Ontology type: schema:ScholarlyArticle Open Access: True
2019-12
AUTHORSThomas P. Jensen, Kaiyu Zheng, Nicholas Cole, Jonathan S. Marvin, Loren L. Looger, Dmitri A. Rusakov
ABSTRACTInformation processing by brain circuits depends on Ca2+-dependent, stochastic release of the excitatory neurotransmitter glutamate. Whilst optical glutamate sensors have enabled detection of synaptic discharges, understanding presynaptic machinery requires simultaneous readout of glutamate release and nanomolar presynaptic Ca2+ in situ. Here, we find that the fluorescence lifetime of the red-shifted Ca2+ indicator Cal-590 is Ca2+-sensitive in the nanomolar range, and employ it in combination with green glutamate sensors to relate quantal neurotransmission to presynaptic Ca2+ kinetics. Multiplexed imaging of individual and multiple synapses in identified axonal circuits reveals that glutamate release efficacy, but not its short-term plasticity, varies with time-dependent fluctuations in presynaptic resting Ca2+ or spike-evoked Ca2+ entry. Within individual presynaptic boutons, we find no nanoscopic co-localisation of evoked presynaptic Ca2+ entry with the prevalent glutamate release site, suggesting loose coupling between the two. The approach enables a better understanding of release machinery at central synapses. More... »
PAGES1414
http://scigraph.springernature.com/pub.10.1038/s41467-019-09216-8
DOIhttp://dx.doi.org/10.1038/s41467-019-09216-8
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