Department of Biology, West Virginia University, Morgantown, West Virginia 26506
Janelia Research Campus, Howard Hughes Medical Institute, Ashburn, Virginia 20147.
J Neurosci. 2020 Aug 12;40(33):6309-6327. doi: 10.1523/JNEUROSCI.0552-20.2020. Epub 2020 Jul 8.
Serotonergic neurons project widely throughout the brain to modulate diverse physiological and behavioral processes. However, a single-cell resolution understanding of the connectivity of serotonergic neurons is currently lacking. Using a whole-brain EM dataset of a female , we comprehensively determine the wiring logic of a broadly projecting serotonergic neuron (the CSDn) that spans several olfactory regions. Within the antennal lobe, the CSDn differentially innervates each glomerulus, yet surprisingly, this variability reflects a diverse set of presynaptic partners, rather than glomerulus-specific differences in synaptic output, which is predominately to local interneurons. Moreover, the CSDn has distinct connectivity relationships with specific local interneuron subtypes, suggesting that the CSDn influences distinct aspects of local network processing. Across olfactory regions, the CSDn has different patterns of connectivity, even having different connectivity with individual projection neurons that also span these regions. Whereas the CSDn targets inhibitory local neurons in the antennal lobe, the CSDn has more distributed connectivity in the LH, preferentially synapsing with principal neuron types based on transmitter content. Last, we identify individual novel synaptic partners associated with other sensory domains that provide strong, top-down input to the CSDn. Together, our study reveals the complex connectivity of serotonergic neurons, which combine the integration of local and extrinsic synaptic input in a nuanced, region-specific manner. All sensory systems receive serotonergic modulatory input. However, a comprehensive understanding of the synaptic connectivity of individual serotonergic neurons is lacking. In this study, we use a whole-brain EM microscopy dataset to comprehensively determine the wiring logic of a broadly projecting serotonergic neuron in the olfactory system of Collectively, our study demonstrates, at a single-cell level, the complex connectivity of serotonergic neurons within their target networks, identifies specific cell classes heavily targeted for serotonergic modulation in the olfactory system, and reveals novel extrinsic neurons that provide strong input to this serotonergic system outside of the context of olfaction. Elucidating the connectivity logic of individual modulatory neurons provides a ground plan for the seemingly heterogeneous effects of modulatory systems.
血清素能神经元广泛投射到大脑中，以调节多种生理和行为过程。然而，目前缺乏对血清素能神经元连接的单细胞分辨率理解。我们使用一个雌性的全脑 EM 数据集，全面确定了一个广泛投射的血清素能神经元（CSDn）的连接逻辑，该神经元跨越几个嗅觉区域。在触角叶中，CSDn 对每个神经球有差异的支配，然而令人惊讶的是，这种可变性反映了一组多样化的突触前伙伴，而不是突触输出的神经球特异性差异，后者主要是到局部中间神经元。此外，CSDn 与特定的局部中间神经元亚型有不同的连接关系，表明 CSDn 影响局部网络处理的不同方面。在嗅觉区域中，CSDn 具有不同的连接模式，甚至与跨越这些区域的单个投射神经元也有不同的连接。CSDn 靶向触角叶中的抑制性局部神经元，而 CSDn 在 LH 中具有更分散的连接，根据递质内容，优先与主要神经元类型形成突触。最后，我们确定了与其他感觉域相关的个别新的突触伙伴，这些伙伴为 CSDn 提供了强烈的自上而下的输入。总的来说，我们的研究揭示了血清素能神经元的复杂连接，这些神经元以细微、区域特异性的方式整合局部和外在的突触输入。所有感觉系统都接收血清素能调制输入。然而，对单个血清素能神经元的突触连接的全面理解是缺乏的。在这项研究中，我们使用全脑 EM 显微镜数据集，全面确定了嗅觉系统中广泛投射的血清素能神经元的连接逻辑。总的来说，我们的研究在单细胞水平上展示了血清素能神经元在其靶网络中的复杂连接，确定了在嗅觉系统中被血清素能调制强烈靶向的特定细胞类群，并揭示了提供强烈输入到这个血清素能系统的新的外在神经元，而这些输入在嗅觉之外的背景下是不存在的。阐明单个调制神经元的连接逻辑为调制系统的看似异质效应提供了一个基础计划。
