Bertsch David J, Palacios Castillo Lesly M, Frye Mark A
Department of Integrative Biology and Physiology, University of California, Los Angeles, Los Angeles, California, United States.
J Neurophysiol. 2025 Sep 1;134(3):962-984. doi: 10.1152/jn.00154.2025. Epub 2025 Aug 19.
Serotonin (5-HT) is a hormonal messenger that confers state-level changes upon the nervous system in both humans and flies. In , lobula columnar (LC) cells are feature-detecting neurons that project from the optic lobe to the central brain, where each population forms an anatomically distinct glomerulus with heterogeneous synaptic partners. Here, we investigated serotonin's effect on two LC populations with different 5-HT receptor expression profiles. Receptor expression does not predict neuromodulatory effects. LC15 expresses inhibitory 5-HT1A and 5-HT1B receptors, yet serotonin increases the amplitude of calcium responses to visual stimuli. LC12 expresses inhibitory 5-HT1A and excitatory 5-HT2A receptors, yet serotonin application does not influence visual responses. Serotonin targets select visual response properties, potentiating LC15 responses to a motion-defined bar and tuning the gain of responses to varying object velocity, but has no influence on contrast sensitivity. Serotonin does not significantly facilitate LC15 responses in postsynaptic dendrites, only in the presynaptic terminals of the glomerulus, which suggests that the neuromodulatory effects are strongest in the central brain. Connectomics confirms that LC12 and LC15 share neither presynaptic inputs nor postsynaptic outputs in the central brain. The wiring diagram shows no synaptic interactions between the LC15 circuit and major serotonergic 5-HTPLP neurons, nor to other serotonergic neurons of the central brain, suggesting that endogenous 5-HT acts via paracrine transmission on nonserotonergic pathways. Lobula- and glomerulus-specific GABAergic and glutamatergic inhibitory partners, positioned to filter visual stimuli, are putative 5-HT targets. These results provide a comparative framework for the neuromodulatory mechanisms involved in visual processing. How does neuromodulatory state affects visual feature detection? In this work, we demonstrate highly specific facilitated visual responses of object-detecting neurons after serotonin bath application in Drosophila. Serotonin potentiates motion-defined bar responses in object-detecting LC15 neurons and tunes response gain to translating bars of mid-range velocities in presynaptic axon terminals. Our calcium imaging extends what is known about extra-synaptic neuromodulation in the visual system and shows that serotonin heightens visual processes that inform object-specific behavior.
血清素(5-羟色胺,5-HT)是一种激素信使,可使人和果蝇的神经系统发生状态级别的变化。在果蝇中,小叶柱状(LC)细胞是特征检测神经元,从视叶投射到中枢脑,每个群体在中枢脑中形成一个解剖学上不同的神经小球,其突触伙伴具有异质性。在这里,我们研究了血清素对两个具有不同5-HT受体表达谱的LC群体的影响。受体表达并不能预测神经调节作用。LC15表达抑制性5-HT1A和5-HT1B受体,但血清素会增加对视觉刺激的钙反应幅度。LC12表达抑制性5-HT1A和兴奋性5-HT2A受体,但应用血清素不会影响视觉反应。血清素靶向特定的视觉反应特性,增强LC15对运动定义条的反应,并调整对不同物体速度的反应增益,但对对比度敏感性没有影响。血清素在突触后树突中不会显著促进LC15反应,仅在神经小球的突触前终末起作用,这表明神经调节作用在中枢脑中最强。连接组学证实,LC12和LC15在中枢脑中既不共享突触前输入也不共享突触后输出。接线图显示LC15回路与主要的血清素能5-HTPLP神经元之间以及与中枢脑的其他血清素能神经元之间没有突触相互作用,这表明内源性5-HT通过旁分泌作用于非血清素能通路。小叶和神经小球特异性的γ-氨基丁酸能和谷氨酸能抑制性伙伴,它们能够过滤视觉刺激,是血清素的假定靶点。这些结果为视觉处理中涉及的神经调节机制提供了一个比较框架。神经调节状态如何影响视觉特征检测?在这项工作中,我们证明了在果蝇中进行血清素浴应用后,目标检测神经元的视觉反应得到了高度特异性的促进。血清素增强了目标检测LC15神经元中运动定义条的反应,并在突触前轴突终末调整了对中等速度平移条的反应增益。我们的钙成像扩展了对视觉系统中突触外神经调节的认识,并表明血清素增强了为目标特异性行为提供信息的视觉过程。