Nicotine excites VIP interneurons to disinhibit pyramidal neurons in auditory cortex
Nicotine excites VIP interneurons to disinhibit pyramidal neurons in auditory cortex
复制标题
DOI：
10.1002/syn.22116
复制
发表时间：
2019-09-01
期刊：
影响因子：
2.3
通讯作者：
Metherate, Raju
中科院分区：
文献类型：
--
作者：
Askew, Caitlin E.;Lopez, Alberto J.;Metherate, Raju
尼古丁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。生理学研究表明，尼古丁放大了感觉皮层中的刺激诱发反应，可能有助于增强感觉处理。然而，具体的细胞类型和电路在感觉皮层的烟碱调制中的作用仍然不清楚。在这里，我们进行了全细胞记录锥体（Pyr）神经元和抑制性中间神经元表达小白蛋白（PV），生长抑素（SOM），血管活性肠肽（VIP）在小鼠听觉皮层，在体外。浴用尼古丁对VIP神经元有强去极化和兴奋作用，对Pyr神经元有弱去极化作用，对SOM和PV神经元的膜电位无影响。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。尼古丁还增强了自发抑制性突触后电流（sIPSC）的Pyr，VIP，SOM，但不是PV，细胞的频率。使用设计师受体专门激活的设计师药物（DREADDs），我们表明，VIP神经元的化学发生抑制阻止尼古丁对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，我们认为尼古丁驱动VIP细胞放电去抑制Pyr细胞胞体，可能使Pyr细胞对听觉刺激更敏感。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作用。
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.