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

Matthias Lübbert; R Oliver Goral; Christian Keine; Connon Thomas; Debbie Guerrero-Given; Travis Putzke; Rachel Satterfield; Naomi Kamasawa; Samuel M Young Jr

doi:10.1016/j.neuron.2018.11.028

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

Journal article

Open access

Peer reviewed

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

Matthias Lübbert, R Oliver Goral, Christian Keine, Connon Thomas, Debbie Guerrero-Given, Travis Putzke, Rachel Satterfield, Naomi Kamasawa and Samuel M Young Jr

Neuron (Cambridge, Mass.), Vol.101(2), pp.260-273.e6

01/16/2019

DOI: 10.1016/j.neuron.2018.11.028

PMCID: PMC6413316

PMID: 30545599

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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.

Biophysics

Animals, Newborn

Calcium Channels, N-Type - genetics

Green Fluorescent Proteins - metabolism

Electric Stimulation

Synaptic Transmission - genetics

Calcium - metabolism

Synapses - physiology

Mice, Inbred C57BL

Neurotransmitter Agents - metabolism

Male

Mice, Transgenic

Synapses - ultrastructure

Green Fluorescent Proteins - genetics

Presynaptic Terminals - physiology

Presynaptic Terminals - ultrastructure

Calcium Channel Blockers - pharmacology

Calcium Channels, N-Type - metabolism

Brain Stem - cytology

Animals

Female

Mice

Cadmium Chloride - pharmacology

Details

Title: Subtitle: CaV2.1 α1 Subunit Expression Regulates Presynaptic CaV2.1 Abundance and Synaptic Strength at a Central Synapse
Creators: Matthias Lübbert - Research Group Molecular Mechanisms of Synaptic Function, Max Planck Florida Institute for Neuroscience, Jupiter, FL 33458, USA
R Oliver Goral - Department of Anatomy and Cell Biology, Iowa Neuroscience Institute, University of Iowa, Iowa City, IA 52242, USA
Christian Keine - Department of Anatomy and Cell Biology, Iowa Neuroscience Institute, University of Iowa, Iowa City, IA 52242, USA
Connon Thomas - Max Planck Florida Electron Microscopy Core, Max Planck Florida Institute for Neuroscience, Jupiter, FL 33458, USA
Debbie Guerrero-Given - Max Planck Florida Electron Microscopy Core, Max Planck Florida Institute for Neuroscience, Jupiter, FL 33458, USA
Travis Putzke - Research Group Molecular Mechanisms of Synaptic Function, Max Planck Florida Institute for Neuroscience, Jupiter, FL 33458, USA
Rachel Satterfield - Research Group Molecular Mechanisms of Synaptic Function, Max Planck Florida Institute for Neuroscience, Jupiter, FL 33458, USA
Naomi Kamasawa - Max Planck Florida Electron Microscopy Core, Max Planck Florida Institute for Neuroscience, Jupiter, FL 33458, USA
Samuel M Young Jr - 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
Resource Type: Journal article
Publication Details: Neuron (Cambridge, Mass.), Vol.101(2), pp.260-273.e6
Publisher: United States
DOI: 10.1016/j.neuron.2018.11.028
PMID: 30545599
PMCID: PMC6413316
ISSN: 0896-6273
eISSN: 1097-4199
Grant note: R01 DC014093 / NIDCD NIH HHS
Language: English
Date published: 01/16/2019
Academic Unit: Anatomy and Cell Biology; Iowa Neuroscience Institute; Otolaryngology
Record Identifier: 9984025465402771

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