Department of Neurophysiology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan.
Division of Neurophysiology, Department of Physiology, School of Medicine, Tokyo Women's Medical University, Tokyo, Japan.
Commun Biol. 2024 Jul 3;7(1):806. doi: 10.1038/s42003-024-06447-4.
Developmental synapse elimination is crucial for shaping mature neural circuits. In the neonatal mouse cerebellum, Purkinje cells (PCs) receive excitatory synaptic inputs from multiple climbing fibers (CFs) and synapses from all but one CF are eliminated by around postnatal day 20. Heterosynaptic interaction between CFs and parallel fibers (PFs), the axons of cerebellar granule cells (GCs) forming excitatory synapses onto PCs and molecular layer interneurons (MLIs), is crucial for CF synapse elimination. However, mechanisms for this heterosynaptic interaction are largely unknown. Here we show that deletion of AMPA-type glutamate receptor functions in GCs impairs CF synapse elimination mediated by metabotropic glutamate receptor 1 (mGlu1) signaling in PCs. Furthermore, CF synapse elimination is impaired by deleting NMDA-type glutamate receptors from MLIs. We propose that PF activity is crucial for CF synapse elimination by directly activating mGlu1 in PCs and indirectly enhancing the inhibition of PCs through activating NMDA receptors in MLIs.
发育性突触消除对于塑造成熟的神经回路至关重要。在新生小鼠小脑，浦肯野细胞（PC）接收来自多个 climbing fibers（CF）的兴奋性突触输入，并且除了一个 CF 之外，所有 CF 的突触都在出生后第 20 天左右被消除。CF 与平行纤维（PF）之间的异突触相互作用，即小脑颗粒细胞（GC）的轴突形成兴奋性突触到 PCs 和分子层中间神经元（MLIs），对于 CF 突触消除至关重要。然而，这种异突触相互作用的机制在很大程度上是未知的。在这里，我们表明在 GC 中删除 AMPA 型谷氨酸受体功能会损害由 PCs 中的代谢型谷氨酸受体 1（mGlu1）信号介导的 CF 突触消除。此外，从 MLIs 中删除 NMDA 型谷氨酸受体也会损害 CF 突触消除。我们提出 PF 活性通过直接激活 PCs 中的 mGlu1 以及通过激活 MLIs 中的 NMDA 受体间接增强对 PCs 的抑制作用，对于 CF 突触消除至关重要。
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