Apr 20, 2020

Rapid 'multi-directed' cholinergic transmission at central synapses

BioRxiv : the Preprint Server for Biology
S. SethuramanujamGautam Bhagwan Awatramani


Acetylcholine (ACh) is a key neurotransmitter that plays diverse roles in many parts of the central nervous system, including the retina. However, assessing the precise spatiotemporal dynamics of ACh is technically challenging and whether ACh transmits signals via rapid, point-to-point synaptic mechanisms, or broader-scale 'non-synaptic' mechanisms has been difficult to ascertain. Here, we examined the properties of cholinergic transmission at individual contacts made between direction-selective starburst amacrine cells and downstream ganglion cells in the retina. Using a combination of electrophysiology, serial block-face electron microscopy, and two-photon ACh imaging, we demonstrate that ACh signaling bears the hallmarks of both non-synaptic and synaptic forms of transmission. ACh co-activates nicotinic ACh receptors located on the intersecting dendrites of pairs of ganglion cells, with equal efficiency (non-synaptic)--and yet retains the ability to generate rapid 'miniature' currents (~1 ms rise times: synaptic). Fast cholinergic signals do not appear to depend on anatomically well-defined synaptic structures. We estimate that ACh spread is limited to ~1-2 m from its sites of release, which may help starbursts drive local d...Continue Reading

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