Abstract
Purpose :
Synapses lacking the functional expression of AMPARs are often considered ‘silent’ (Kerchner and Nicoll, 2008), as glutamate binding to NMDARs alone does not substantially activate them (due to the voltage-dependent block of NMDARs by external Mg2+ ions). While silent synapses have been studied extensively throughout the central nervous system, whether they arise presynaptically (‘whispering synapses’ and/or glutamate ‘spill-over’ hypothesis) or post-synaptically (‘deaf synapses’ hypothesis: lacking AMPAR expression) still remain unclear.
Methods :
Here we use electrophysiological patch-clamp and 2-P imaging techniques to investigate the synaptic mechanisms underlying silent synapses in the direction-selective ganglion cell (DSGC) circuit of mature mouse retina, where these synapses play an important role in amplifying responses.
Results :
NMDAR-mediated miniature-like events could be detected in DSGCs under pharmacological isolation (0 Mg2+, NBQX), suggesting that NMDARs were located at synaptic sites and were able to respond to quantal glutamate release. These events could be distinguished from AMPA EPSCs based on their slower kinetics. Under control conditions, analysis of sEPSCs reveals two distinct populations of AMPA and NMDA-like sEPSCs, suggesting that the receptors are spatially segregated at individual synapses. Consistent with these findings, NMDAR-mediated ‘optical quantal’ activity could be detected at discrete dendritic sites using 2-P Ca2+ imaging techniques.
Conclusions :
Silent synapses in mature DSGCs represent synapses lacking the postsynaptic expression of AMPA receptors.
This is an abstract that was submitted for the 2018 ARVO Annual Meeting, held in Honolulu, Hawaii, April 29 - May 3, 2018.