{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,28]],"date-time":"2026-09-28T22:50:11Z","timestamp":1790635811466,"version":"4.1.0"},"reference-count":45,"publisher":"American Physiological Society","issue":"3","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Journal of Neurophysiology"],"published-print":{"date-parts":[[1999,9,1]]},"abstract":"<jats:p>Long-term depression (LTD) of synaptic transmission can be induced by several mechanisms, one thought to involve Ca<jats:sup>2+<\/jats:sup>-dependent activation of postsynaptic nitric oxide (NO) synthase and subsequent diffusion of NO to the presynaptic terminal. We used the stable NO donor S-nitroso- N-acetylpenicillamine (SNAP) to study the NO-dependent form of LTD at Schaffer collateral-CA1 synapses in vitro. SNAP (100 \u03bcM) enhanced the induction of LTD via a cascade that was blocked by the N-methyl-d-aspartate receptor antagonist d-2-amino-5-phosphonopentanoic acid (50 \u03bcM), NO guanylyl cyclase inhibitor 1H-[1,2,4] oxadiazolo [4,3-a] quinoxalin-1-one (10 \u03bcM), and the PKG inhibitor KT5823 (1 \u03bcM). We further show that LTD induced by low-frequency stimulation in the absence of SNAP also is blocked by KT5823 or Rp-8-(4-chlorophenylthio)-guanosine 3\u2032,5\u2032-cyclic monophosphorothioate (10 \u03bcM), cyclic guanosine 3\u2032,5\u2032 monophosphate-dependent protein kinase (PKG) inhibitors with different mechanisms of action. Furthermore SNAP-facilitated LTD was blocked when release from intracellular calcium stores was inhibited by ryanodine (10 \u03bcM). Finally, two cell-permeant antagonists of the cyclic ADP-ribose binding site on ryanodine receptors also were able to block the induction of LTD. These results support a cascade for induction of homosynaptic, NO-dependent LTD involving activation of guanylyl cyclase, production of guanosine 3\u2032,5\u2032 cyclic monophosphate and subsequent PKG activation. This process has an additional requirement for release of Ca<jats:sup>2+<\/jats:sup>from ryanodine-sensitive stores, perhaps dependent on the second-messenger cyclic ADP ribose.<\/jats:p>","DOI":"10.1152\/jn.1999.82.3.1569","type":"journal-article","created":{"date-parts":[[2017,12,25]],"date-time":"2017-12-25T05:29:51Z","timestamp":1514179791000},"page":"1569-1576","source":"Crossref","is-referenced-by-count":91,"title":["Induction of Hippocampal LTD Requires Nitric-Oxide-Stimulated PKG Activity and Ca<sup>2+<\/sup>Release From Cyclic ADP-Ribose-Sensitive Stores"],"prefix":"10.1152","volume":"82","author":[{"given":"Magali","family":"Reyes-Harde","sequence":"first","affiliation":[{"name":"Departments of Neuroscience and Neurology, Albert Einstein College of Medicine, Bronx, New York 10461;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Barry V. 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