First Author | Midorikawa M | Year | 2024 |
Journal | Cell Rep | Volume | 43 |
Issue | 10 | Pages | 114770 |
PubMed ID | 39321021 | Mgi Jnum | J:358148 |
Mgi Id | MGI:7779423 | Doi | 10.1016/j.celrep.2024.114770 |
Citation | Midorikawa M, et al. (2024) Developmental refinement of the active zone nanotopography and axon wiring at the somatosensory thalamus. Cell Rep 43(10):114770 |
abstractText | Functional refinement of neural circuits is a crucial developmental process in the brain. However, how synaptic maturation and axon wiring proceed cooperatively to establish reliable signal transmission is unclear. Here, we combined nanotopography of release machinery at the active zone (AZ), nanobiophysics of neurotransmitter release, and single-neuron reconstruction of axon arbors of lemniscal fibers (LFs) in the developing mouse somatosensory thalamus. With development, the cluster of Cav2.1 enlarges and translocates closer to vesicle release sites inside the bouton, and LFs drastically shrink their arbors and form larger boutons on the perisomatic region of target neurons. Experimentally constrained simulations show that the nanotopography of mature synapses enables not only rapid vesicular release but also reliable transmission following repetitive firing. Sensory deprivation impairs the developmental shift of molecular nanotopography and axon wiring. Thus, we uncovered the cooperative nanotopographical and morphological mechanisms underlying the developmental establishment of reliable synaptic transmission. |