TY - JOUR T1 - GluA2-Lacking AMPA Receptors and Nitric Oxide Signaling Gate Spike-Timing–Dependent Potentiation of Glutamate Synapses in the Dorsal Raphe Nucleus JF - eneuro JO - eNeuro DO - 10.1523/ENEURO.0116-17.2017 VL - 4 IS - 3 SP - ENEURO.0116-17.2017 AU - Samir Haj-Dahmane AU - Jean Claude Béïque AU - Roh-Yu Shen Y1 - 2017/05/01 UR - http://www.eneuro.org/content/4/3/ENEURO.0116-17.2017.abstract N2 - The dorsal raphe nucleus (DRn) receives glutamatergic inputs from numerous brain areas that control the function of DRn serotonin (5-HT) neurons. 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–dependent 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. ER -