Brill Julia, Shao Zuoyi, Puche Adam C, Wachowiak Matt, Shipley Michael T
Department of Anatomy and Neurobiology, University of Maryland School of Medicine, Baltimore, Maryland; and.
Department of Neurobiology and Anatomy, and Brain Institute, University of Utah, Salt Lake City, Utah.
J Neurophysiol. 2016 Mar;115(3):1208-19. doi: 10.1152/jn.00847.2015. Epub 2015 Dec 9.
Serotoninergic fibers densely innervate olfactory bulb glomeruli, the first sites of synaptic integration in the olfactory system. Acting through 5HT2A receptors, serotonin (5HT) directly excites external tufted cells (ETCs), key excitatory glomerular neurons, and depolarizes some mitral cells (MCs), the olfactory bulb's main output neurons. We further investigated 5HT action on MCs and determined its effects on the two major classes of glomerular interneurons: GABAergic/dopaminergic short axon cells (SACs) and GABAergic periglomerular cells (PGCs). In SACs, 5HT evoked a depolarizing current mediated by 5HT2C receptors but did not significantly impact spike rate. 5HT had no measurable direct effect in PGCs. Serotonin increased spontaneous excitatory and inhibitory postsynaptic currents (sEPSCs and sIPSCs) in PGCs and SACs. Increased sEPSCs were mediated by 5HT2A receptors, suggesting that they are primarily due to enhanced excitatory drive from ETCs. Increased sIPSCs resulted from elevated excitatory drive onto GABAergic interneurons and augmented GABA release from SACs. Serotonin-mediated GABA release from SACs was action potential independent and significantly increased miniature IPSC frequency in glomerular neurons. When focally applied to a glomerulus, 5HT increased MC spontaneous firing greater than twofold but did not increase olfactory nerve-evoked responses. Taken together, 5HT modulates glomerular network activity in several ways: 1) it increases ETC-mediated feed-forward excitation onto MCs, SACs, and PGCs; 2) it increases inhibition of glomerular interneurons; 3) it directly triggers action potential-independent GABA release from SACs; and 4) these network actions increase spontaneous MC firing without enhancing responses to suprathreshold sensory input. This may enhance MC sensitivity while maintaining dynamic range.
5-羟色胺能纤维密集地支配嗅球小球，这是嗅觉系统中突触整合的首个位点。5-羟色胺（5HT）通过5HT2A受体发挥作用，直接兴奋外侧簇状细胞（ETC），即关键的兴奋性小球神经元，并使一些主细胞（MC）去极化，主细胞是嗅球的主要输出神经元。我们进一步研究了5HT对主细胞的作用，并确定了其对两类主要的小球中间神经元的影响：γ-氨基丁酸能/多巴胺能短轴突细胞（SAC）和γ-氨基丁酸能球周细胞（PGC）。在SAC中，5HT诱发了由5HT2C受体介导的去极化电流，但对放电频率没有显著影响。5HT对PGC没有可测量的直接作用。5-羟色胺增加了PGC和SAC中的自发性兴奋性和抑制性突触后电流（sEPSC和sIPSC）。sEPSC的增加由5HT2A受体介导，表明它们主要是由于来自ETC的兴奋性驱动增强。sIPSC的增加是由于对γ-氨基丁酸能中间神经元的兴奋性驱动增加以及SAC释放的γ-氨基丁酸增加所致。5-羟色胺介导的SAC释放γ-氨基丁酸不依赖动作电位，并显著增加了小球神经元中的微小IPSC频率。当局部应用于一个小球时，5HT使主细胞的自发放电增加两倍以上，但没有增加嗅神经诱发的反应。综上所述，5HT以多种方式调节小球网络活动：1）它增加了ETC介导的对主细胞、SAC和PGC的前馈兴奋；2）它增加了对小球中间神经元的抑制；3）它直接触发SAC释放不依赖动作电位的γ-氨基丁酸；4）这些网络作用增加了主细胞的自发放电，而不增强对阈上感觉输入的反应。这可能在维持动态范围的同时提高主细胞的敏感性。
