Mesh : Animals Amacrine Cells / metabolism Mice Acetylcholine / pharmacology metabolism Mice, Inbred C57BL gamma-Aminobutyric Acid / metabolism Receptors, Muscarinic / metabolism Receptors, Nicotinic / metabolism

来  源:   DOI:10.1085/jgp.202413550   PDF(Pubmed)

Abstract:
Cholinergic signaling in the retina is mediated by acetylcholine (ACh) released from starburst amacrine cells (SACs), which are key neurons for motion detection. SACs comprise ON and OFF subtypes, which morphologically show mirror symmetry to each other. Although many physiological studies on SACs have targeted ON cells only, the synaptic computation of ON and OFF SACs is assumed to be similar. Recent studies demonstrated that gene expression patterns and receptor types differed between ON and OFF SACs, suggesting differences in their functions. Here, we compared cholinergic signaling pathways between ON and OFF SACs in the mouse retina using the patch clamp technique. The application of ACh increased GABAergic feedback, observed as postsynaptic currents to SACs, in both ON and OFF SACs; however, the mode of GABAergic feedback differed. Nicotinic receptors mediated GABAergic feedback in both ON and OFF SACs, while muscarinic receptors mediated GABAergic feedback in ON SACs only in adults. Neither tetrodotoxin, which blocked action potentials, nor LY354740, which blocked neurotransmitter release from SACs, eliminated ACh-induced GABAergic feedback in SACs. These results suggest that ACh-induced GABAergic feedback in ON and OFF SACs is regulated by different feedback mechanisms in adults and mediated by non-spiking amacrine cells other than SACs.
摘要:
视网膜中的胆碱能信号是由星状无长突细胞(SAC)释放的乙酰胆碱(ACh)介导的,它们是运动检测的关键神经元。SAC包括ON和OFF亚型,在形态上显示出相互镜像对称。尽管许多关于SAC的生理学研究仅针对ON细胞,假设ON和OFFSAC的突触计算是相似的。最近的研究表明,基因表达模式和受体类型在ON和OFFSACs之间有所不同,表明它们的功能差异。这里,我们使用膜片钳技术比较了小鼠视网膜中ON和OFFSACs之间的胆碱能信号通路.ACh的应用增加了GABA能反馈,观察到SAC的突触后电流,在ON和OFFSAC中;然而,GABA能反馈模式不同。烟碱受体在ON和OFFSAC中介导GABA能反馈,而毒蕈碱受体仅在成人中介导ONSACs中的GABA能反馈。都不是河豚毒素,阻止动作电位,也没有LY354740,它阻止了SAC释放神经递质,在SAC中消除ACh诱导的GABA能反馈。这些结果表明,ACh在ON和OFFSACs中诱导的GABA能反馈受到成人不同反馈机制的调节,并由SACs以外的非尖峰无长突细胞介导。
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