Long-term depression of presynaptic release from the readily releasable vesicle pool induced by NMDA receptor-dependent retrograde nitric oxide.
Postsynaptic alterations are currently believed to be able to fully account for NMDA-receptor-dependent long-term depression (LTD) and long-term potentiation of synaptic strength, although there is also evidence supporting changes in presynaptic release. Using dualphoton laser scan microscopy of N-(3-triethylammoniumpropyl)-4-(4-(dibutylamino)styryl) pyridinium dibromide (FM1-43) to directly visualize presynaptic vesicular release at Schaffer collateral-CA1 excitatory synapses in hippocampal slices, we demonstrate reduced vesicular release associated with LTD. Selective loading, by hypertonic shock, of the readily releasable vesicle pool (RRP) showed that LTD of release is a selective modification of release from the RRP. Presynaptic LTD of RRP release required activation of NMDA receptors, production and extracellular diffusion of the intercellular messenger NO, and activation of cGMP-dependent protein kinase.
Stanton
Patric K
PK
Department of Neuroscience, Albert Einstein College of Medicine, Bronx, New York 10461-1602, USA. stanton@aecom.yu.edu
Winterer
Jochen
J
Bailey
Christopher P
CP
Kyrozis
Andreas
A
Raginov
Ivan
I
Laube
Gregor
G
Veh
Rüdiger W
RW
Nguyen
Can Q
CQ
Müller
Wolfgang
W
D000818:Animals; D017869:Cyclic GMP-Dependent Protein Kinases / Q000378:metabolism; D005456:Fluorescent Dyes / Q000493:pharmacokinetics; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism*; D006982:Hypertonic Solutions / Q000494:pharmacology; D066298:In Vitro Techniques; D036881:Long-Term Synaptic Depression / Q000502:physiology*; D009569:Nitric Oxide / Q000378:metabolism*; D017729:Presynaptic Terminals / Q000378:metabolism*; D011726:Pyridinium Compounds / Q000493:pharmacokinetics; D000644:Quaternary Ammonium Compounds / Q000493:pharmacokinetics; D051381:Rats; D017208:Rats, Wistar; D016194:Receptors, N-Methyl-D-Aspartate / Q000378:metabolism*; D015290:Second Messenger Systems / Q000502:physiology; D013572:Synaptic Vesicles / Q000378:metabolism*
C073804:FM1 43; D005456:Fluorescent Dyes; D006982:Hypertonic Solutions; D011726:Pyridinium Compounds; D000644:Quaternary Ammonium Compounds; D016194:Receptors, N-Methyl-D-Aspartate; D009569:Nitric Oxide; D017869:Cyclic GMP-Dependent Protein Kinases