scholarly journals Calcium-independent but voltage-dependent secretion (CiVDS) mediates synaptic transmission in a mammalian central synapse

2021 ◽  
Author(s):  
Yuan Wang ◽  
Rong Huang ◽  
Zuying Chai ◽  
Changhe Wang ◽  
Xingyu Du ◽  
...  
Keyword(s):  
Action Potential ◽  
Synaptic Transmission ◽  
Sympathetic Neurons ◽  
Fusion Pore ◽  
Short Term ◽  
Vesicle Recycling ◽  
Dorsal Horn Neurons ◽  
Central Synapse ◽  
Voltage Dependent ◽  
Intracellular Ca

A central principle of synaptic transmission is that action potential induced presynaptic neurotransmitter release occurs exclusively via Ca2+ dependent secretion (CDS). T he discovery and mechanistic investigations of Ca2+ independent but voltage dependent secretion (CiVDS) have demonstrated that the action potential per se is sufficient to trigger neurotransmission in the somata of primary sensory and sympathetic neurons in mammals. One key question remains, however, whether CiVDS contributes to central synaptic transmission. Here we report, in the central transmission from presynaptic (dorsal root ganglion) to postsynaptic (spinal dorsal horn) neurons, (1) excitatory postsynaptic currents (EPSCs) are mediated by glutamate transmission through both CiVDS up to 87%) and CDS; (2) CiVDS EPSC s are in dependent of extracellular and intracellular Ca2+; (3) CiVDS is >100 times faster than CDS in vesicle recycling with much less short term depression; 4) the fusion machinery of CiVDS includes Cav2.2 (voltage sensor) and SNARE (fusion pore). Together, an essential component of activity induced EPSCs is mediated by CiVDS in a central synapse.

scholarly journals Activity and cytosolic Na+ regulates synaptic vesicle endocytosis

2019 ◽  
Author(s):  
Yun Zhu ◽  
Dainan Li ◽  
Hai Huang
Keyword(s):  
Synaptic Transmission ◽  
High Frequency ◽  
Synaptic Vesicles ◽  
Glutamate Uptake ◽  
High Frequencies ◽  
Vesicle Recycling ◽  
Two Photon ◽  
Readily Releasable Pool ◽  
Content Change ◽  
Intracellular Ca

ABSTRACTRetrieval of synaptic vesicles via endocytosis is essential for maintaining sustained synaptic transmission, especially for neurons that fire action potentials at high frequencies. However, how activity regulates synaptic vesicles recycling is largely unknown. Here we report that Na+ substantially accumulated in the mouse calyx of Held terminals during repetitive high-frequency spiking. Elevated presynaptic Na+ accelerated both slow and rapid forms of endocytosis and facilitated endocytosis overshoot but did not affect the readily releasable pool size, Ca2+ influx, or exocytosis. To examine whether this facilitation of endocytosis is related to the Na+-dependent vesicular content change, we dialyzed increasing concentrations of glutamate into the presynaptic cytosol or blocked the vesicular glutamate uptake with bafilomycin and found the rate of endocytosis was not affected by regulating the glutamate content in the presynaptic terminal. Endocytosis is critically dependent on intracellular Ca2+, and the activity of Na+/Ca2+ exchanger (NCX) may be altered when the Na+ gradient is changed. However, neither NCX blocker nor change of extracellular Na+ concentration affected the endocytosis rate. Moreover, two-photon Ca2+ imaging showed that presynaptic Na+ did not affect the action potential-evoked intracellular Ca2+ transient and decay. Therefore, we revealed a novel mechanism of cytosolic Na+ in accelerating vesicle endocytosis. During high-frequency synaptic transmission, when large amounts of synaptic vesicles are fused, Na+ accumulated in terminals, facilitated vesicle recycling and sustained reliable synaptic transmission.

Modulation of Transmitter Release by Action Potential Duration at the Hippocampal CA3-CA1 Synapse

1999 ◽  
Vol 81 (1) ◽  
pp. 288-298 ◽  
Author(s):  
Jing Qian ◽  
Peter Saggau
Keyword(s):  
Action Potential ◽  
Synaptic Transmission ◽  
Action Potential Duration ◽  
Transmitter Release ◽  
Neurotransmitter Release ◽  
Channel Blocker ◽  
Transmission Curve ◽  
Similar Reduction ◽  
Voltage Dependent ◽  
Hippocampal Ca3

Qian, Jing and Peter Saggau. Modulation of transmitter release by action potential duration at the hippocampal CA3-CA1 synapse. J. Neurophysiol. 81: 288–298, 1999. Presynaptic Ca2+ influx through voltage-dependent Ca2+ channels triggers neurotransmitter release. Action potential duration plays a determinant role in the dynamics of presynaptic Ca2+ influx. In this study, the presynaptic Ca2+ influx was optically measured with a low-affinity Ca2+ indicator (Furaptra). The effect of action potential duration on Ca2+ influx and transmitter release was investigated. The K+ channel blocker 4-aminopyridine (4-AP) was applied to broaden the action potential and thereby increase presynaptic Ca2+ influx. This increase of Ca2+ influx appeared to be much less effective in enhancing transmitter release than raising the extracellular Ca2+ concentration. 4-AP did not change the Ca2+ dependence of transmitter release but instead shifted the synaptic transmission curve toward larger total Ca2+ influx. These results suggest that changing the duration of Ca2+ influx is not equivalent to changing its amplitude in locally building up an effective Ca2+ concentration near the Ca2+ sensor of the release machinery. Furthermore, in the presence of 4-AP, the N-type Ca2+ channel blocker ωCgTx GVIA was much less effective in blocking transmitter release. This phenomenon was not simply due to a saturation of the release machinery by the increased overall Ca2+ influx because a similar reduction of Ca2+ influx by application of the nonspecific Ca2+ channel blocker Cd2+ resulted in much more inhibition of transmitter release. Rather, the different potencies of ω-CgTx GVIA and Cd2+ in inhibiting transmitter release suggest that the Ca2+ sensor is possibly located at a distance from a cluster of Ca2+ channels such that it is sensitive to the location of Ca2+ channels within the cluster.

Effects of Temperature on Calcium Transients and Ca2+-Dependent Afterhyperpolarizations in Neocortical Pyramidal Neurons

2005 ◽  
Vol 93 (4) ◽  
pp. 2012-2020 ◽  
Author(s):  
J. C. F. Lee ◽  
J. C. Callaway ◽  
R. C. Foehring
Keyword(s):  
Action Potential ◽  
Temperature Sensitivity ◽  
Pyramidal Neurons ◽  
Membrane Properties ◽  
Temperature Sensitive ◽  
Voltage Dependent ◽  
Intracellular Ca ◽  
Slow Rise ◽  
Kinetics Of ◽  
Neocortical Pyramidal Neurons

In neocortical pyramidal neurons, the medium (mAHP) and slow AHP (sAHP) have different relationships with intracellular [Ca2+]. To further explore these differences, we varied bath temperature and compared passive and active membrane properties and Ca2+ transients in response to a single action potential (AP) or trains of APs. We tested whether Ca2+-dependent events are more temperature sensitive than voltage-dependent ones, the slow rise time of the sAHP is limited by diffusion, and temperature sensitivity differs between the mAHP and sAHP. The onset and decay kinetics of the sAHP were very temperature sensitive (more so than diffusion). We found that the decay time course of Ca2+ transients was also very temperature sensitive. In contrast, the mAHP (amplitude, time to peak, and exponential decay) and sAHP peak amplitude were moderately sensitive to temperature. The amplitudes of intracellular Ca2+ transients evoked either by a single spike or a train of spikes showed modest temperature sensitivities. Pyramidal neuron input resistance was increased by cooling. With the exception of threshold, which remained unchanged between 22 and 35°C, action potential parameters (amplitude, half-width, maximum rates of rise and fall) were modestly affected by temperature. Collectively, these data suggest that temperature sensitivity was higher for the Ca2+-dependent sAHP than for voltage-dependent AP parameters or for the mAHP, diffusion of Ca2+ over distance cannot explain the slow rise of the sAHP in these cells, and the kinetics of the sAHP and mAHP are affected differently by temperature.

scholarly journals Role of Apamin-Sensitive KCa Channels for Reticulospinal Synaptic Transmission to Motoneuron and for the Afterhyperpolarization

2002 ◽  
Vol 88 (1) ◽  
pp. 289-299 ◽  
Author(s):  
Lorenzo Cangiano ◽  
Peter Wallén ◽  
Sten Grillner
Keyword(s):  
Synaptic Transmission ◽  
Nmda Receptors ◽  
Time Course ◽  
Frequency Regulation ◽  
Similar Time ◽  
Calcium Dependent ◽  
Before And After ◽  
Voltage Dependent ◽  
Intracellular Ca

Single motoneurons and pairs of a presynaptic reticulospinal axon and a postsynaptic motoneuron were recorded in the isolated lamprey spinal cord, to investigate the role of calcium-dependent K+ channels (KCa) during the afterhyperpolarization following the action potential (AHP), and glutamatergic synaptic transmission on the dendritic level. The AHP consists of a fast phase due to transient K+ channels (fAHP) and a slower phase lasting 100–200 ms (sAHP), being the main determinant of spike frequency regulation. We now present evidence that the sAHP has two components. The larger part, around 80%, is abolished by superfusion of Cd2+ (blocker of voltage-dependent Ca2+ channels), by intracellular injection of 1,2-bis-( 2-aminophenoxy)-ethane- N,N,N′,N′-tetraacetic acid (BAPTA; fast Ca2+ chelator), and by apamin (selective toxin for KCa channels of the SK subtype). While 80% of the sAHP is thus due to KCa channels, the remaining 20% is not mediated by Ca2+, either entering through voltage-dependent Ca2+ channels or released from intracellular Ca2+ stores. This Ca2+-independent sAHP component has a similar time course as the KCa portion and is not due to a Cl− conductance. It may be caused by Na+-activated K+ channels. Glutamatergic excitatory postsynaptic potentials (EPSPs) evoked by single reticulospinal axons give rise to a local Ca2+ increase in the postsynaptic dendrite, mediated in part by N-methyl-d-aspartate (NMDA) receptors. The Ca2+ levels remain elevated for several hundred milliseconds and could be expected to activate KCa channels. If so, this activation should cause a local conductance increase in the dendrite that would shunt EPSPs following the first EPSP in a spike train. We have tested this in reticulospinal/motoneuronal pairs, by stimulating the presynaptic axon with spike trains at different frequencies. We compared the first EPSP and the following EPSPs in the control and after blockade with apamin. No difference was observed in EPSP amplitude or shape before and after apamin, either in normal Ringer or in Mg2+-free Ringer removing the voltage-dependent block of NMDA receptors. In conclusion, the local Ca2+ entry during reticulospinal EPSPs does not cause an activation of KCa channels sufficient to affect the efficacy of synaptic transmission. Thus the integration of synaptic signals at the dendritic level in motoneurons appears simpler than would otherwise have been the case.

scholarly journals Short-Term Synaptic Depression and Recovery at the Mature Mammalian Endbulb of Held Synapse in Mice

2008 ◽  
Vol 100 (3) ◽  
pp. 1255-1264 ◽  
Author(s):  
Yong Wang ◽  
Paul B. Manis
Keyword(s):  
Synaptic Transmission ◽  
Auditory Nerve ◽  
Synaptic Depression ◽  
Nerve Fibers ◽  
Short Term ◽  
Endbulb Of Held ◽  
Intracellular Ca ◽  
Auditory Nerve Fibers ◽  
Spontaneous Firing Rate

The endbulb of Held synapses between the auditory nerve fibers (ANF) and cochlear nucleus bushy neurons convey fine temporal information embedded in the incoming acoustic signal. The dynamics of synaptic depression and recovery is a key in regulating synaptic transmission at the endbulb synapse. We studied short-term synaptic depression and recovery in mature (P22-38) CBA mice with stimulation rates that were comparable to sound-driven activities recorded in vivo. Synaptic depression in mature mice is less severe (∼40% at 100 Hz) than reported for immature animals and the depression is predominately due to depletion of releasable vesicles. Recovery from depression depends on the rate of activity and accumulation of intracellular Ca2+ at the presynaptic terminal. With a regular stimulus train at 100 Hz in 2 mM external [Ca2+], the recovery from depletion was slow (τslow, ∼2 s). In contrast, a fast (τfast, ∼25 ms), Ca2+-dependent recovery followed by a slower recovery (τslow, ∼2 s) was seen when stimulus rates or external [Ca2+] increased. In normal [Ca2+], recovery from a 100-Hz Poisson-like train is rapid, suggesting that Poisson-like trains produce a higher internal [Ca2+] than regular trains. Moreover, the fast recovery was slowed by approximately twofold in the presence of calmidazolium, a Ca2+/calmodulin inhibitor. Our results suggest that endbulb synapses from high spontaneous firing rate auditory nerve fibers normally operate in a depressed state. The accelerated synaptic recovery during high rates of activity is likely to ensure that reliable synaptic transmission can be achieved at the endbulb synapse.

Synaptic Current at the Rat Ganglionic Synapse and Its Interactions With the Neuronal Voltage-Dependent Currents

1998 ◽  
Vol 79 (2) ◽  
pp. 727-742 ◽  
Author(s):  
Oscar Sacchi ◽  
Maria Lisa Rossi ◽  
Rita Canella ◽  
Riccardo Fesce
Keyword(s):  
Steady State ◽  
Action Potential ◽  
Time Constant ◽  
Voltage Dependence ◽  
Sympathetic Neurons ◽  
Excitatory Postsynaptic Potential ◽  
Synaptic Current ◽  
Inactivation Curve ◽  
Voltage Dependent ◽  
Steady State Inactivation

Sacchi, Oscar, Maria Lisa Rossi, Rita Canella, and Riccardo Fesce. Synaptic current at the rat ganglionic synapse and its interactions with the neuronal voltage-dependent currents. J. Neurophysiol. 79: 727–742, 1998. The membrane current activated by fast nicotinic excitation of intact and mature rat sympathetic neurons was studied at 37°C, by using the two-microelectrode voltage-clamp technique. The excitatory postsynaptic current (EPSC) was modeled as the difference between two exponentials. A fast time constant (τ2; mean value 0.57 ms), which proves to be virtually voltage-independent, governs the current rise phase and a longer time constant (τ1; range 5.2–6.8 ms in 2 mM Ca2+) describes the current decay and shows a small negative voltage dependence. A mean peak synaptic conductance of 0.58 μS per neuron is measured after activation of the whole presynaptic input in 5 mM Ca2+ external solution (0.40 μS in 2 mM Ca2+). The miniature EPSCs also rise and decay with exponential time constants very similar to those of the compound EPSC recorded at the same voltage. A mean peak conductance of 4.04 nS is estimated for the unitary event. Deconvolution procedures were employed to decompose evoked macrocurrents. It is shown that under appropriate conditions the duration of the driving function describing quantal secretion can be reduced to <1 ms. The shape of the EPSC is accurately mimicked by a complete mathematical model of the sympathetic neuron incorporating the kinetic properties of five different voltage-dependent current types, which were characterized in a previous work. We show that I A channels are opened by depolarizing voltage steps or by synaptic potentials in the subthreshold voltage range, provided that the starting holding voltage is sufficiently negative to remove I A steady-state inactivation (less than −50 mV) and the voltage trajectories are sufficiently large to enter the I A activation range (greater than −65 mV). Under current-clamp conditions, this gives rise to an additional fast component in the early phase of membrane repolarization—in response to voltage pulses—and to a consistent distortion of the excitatory postsynaptic potential (EPSP) time course around its peak—in response to the synaptic signal. When the stimulation initiates an action potential, I A is shown to significantly increase the synaptic threshold conductance (up to a factor of 2 when I A is fully deinactivated), compared with that required when I A is omitted. The voltage dependence of this effect is consistent with the I A steady-state inactivation curve. It is concluded that I A, in addition to speeding up the spike repolarization process, also shunts the excitatory drive and delays or prevents the firing of the neuron action potential.

scholarly journals Activity-Dependent Potentiation of Synaptic Transmission From L30 Inhibitory Interneurons of Aplysia Depends on Residual Presynaptic Ca2+ But Not on Postsynaptic Ca2+

1997 ◽  
Vol 78 (4) ◽  
pp. 2061-2071 ◽  
Author(s):  
Thomas M. Fischer ◽  
Robert S. Zucker ◽  
Thomas J. Carew
Keyword(s):  
Synaptic Transmission ◽  
Time Course ◽  
Common Property ◽  
Free Calcium ◽  
Inhibitory Interneurons ◽  
Short Term ◽  
Intracellular Ca ◽  
Frequency Facilitation ◽  
Activity Dependent

Fischer, Thomas M., Robert S. Zucker, and Thomas J. Carew. Activity-dependent potentiation of synaptic transmission from L30 inhibitory interneurons of Aplysia depends on residual presynaptic Ca2+ but not on postsynaptic Ca2+. J. Neurophysiol. 78: 2061–2071, 1997. Activity-induced short-term synaptic enhancement (STE) is a common property of neurons, one that can endow neural circuits with the capacity for rapid and flexible information processing. Evidence from a variety of systems indicates that the expression of STE depends largely on the action of residual Ca2+, which enters the presynaptic terminal during activity. We have shown previously that a Ca2+-dependent STE in the inhibitory synapse between interneurons L30 and L29 in the abdominal ganglion of Aplysia californica has a functional role in regulating the gain of the siphon withdrawal circuit through facilitated recurrent inhibition onto the L29s. In the present paper, we further explore the role of Ca2+ in L30 STE by examining two basic issues: 1) What is the role of residual presynaptic Ca2+ in the maintenance of L30 STE? We examine this question by first inducing STE in the L30s then rapidly buffering presynaptic free calcium through the use of the photoactivated Ca2+ chelator diazo-4, which was preloaded into the L30 neurons. Three forms of STE in the L30s were examined: frequency facilitation (FF), augmentation (AUG), and posttetanic potentiation (PTP). In each case, the activation-induced enhancement of the L30 to L29 synapse was reduced to preactivation levels at the first test pulse following photolysis of diazo-4. 2) What is the role of postsynaptic Ca2+ in the induction of L30 STE? We examine whether there is a postsynaptic requirement of elevated Ca2+ for the induction of L30 STE by first injecting the calcium chelator bis-( o-aminophenoxy)- N,N,N′,N′-tetraacetic acid (BAPTA) into the postsynaptic cell L29 (at levels sufficient to block transmitter release from the L29s), to prevent any increase in postsynaptic intracellular Ca2+ that may occur during L30 (presynaptic) activation. We found that BAPTA injection did not effect either the induction or the time course of FF, AUG, or PTP in the L30s. Taken collectively, our data indicate that all forms of STE in the L30s depend on presynaptic free cytosolic Ca2+ for their maintenance but do not require the elevation of postsynaptic Ca2+ for their induction.

scholarly journals Ketamine Alters Functional Plasticity of Astroglia: An Implication for Antidepressant Effect

Life ◽  
2021 ◽  
Vol 11 (6) ◽  
pp. 573
Author(s):  
Matjaž Stenovec
Keyword(s):  
Molecular Mechanisms ◽  
Neuronal Firing ◽  
Fusion Pore ◽  
Antidepressant Effect ◽  
Intracellular Camp ◽  
Lateral Habenula ◽  
Vesicle Recycling ◽  
The Central Nervous System ◽  
Inward Rectifying Potassium Channel ◽  
Antidepressant Action

Ketamine, a non-competitive N–methyl–d–aspartate receptor (NMDAR) antagonist, exerts a rapid, potent and long-lasting antidepressant effect, although the cellular and molecular mechanisms of this action are yet to be clarified. In addition to targeting neuronal NMDARs fundamental for synaptic transmission, ketamine also affects the function of astrocytes, the key homeostatic cells of the central nervous system that contribute to pathophysiology of major depressive disorder. Here, I review studies revealing that (sub)anesthetic doses of ketamine elevate intracellular cAMP concentration ([cAMP]i) in astrocytes, attenuate stimulus-evoked astrocyte calcium signaling, which regulates exocytotic secretion of gliosignaling molecules, and stabilize the vesicle fusion pore in a narrow configuration, possibly hindering cargo discharge or vesicle recycling. Next, I discuss how ketamine affects astrocyte capacity to control extracellular K+ by reducing vesicular delivery of the inward rectifying potassium channel (Kir4.1) to the plasmalemma that reduces the surface density of Kir4.1. Modified astroglial K+ buffering impacts upon neuronal firing pattern as demonstrated in lateral habenula in a rat model of depression. Finally, I highlight the discovery that ketamine rapidly redistributes cholesterol in the astrocyte plasmalemma, which may alter the flux of cholesterol to neurons. This structural modification may further modulate a host of processes that synergistically contribute to ketamine’s rapid antidepressant action.

Sign in / Sign up

Export Citation Format

Share Document