Journal
JOURNAL OF NEUROSCIENCE
Volume 37, Issue 16, Pages 4301-4310Publisher
SOC NEUROSCIENCE
DOI: 10.1523/JNEUROSCI.3488-16.2017
Keywords
calcium channel; mEPSC; minis; mIPSC; spontaneous; VGCC
Categories
Funding
- National Institute of General Medical Sciences [R01 GM097433]
- U.S. Department of Veterans Affairs [BX002547]
- NIDCD [DC012938]
- National Heart, Lung, and Blood Institute [T32HL083808]
- NINDS [1F31NS083309]
- European Union
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At chemical synapses, voltage-activated calcium channels (VACCs) mediate Ca2+ influx to trigger action potential-evoked neurotransmitter release. However, the mechanisms by which Ca2+ regulates spontaneous transmission have not been fully determined. We have shown that VACCs are a major trigger of spontaneous release at neocortical inhibitory synapses but not at excitatory synapses, suggesting fundamental differences in spontaneous neurotransmission at GABAergic and glutamatergic synapses. Recently, VACC blockers were reported to reduce spontaneous release of glutamate and it was proposed that there was conservation of underlying mechanisms of neurotransmission at excitatory and inhibitory synapses. Furthermore, it was hypothesized that the different effects on excitatory and inhibitory synapses may have resulted from off-target actions of Cd2+, a nonselective VACC blocker, or other variations in experimental conditions. Here we report that in mouse neocortical neurons, selective and nonselective VACC blockers inhibit spontaneous release at inhibitory but not at excitatory terminals, and that this pattern is observed in culture and slice preparations as well as in synapses from acute slices of the auditory brainstem. The voltage dependence of Cd2+ block of VACCs accounts for the apparent lower potency of Cd2+ on spontaneous release of GABA than on VACC current amplitudes. Our findings indicate fundamental differences in the regulation of spontaneous release at inhibitory and excitatory synapses by stochastic VACC activity that extend beyond the cortex to the brainstem.
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