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 SP - ENEURO.0116-17.2017 AU - Samir Haj-Dahmane AU - Jean Claude Béïque AU - Roh-Yu Shen Y1 - 2017/05/25 UR - http://www.eneuro.org/content/early/2017/05/25/ENEURO.0116-17.2017.abstract N2 - The dorsal raphe nucleus (DRn) receives glutamatergic inputs from numerous brain areas, which control the function of DRn serotonin (5-HT) neurons. By integrating these synaptic inputs, 5-HT neurons modulate plethora of behaviors and physiological functions. However, whether the excitatory inputs onto DRn 5-HT neurons can undergo activity-dependent change of their strength and the mechanisms that control their plasticity remain unknown. 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 NMDARs, but requires the activation of calcium permeable AMPA receptors (CP-AMPARs) 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 previously unsuspected role of NO in controlling synaptic function and plasticity in the DRn.Significance Statement Glutamatergic inputs to DRn 5-HT neurons are involved in the regulation of numerous physiologic functions and behavior tasks that require associative learning. However, it remains unknown whether glutamate synapses onto DRn 5-HT neuron can undergo activity-dependent change in their strength. Here, we described a novel form of spike-timing dependent LTP in the DRn gated by the activation of CP-AMPARs, voltage-dependent calcium channels and NO signaling. This form of plasticity may represent a cellular mechanism by which 5-HT neurons can regulate associative learning. It also unravels the role of NO in controlling synaptic function and plasticity in the DRn. ER -