Singh Alvarado Jonnathan, Lutas Andrew, Madara Joseph C, Isaac Jeremiah, Lommer Caroline, Massengill Crystian, Andermann Mark L
Division of Endocrinology, Metabolism, and Diabetes, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02115, USA.
Division of Endocrinology, Metabolism, and Diabetes, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02115, USA; Diabetes, Endocrinology, and Obesity Branch, National Institutes of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD 20892, USA.
Neuron. 2024 May 1;112(9):1416-1425.e5. doi: 10.1016/j.neuron.2024.02.002. Epub 2024 Feb 27.
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 (PBN) neurons regulate sustained brain states such as pain and express G-coupled GPCRs that increase cAMP signaling. We asked whether cAMP in PBN neurons directly influences their excitability and effects on behavior. Both brief tail shocks and brief optogenetic stimulation of cAMP production in PBN 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 PBN neurons helps prolong neural activity and behavioral states evoked by brief, salient bodily stimuli.
短暂的刺激能够触发持续时间更长的脑状态。G蛋白偶联受体（GPCRs）可通过将慢时标分子信号与神经元兴奋性相偶联，来帮助维持此类状态。脑干臂旁核谷氨酸能（PBN）神经元调节诸如疼痛等持续性脑状态，并表达能增加环磷酸腺苷（cAMP）信号传导的G偶联GPCRs。我们探究了PBN神经元中的cAMP是否直接影响其兴奋性及对行为的作用。短暂的尾部电击和对PBN神经元中cAMP生成的短暂光遗传学刺激，均导致长达数分钟的进食抑制。这种抑制与体内和体外cAMP、蛋白激酶A（PKA）活性及钙活性的长时间升高持续时间相匹配，也与体外动作电位发放中持续的、PKA依赖性增加相匹配。缩短cAMP的这种升高会减少尾部电击后进食抑制的持续时间。因此，PBN神经元中的分子信号传导有助于延长由短暂、显著的身体刺激所诱发的神经活动和行为状态。
