Disinhibitory neurons throughout the mammalian cortex are powerful enhancers of circuit excitability and plasticity. The differential expression of neuropeptide receptors in disinhibitory, inhibitory and excitatory neurons suggests that each circuit motif is controlled by distinct neuropeptidergic systems. Here, we reveal that a bombesin-like neuropeptide, gastrin-releasing peptide (GRP), recruits disinhibitory cortical microcircuits through selective targeting and activation of vasoactive intestinal peptide (VIP)-expressing cells. Using a newly-developed genetically-encoded GRP sensor and trans-synaptic tracing we reveal that GRP regulates VIP cells via extrasynaptic diffusion from several putative local and long-range sources. In vivo photometry and CRISPR/Cas9-mediated knockout of the GRP receptor (GRPR) in auditory cortex indicate that VIP cells are strongly recruited by novel sounds and aversive shocks, and that GRP-GRPR signaling enhances auditory fear memories. Our data establish peptidergic recruitment of selective disinhibitory cortical microcircuits as a mechanism to regulate fear memories.

中文翻译：

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类似于炸弹蛋白的肽可吸收抑制性皮层回路并增强恐惧记忆

整个哺乳动物皮质中的抑制性神经元是回路兴奋性和可塑性的有力增强剂。在抑制性，抑制性和兴奋性神经元中神经肽受体的差异表达表明，每个电路基序均由不同的神经肽能系统控制。在这里，我们揭示了一种类似于蛙蛙蛋白的神经肽，胃泌素释放肽（GRP），通过选择性靶向和激活表达血管活性肠肽（VIP）的细胞来募集抑制性皮层微电路。使用新开发的基因编码的GRP传感器和跨突触追踪，我们揭示了GRP通过突触外扩散从几个假定的本地和远程来源调节VIP细胞。体内光度法和CRISPR / Cas9介导的听觉皮层GRP受体（GRPR）的敲除表明，新的声音和厌恶性休克强烈招募VIP细胞，并且GRP-GRPR信号传导增强听觉恐惧记忆。我们的数据建立了选择性抑制性皮层微电路的肽能募集作为调节恐惧记忆的机制。