Takahashi Hiroo, Ogawa Yoichi, Yoshihara Sei-Ichi, Asahina Ryo, Kinoshita Masahito, Kitano Tatsuro, Kitsuki Michiko, Tatsumi Kana, Okuda Mamiko, Tatsumi Kouko, Wanaka Akio, Hirai Hirokazu, Stern Peter L, Tsuboi Akio
Laboratory for Molecular Biology of Neural System, Advanced Medical Research Center.
Department of Physiology I, and.
J Neurosci. 2016 Aug 3;36(31):8210-27. doi: 10.1523/JNEUROSCI.2783-15.2016.
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.
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.
嗅球（OB）中由新生中间神经元进行重组的神经回路对于气味检测与辨别、嗅觉记忆以及包括躲避捕食者和性行为在内的先天嗅觉反应是必需的。OB拥有许多中间神经元，包括各种类型的颗粒细胞（GCs）；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。在此，我们研究了癌胚滋养层糖蛋白5T4在体内的功能作用，5T4是表达5T4的GCs（5T4 GCs）树突分支的调节因子，其在5T4基因敲除（KO）小鼠的OB中的水平降低。对急性OB切片进行的电生理记录表明，外侧簇状细胞（ETCs）可分为两种类型，爆发型和非爆发型。对5T4 GCs进行光遗传学刺激揭示了它们与爆发型和非爆发型ETCs以及与二尖瓣细胞（MCs）的连接。有趣的是，在5T4 KO小鼠中，非爆发型ETCs从GCs接收的抑制性输入比野生型（WT）小鼠中的少，而在两种小鼠中爆发型ETCs和MCs接收的输入相似。此外，在5T4 KO小鼠中，5T4 GCs接收的兴奋性输入明显减少。值得注意的是，在嗅觉行为测试中，5T4 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，5T4的缺失减弱了从5T4 GCs到非爆发型ETCs的抑制性输入以及到5T4 GCs的兴奋性输入，导致嗅觉行为紊乱。我们的新发现表明，在各种类型的OB中间神经元中，5T4 GC亚型对于气味检测和辨别行为是必需的。
大脑中的神经回路包括谷氨酸能主神经元和GABA能中间神经元。尽管后者是少数细胞类型，但它们对于正常脑功能至关重要，因为它们调节主神经元的活动。如果中间神经元功能受损，脑功能可能会受损，导致行为障碍。嗅球（OB）拥有各种类型的中间神经元，包括颗粒细胞（GCs）；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。在此，我们通过电生理和行为分析了癌胚滋养层糖蛋白5T4的功能，5T4是OB中GCs树突分支的调节因子。我们发现，在各种类型的OB中间神经元中，5T4 GC亚型对于气味检测和气味辨别行为是必需的。
