MRC Laboratory of Molecular Biology, Cambridge CB2 0QH, United Kingdom.
MRC Laboratory of Molecular Biology, Cambridge CB2 0QH, United Kingdom
J Neurosci. 2023 Feb 15;43(7):1111-1124. doi: 10.1523/JNEUROSCI.1516-22.2022. Epub 2023 Jan 5.
Fast cholinergic neurotransmission is mediated by acetylcholine-gated ion channels; in particular, excitatory nicotinic acetylcholine receptors play well established roles in virtually all nervous systems. Acetylcholine-gated inhibitory channels have also been identified in some invertebrate phyla, yet their roles in the nervous system are less well understood. We report the existence of multiple new inhibitory ion channels with diverse ligand activation properties in We identify three channels, LGC-40, LGC-57, and LGC-58, whose primary ligand is choline rather than acetylcholine, as well as the first evidence of a truly polymodal channel, LGC-39, which is activated by both cholinergic and aminergic ligands. Using our new ligand-receptor pairs we uncover the surprising extent to which single neurons in the hermaphrodite nervous system express both excitatory and inhibitory channels, not only for acetylcholine but also for the other major neurotransmitters. The results presented in this study offer new insight into the potential evolutionary benefit of a vast and diverse repertoire of ligand-gated ion channels to generate complexity in an anatomically compact nervous system. Here we describe the diversity of cholinergic signaling in the nematode We identify and characterize a novel family of ligand-gated ion channels and show that they are preferentially gated by choline rather than acetylcholine and expressed broadly in the nervous system. Interestingly, we also identify one channel gated by chemically diverse ligands including acetylcholine and aminergic ligands. By using our new knowledge of these ligand-gated ion channels, we built a model to predict the synaptic polarity in the connectome. This model can be used for generating hypotheses on neural circuit function.
快速的胆碱能神经传递是由乙酰胆碱门控离子通道介导的；特别是，兴奋性烟碱型乙酰胆碱受体在几乎所有的神经系统中都起着重要的作用。在一些无脊椎动物门中也发现了乙酰胆碱门控抑制性通道，但它们在神经系统中的作用还不太清楚。我们报告了在存在多种具有不同配体激活特性的新型抑制性离子通道在 中。我们鉴定出了三个通道，LGC-40、LGC-57 和 LGC-58，它们的主要配体是胆碱而不是乙酰胆碱，以及第一个真正的多模态通道 LGC-39 的证据，它被胆碱能和胺能配体激活。使用我们的新配体-受体对，我们揭示了一个令人惊讶的事实，即雌雄同体神经系统中的单个神经元不仅表达兴奋性和抑制性通道，而且还表达乙酰胆碱和其他主要神经递质的通道。本研究的结果为广泛而多样的配体门控离子通道在一个解剖上紧凑的神经系统中产生复杂性的潜在进化优势提供了新的见解。在这里，我们描述了线虫中胆碱能信号传递的多样性。我们鉴定并表征了一个新型的配体门控离子通道家族，并表明它们主要由胆碱而不是乙酰胆碱门控，并广泛表达在神经系统中。有趣的是，我们还鉴定出一个由包括乙酰胆碱和胺能配体在内的化学多样性配体门控的通道。通过使用我们对这些配体门控离子通道的新知识，我们构建了一个模型来预测在 连接组中的突触极性。该模型可用于生成关于神经回路功能的假设。
