血管活性肠肽
光遗传学
神经科学
生物
神经肽
抑制性突触后电位
胃泌素释放肽
蛙皮素
受体
生物化学
作者
Sarah Melzer,Elena Newmark,Grace O. Mizuno,Minsuk Hyun,Adrienne C. Philson,Eleonora Quiroli,Beatrice Righetti,Malika R. Gregory,Kee Wui Huang,James Levasseur,Lin Tian,Bernardo L. Sabatini
出处
期刊:Cell
[Elsevier]
日期:2021-10-01
卷期号:184 (22): 5622-5634.e25
被引量:38
标识
DOI:10.1016/j.cell.2021.09.013
摘要
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 may be 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 genetically encoded GRP sensor, optogenetic anterograde stimulation, and trans-synaptic tracing, we reveal that GRP regulates VIP cells most likely via extrasynaptic diffusion from several 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 GRP-GRPR signaling enhances auditory fear memories. Our data establish peptidergic recruitment of selective disinhibitory cortical microcircuits as a mechanism to regulate fear memories.
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