PDF(Pubmed)
Abstract：
Brief stimuli can trigger longer-lasting brain states. G-protein-coupled receptors (GPCRs) could help sustain such states by coupling slow-timescale molecular signals to neuronal excitability. Brainstem parabrachial nucleus glutamatergic (PBNGlut) neurons regulate sustained brain states such as pain and express Gs-coupled GPCRs that increase cAMP signaling. We asked whether cAMP in PBNGlut neurons directly influences their excitability and effects on behavior. Both brief tail shocks and brief optogenetic stimulation of cAMP production in PBNGlut neurons drove minutes-long suppression of feeding. This suppression matched the duration of prolonged elevations in cAMP, protein kinase A (PKA) activity, and calcium activity in vivo and ex vivo, as well as sustained, PKA-dependent increases in action potential firing ex vivo. Shortening this elevation in cAMP reduced the duration of feeding suppression following tail shocks. Thus, molecular signaling in PBNGlut neurons helps prolong neural activity and behavioral states evoked by brief, salient bodily stimuli.
摘要：
短暂的刺激可以触发更持久的大脑状态。G蛋白偶联受体（GPCRs）可以通过将慢时间尺度的分子信号与神经元兴奋性耦合来帮助维持这种状态。脑干臂旁核谷氨酸能（PBNGlut）神经元调节持续的大脑状态，例如疼痛，并表达Gs偶联的GPCRs，从而增加cAMP信号传导。我们询问PBNGlut神经元中的cAMP是否直接影响其兴奋性和对行为的影响。短暂的尾巴冲击和短暂的光遗传学刺激对PBNGlut神经元中cAMP的产生都会导致长达数分钟的摄食抑制。这种抑制与cAMP长期升高的持续时间相匹配，蛋白激酶A（PKA）活性，体内和离体的钙活性，以及持续的，体外动作电位放电的PKA依赖性增加。缩短cAMP的升高减少了尾部电击后进食抑制的持续时间。因此，PBNGlut神经元中的分子信号有助于延长短暂诱发的神经活动和行为状态，显著的身体刺激。
