scholarly journals Using ephaptic coupling to estimate the synaptic cleft resistivity of the calyx of Held synapse

2021 ◽  
Vol 17 (10) ◽  
pp. e1009527
Author(s):  
Martijn C. Sierksma ◽  
J. Gerard G. Borst
Keyword(s):  
Action Potential ◽  
Synaptic Cleft ◽  
Calcium Currents ◽  
Fourth Power ◽  
Scale Invariant ◽  
Calyx Of Held ◽  
Presynaptic Action ◽  
Medial Nucleus ◽  
Presynaptic Calcium ◽  
Ephaptic Coupling

At synapses, the pre- and postsynaptic cells get so close that currents entering the cleft do not flow exclusively along its conductance, gcl. A prominent example is found in the calyx of Held synapse in the medial nucleus of the trapezoid body (MNTB), where the presynaptic action potential can be recorded in the postsynaptic cell in the form of a prespike. Here, we developed a theoretical framework for ephaptic coupling via the synaptic cleft, and we tested its predictions using the MNTB prespike recorded in voltage-clamp. The shape of the prespike is predicted to resemble either the first or the second derivative of the inverted presynaptic action potential if cleft currents dissipate either mostly capacitively or resistively, respectively. We found that the resistive dissipation scenario provided a better description of the prespike shape. Its size is predicted to scale with the fourth power of the radius of the synapse, explaining why intracellularly recorded prespikes are uncommon in the central nervous system. We show that presynaptic calcium currents also contribute to the prespike shape. This calcium prespike resembled the first derivative of the inverted calcium current, again as predicted by the resistive dissipation scenario. Using this calcium prespike, we obtained an estimate for gcl of ~1 μS. We demonstrate that, for a circular synapse geometry, such as in conventional boutons or the immature calyx of Held, gcl is scale-invariant and only defined by extracellular resistivity, which was ~75 Ωcm, and by cleft height. During development the calyx of Held develops fenestrations. We show that these fenestrations effectively minimize the cleft potentials generated by the adult action potential, which might otherwise interfere with calcium channel opening. We thus provide a quantitative account of the dissipation of currents by the synaptic cleft, which can be readily extrapolated to conventional, bouton-like synapses.

scholarly journals Using ephaptic coupling to estimate the synaptic cleft resistivity of the calyx of Held synapse.

2021 ◽  
Author(s):  
Martijn C Sierksma ◽  
J. Gerard G. Borst
Keyword(s):  
Action Potential ◽  
Time Derivative ◽  
Synaptic Cleft ◽  
Calcium Currents ◽  
Fourth Power ◽  
Calyx Of Held ◽  
Presynaptic Action ◽  
Postsynaptic Cell ◽  
Presynaptic Calcium ◽  
Ephaptic Coupling

At synapses, the pre- and postsynaptic cell get so close that currents entering the cleft do not flow exclusively along its conductance, gcl. A prominent example is found in the calyx of Held synapse in the medial nucleus of the trapezoid body, where the presynaptic action potential can be recorded in the postsynaptic cell in the form of a prespike. Here, we developed a theoretical framework for ephaptic coupling via the synaptic cleft. We found that the capacitive component of the prespike recorded in voltage clamp is closely approximated by the second time derivative of the presynaptic action potential. Its size scales with the fourth power of the radius of the synapse, explaining why intracellularly recorded prespikes are uncommon in the CNS. We show that presynaptic calcium currents can contribute to the prespike and that their contribution is closely approximated by the scaled first derivative of these currents. We confirmed these predictions in juvenile rat brainstem slices, and used the presynaptic calcium currents to obtain an estimate for gcl of ~1 μS. We demonstrate that for a typical synapse geometry, gcl is scale-invariant and only defined by extracellular resistivity, which was ~75 Ωcm, and by cleft height. During development the calyx of Held develops fenestrations. These fenestrations effectively minimize the cleft potentials generated by the adult action potential, which would otherwise interfere with calcium channel opening. We thus provide a quantitative account of the dissipation of currents by the synaptic cleft, which can be readily extrapolated to conventional, bouton-like synapses.

scholarly journals Effect of changes in action potential shape on calcium currents and transmitter release in a calyx–type synapse of the rat auditory brainstem

1999 ◽  
Vol 354 (1381) ◽  
pp. 347-355 ◽  
Author(s):  
J. G. G. Borst ◽  
B. Sakmann
Keyword(s):  
Action Potential ◽  
Transmitter Release ◽  
Time Course ◽  
Calcium Influx ◽  
Auditory Brainstem ◽  
Calcium Currents ◽  
Medial Nucleus ◽  
Potential Shape ◽  
Presynaptic Calcium ◽  
Rat Brainstem

We studied the relation between the size of presynaptic calcium influx and transmitter release by making simultaneous voltage clamp recordings from presynaptic terminals, the calyces of Held and postsynaptic cells, the principal cells of the medial nucleus of the trapezoid body, in slices of the rat brainstem. Calyces were voltage clamped with different action potential waveforms. The amplitude of the excitatory postsynaptic currents depended supralinearly on the size of the calcium influx, in the absence of changes in the time–course of the calcium influx. This result is in agreement with the view thact at this synapse most vesicles are released by the combined action of multiple calcium channels.

An Increase in Calcium Influx Contributes to Post-Tetanic Potentiation at the Rat Calyx of Held Synapse

2006 ◽  
Vol 96 (6) ◽  
pp. 2868-2876 ◽  
Author(s):  
Ron L. P. Habets ◽  
J. Gerard G. Borst
Keyword(s):  
Action Potential ◽  
Calcium Influx ◽  
Calcium Currents ◽  
Calyx Of Held ◽  
Calcium Buffer ◽  
Whole Cell Patch Clamp ◽  
Auditory Brain Stem ◽  
Post Tetanic Potentiation ◽  
Presynaptic Calcium ◽  
Fluorescence Transients

We studied the contribution of a change in presynaptic calcium influx to posttetanic potentiation (PTP) in the calyx of Held synapse, an axosomatic synapse in the auditory brain stem. We made whole cell patch-clamp recordings of a principal cell after loading of the presynaptic terminal with a calcium dye. After induction of PTP by a high-frequency train of afferent stimuli, the Fluo-4 fluorescence transients evoked by an action potential became on average 15 ± 4% larger ( n = 7). Model predictions did not match the fluorescence transients evoked by trains of brief calcium currents unless the endogenous calcium buffer had low affinity for calcium, making a contribution of saturation of the endogenous buffer to the synaptic potentiation we observed in the present experiments less likely. Our data therefore suggest that the increase of release probability during PTP at the calyx of Held synapse is largely explained by an increase in the calcium influx per action potential.

scholarly journals Gain of Function in FHM-1 Cav2.1 Knock-In Mice Is Related to the Shape of the Action Potential

2010 ◽  
Vol 104 (1) ◽  
pp. 291-299 ◽  
Author(s):  
Carlota González Inchauspe ◽  
Francisco J. Urbano ◽  
Mariano N. Di Guilmi ◽  
Ian D. Forsythe ◽  
Michel D. Ferrari ◽  
...  
Keyword(s):  
Pyramidal Cells ◽  
Familial Hemiplegic Migraine ◽  
Cortical Layer ◽  
Calcium Currents ◽  
Inhibitory Neurons ◽  
Missense Mutations ◽  
Calyx Of Held ◽  
Gain Of Function ◽  
Layer 2 ◽  
Presynaptic Calcium

Familial hemiplegic migraine type-1 FHM-1 is caused by missense mutations in the CACNA1A gene that encodes the α1A pore-forming subunit of CaV2.1 Ca2+ channels. We used knock-in (KI) transgenic mice harboring the pathogenic FHM-1 mutation R192Q to study neurotransmission at the calyx of Held synapse and cortical layer 2/3 pyramidal cells (PCs). Using whole cell patch-clamp recordings in brain stem slices, we confirmed that KI CaV2.1 Ca2+ channels activated at more hyperpolarizing potentials. However, calyceal presynaptic calcium currents ( IpCa) evoked by presynaptic action potentials (APs) were similar in amplitude, kinetic parameters, and neurotransmitter release. CaV2.1 Ca2+ channels in cortical layer 2/3 PCs from KI mice also showed a negative shift in their activation voltage. PCs had APs with longer durations and smaller amplitudes than the calyx of Held. AP-evoked Ca2+ currents ( ICa) from PCs were larger in KI compared with wild-type (WT) mice. In contrast, when ICawas evoked in PCs by calyx of Held AP waveforms, we observed no amplitude differences between WT and KI mice. In the same way, Ca2+ currents evoked at the presynaptic terminals ( IpCa)of the calyx of Held by the AP waveforms of the PCs had larger amplitudes in R192Q KI mice that in WT. These results suggest that longer time courses of pyramidal APs were a key factor for the expression of a synaptic gain of function in the KI mice. In addition, our results indicate that consequences of FHM-1 mutations might vary according to the shape of APs in charge of triggering synaptic transmission (neurons in the calyx of Held vs. excitatory/inhibitory neurons in the cortex), adding to the complexity of the pathophysiology of migraine.

Spike Transmission Delay at the Calyx of Held In Vivo: Rate Dependence, Phenomenological Modeling, and Relevance for Sound Localization

2009 ◽  
Vol 102 (2) ◽  
pp. 1206-1217 ◽  
Author(s):  
Sandra Tolnai ◽  
Bernhard Englitz ◽  
Jonathan Scholbach ◽  
Jürgen Jost ◽  
Rudolf Rübsamen
Keyword(s):  
Action Potential ◽  
Sound Localization ◽  
Temporal Dynamics ◽  
Transmission Delay ◽  
Mongolian Gerbils ◽  
Calyx Of Held ◽  
Time Constants ◽  
Medial Nucleus ◽  
Central Synapses

Transmission at central synapses exhibits rapid changes in response amplitude under different patterns of stimulation. Whether the delay associated with the transmission of action potentials is similarly modifiable is important for temporally precise computations. We address this question at the calyx of Held of the medial nucleus of the trapezoid body (MNTB) in Mongolian gerbils in vivo using extracellular recordings. Here the pre- and postsynaptic activity can be observed simultaneously, allowing the definition of an action potential transmission delay (ATD) from the pre- to the postsynaptic side. We find the ATD to increase as a function of spike rate (10–40%). The temporal dynamics of the ATD increase exhibit an exponential shape with activity-dependent time constants (∼15–25 ms). Recovery dynamics of ATD were mono- (20–70 ms) or biexponential with fast (3–20 ms) and slow time constants (50–500 ms). Using a phenomenological model to capture ATD dynamics, we estimated ΔATD = 5–30 μs per transmitted action potential. Using vocalizations and cage noise stimuli, we confirm that substantial changes in ATD occur in natural situations. Because the ATD changes cover the behaviorally relevant range of interaural time differences in gerbils, these results could provide constraints for models of sound localization.

Perinatal Development of the Medial Nucleus of the Trapezoid Body

2018 ◽  
pp. 244-272
Author(s):  
Shobhana Sivaramakrishnan ◽  
Ashley Brandebura ◽  
Paul Holcomb ◽  
Daniel Heller ◽  
Douglas Kolson ◽  
...  
Keyword(s):  
Axon Guidance ◽  
Neural Circuit ◽  
Neural Cells ◽  
Calyx Of Held ◽  
Medial Nucleus ◽  
Target Neuron ◽  
Circuit Formation ◽  
Key Events ◽  
The Brain ◽  
Trapezoid Body

Bushy cells (BC) of the cochlear nucleus mono-innervate their target neuron, the principal cell of the medial nucleus of the trapezoid body (MNTB), via the calyx of Held (CH) terminal, which is a typically mammalian structure and perhaps the largest nerve terminal in the brain. CH:MNTB innervation has become an attractive model to study neural circuit formation because it forms quickly, passing through stages of competition in mice within 2–4 days. BCs innervate MNTB neurons by E17, but CHs do not begin to grow for another five days (P3). Progress has been made to identify molecular factors for axon guidance, CH growth, and physiological maturation of synaptic partners, but important details remain to be discovered. We summarize key events in CH formation and highlight unresolved issues in molecular and physiological signaling, roles for non-neural cells, and the nature of competition during the first postnatal week.

Action potential propagation through embryonic dorsal root ganglion cells in culture. II. Decrease of conduction reliability during repetitive stimulation

1994 ◽  
Vol 72 (2) ◽  
pp. 634-643 ◽  
Author(s):  
C. Luscher ◽  
J. Streit ◽  
P. Lipp ◽  
H. R. Luscher
Keyword(s):  
Dorsal Root Ganglion ◽  
Action Potential ◽  
Intracellular Calcium ◽  
Dorsal Root ◽  
Channel Blocker ◽  
Extracellular Calcium ◽  
Repetitive Stimulation ◽  
Calcium Currents ◽  
Double Pulse ◽  
Extracellular Potassium

1. The reliability of the propagation of action potentials (AP) through dorsal root ganglion (DRG) cells in embryonic slice cultures was investigated during repetitive stimulation at 1–20 Hz. Membrane potentials of DRG cells were recorded intracellularly while the axons were stimulated by an extracellular electrode. 2. In analogy to the double-pulse experiments reported previously, either one or two types of propagation failures were recorded during repetitive stimulation, depending on the cell morphology. In contrast to the double-pulse experiments, the failures appeared at longer interpulse intervals and usually only after several tens of stimuli with reliable propagation. 3. In the period with reliable propagation before the failures, a decrease in the conduction velocity and in the amplitude of the afterhyperpolarization (AHP), an increase in the total membrane conductance, and the disappearance of the action potential “shoulder” were observed. 4. The reliability of conduction during repetitive stimulation was improved by lowering the extracellular calcium concentration or by replacing the extracellular calcium by strontium. The reliability of conduction decreased by the application of cadmium, a calcium channel blocker, 4-amino pyridine, a fast potassium channel blocker, or apamin or muscarine, the blockers of calcium-dependent potassium channels. The reliability of conduction was not effected by blocking the sodium potassium pump with ouabain or by replacing extracellular sodium with lithium. 5. In the period with reliable propagation cadmium, apamin, and muscarine reduced the amplitude of the AHP. The shoulder of the action potential was more pronounced and not sensitive to repetitive stimulation when extracellular calcium was replaced by strontium. It disappeared when cadmium was applied. 6. In DRG somata changes of the intracellular Ca2+ concentration were monitored by measuring the fluorescence of the Ca2+ indicator Fluo-3 with a laser-scanning confocal microscope. During repetitive stimulation, an accumulation of intracellular calcium occurred that recovered very slowly (tens of seconds) after the AP trains. 7. Computer model simulations performed in analogy to the experimental protocols produced conduction failures during repetitive stimulation only when the calcium currents during the APs were reduced. 8. From these findings it is concluded that conduction failures during repetitive stimulation are dependent on an accumulation of intracellular calcium leading to an inactivation of calcium currents, combined with small contributions of an accumulation of extracellular potassium and a summation of slow potassium conductances.

scholarly journals Homeostatic synaptic depression is achieved through a regulated decrease in presynaptic calcium channel abundance

eLife ◽  
2015 ◽  
Vol 4 ◽  
Author(s):  
Michael A Gaviño ◽  
Kevin J Ford ◽  
Santiago Archila ◽  
Graeme W Davis
Keyword(s):  
Synaptic Plasticity ◽  
Neuromuscular Junction ◽  
Action Potential ◽  
Calcium Channel ◽  
Neurotransmitter Release ◽  
Calcium Influx ◽  
Homeostatic Synaptic Plasticity ◽  
Action Potential Waveform ◽  
Presynaptic Calcium ◽  
Potential Waveform

Homeostatic signaling stabilizes synaptic transmission at the neuromuscular junction (NMJ) of Drosophila, mice, and human. It is believed that homeostatic signaling at the NMJ is bi-directional and considerable progress has been made identifying mechanisms underlying the homeostatic potentiation of neurotransmitter release. However, very little is understood mechanistically about the opposing process, homeostatic depression, and how bi-directional plasticity is achieved. Here, we show that homeostatic potentiation and depression can be simultaneously induced, demonstrating true bi-directional plasticity. Next, we show that mutations that block homeostatic potentiation do not alter homeostatic depression, demonstrating that these are genetically separable processes. Finally, we show that homeostatic depression is achieved by decreased presynaptic calcium channel abundance and calcium influx, changes that are independent of the presynaptic action potential waveform. Thus, we identify a novel mechanism of homeostatic synaptic plasticity and propose a model that can account for the observed bi-directional, homeostatic control of presynaptic neurotransmitter release.

scholarly journals Calcium-Dependent Action Potentials in the Second-Order Neurones of Cockroach Ocelli

1987 ◽  
Vol 130 (1) ◽  
pp. 259-274
Author(s):  
MAKOTO MIZUNAMI ◽  
SHIGEKI YAMASHITA ◽  
HIDEKI TATEDA
Keyword(s):  
Action Potential ◽  
Action Potentials ◽  
Periplaneta Americana ◽  
Fold Increase ◽  
Second Order ◽  
Calcium Currents ◽  
Light Responses ◽  
Calcium Dependent ◽  
Major Carrier ◽  
Visual Neurones

The ionic basis of the action potential in the large second-order neurones (L-neurones) of the ocellus of the cockroach, Periplaneta americana, was studied. L-neurones generated action potentials, usually once, at the off-set of hyperpolarizing light responses, or at the termination of hyperpolarizing current stimuli. The action potential was blocked by replacing saline Ca2+ with Mg2+ but maintained when Ba2+ was substituted. A block was produced by 2 mmoll l−1 Cd2+ or 20 mmol l−l Co2+. The peak amplitude of the action potential increased by 26 mV for a 10-fold increase in external Ca2+ concentration, at concentrations below 1.8 mmol l−1. The action potential was not affected by sodium-free saline or by 3×10−6mol l−1 tetrodotoxin (TTX). These observations suggest that calcium ions are the major carrier for the inward current of the action potential. This finding supports the suggestion that the off-set responses of hyperpolarizing visual neurones of both vertebrates and invertebrates have a common ionic mechanism, including voltage-sensitive calcium currents.

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