Mechanisms underlying short‐term modulation of transmitter release by presynaptic depolarization

Presynaptic terminal depolarization modulates the efficacy of transmitter release. Residual Ca2+ remaining after presynaptic depolarization is thought to play a critical role in facilitation of transmitter release, but its downstream mechanism remains unclear. By making simultaneous pre‐ and postsynaptic recordings at the rodent calyx of Held synapse, we have investigated mechanisms involved in the facilitation and depression of postsynaptic currents induced by presynaptic depolarization. In voltage‐clamp experiments, cancellation of the Ca2+‐dependent presynaptic Ca2+ current (IpCa) facilitation revealed that this mechanism can account for 50% of postsynaptic current facilitation, irrespective of intraterminal EGTA concentrations. Intraterminal EGTA, loaded at 10 mm, failed to block postsynaptic current facilitation, but additional BAPTA at 1 mm abolished it. Potassium‐induced sustained depolarization of non‐dialysed presynaptic terminals caused a facilitation of postsynaptic currents, superimposed on a depression, with the latter resulting from reductions in presynaptic action potential amplitude and number of releasable vesicles. We conclude that presynaptic depolarization bidirectionally modulates transmitter release, and that the residual Ca2+ mechanism for synaptic facilitation operates in the immediate vicinity of voltage‐gated Ca2+ channels in the nerve terminal.

[1]  W. Regehr,et al.  Determinants of the Time Course of Facilitation at the Granule Cell to Purkinje Cell Synapse , 1996, The Journal of Neuroscience.

[2]  L. Trussell,et al.  Desensitization of AMPA receptors upon multiquantal neurotransmitter release , 1993, Neuron.

[3]  Tomoyuki Takahashi,et al.  Cellular/molecular Mechanisms Underlying Developmental Speeding in Ampa-epsc Decay Time at the Calyx of Held , 2022 .

[4]  J. Roder,et al.  Neuronal Calcium Sensor 1 and Activity-Dependent Facilitation of P/Q-Type Calcium Currents at Presynaptic Nerve Terminals , 2002, Science.

[5]  Maria Blatow,et al.  Ca2+ Buffer Saturation Underlies Paired Pulse Facilitation in Calbindin-D28k-Containing Terminals , 2003, Neuron.

[6]  C. Jahr,et al.  Dendritic NMDA Receptors Activate Axonal Calcium Channels , 2008, Neuron.

[7]  R. Zucker,et al.  Facilitation through buffer saturation: constraints on endogenous buffering properties. , 2004, Biophysical journal.

[8]  I. Forsythe,et al.  Pre‐ and postsynaptic glutamate receptors at a giant excitatory synapse in rat auditory brainstem slices. , 1995, The Journal of physiology.

[9]  Felix Felmy,et al.  Probing the Intracellular Calcium Sensitivity of Transmitter Release during Synaptic Facilitation , 2003, Neuron.

[10]  Y. Sahara,et al.  Quantal components of the excitatory postsynaptic currents at a rat central auditory synapse , 2001, The Journal of physiology.

[11]  B Sakmann,et al.  Effect of changes in action potential shape on calcium currents and transmitter release in a calyx-type synapse of the rat auditory brainstem. , 1999, Philosophical transactions of the Royal Society of London. Series B, Biological sciences.

[12]  T. Südhof,et al.  Proteolysis of SNAP-25 by types E and A botulinal neurotoxins. , 1994, The Journal of biological chemistry.

[13]  Takeshi Sakaba,et al.  Distinct Kinetic Changes in Neurotransmitter Release After SNARE Protein Cleavage , 2005, Science.

[14]  R. Bertram,et al.  Single-domain/bound calcium hypothesis of transmitter release and facilitation. , 1996, Journal of neurophysiology.

[15]  R. Schneggenburger,et al.  Presynaptic Ca2+ Requirements and Developmental Regulation of Posttetanic Potentiation at the Calyx of Held , 2005, The Journal of Neuroscience.

[16]  Christian Henneberger,et al.  Analog Modulation of Mossy Fiber Transmission Is Uncoupled from Changes in Presynaptic Ca2+ , 2008, The Journal of Neuroscience.

[17]  R. Werman,et al.  Correlation of Transmitter Release with Membrane Properties of the Presynaptic Fiber of the Squid Giant Synapse , 1967, The Journal of general physiology.

[18]  R. Schneggenburger,et al.  Developmental expression of the Ca2+‐binding proteins calretinin and parvalbumin at the calyx of Held of rats and mice , 2004, The European journal of neuroscience.

[19]  E. Friauf,et al.  Pre‐ and postnatal development of efferent connections of the cochlear nucleus in the rat , 1993, The Journal of comparative neurology.

[20]  R. Schneggenburger,et al.  A limited contribution of Ca2+ current facilitation to paired‐pulse facilitation of transmitter release at the rat calyx of Held , 2008, The Journal of physiology.

[21]  Margaret Barnes-Davies,et al.  Inactivation of Presynaptic Calcium Current Contributes to Synaptic Depression at a Fast Central Synapse , 1998, Neuron.

[22]  E. Kandel,et al.  Presynaptic membrane potential affects transmitter release in an identified neuron in Aplysia by modulating the Ca2+ and K+ currents. , 1980, Proceedings of the National Academy of Sciences of the United States of America.

[23]  Yukihiro Nakamura,et al.  Distinct Roles of Kv1 and Kv3 Potassium Channels at the Calyx of Held Presynaptic Terminal , 2003, The Journal of Neuroscience.

[24]  B. Katz,et al.  The role of calcium in neuromuscular facilitation , 1968, The Journal of physiology.

[25]  B. Katz,et al.  A study of synaptic transmission in the absence of nerve impulses , 1967, The Journal of physiology.

[26]  Takeshi Nakamura,et al.  Developmental changes in calcium/calmodulin‐dependent inactivation of calcium currents at the rat calyx of Held , 2008, The Journal of physiology.

[27]  I. Forsythe,et al.  Functional Compensation of P/Q by N-Type Channels Blocks Short-Term Plasticity at the Calyx of Held Presynaptic Terminal , 2004, The Journal of Neuroscience.

[28]  W. Regehr,et al.  Short-term synaptic plasticity. , 2002, Annual review of physiology.

[29]  B. Gähwiler,et al.  Ca2+ or Sr2+ Partially Rescues Synaptic Transmission in Hippocampal Cultures Treated with Botulinum Toxin A and C, But Not Tetanus Toxin , 1997, The Journal of Neuroscience.

[30]  Kahori Yamada,et al.  Benzothiadiazides inhibit rapid glutamate receptor desensitization and enhance glutamatergic synaptic currents , 1993, The Journal of neuroscience : the official journal of the Society for Neuroscience.

[31]  S. Hagiwara,et al.  A study on the mechanism of impulse transmission across the giant synapse of the squid , 1958, The Journal of physiology.

[32]  L. Trussell,et al.  Presynaptic glycine receptors enhance transmitter release at a mammalian central synapse , 2001, Nature.

[33]  B. Katz,et al.  Changes in end‐plate activity produced by pre‐synaptic polarization , 1954, The Journal of physiology.

[34]  W. Yamada,et al.  Time course of transmitter release calculated from simulations of a calcium diffusion model. , 1992, Biophysical journal.

[35]  R S Zucker,et al.  Effects of mobile buffers on facilitation: experimental and computational studies. , 2000, Biophysical journal.

[36]  Dirk Dietrich,et al.  Endogenous Ca2+ Buffer Concentration and Ca2+ Microdomains in Hippocampal Neurons , 2005, The Journal of Neuroscience.

[37]  M. Naraghi,et al.  T-jump study of calcium binding kinetics of calcium chelators. , 1997, Cell calcium.

[38]  B Sakmann,et al.  Calcium current during a single action potential in a large presynaptic terminal of the rat brainstem , 1998, The Journal of physiology.

[39]  E. Neher,et al.  Linearized Buffered Ca2+ Diffusion in Microdomains and Its Implications for Calculation of [Ca2+] at the Mouth of a Calcium Channel , 1997, The Journal of Neuroscience.

[40]  I. Forsythe,et al.  Facilitation of the presynaptic calcium current at an auditory synapse in rat brainstem , 1998, The Journal of physiology.

[41]  E. Neher,et al.  Quantitative Relationship between Transmitter Release and Calcium Current at the Calyx of Held Synapse , 2001, The Journal of Neuroscience.

[42]  Lu-Yang Wang,et al.  Developmental Transformation of the Release Modality at the Calyx of Held Synapse , 2005, The Journal of Neuroscience.

[43]  B. Sakmann,et al.  Facilitation of presynaptic calcium currents in the rat brainstem , 1998, The Journal of physiology.

[44]  D. T. Yue,et al.  Calmodulin bifurcates the local Ca2+ signal that modulates P/Q-type Ca2+ channels , 2001, Nature.

[45]  Anatol C. Kreitzer,et al.  Interplay between Facilitation, Depression, and Residual Calcium at Three Presynaptic Terminals , 2000, The Journal of Neuroscience.

[46]  M. Tsodyks,et al.  Synaptic Theory of Working Memory , 2008, Science.

[47]  Tomoyuki Takahashi,et al.  Involvement of AMPA receptor desensitization in short‐term synaptic depression at the calyx of Held in developing rats , 2008, The Journal of physiology.

[48]  R. Schneggenburger,et al.  Parvalbumin Is a Mobile Presynaptic Ca2+ Buffer in the Calyx of Held that Accelerates the Decay of Ca2+ and Short-Term Facilitation , 2007, The Journal of Neuroscience.

[49]  B. Sakmann,et al.  Calcium influx and transmitter release in a fast CNS synapse , 1996, Nature.

[50]  Lu-Yang Wang,et al.  Amplitude and Kinetics of Action Potential-Evoked Ca2+ Current and Its Efficacy in Triggering Transmitter Release at the Developing Calyx of Held Synapse , 2006, The Journal of Neuroscience.

[51]  Gautam B. Awatramani,et al.  Modulation of Transmitter Release by Presynaptic Resting Potential and Background Calcium Levels , 2005, Neuron.

[52]  S G Waxman,et al.  Modulation of parallel fiber excitability by postsynaptically mediated changes in extracellular potassium. , 1981, Science.

[53]  D. Pinkel,et al.  Supporting Online Material Materials and Methods Figs. S1 and S2 Tables S1 and S2 References Combined Analog and Action Potential Coding in Hippocampal Mossy Fibers , 2022 .

[54]  W. Singer,et al.  Presynaptic depolarization and extracellular potassium in the cat lateral geniculate nucleus. , 1973, Brain research.

[55]  Presynaptic inhibition produced by an identified presynaptic inhibitory neuron. II. Presynaptic conductance changes caused by histamine. , 1986, Journal of neurophysiology.

[56]  R. Zucker,et al.  Role of presynaptic calcium ions and channels in synaptic facilitation and depression at the squid giant synapse. , 1982, The Journal of physiology.

[57]  T. Ishikawa,et al.  Presynaptic N‐type and P/Q‐type Ca2+ channels mediating synaptic transmission at the calyx of Held of mice , 2005, The Journal of physiology.

[58]  Y. Takai,et al.  Presynaptic Mechanism for Phorbol Ester-Induced Synaptic Potentiation , 1999, The Journal of Neuroscience.

[59]  Leonard K. Kaczmarek,et al.  High-frequency firing helps replenish the readily releasable pool of synaptic vesicles , 1998, Nature.