast Cholinergic Transmission in Direction-Selective Retinal Circuitry

Frontiers in Cellular Neuroscience

Joshua H. Singer¹  Jonathan B. Demb³  Joseph Pottackal⁵ 

[1] Department of Biology, University of Maryland, College Park, MD, United States;Department of Cellular and Molecular Physiology, Yale University, New Haven, CT, United States;Department of Neuroscience, Yale University, New Haven, CT, United States;Department of Ophthalmology and Visual Science, Yale University, New Haven, CT, United States;Interdepartmental Neuroscience Program, Yale University, New Haven, CT, United States;

关键词: acetylcholine;    direction selectivity;    GABA;    neural circuits;    optogenetics;    paracrine transmission;   

DOI  :  10.3389/fncel.2020.604163

来源: DOAJ

【 摘 要 】

Direction selectivity represents an elementary sensory computation that can be related to underlying synaptic mechanisms. In mammalian retina, direction-selective ganglion cells (DSGCs) respond strongly to visual motion in a “preferred” direction and weakly to motion in the opposite, “null” direction. The DS mechanism depends on starburst amacrine cells (SACs), which provide null direction-tuned GABAergic inhibition and untuned cholinergic excitation to DSGCs. GABAergic inhibition depends on conventional synaptic transmission, whereas cholinergic excitation apparently depends on paracrine (i.e., non-synaptic) transmission. Despite its paracrine mode of transmission, cholinergic excitation is more transient than GABAergic inhibition, yielding a temporal difference that contributes essentially to the DS computation. To isolate synaptic mechanisms that generate the distinct temporal properties of cholinergic and GABAergic transmission from SACs to DSGCs, we optogenetically stimulated SACs while recording postsynaptic currents (PSCs) from DSGCs in mouse retina. Direct recordings from channelrhodopsin-2-expressing (ChR2+) SACs during quasi-white noise (WN) (0-30 Hz) photostimulation demonstrated precise, graded optogenetic control of SAC membrane current and potential. Linear systems analysis of ChR2-evoked PSCs recorded in DSGCs revealed cholinergic transmission to be faster than GABAergic transmission. A deconvolution-based analysis showed that distinct postsynaptic receptor kinetics fully account for the temporal difference between cholinergic and GABAergic transmission. Furthermore, GABAA receptor blockade prolonged cholinergic transmission, identifying a new functional role for GABAergic inhibition of SACs. Thus, fast cholinergic transmission from SACs to DSGCs arises from at least two distinct mechanisms, yielding temporal properties consistent with conventional synapses despite its paracrine nature.

【 授权许可】

Unknown