Somatostatin Contributes to In Vivo Gamma Oscillation Modulation and Odor Discrimination in the Olfactory Bulb
Somatostatin Contributes to In Vivo Gamma Oscillation Modulation and Odor Discrimination in the Olfactory Bulb
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DOI：
10.1523/jneurosci.4958-09.2010
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发表时间：
2010-01-20
影响因子：
5.3
通讯作者：
Viollet, Cecile
中科院分区：
文献类型：
--
作者：
Lepousez, Gabriel;Mouret, Aurelie;Viollet, Cecile
神经肽系统地存在于局部中间神经元中，但其在神经网络中的功能贡献文献很少。在小鼠主嗅球（MOB）中，生长抑素主要集中于局限于外丛状层（EPL）的局部gaba能中间神经元。免疫组化实验显示，sst2受体是端脑生长抑素受体的主要亚型，在MOB主细胞二尖瓣细胞中表达。当气味激活的二尖瓣细胞同步并产生局部场电位的伽马振荡时，我们研究了sst2受体的药理操作是否会影响自由行为小鼠的这些振荡。在野生型sst2敲除小鼠中，球内注射sst2选择性拮抗剂（bm -23627）后，伽马振荡功率持续下降，而sst2选择性激动剂（奥曲肽和L-779976）持续增加伽马振荡功率。sst2介导的振荡变化与二尖瓣细胞和颗粒细胞之间树突突触传递的改变有关。最后，双侧注射BIM-23627和奥曲肽分别降低和提高了气味识别性能。综上所述，这些结果表明，内源性生长抑素（可能是由EPL中间神经元释放的）通过树突相互突触影响伽马振荡，并有助于嗅觉加工。这提供了由内在神经调节剂诱导的突触、振荡和知觉效应之间的第一个直接关联。
Neuropeptides are systematically encountered in local interneurons, but their functional contribution in neural networks is poorly documented. In the mouse main olfactory bulb (MOB), somatostatin is mainly concentrated in local GABAergic interneurons restricted to the external plexiform layer (EPL). Immunohistochemical experiments revealed that the sst2 receptor, the major somatostatin receptor subtype in the telencephalon, is expressed by mitral cells, the MOB principal cells. As odor-activated mitral cells synchronize and generate gamma oscillations of the local field potentials, we investigated whether pharmacological manipulations of sst2 receptors could influence these oscillations in freely behaving mice. In wild-type, but not in sst2 knock-out mice, gamma oscillation power decreased lastingly after intrabulbar injection of an sst2-selective antagonist (BIM-23627), while sst2-selective agonists (octreotide and L-779976) durably increased it. Sst2-mediated oscillation changes were correlated with modifications of the dendrodendritic synaptic transmission between mitral and granule cells. Finally, bilateral injections of BIM-23627 and octreotide respectively decreased and increased odor discrimination performances. Together, these results suggest that endogenous somatostatin, presumably released from EPL interneurons, affects gamma oscillations through the dendrodendritic reciprocal synapse and contributes to olfactory processing. This provides the first direct correlation between synaptic, oscillatory, and perceptual effects induced by an intrinsic neuromodulator.