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By integrating these synaptic inputs, 5-HT neurons modulate a plethora of behaviors and physiological functions. However, it remains unknown whether the excitatory inputs onto DRn 5-HT neurons can undergo activity-dependent change of strength, as well as the mechanisms that control their plasticity. Here, we describe a novel form of spike-timing\u2013dependent long-term potentiation (tLTP) of glutamate synapses onto rat DRn 5-HT neurons. This form of synaptic plasticity is initiated by an increase in postsynaptic intracellular calcium but is maintained by a persistent increase in the probability of glutamate release. The tLTP of glutamate synapses onto DRn 5-HT is independent of NMDA receptors but requires the activation of calcium-permeable AMPA receptors and voltage-dependent calcium channels. The presynaptic expression of the tLTP is mediated by the retrograde messenger nitric oxide (NO) and activation of cGMP\/PKG pathways. Collectively, these results indicate that glutamate synapses in the DRn undergo activity-dependent synaptic plasticity gated by NO signaling and unravel a previously unsuspected role of NO in controlling synaptic function and plasticity in the DRn.<\/jats:p>","DOI":"10.1523\/eneuro.0116-17.2017","type":"journal-article","created":{"date-parts":[[2017,5,26]],"date-time":"2017-05-26T00:50:16Z","timestamp":1495759816000},"page":"ENEURO.0116-17.2017","source":"Crossref","is-referenced-by-count":16,"title":["GluA2-Lacking AMPA Receptors and Nitric Oxide Signaling Gate Spike-Timing\u2013Dependent Potentiation of Glutamate Synapses in the Dorsal Raphe Nucleus"],"prefix":"10.1523","volume":"4","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6012-7199","authenticated-orcid":false,"given":"Samir","family":"Haj-Dahmane","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jean 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