Adenosine modulates transmission at the hippocampal mossy fibre synapse via direct inhibition of presynaptic calcium channels.
The modulation of synaptic transmission by presynaptic ionotropic and metabotropic receptors is an important means to control and dynamically adjust synaptic strength. Even though synaptic transmission and plasticity at the hippocampal mossy fibre synapse are tightly controlled by presynaptic receptors, little is known about the downstream signalling mechanisms and targets of the different receptor systems. In the present study, we identified the cellular signalling cascade by which adenosine modulates mossy fibre synaptic transmission. By means of electrophysiological and optical recording techniques, we found that adenosine activates presynaptic A1 receptors and reduces Ca2+ influx into mossy fibre terminals. Ca2+ currents are directly modulated via a membrane-delimited pathway and the reduction of presynaptic Ca2+ influx can explain the inhibition of synaptic transmission. Specifically, we found that adenosine modulates both P/Q- and N-type presynaptic voltage-dependent Ca2+ channels and thereby controls transmitter release at the mossy fibre synapse.
Gundlfinger
A
A
Neurowissenschaftliches Forschungszentrum der Charité, Universitätsmedizin Berlin, Germany.
Bischofberger
J
J
Johenning
F W
FW
Torvinen
M
M
Schmitz
D
D
Breustedt
J
J
D000241:Adenosine / Q000378:metabolism*; D000814:Aniline Compounds; D000818:Animals; D020864:Calcium Channels, N-Type / Q000378:metabolism*; D020013:Calcium Signaling; D004558:Electric Stimulation; D005452:Fluoresceins; D005456:Fluorescent Dyes; D066298:In Vitro Techniques; D015640:Ion Channel Gating; D051379:Mice; D008810:Mice, Inbred C57BL; D018613:Microscopy, Confocal; D008959:Models, Neurological; D019599:Mossy Fibers, Hippocampal / Q000378:metabolism*; D009433:Neural Inhibition; D018408:Patch-Clamp Techniques; D017729:Presynaptic Terminals / Q000378:metabolism*; D043682:Receptor, Adenosine A1 / Q000378:metabolism*; D009435:Synaptic Transmission; D013997:Time Factors
D000241:Adenosine; D000814:Aniline Compounds; D020864:Calcium Channels, N-Type; D005452:Fluoresceins; D005456:Fluorescent Dyes; D043682:Receptor, Adenosine A1; C503942:Oregon green 488 BAPTA-1