Alvarado Jonnathan Singh, Lutas Andrew, Madara Joseph C, Isaac Jeremiah, Lommer Caroline, Andermann Mark L
bioRxiv. 2023 Mar 1:2023.02.25.530033. doi: 10.1101/2023.02.25.530033.
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 neurons (PBN ) regulate sustained brain states such as pain, and express G -coupled GPCRs that increase cAMP signaling. We asked whether cAMP directly influences PBN excitability and 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), and calcium activity and Shortening this elevation in cAMP reduced the duration of feeding suppression following tail shocks. cAMP elevations in PBN neurons rapidly lead to sustained increases in action potential firing via PKA-dependent mechanisms. Thus, molecular signaling in PBN neurons helps prolong neural activity and behavioral states evoked by brief, salient bodily stimuli.
短暂的刺激可以触发持续时间更长的脑状态。G蛋白偶联受体（GPCRs）可能通过将慢时标分子信号与神经元兴奋性相偶联来维持此类状态。脑干臂旁核谷氨酸能神经元（PBN ）调节诸如疼痛等持续性脑状态，并表达增加cAMP信号传导的G 偶联GPCRs。我们研究了cAMP是否直接影响PBN 的兴奋性和行为。短暂的尾部电击和对PBN 神经元中cAMP产生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cAMP、蛋白激酶A（PKA）和钙活性的长时间升高持续时间相匹配 并且 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。PBN 神经元中cAMP的升高通过PKA依赖性机制迅速导致动作电位发放的持续增加。因此，PBN 神经元中的分子信号传导有助于延长由短暂、显著的身体刺激诱发的神经活动和行为状态。
