Department of Physiology, Faculty of Medicine, National Autonomous University of Mexico, Mexico City, Mexico.
Section on Molecular Neuroscience, National Institute of Mental Health, Intramural Research Program, Bethesda, United States.
Elife. 2021 Jan 19;10:e61718. doi: 10.7554/eLife.61718.
The neuropeptide PACAP, acting as a co-transmitter, increases neuronal excitability, which may enhance anxiety and arousal associated with threat conveyed by multiple sensory modalities. The distribution of neurons expressing PACAP and its receptor, PAC1, throughout the mouse nervous system was determined, in register with expression of glutamatergic and GABAergic neuronal markers, to develop a coherent chemoanatomical picture of PACAP role in brain motor responses to sensory input. A circuit role for PACAP was tested by observing activation of brain neurons after olfactory threat cue in wild-type and PACAP knockout mice. Neuronal activation and behavioral response, were blunted in PACAP knock-out mice, accompanied by sharply downregulated vesicular transporter expression in both GABAergic and glutamatergic neurons expressing PACAP and its receptor. This report signals a new perspective on the role of neuropeptide signaling in supporting excitatory and inhibitory neurotransmission in the nervous system within functionally coherent polysynaptic circuits.
神经肽 PACAP 作为一种共递质，增加神经元的兴奋性，这可能增强与多种感觉模式传达的威胁相关的焦虑和觉醒。通过与谷氨酸能和 GABA 能神经元标记物的表达相匹配，确定了表达 PACAP 和其受体 PAC1 的神经元在整个小鼠神经系统中的分布，以建立 PACAP 在大脑对感觉输入的运动反应中的作用的连贯的化学解剖学图像。通过观察野生型和 PACAP 敲除小鼠在嗅觉威胁线索后的大脑神经元激活来测试 PACAP 的回路作用。PACAP 敲除小鼠的神经元激活和行为反应减弱，同时表达 PACAP 和其受体的 GABA 能和谷氨酸能神经元中的囊泡转运体表达明显下调。本报告为神经肽信号在支持功能上连贯的多突触回路中的神经系统中兴奋性和抑制性神经传递提供了新的视角。
