A Subtype of Olfactory Bulb Interneurons Is Required for Odor Detection and Discrimination Behaviors
A Subtype of Olfactory Bulb Interneurons Is Required for Odor Detection and Discrimination Behaviors
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DOI：
10.1523/jneurosci.2783-15.2016
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发表时间：
2016-08
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通讯作者：
Hiroo Takahashi;Y. Ogawa;Sei-Ichi Yoshihara;Ryo Asahina;M. Kinoshita;Tatsuro Kitano;Michiko Kitsuki;Kana Tatsumi;T. Okuda;K. Tatsumi;A. Wanaka;H. Hirai;P. Stern;A. Tsuboi
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作者：
Hiroo Takahashi;Y. Ogawa;Sei-Ichi Yoshihara;Ryo Asahina;M. Kinoshita;Tatsuro Kitano;Michiko Kitsuki;Kana Tatsumi;T. Okuda;K. Tatsumi;A. Wanaka;H. Hirai;P. Stern;A. Tsuboi
嗅球（OB）中新生中间神经元进行重组的神经回路对于气味检测和辨别、嗅觉记忆和先天嗅觉反应（包括捕食者回避和性行为）是必要的。OB具有许多中间神经元，包括各种类型的颗粒细胞（GC），然而，每种类型的中间神经元对嗅觉行为控制的贡献仍然未知。在这里，我们研究了癌胚滋养层糖蛋白5 T4的体内功能作用，5 T4表达的GC（5 T4 GC）的树突状分支的调节器，其水平在5 T4基因敲除（KO）小鼠的OB中降低。急性OB切片的电生理记录表明，外部簇状细胞（ETCs）可分为两种类型，爆发和非爆发。5 T4 GCs的光遗传刺激揭示了它们与爆发性和非爆发性ETCs以及二尖瓣细胞（MCs）的连接。有趣的是，在5 T4 KO小鼠中，非爆发性ETC从GC接收到的抑制性输入少于野生型（WT）小鼠，而爆发性ETC和MC在两种小鼠中接收到相似的输入。此外，在5 T4 KO小鼠中，5 T4 GC接收显著更少的兴奋性输入。值得注意的是，在嗅觉行为测试中，5 T4 KO小鼠的气味检测阈值高于WT小鼠，并且在气味辨别学习方面存在缺陷。因此，5 T4的缺失减弱了从5 T4 GC到非爆发性ETC的抑制性输入和到5 T4 GC的兴奋性输入，从而导致嗅觉行为的紊乱。我们的新发现表明，在各种类型的OB中间神经元中，5 T4 GC亚型是气味检测和辨别行为所必需的。脑中的神经元回路包括多巴胺能主神经元和γ-氨基丁酸能中间神经元。虽然后者是少数细胞类型，但它们对正常的大脑功能至关重要，因为它们调节主要神经元的活动。如果中间神经元功能受损，大脑功能可能会受损，导致行为障碍。嗅球（OB）具有各种类型的中间神经元，包括颗粒细胞（GC）;然而，每种类型的中间神经元对嗅觉行为控制的贡献仍然未知。在这里，我们分析了电生理和行为的功能，癌胚滋养层糖蛋白5 T4，调节器的树突状分支在OB GC。我们发现，在各种类型的OB中间神经元，5 T4 GC亚型是气味检测和气味辨别行为所需的。
Neural circuits that undergo reorganization by newborn interneurons in the olfactory bulb (OB) are necessary for odor detection and discrimination, olfactory memory, and innate olfactory responses, including predator avoidance and sexual behaviors. The OB possesses many interneurons, including various types of granule cells (GCs); however, the contribution that each type of interneuron makes to olfactory behavioral control remains unknown. Here, we investigated the in vivo functional role of oncofetal trophoblast glycoprotein 5T4, a regulator for dendritic arborization of 5T4-expressing GCs (5T4 GCs), the level of which is reduced in the OB of 5T4 knock-out (KO) mice. Electrophysiological recordings with acute OB slices indicated that external tufted cells (ETCs) can be divided into two types, bursting and nonbursting. Optogenetic stimulation of 5T4 GCs revealed their connection to both bursting and nonbursting ETCs, as well as to mitral cells (MCs). Interestingly, nonbursting ETCs received fewer inhibitory inputs from GCs in 5T4 KO mice than from those in wild-type (WT) mice, whereas bursting ETCs and MCs received similar inputs in both mice. Furthermore, 5T4 GCs received significantly fewer excitatory inputs in 5T4 KO mice. Remarkably, in olfactory behavior tests, 5T4 KO mice had higher odor detection thresholds than the WT, as well as defects in odor discrimination learning. Therefore, the loss of 5T4 attenuates inhibitory inputs from 5T4 GCs to nonbursting ETCs and excitatory inputs to 5T4 GCs, contributing to disturbances in olfactory behavior. Our novel findings suggest that, among the various types of OB interneurons, the 5T4 GC subtype is required for odor detection and discrimination behaviors. SIGNIFICANCE STATEMENT Neuronal circuits in the brain include glutamatergic principal neurons and GABAergic interneurons. Although the latter is a minority cell type, they are vital for normal brain function because they regulate the activity of principal neurons. If interneuron function is impaired, brain function may be damaged, leading to behavior disorder. The olfactory bulb (OB) possesses various types of interneurons, including granule cells (GCs); however, the contribution that each type of interneuron makes to the control of olfactory behavior remains unknown. Here, we analyzed electrophysiologically and behaviorally the function of oncofetal trophoblast glycoprotein 5T4, a regulator for dendritic branching in OB GCs. We found that, among the various types of OB interneuron, the 5T4 GC subtype is required for odor detection and odor discrimination behaviors.