Cell-Type-Specific Modulation of Sensory Responses in Olfactory Bulb Circuits by Serotonergic Projections from the Raphe Nuclei

Cell-Type-Specific Modulation of Sensory Responses in Olfactory Bulb Circuits by Serotonergic Projections from the Raphe Nuclei
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DOI:
10.1523/jneurosci.3667-15.2016
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发表时间:
2016-06-22
影响因子:
5.3
通讯作者:
Wachowiak, Matt
Wachowiak, Matt
中科院分区:
医学1区
文献类型:
--
作者:
Brunert, Daniela;Tsuno, Yusuke;Wachowiak, Matt

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脑干中缝核中的血清素能神经元密集地支配嗅球(OB),它们可以调节嗅觉信息的初始表征和处理。特定 OB 细胞类型中感觉反应的血清素调节在体内的特征还很不清楚。在这里,我们使用光学报告基因的细胞类型特异性表达来可视化中缝刺激如何改变小鼠 OB 肾小球层两类 GABA 能神经元、肾小球周 (PG) 和短轴突 (SA) 细胞,以及携带 OB 输出到梨状皮层的二尖瓣/簇状 (MT) 细胞的感觉反应。在 PG 和 SA 细胞中,短暂(1-4 s)的中缝刺激引起与吸入环境空气相关的反应幅度的大幅增加,以及气味诱发反应幅度的适度增加。当谷氨酸能传递 iGluSn FR 的光学报告基因在 PG 和 SA 细胞中表达时,观察到几乎相同的效果,表明这些神经元的兴奋性输入增强。相比之下,在从背侧 OB 成像的 MT 细胞中,中缝刺激引起静息 GCaMP 荧光的强烈增加,而对气味剂的吸入相关反应仅略有增强。最后,OB 中的光遗传学刺激中缝血清素能传入对细胞外记录的推定 MT 细胞具有异质性影响,在血清素能传入刺激期间,静息和气味诱发的反应总体上适度增加。这些结果表明,来自中缝的血清素能传入神经通过对多个 OB 目标的不同影响来动态调节嗅觉处理,并且可能改变行为过程中抑制形成的 OB 输出的程度。
Serotonergic neurons in the brainstem raphe nuclei densely innervate the olfactory bulb (OB), where they can modulate the initial representation and processing of olfactory information. Serotonergic modulation of sensory responses among defined OB cell types is poorly characterized in vivo. Here, we used cell-type-specific expression of optical reporters to visualize how raphe stimulation alters sensory responses in two classes of GABAergic neurons of the mouse OB glomerular layer, periglomerular (PG) and short axon (SA) cells, as well as mitral/tufted (MT) cells carrying OB output to piriform cortex. In PG and SA cells, brief (1-4 s) raphe stimulation elicited a large increase in the magnitude of responses linked to inhalation of ambient air, as well as modest increases in the magnitude of odorantevoked responses. Near-identical effects were observed when the optical reporter of glutamatergic transmission iGluSn FR was expressed in PG and SA cells, suggesting enhanced excitatory input to these neurons. In contrast, in MT cells imaged from the dorsal OB, raphe stimulation elicited a strong increase in resting GCaMP fluorescence with only a slight enhancement of inhalation-linked responses to odorant. Finally, optogenetically stimulating raphe serotonergic afferents in the OB had heterogeneous effects on presumptive MT cells recorded extracellularly, with an overall modest increase in resting and odorant-evoked responses during serotonergic afferent stimulation. These results suggest that serotonergic afferents from raphe dynamically modulate olfactory processing through distinct effects on multiple OB targets, and may alter the degree to which OB output is shaped by inhibition during behavior.