@article{14843,
  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.},
  author       = {Chen, JingJing and Kaufmann, Walter and Chen, Chong and Arai, Itaru and Kim, Olena and Shigemoto, Ryuichi and Jonas, Peter M},
  issn         = {1097-4199},
  journal      = {Neuron},
  number       = {5},
  pages        = {755--771.e9},
  publisher    = {Elsevier},
  title        = {{Developmental transformation of Ca2+ channel-vesicle nanotopography at a central GABAergic synapse}},
  doi          = {10.1016/j.neuron.2023.12.002},
  volume       = {112},
  year         = {2024},
}

@phdthesis{15101,
  abstract     = {The coupling between presynaptic Ca2+ channels and release sensors is a key factor that
determines speed and efficacy of synapse transmission. At some excitatory synapses,
channel–sensor coupling becomes tighter during development, and tightening is often
associated with a switch in the reliance on different Ca2+ channel subtypes. However, the
coupling topography at many synapses remains unknown, and it is unclear how it changes
during development. To address this question, we analyzed the coupling configuration at the
cerebellar basket cell (BC) to Purkinje cell (PC) synapse at different developmental stages,
combining biophysical analysis, structural analysis, and modeling.
Quantal analysis of BC–PC indicated that release probability decreased, while the
number of functional sites increased during development. Although transmitter release
persistently relied on P/Q-type Ca2+ channels in the time period postnatal day 7–23, effects
of the Ca2+ chelator EGTA and BAPTA applied by intracellular pipette perfusion decreased
during development, indicative of tightening of source-sensor coupling. Furthermore,
presynaptic action potentials became shorter during development, suggesting reduced
efficacy of Ca2+ channel activation.
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. The number of functional release sites correlated better with the AZ
number early in development, but match better with the Ca2+ channel cluster number at later
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.},
  author       = {Chen, JingJing},
  issn         = {2663-337X},
  pages        = {84},
  publisher    = {Institute of Science and Technology Austria},
  title        = {{Developmental transformation of nanodomain coupling between Ca2+ channels and release sensors at a central GABAergic synapse}},
  doi          = {10.15479/at:ista:15101},
  year         = {2024},
}