Nicotine activates nicotinic acetylcholine receptors and improves cognitive and sensory function, in part by its actions in cortical regions. Physiological studies show that nicotine amplifies stimulus-evoked responses in sensory cortex, potentially contributing to enhancement of sensory processing. However, the role of specific cell types and circuits in the nicotinic modulation of sensory cortex remains unclear. Here, we performed whole-cell recordings from pyramidal (Pyr) neurons and inhibitory interneurons expressing parvalbumin (PV), somatostatin (SOM), and vasoactive intestinal peptide (VIP) in mouse auditory cortex, in vitro. Bath application of nicotine strongly depolarized and excited VIP neurons, weakly depolarized Pyr neurons, and had no effect on the membrane potential of SOM or PV neurons. The use of receptor antagonists showed that nicotine's effects on VIP and Pyr neurons were direct and indirect, respectively. Nicotine also enhanced the frequency of spontaneous inhibitory postsynaptic currents (sIPSCs) in Pyr, VIP, and SOM, but not PV, cells. Using Designer Receptors Exclusively Activated by Designer Drugs (DREADDs), we show that chemogenetic inhibition of VIP neurons prevents nicotine's effects on Pyr neurons. Since VIP cells preferentially contact other inhibitory interneurons, we suggest that nicotine drives VIP cell firing to disinhibit Pyr cell somata, potentially making Pyr cells more responsive to auditory stimuli. In parallel, activation of VIP cells also directly inhibits Pyr neurons, likely altering integration of other synaptic inputs. These cellular and synaptic mechanisms likely contribute to nicotine's beneficial effects on cognitive and sensory function.

中文翻译：

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尼古丁会兴奋 VIP 中间神经元，从而抑制听觉皮层的锥体神经元。


尼古丁可激活烟碱乙酰胆碱受体并改善认知和感觉功能，部分是通过其在皮质区域的作用来实现的。生理学研究表明，尼古丁会放大感觉皮层的刺激诱发反应，可能有助于增强感觉处理。然而，特定细胞类型和电路在感觉皮层烟碱调节中的作用仍不清楚。在这里，我们在体外对小鼠听觉皮层中表达小清蛋白 (PV)、生长抑素 (SOM) 和血管活性肠肽 (VIP) 的锥体 (Pyr) 神经元和抑制​​性中间神经元进行全细胞记录。尼古丁浴的应用使VIP神经元强去极化和兴奋，对Pyr神经元弱去极化，并且对SOM或PV神经元的膜电位没有影响。受体拮抗剂的使用表明尼古丁对 VIP 和 Pyr 神经元的影响分别是直接和间接的。尼古丁还提高了 Pyr、VIP 和 SOM 细胞（但不是 PV）中自发抑制性突触后电流 (sIPSC) 的频率。使用设计药物专门激活的设计受体 (DREADD)，我们发现 VIP 神经元的化学遗传学抑制可以防止尼古丁对 Pyr 神经元的影响。由于 VIP 细胞优先接触其他抑制性中间神经元，因此我们认为尼古丁驱动 VIP 细胞放电以抑制 Pyr 细胞胞体，可能使 Pyr 细胞对听觉刺激更加敏感。与此同时，VIP 细胞的激活也直接抑制 Pyr 神经元，可能改变其他突触输入的整合。这些细胞和突触机制可能有助于尼古丁对认知和感觉功能的有益影响。