CAST/ELKS Proteins Control Voltage-Gated Ca2+ Channel Density and Synaptic Release Probability at a Mammalian Central Synapse

In contrast to mammalian brain, which exhibits rapid degeneration during anoxia, the brains of certain species of turtles show an extraordinary capacity to survive prolonged anoxia. The decrease in energy expenditure shown by the anoxic turtle brain is likely to be a key factor for anoxic survival. The "channel arrest" hypothesis proposes that ion channels, which regulate brain electrical activity in normoxia, may be altered during anoxia in the turtle brain as a mechanism to spare energy. Goals of present research were to test this hypothesis and to determine whether down-regulation of sodium channels is a possible explanation for spike threshold shifts seen during anoxia in isolated turtle cerebellum. We report here that anoxia induced a significant (42%) decline in voltage-gated sodium channel density as determined by studies of the binding of a sodium channel ligand, [3H]brevetoxin. This study demonstrates that sodium channel densities in brain may be regulated by tissue oxygenation or by physiological events associated with anoxia. Moreover, it also suggests that downregulation of sodium channels may be a basis for changes in action potential thresholds, the electrical depression and energy conservation that provide the unique anoxic tolerance of turtle brain.

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RIM1 and RIM2 redundantly determine Ca2+ channel density and readily releasable pool size at a large hindbrain synapse

Journal of Neurophysiology ◽

10.1152/jn.00488.2014 ◽

2015 ◽

Vol 113 (1) ◽

pp. 255-263 ◽

Cited By ~ 21

Author(s):

Yunyun Han ◽

Norbert Babai ◽

Pascal Kaeser ◽

Thomas C. Südhof ◽

Ralf Schneggenburger

Keyword(s):

Pdz Domain ◽

Decisive Role ◽

Scaffolding Proteins ◽

Calyx Of Held ◽

C2 Domains ◽

Voltage Gated ◽

Channel Density ◽

Readily Releasable Pool ◽

Vesicle Pool ◽

Kinetics Of

The localization and density of voltage-gated Ca2+ channels at active zones are essential for the amount and kinetics of transmitter release at synapses. RIM proteins are scaffolding proteins at the active zone that bind to several other presynaptic proteins, including voltage-gated Ca2+ channel α-subunits. The long isoforms of RIM proteins, which contain NH2-terminal Rab3- and Munc13-interacting domains, as well as a central PDZ domain and two COOH-terminal C2 domains, are encoded by two genes, Rim1 and Rim2. Here, we used the ideal accessibility of the large calyx of Held synapse for direct presynaptic electrophysiology to investigate whether the two Rim genes have redundant, or separate, functions in determining the presynaptic Ca2+ channel density, and the size of a readily releasable vesicle pool (RRP). Quantitative PCR showed that cochlear nucleus neurons, which include calyx of Held generating neurons, express both RIM1 and RIM2. Conditional genetic inactivation of RIM2 at the calyx of Held led to a subtle reduction in presynaptic Ca2+ current density, whereas deletion of RIM1 was ineffective. The release efficiency of brief presynaptic Ca2+ “tail” currents and the RRP were unaffected in conditional single RIM1 and RIM2 knockout (KO) mice, whereas both parameters were strongly reduced in RIM1/2 double KO mice. Thus, despite a somewhat more decisive role for RIM2 in determining presynaptic Ca2+ channel density, RIM1 and RIM2 can overall replace each other's presynaptic functions at a large relay synapse in the hindbrain, the calyx of Held.

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Proteolytic maturation of α2δ controls the probability of synaptic vesicular release

eLife ◽

10.7554/elife.37507 ◽

2018 ◽

Vol 7 ◽

Cited By ~ 16

Author(s):

Laurent Ferron ◽

Ivan Kadurin ◽

Annette C Dolphin

Keyword(s):

Calcium Channels ◽

Inhibitory Effect ◽

Wild Type ◽

Voltage Gated ◽

Synaptic Release ◽

Voltage Gated Calcium Channels ◽

Vesicular Release ◽

Active Zones ◽

Asynchronous Release

Auxiliary α2δ subunits are important proteins for trafficking of voltage-gated calcium channels (CaV) at the active zones of synapses. We have previously shown that the post-translational proteolytic cleavage of α2δ is essential for their modulatory effects on the trafficking of N-type (CaV2.2) calcium channels (Kadurin et al., 2016). We extend these results here by showing that the probability of presynaptic vesicular release is reduced when an uncleaved α2δ is expressed in rat neurons and that this inhibitory effect is reversed when cleavage of α2δ is restored. We also show that asynchronous release is influenced by the maturation of α2δ−1, highlighting the role of CaV channels in this component of vesicular release. We present additional evidence that CaV2.2 co-immunoprecipitates preferentially with cleaved wild-type α2δ. Our data indicate that the proteolytic maturation increases the association of α2δ−1 with CaV channel complex and is essential for its function on synaptic release.

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Aversive Learning Increases Release Probability of Olfactory Sensory Neurons

10.1101/642751 ◽

2019 ◽

Author(s):

Janardhan P. Bhattarai ◽

Mary Schreck ◽

Andrew H. Moberly ◽

Wenqin Luo ◽

Minghong Ma

Keyword(s):

Sensory Neurons ◽

Receptor Expression ◽

Olfactory Sensory Neurons ◽

Aversive Learning ◽

Sensory Stimuli ◽

Release Probability ◽

Synaptic Release ◽

Underlying Mechanisms ◽

Peripheral Sensory ◽

Cortical Influence

AbstractPredicting danger from previously associated sensory stimuli is essential for survival. Contributions from altered peripheral sensory inputs are implicated in this process, but the underlying mechanisms remain elusive. Here we use the mammalian olfactory system to investigate such mechanisms. Primary olfactory sensory neurons (OSNs) project their axons directly to the olfactory bulb (OB) glomeruli where their synaptic release is subject to local and cortical influence and neuromodulation. Pairing optogenetic activation of a single glomerulus with foot shock in mice induces freezing to the light stimulation alone during fear retrieval. This is accompanied by an increase in OSN release probability and a reduction in GABAB receptor expression in the conditioned glomerulus. Furthermore, freezing time is positively correlated with the release probability of OSNs in fear conditioned mice. These results suggest that aversive learning increases peripheral olfactory inputs at the first synapse, which may contribute to the behavioral outcome.

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Examining size–strength relationships at hippocampal synapses using an ultrastructural measurement of synaptic release probability

Journal of Structural Biology ◽

10.1016/j.jsb.2009.10.014 ◽

2010 ◽

Vol 172 (2) ◽

pp. 203-210 ◽

Cited By ~ 32

Author(s):

Tiago Branco ◽

Vincenzo Marra ◽

Kevin Staras

Keyword(s):

Release Probability ◽

Synaptic Release ◽

Hippocampal Synapses

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RIM-Binding Protein 2 organizes Ca2+ channel topography and regulates release probability and vesicle replenishment at a fast central synapse

Journal of Neuroscience ◽

10.1523/jneurosci.0586-21.2021 ◽

2021 ◽

pp. JN-RM-0586-21

Author(s):

Tanvi Butola ◽

Theocharis Alvanos ◽

Anika Hintze ◽

Peter Koppensteiner ◽

David Kleindienst ◽

...

Keyword(s):

Binding Protein ◽

Release Probability ◽

Central Synapse

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Regulation of synaptic release-site Ca2+ channel coupling as a mechanism to control release probability and short-term plasticity

FEBS Letters ◽

10.1002/1873-3468.13188 ◽

2018 ◽

Vol 592 (21) ◽

pp. 3516-3531 ◽

Cited By ~ 15

Author(s):

Mathias A. Böhme ◽

Andreas T. Grasskamp ◽

Alexander M. Walter

Keyword(s):

Control Release ◽

Release Site ◽

Short Term ◽

Channel Coupling ◽

Short Term Plasticity ◽

Release Probability ◽

Synaptic Release

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Synaptic Information Transmission in a Two-State Model of Short-Term Facilitation

Entropy ◽

10.3390/e21080756 ◽

2019 ◽

Vol 21 (8) ◽

pp. 756 ◽

Cited By ~ 1

Author(s):

Mehrdad Salmasi ◽

Martin Stemmler ◽

Stefan Glasauer ◽

Alex Loebel

Keyword(s):

Action Potential ◽

Information Transmission ◽

Action Potentials ◽

Synaptic Activity ◽

Information Rate ◽

Short Term ◽

Release Probability ◽

Synaptic Facilitation ◽

Synaptic Release ◽

Asynchronous Release

Action potentials (spikes) can trigger the release of a neurotransmitter at chemical synapses between neurons. Such release is uncertain, as it occurs only with a certain probability. Moreover, synaptic release can occur independently of an action potential (asynchronous release) and depends on the history of synaptic activity. We focus here on short-term synaptic facilitation, in which a sequence of action potentials can temporarily increase the release probability of the synapse. In contrast to the phenomenon of short-term depression, quantifying the information transmission in facilitating synapses remains to be done. We find rigorous lower and upper bounds for the rate of information transmission in a model of synaptic facilitation. We treat the synapse as a two-state binary asymmetric channel, in which the arrival of an action potential shifts the synapse to a facilitated state, while in the absence of a spike, the synapse returns to its baseline state. The information bounds are functions of both the asynchronous and synchronous release parameters. If synchronous release facilitates more than asynchronous release, the mutual information rate increases. In contrast, short-term facilitation degrades information transmission when the synchronous release probability is intrinsically high. As synaptic release is energetically expensive, we exploit the information bounds to determine the energy–information trade-off in facilitating synapses. We show that unlike information rate, the energy-normalized information rate is robust with respect to variations in the strength of facilitation.

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