Cholecystokinin: an excitatory modulator of mitral/tufted cells in the mouse olfactory bulb.
Cholecystokinin: an excitatory modulator of mitral/tufted cells in the mouse olfactory bulb.
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DOI：
10.1371/journal.pone.0064170
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发表时间：
2013
期刊：
影响因子：
3.7
通讯作者：
Lowe G
中科院分区：
文献类型：
--
作者：
Ma J;Dankulich-Nagrudny L;Lowe G
胆囊收缩素（CCK）作为一种硫酸化的八肽（CCK - 8S）广泛分布于大脑中。在嗅球中，CCK - 8S集中在两层：外丛状层的球下带和内丛状层（IPL）的僧帽细胞下带，对应于具有球内投射的浅层簇状细胞的胞体和终末，这些投射连接着嗅觉受体的重复肾小球图谱。CCK在该回路中的生理作用尚不清楚。我们通过膜片钳记录了CCK对小鼠嗅球切片中僧帽细胞放电活动的影响，并应用免疫组织化学方法定位CCKB受体。在细胞贴附式记录中，僧帽细胞对300 nM - 1 µM的CCK - 8S表现出放电兴奋、抑制或兴奋 - 抑制混合的反应。GABAA和离子型谷氨酸受体拮抗剂阻断了抑制作用，但兴奋作用仍然存在。全细胞记录显示，兴奋是由缓慢的内向电流介导的，抑制是由放电失活或抑制性突触输入介导的。CCKB受体选择性激动剂CCK - 4（1 µM）也能引起类似的反应。当CCKB受体被LY225910阻断或在CCKB基因敲除小鼠中被破坏时，兴奋发生的频率降低但仍会发生，在CCKA基因敲除小鼠中也观察到了兴奋现象。在僧帽细胞和浅层簇状细胞上检测到CCKB受体免疫反应性，与Tbx21共定位，而在颗粒细胞和IPL中未检测到。我们的数据表明，CCK通过CCKA和CCKB受体在突触后兴奋僧帽细胞。我们假设，从IPL中的簇状细胞终末释放的突触外CCK可能扩散并直接兴奋僧帽细胞体，形成一个正反馈回路，能够放大来自接收由同一嗅觉受体编码的感觉输入的成对肾小球的输出。球内投射的动态可塑性表明，这可能是一种依赖经验的放大机制，用于在不同气味环境中调节和优化嗅球信号处理。
Cholecystokinin (CCK) is widely distributed in the brain as a sulfated octapeptide (CCK-8S). In the olfactory bulb, CCK-8S is concentrated in two laminae: an infraglomerular band in the external plexiform layer, and an inframitral band in the internal plexiform layer (IPL), corresponding to somata and terminals of superficial tufted cells with intrabulbar projections linking duplicate glomerular maps of olfactory receptors. The physiological role of CCK in this circuit is unknown. We made patch clamp recordings of CCK effects on mitral cell spike activity in mouse olfactory bulb slices, and applied immunohistochemistry to localize CCKB receptors. In cell-attached recordings, mitral cells responded to 300 nM –1 µM CCK-8S by spike excitation, suppression, or mixed excitation-suppression. Antagonists of GABAA and ionotropic glutamate receptors blocked suppression, but excitation persisted. Whole-cell recordings revealed that excitation was mediated by a slow inward current, and suppression by spike inactivation or inhibitory synaptic input. Similar responses were elicited by the CCKB receptor-selective agonist CCK-4 (1 µM). Excitation was less frequent but still occurred when CCKB receptors were blocked by LY225910, or disrupted in CCKB knockout mice, and was also observed in CCKA knockouts. CCKB receptor immunoreactivity was detected on mitral and superficial tufted cells, colocalized with Tbx21, and was absent from granule cells and the IPL. Our data indicate that CCK excites mitral cells postsynaptically, via both CCKA and CCKB receptors. We hypothesize that extrasynaptic CCK released from tufted cell terminals in the IPL may diffuse to and directly excite mitral cell bodies, creating a positive feedback loop that can amplify output from pairs of glomeruli receiving sensory inputs encoded by the same olfactory receptor. Dynamic plasticity of intrabulbar projections suggests that this could be an experience-dependent amplification mechanism for tuning and optimizing olfactory bulb signal processing in different odor environments.
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DOI：
10.1073/pnas.76.1.521
发表时间：
1979-01-01
影响因子：
11.1
作者：
INNIS, RB;CORREA, FMA;SNYDER, SH
通讯作者：
SNYDER, SH
影响因子：
2.5
作者：
Chung, Leeyup;Moore, Scott D.
通讯作者：
Moore, Scott D.
影响因子：
2.5
作者：
Fletcher, Max L.;Masurkar, Arjun V.;Chen, Wei R.
通讯作者：
Chen, Wei R.
影响因子：
4.2
作者：
Baltanas, Fernando C.;Curto, Gloria G.;Weruaga, Eduardo
通讯作者：
Weruaga, Eduardo
影响因子：
1.7
作者：
Driesang, RB;Pape, HC
通讯作者：
Pape, HC