α4*Nicotinic Acetylcholine Receptors Modulate Experience-Based Cortical Depression in the Adult Mouse Somatosensory Cortex
α4*Nicotinic Acetylcholine Receptors Modulate Experience-Based Cortical Depression in the Adult Mouse Somatosensory Cortex
复制标题
DOI：
10.1523/jneurosci.4568-11.2012
复制
发表时间：
2012-01-25
影响因子：
5.3
通讯作者：
Nashmi, Raad
中科院分区：
文献类型：
--
作者：
Brown, Craig E.;Sweetnam, Danielle;Nashmi, Raad
调节大脑皮层功能的基于经验的变化的分子机制，特别是在成年动物中，知之甚少。在这里，我们显示使用在体内电压敏感染料成像，胡须修剪导致抑郁症的胡须诱发的感觉反应，在初级，次级和关联的躯体感觉皮层区域。鉴于胆碱能神经传递在认知和感觉功能中的重要性，我们研究了含α 4（α 4*）烟碱乙酰胆碱受体（nAChRs）是否介导皮质抑制。使用基因敲入小鼠表达YFP标记的α 4 nAChRs亚基，我们表明，晶须修剪选择性地增加了24小时内剥夺桶列的第4层中的α 4*-YFP nAChRs的数量，这种情况一直持续到晶须重新生长。共聚焦显微镜和电子显微镜显示，这些受体优先增加的GABA能神经元的细胞体。为了直接将这些受体与功能性皮质抑郁联系起来，我们表明，在正常小鼠中，通过在躯体感觉皮质中局部应用或微量注射α 4* nAChR激动剂可以诱导抑郁。此外，皮质抑郁症可以阻止胡须修剪后，慢性输液的α 4* nAChR拮抗剂。总的来说，这些结果揭示了α 4* nAChRs在调节成人体感皮层功能反应性快速变化中的新作用。
The molecular mechanisms that mediate experience-based changes in the function of the cerebral cortex, particularly in the adult animal, are poorly understood. Here we show using in vivo voltage-sensitive dye imaging, that whisker trimming leads to depression of whisker-evoked sensory responses in primary, secondary and associative somatosensory cortical regions. Given the importance of cholinergic neurotransmission in cognitive and sensory functions, we examined whether alpha 4-containing (alpha 4*) nicotinic acetylcholine receptors (nAChRs) mediate cortical depression. Using knock-in mice that express YFP-tagged alpha 4 nAChRs subunits, we show that whisker trimming selectively increased the number alpha 4*-YFP nAChRs in layer 4 of deprived barrel columns within 24 h, which persisted until whiskers regrew. Confocal and electron microscopy revealed that these receptors were preferentially increased on the cell bodies of GABAergic neurons. To directly link these receptors with functional cortical depression, we show that depression could be induced in normal mice by topical application or micro-injection of alpha 4* nAChR agonist in the somatosensory cortex. Furthermore, cortical depression could be blocked after whisker trimming with chronic infusions of an alpha 4* nAChR antagonist. Collectively, these results uncover a new role for alpha 4* nAChRs in regulating rapid changes in the functional responsiveness of the adult somatosensory cortex.