担当：薬理学講座・中村
Cell Reports, 2024, 43, 114770
Midorikawa et al,
Highlights
•The nanotopography of release site proteins is refined with development
•Topological refinement of Cav2.1 clusters and release site promotes
stable release
•The axon arbor shrinks but the presynaptic bouton expands with
development
•Sensory deprivation impairs fine-tuning of molecular nanotopography and
axon wiring
Summary
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.