Format

Send to

Choose Destination
Neuron. 2019 Jan 16;101(2):260-273.e6. doi: 10.1016/j.neuron.2018.11.028. Epub 2018 Dec 10.

CaV2.1 α1 Subunit Expression Regulates Presynaptic CaV2.1 Abundance and Synaptic Strength at a Central Synapse.

Author information

1
Research Group Molecular Mechanisms of Synaptic Function, Max Planck Florida Institute for Neuroscience, Jupiter, FL 33458, USA.
2
Department of Anatomy and Cell Biology, Iowa Neuroscience Institute, University of Iowa, Iowa City, IA 52242, USA.
3
Max Planck Florida Electron Microscopy Core, Max Planck Florida Institute for Neuroscience, Jupiter, FL 33458, USA.
4
Department of Anatomy and Cell Biology, Iowa Neuroscience Institute, University of Iowa, Iowa City, IA 52242, USA; Department of Otolaryngology, Iowa Neuroscience Institute, Aging Mind Brain Initiative, University of Iowa, Iowa City, IA 52242, USA. Electronic address: samuel-m-young@uiowa.edu.

Abstract

The abundance of presynaptic CaV2 voltage-gated Ca2+ channels (CaV2) at mammalian active zones (AZs) regulates the efficacy of synaptic transmission. It is proposed that presynaptic CaV2 levels are saturated in AZs due to a finite number of slots that set CaV2 subtype abundance and that CaV2.1 cannot compete for CaV2.2 slots. However, at most AZs, CaV2.1 levels are highest and CaV2.2 levels are developmentally reduced. To investigate CaV2.1 saturation states and preference in AZs, we overexpressed the CaV2.1 and CaV2.2 α1 subunits at the calyx of Held at immature and mature developmental stages. We found that AZs prefer CaV2.1 to CaV2.2. Remarkably, CaV2.1 α1 subunit overexpression drove increased CaV2.1 currents and channel numbers and increased synaptic strength at both developmental stages examined. Therefore, we propose that CaV2.1 levels in the AZ are not saturated and that synaptic strength can be modulated by increasing CaV2.1 levels to regulate neuronal circuit output. VIDEO ABSTRACT.

KEYWORDS:

Ca(V)2.1; active zone; calcium channels; calyx of Held; neuronal circuits; release probability; synaptic plasticity; synaptic strength; synaptic transmission; viral vectors

PMID:
30545599
PMCID:
PMC6413316
[Available on 2020-01-16]
DOI:
10.1016/j.neuron.2018.11.028

Supplemental Content

Full text links

Icon for Elsevier Science
Loading ...
Support Center