Rapid, Activity-Independent Turnover of Vesicular Transmitter Content at a Mixed Glycine/GABA Synapse
Open Access
- 13 March 2013
- journal article
- Published by Society for Neuroscience in Journal of Neuroscience
- Vol. 33 (11), 4768-4781
- https://doi.org/10.1523/jneurosci.5555-12.2013
Abstract
The release of neurotransmitter via the fusion of transmitter-filled, presynaptic vesicles is the primary means by which neurons relay information. However, little is known regarding the molecular mechanisms that supply neurotransmitter destined for vesicle filling, the endogenous transmitter concentrations inside presynaptic nerve terminals, or the dynamics of vesicle refilling after exocytosis. We addressed these issues by recording from synaptically coupled pairs of glycine/GABA coreleasing interneurons (cartwheel cells) of the mouse dorsal cochlear nucleus. We find that the plasma membrane transporter GlyT2 and the intracellular enzyme glutamate decarboxylase supply the majority of glycine and GABA, respectively. Pharmacological block of GlyT2 or glutamate decarboxylase led to rapid and complete rundown of transmission, whereas increasing GABA synthesis via intracellular glutamate uncaging dramatically potentiated GABA release within 1 min. These effects were surprisingly independent of exocytosis, indicating that prefilled vesicles re-equilibrated upon acute changes in cytosolic transmitter. Titration of cytosolic transmitter with postsynaptic responses indicated that endogenous, nonvesicular glycine/GABA levels in nerve terminals are 5–7 mm, and that vesicular transport mechanisms are not saturated under basal conditions. Thus, cytosolic transmitter levels dynamically set the strength of inhibitory synapses in a release-independent manner.Keywords
This publication has 67 references indexed in Scilit:
- Readily releasable pool of synaptic vesicles measured at single synaptic contactsProceedings of the National Academy of Sciences of the United States of America, 2012
- Spontaneous Spiking and Synaptic Depression Underlie Noradrenergic Control of Feed-Forward InhibitionNeuron, 2011
- P2Y Purinergic Regulation of the Glycine Neurotransmitter TransportersJournal of Biological Chemistry, 2011
- Molecular Layer Inhibitory Interneurons Provide Feedforward and Lateral Inhibition in the Dorsal Cochlear NucleusJournal of Neurophysiology, 2010
- Two Distinct Types of Inhibition Mediated by Cartwheel Cells in the Dorsal Cochlear NucleusJournal of Neurophysiology, 2009
- Axon Initial Segment Ca2+ Channels Influence Action Potential Generation and TimingNeuron, 2009
- Blockade of GABA synthesis only affects neural excitability under activated conditions in rat hippocampal slicesNeurochemistry International, 2008
- The Time Course of Transmitter at Glycinergic Synapses onto MotoneuronsJournal of Neuroscience, 2008
- The kinetics of inhibition of rat recombinant heteromeric α1β glycine receptors by the low‐affinity antagonist SR‐95531The Journal of Physiology, 2007
- Dynamic Regulation of Synaptic GABA Release by the Glutamate-Glutamine Cycle in Hippocampal Area CA1Journal of Neuroscience, 2006