Spike Activity Regulates Vesicle Filling at a Glutamatergic Synapse

Overview

Journal J Neurosci

Specialty Neurology

Date 2020 May 21

PMID 32430294

Citations 7

Authors

Dainan Li

Yun Zhu

Hai Huang

Affiliations

Soon will be listed here.

Abstract

Synaptic vesicles need to be recycled and refilled rapidly to maintain high-frequency synaptic transmission. However, little is known about the control of neurotransmitter transport into synaptic vesicles, which determines the contents of synaptic vesicles and the strength of synaptic transmission. Here, we report that Na substantially accumulated in the calyx of Held terminals of juvenile mice of either sex during high-frequency spiking. The activity-induced elevation of cytosolic Na activated vesicular Na/H exchanger, facilitated glutamate loading into synaptic vesicles, and increased quantal size of asynchronous released vesicles but did not affect the vesicle pool size or release probability. Consequently, presynaptic Na increased the EPSCs and was required to maintain the reliable high-frequency signal transmission from the presynaptic calyces to the postsynaptic medial nucleus of the trapezoid body (MNTB) neurons. Blocking Na/H exchange activity decreased the postsynaptic current and caused failures in postsynaptic firing. Therefore, during high-frequency synaptic transmission, when large amounts of glutamate are released, Na accumulated in the terminals, activated vesicular Na/H exchanger, and regulated glutamate loading as a function of the level of vesicle release. Auditory information is encoded by action potentials (APs) phase-locked to sound frequency at high rates. A large number of synaptic vesicles are released during high-frequency synaptic transmission; accordingly, synaptic vesicles need to be recycled and refilled rapidly. We have recently found that a Na/H exchanger expressed on synaptic vesicles promotes vesicle filling with glutamate. Here, we showed that when a large number of synaptic vesicles are released during high-frequency synaptic transmission, Na accumulates in axon terminals and facilitates glutamate uptake into synaptic vesicles. Na thus accelerates vesicle replenishment and sustains reliable synaptic transmission.

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References

McCormick D, Connors B, Lighthall J, Prince D . Comparative electrophysiology of pyramidal and sparsely spiny stellate neurons of the neocortex. J Neurophysiol. 1985; 54(4):782-806. DOI: 10.1152/jn.1985.54.4.782. View

Meyer J, Untiet V, Fahlke C, Gensch T, Rose C . Quantitative determination of cellular [Na] by fluorescence lifetime imaging with CoroNaGreen. J Gen Physiol. 2019; 151(11):1319-1331. PMC: 6829561. DOI: 10.1085/jgp.201912404. View

Maycox P, Deckwerth T, Hell J, Jahn R . Glutamate uptake by brain synaptic vesicles. Energy dependence of transport and functional reconstitution in proteoliposomes. J Biol Chem. 1988; 263(30):15423-8. View

Hu H, Jonas P . A supercritical density of Na(+) channels ensures fast signaling in GABAergic interneuron axons. Nat Neurosci. 2014; 17(5):686-93. PMC: 4286295. DOI: 10.1038/nn.3678. View

Kushmerick C, Renden R, von Gersdorff H . Physiological temperatures reduce the rate of vesicle pool depletion and short-term depression via an acceleration of vesicle recruitment. J Neurosci. 2006; 26(5):1366-77. PMC: 6675486. DOI: 10.1523/JNEUROSCI.3889-05.2006. View

Ishikawa T, Sahara Y, Takahashi T . A single packet of transmitter does not saturate postsynaptic glutamate receptors. Neuron. 2002; 34(4):613-21. DOI: 10.1016/s0896-6273(02)00692-x. View

Mayer M, Armstrong N . Structure and function of glutamate receptor ion channels. Annu Rev Physiol. 2004; 66:161-81. DOI: 10.1146/annurev.physiol.66.050802.084104. View

Wang L, Kaczmarek L . High-frequency firing helps replenish the readily releasable pool of synaptic vesicles. Nature. 1998; 394(6691):384-8. DOI: 10.1038/28645. View

Conti R, Lisman J . The high variance of AMPA receptor- and NMDA receptor-mediated responses at single hippocampal synapses: evidence for multiquantal release. Proc Natl Acad Sci U S A. 2003; 100(8):4885-90. PMC: 404698. DOI: 10.1073/pnas.0630290100. View

10.

Ford M, Alexandrova O, Cossell L, Stange-Marten A, Sinclair J, Kopp-Scheinpflug C . Tuning of Ranvier node and internode properties in myelinated axons to adjust action potential timing. Nat Commun. 2015; 6:8073. PMC: 4560803. DOI: 10.1038/ncomms9073. View

11.

Bender K, Ford C, Trussell L . Dopaminergic modulation of axon initial segment calcium channels regulates action potential initiation. Neuron. 2010; 68(3):500-11. PMC: 2987607. DOI: 10.1016/j.neuron.2010.09.026. View

12.

Chanaday N, Kavalali E . Presynaptic origins of distinct modes of neurotransmitter release. Curr Opin Neurobiol. 2018; 51:119-126. PMC: 6066415. DOI: 10.1016/j.conb.2018.03.005. View

13.

Tabb J, Kish P, Van Dyke R, Ueda T . Glutamate transport into synaptic vesicles. Roles of membrane potential, pH gradient, and intravesicular pH. J Biol Chem. 1992; 267(22):15412-8. View

14.

Goh G, Huang H, Ullman J, Borre L, Hnasko T, Trussell L . Presynaptic regulation of quantal size: K+/H+ exchange stimulates vesicular glutamate transport. Nat Neurosci. 2011; 14(10):1285-92. PMC: 3183113. DOI: 10.1038/nn.2898. View

15.

Kim J, Sizov I, Dobretsov M, von Gersdorff H . Presynaptic Ca2+ buffers control the strength of a fast post-tetanic hyperpolarization mediated by the alpha3 Na(+)/K(+)-ATPase. Nat Neurosci. 2007; 10(2):196-205. DOI: 10.1038/nn1839. View

16.

Esteban J, Shi S, Wilson C, Nuriya M, Huganir R, Malinow R . PKA phosphorylation of AMPA receptor subunits controls synaptic trafficking underlying plasticity. Nat Neurosci. 2003; 6(2):136-43. DOI: 10.1038/nn997. View

17.

Gronborg M, Pavlos N, Brunk I, Chua J, Munster-Wandowski A, Riedel D . Quantitative comparison of glutamatergic and GABAergic synaptic vesicles unveils selectivity for few proteins including MAL2, a novel synaptic vesicle protein. J Neurosci. 2010; 30(1):2-12. PMC: 6632534. DOI: 10.1523/JNEUROSCI.4074-09.2010. View

18.

Klingauf J, Kavalali E, Tsien R . Kinetics and regulation of fast endocytosis at hippocampal synapses. Nature. 1998; 394(6693):581-5. DOI: 10.1038/29079. View

19.

Sun J, Wu L . Fast kinetics of exocytosis revealed by simultaneous measurements of presynaptic capacitance and postsynaptic currents at a central synapse. Neuron. 2001; 30(1):171-82. DOI: 10.1016/s0896-6273(01)00271-9. View

20.

Huang H, Trussell L . Presynaptic HCN channels regulate vesicular glutamate transport. Neuron. 2014; 84(2):340-6. PMC: 4254032. DOI: 10.1016/j.neuron.2014.08.046. View