Neurobiology Department, University of California San Diego, La Jolla, CA 92093.
Kavli Institute for Brain & Mind, University of California San Diego, La Jolla, CA 92093.
Proc Natl Acad Sci U S A. 2024 Apr 9;121(15):e2318041121. doi: 10.1073/pnas.2318041121. Epub 2024 Apr 3.
Stable matching of neurotransmitters with their receptors is fundamental to synapse function and reliable communication in neural circuits. Presynaptic neurotransmitters regulate the stabilization of postsynaptic transmitter receptors. Whether postsynaptic receptors regulate stabilization of presynaptic transmitters has received less attention. Here, we show that blockade of endogenous postsynaptic acetylcholine receptors (AChR) at the neuromuscular junction destabilizes the cholinergic phenotype in motor neurons and stabilizes an earlier, developmentally transient glutamatergic phenotype. Further, expression of exogenous postsynaptic gamma-aminobutyric acid type A receptors (GABA receptors) in muscle cells stabilizes an earlier, developmentally transient GABAergic motor neuron phenotype. Both AChR and GABA receptors are linked to presynaptic neurons through transsynaptic bridges. Knockdown of specific components of these transsynaptic bridges prevents stabilization of the cholinergic or GABAergic phenotypes. Bidirectional communication can enforce a match between transmitter and receptor and ensure the fidelity of synaptic transmission. Our findings suggest a potential role of dysfunctional transmitter receptors in neurological disorders that involve the loss of the presynaptic transmitter.
神经递质与其受体的稳定匹配是突触功能和神经回路中可靠通讯的基础。突触前神经递质调节突触后递质受体的稳定。然而，突触后受体是否调节突触前递质的稳定，这方面的研究还较少。本文中，我们发现，在神经肌肉接头处阻断内源性的突触后乙酰胆碱受体（AChR）会使运动神经元中的胆碱能表型不稳定，并稳定早期、发育过程中短暂存在的谷氨酸能表型。此外，在肌肉细胞中表达外源性的突触后γ-氨基丁酸 A 型受体（GABA 受体）会稳定早期、发育过程中短暂存在的 GABA 能运动神经元表型。AChR 和 GABA 受体都通过突触前神经元之间的突触桥与突触前神经元相连。这些突触桥的特定成分的敲低会阻止胆碱能或 GABA 能表型的稳定。双向通讯可以在递质和受体之间建立匹配，并确保突触传递的保真度。我们的发现表明，在涉及突触前递质丢失的神经紊乱中，功能失调的递质受体可能起作用。
