Developmental transformation of Ca2+ channel-vesicle nanotopography at a central GABAergic synapse

Jing Jing Chen, Walter A. Kaufmann, Chong Chen, Itaru Arai, Olena Kim, Ryuichi Shigemoto, Peter Jonas

Research output: Contribution to journalArticlepeer-review

1 Citation (Scopus)

Abstract

The coupling between Ca2+ channels and release sensors is a key factor defining the signaling properties of a synapse. However, the coupling nanotopography at many synapses remains unknown, and it is unclear how it changes during development. To address these questions, we examined coupling at the cerebellar inhibitory basket cell (BC)-Purkinje cell (PC) synapse. Biophysical analysis of transmission by paired recording and intracellular pipette perfusion revealed that the effects of exogenous Ca2+ chelators decreased during development, despite constant reliance of release on P/Q-type Ca2+ channels. Structural analysis by freeze-fracture replica labeling (FRL) and transmission electron microscopy (EM) indicated that presynaptic P/Q-type Ca2+ channels formed nanoclusters throughout development, whereas docked vesicles were only clustered at later developmental stages. Modeling suggested a developmental transformation from a more random to a more clustered coupling nanotopography. Thus, presynaptic signaling developmentally approaches a point-to-point configuration, optimizing speed, reliability, and energy efficiency of synaptic transmission.

Original languageEnglish
Pages (from-to)755-771.e9
JournalNeuron
Volume112
Issue number5
DOIs
Publication statusPublished - 2024 Mar 6
Externally publishedYes

Keywords

  • Ca sensor
  • GABAergic synapses
  • P/Q-type Ca channels
  • basket cells
  • cerebellum
  • coupling topography
  • development
  • transmitter release

ASJC Scopus subject areas

  • General Neuroscience

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