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 fos 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 down-regulated 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.

中文翻译：

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PACAP 的行为作用反映了其在谷氨酸能和 GABA 能神经元亚群中的选择性分布

作为共递质的神经肽 PACAP 可增加神经元的兴奋性，这可能会增强与多种感觉方式传达的威胁相关的焦虑和觉醒。确定了在整个小鼠神经系统中表达 PACAP 及其受体 PAC1 的神经元的分布，与谷氨酸能和 GABA 能神经元标志物的表达相一致，以形成 PACAP 在大脑对感觉输入的运动反应中作用的连贯化学解剖图。通过在野生型和 PACAP 敲除小鼠中观察嗅觉威胁提示后脑神经元的 fos 激活来测试 PACAP 的电路作用。在 PACAP 敲除小鼠中，神经元激活和行为反应迟钝，伴随着表达PACAP及其受体的GABA能和谷氨酸能神经元中的水泡转运蛋白表达急剧下调。本报告为神经肽信号传导在功能一致的多突触回路中支持神经系统中的兴奋性和抑制性神经传递中的作用提供了一个新的视角。