scholarly journals Presynaptic Endoplasmic Reticulum Contributes Crucially to Short-term Plasticity in Small Hippocampal Synapses

2018 ◽  
Author(s):  
Nishant Singh ◽  
Thomas Bartol ◽  
Herbert Levine ◽  
Terrence Sejnowski ◽  
Suhita Nadkarni
Keyword(s):  
Endoplasmic Reticulum ◽  
Calcium Influx ◽  
Critical Role ◽  
Presynaptic Terminal ◽  
Calcium Stores ◽  
Pathological State ◽  
Calcium Dynamics ◽  
Short Term ◽  
Short Term Plasticity ◽  
Release Probability

Short-term plasticity (STP) of the presynaptic terminal maintains a brief history of activity experienced by the synapse that may otherwise remain unseen by the postsynaptic neuron. These synaptic changes are primarily regulated by calcium dynamics in the presynaptic terminal. A rapid increase in intracellular calcium is initiated by the opening of voltage-dependent calcium channels in response to depolarization, the main source of calcium required for vesicle fusion. Separately, electron-microscopic studies of hippocampal CA3-CA1 synapses reveal the strong presence of endoplasmic reticulum (ER) in all presynaptic terminals. However, the precise role of the ER in modifying STP at the presynaptic terminal remains unexplored. To investigate the contribution of ER in modulating calcium dynamics in small hippocampal boutons, we performed in silico experiments in a physiologically-realistic canonical synaptic geometry based on reconstructions of CA3-CA1 Schaffer collaterals in the rat hippocampus. The model predicts that presynaptic calcium stores are critical in generating the observed paired-pulse ratio (PPR) of normal CA3-CA1 synapses. In control synapses with intact ER, SERCA pumps act as additional calcium buffers, lowering the intrinsic release probability of vesicle release and increasing PPR. In addition, the presence of ER allows ongoing activity to trigger calcium influx from the presynaptic ER via ryanodine receptors (RyRs) and inositol trisphosphate receptors (IP3Rs). Intracellular stores and their associated machinery also allows a synapse with a low release probability to operate more reliably due to attenuation of calcium fluctuations. Finally, blocking ER activity in the presynaptic terminal mimics the pathological state of a low facilitating synapse characterized in animal models of Alzheimer’s disease, and underscores the critical role played by presynaptic stores in normal function.

scholarly journals Author Correction: Presynaptic endoplasmic reticulum regulates short-term plasticity in hippocampal synapses

2021 ◽  
Vol 4 (1) ◽  
Author(s):  
Nishant Singh ◽  
Thomas Bartol ◽  
Herbert Levine ◽  
Terrence Sejnowski ◽  
Suhita Nadkarni
Keyword(s):  
Endoplasmic Reticulum ◽  
Short Term ◽  
Short Term Plasticity ◽  
Hippocampal Synapses

scholarly journals Ca2+/Calmodulin and Presynaptic Short-Term Plasticity

2011 ◽  
Vol 2011 ◽  
pp. 1-7 ◽  
Author(s):  
Sumiko Mochida
Keyword(s):  
Transmitter Release ◽  
Presynaptic Terminal ◽  
Neuronal Firing ◽  
Firing Activity ◽  
Short Term ◽  
Short Term Plasticity ◽  
Readily Releasable Pool ◽  
Ef Hand ◽  
Sensor Protein ◽  
Activity Dependent

Synaptic efficacy is remodeled by neuronal firing activity at the presynaptic terminal. Presynaptic activity-dependent changes in transmitter release induce postsynaptic plasticity, including morphological change in spine, gene transcription, and protein synthesis and trafficking. The presynaptic transmitter release is triggered and regulated by Ca2+, which enters through voltage-gated Ca2+ (CaV) channels and diffuses into the presynaptic terminal accompanying action potential firings. Residual Ca2+ is sensed by Ca2+-binding proteins, among other potential actions, it mediates time- and space-dependent synaptic facilitation and depression via effects on CaV2 channel gating and vesicle replenishment in the readily releasable pool (RRP). Calmodulin, a Ca2+-sensor protein with an EF-hand motif that binds Ca2+, interacts with CaV2 channels and autoreceptors in modulation of SNARE-mediated exocytosis.

scholarly journals Rapid regulation of vesicle priming explains synaptic facilitation despite heterogeneous vesicle:Ca2+ channel distances

eLife ◽  
2020 ◽  
Vol 9 ◽  
Author(s):  
Janus RL Kobbersmed ◽  
Andreas T Grasskamp ◽  
Meida Jusyte ◽  
Mathias A Böhme ◽  
Susanne Ditlevsen ◽  
...  
Keyword(s):  
Super Resolution ◽  
Release Site ◽  
Stochastic Simulations ◽  
Short Term ◽  
Short Term Plasticity ◽  
Release Probability ◽  
Vesicular Release ◽  
Dependent Inhibition ◽  
Super Resolution Microscopy ◽  
Activity Dependent

Chemical synaptic transmission relies on the Ca2+-induced fusion of transmitter-laden vesicles whose coupling distance to Ca2+ channels determines synaptic release probability and short-term plasticity, the facilitation or depression of repetitive responses. Here, using electron- and super-resolution microscopy at the Drosophila neuromuscular junction we quantitatively map vesicle:Ca2+ channel coupling distances. These are very heterogeneous, resulting in a broad spectrum of vesicular release probabilities within synapses. Stochastic simulations of transmitter release from vesicles placed according to this distribution revealed strong constraints on short-term plasticity; particularly facilitation was difficult to achieve. We show that postulated facilitation mechanisms operating via activity-dependent changes of vesicular release probability (e.g. by a facilitation fusion sensor) generate too little facilitation and too much variance. In contrast, Ca2+-dependent mechanisms rapidly increasing the number of releasable vesicles reliably reproduce short-term plasticity and variance of synaptic responses. We propose activity-dependent inhibition of vesicle un-priming or release site activation as novel facilitation mechanisms.

scholarly journals Peroxisomes contribute to intracellular calcium dynamics

2020 ◽  
Author(s):  
Yelena Sargsyan ◽  
Uta Bickmeyer ◽  
Katrin Streckfuss-Bömeke ◽  
Ivan Bogeski ◽  
Sven Thoms
Keyword(s):  
Intracellular Calcium ◽  
Hela Cells ◽  
Calcium Influx ◽  
Induced Pluripotent Stem Cell ◽  
Cytosolic Calcium ◽  
Neonatal Rat ◽  
Calcium Handling ◽  
Calcium Stores ◽  
Calcium Dynamics ◽  
Rat Cardiomyocytes

AbstractPeroxisomes communicate with other cellular compartments by transfer of various metabolites. However, whether peroxisomes are sites for calcium handling and exchange has remained contentious. Here we generated sensors for assessment of peroxisomal calcium and applied them for single cell-based calcium imaging in HeLa cells and cardiomyocytes. We found that peroxisomes in HeLa cells take up calcium upon depletion of intracellular calcium stores and upon calcium influx across the plasma membrane. Further, we show that peroxisomes of neonatal rat cardiomyocytes and human induced pluripotent stem cell-derived cardiomyocytes can take up calcium in a controlled manner. Our results indicate that peroxisomal and cytosolic calcium signals are tightly interconnected. Hence, peroxisomes may play an important role in shaping cellular calcium dynamics by serving as buffers or sources of intracellular calcium.

scholarly journals Nanoscale organization and calcium influx in dendritic spines guarantee ER store refilling without depletion

2021 ◽  
Author(s):  
Kanishka Basnayake ◽  
David Mazaud ◽  
Lilia Kushnireva ◽  
Alexis Bemelmans ◽  
nathalie Rouach ◽  
...  
Keyword(s):  
Dendritic Spines ◽  
Plasma Membranes ◽  
Calcium Release ◽  
Calcium Influx ◽  
Smooth Endoplasmic Reticulum ◽  
Super Resolution ◽  
Calcium Stores ◽  
Calcium Dynamics ◽  
Store Operated Calcium Entry ◽  
Critical Components

Dendritic spines are critical components of the neuronal synapse as they receive and transform the synaptic input into a succession of biochemical events regulated by calcium signaling. The spine apparatus (SA), an extension of smooth endoplasmic reticulum (ER), regulates slow and fast calcium dynamics in spines. Calcium release events from SA result in a rapid depletion of calcium ion reservoir, yet the next cycle of signaling requires replenishment of SA calcium stores. How dendritic spines achieve this without triggering calcium release remains unclear. Using computational modeling, calcium and STED super-resolution imaging, we showed that the refilling of calcium-deprived SA involves store-operated calcium entry during spontaneous calcium transients in spine heads. We identified two main conditions that guarantee SA replenishment without depletion: (1) a small amplitude and slow timescale for calcium influx, and (2) a close proximity between SA and plasma membranes. Thereby, molecular nano-organization creates the conditions for a clear separation between SA replenishment and depletion. We further conclude that the nanoscale organization of SA receptors underlies the specificity of calcium dynamics patterns during the induction of long-term synaptic changes.

scholarly journals Regulation of a subset of release-ready vesicles by the presynaptic protein Mover

2021 ◽  
Vol 118 (3) ◽  
pp. e2022551118
Author(s):  
Ermis Pofantis ◽  
Erwin Neher ◽  
Thomas Dresbach
Keyword(s):  
Synaptic Vesicles ◽  
Wild Type ◽  
Short Term ◽  
Calyx Of Held ◽  
Short Term Plasticity ◽  
Release Probability ◽  
Pulse Ratio ◽  
Vesicular Release ◽  
Evolutionarily Conserved ◽  
Presynaptic Protein

Neurotransmitter release occurs by regulated exocytosis from synaptic vesicles (SVs). Evolutionarily conserved proteins mediate the essential aspects of this process, including the membrane fusion step and priming steps that make SVs release-competent. Unlike the proteins constituting the core fusion machinery, the SV protein Mover does not occur in all species and all synapses. Its restricted expression suggests that Mover may modulate basic aspects of transmitter release and short-term plasticity. To test this hypothesis, we analyzed synaptic transmission electrophysiologically at the mouse calyx of Held synapse in slices obtained from wild-type mice and mice lacking Mover. Spontaneous transmission was unaffected, indicating that the basic release machinery works in the absence of Mover. Evoked release and vesicular release probability were slightly reduced, and the paired pulse ratio was increased in Mover knockout mice. To explore whether Mover’s role is restricted to certain subpools of SVs, we analyzed our data in terms of two models of priming. A model assuming two SV pools in parallel showed a reduced release probability of so-called “superprimed vesicles” while “normally primed” ones were unaffected. For the second model, which holds that vesicles transit sequentially from a loosely docked state to a tightly docked state before exocytosis, we found that knocking out Mover selectively decreased the release probability of tight state vesicles. These results indicate that Mover regulates a subclass of primed SVs in the mouse calyx of Held.

scholarly journals Release probability modulates short‐term plasticity at a rat giant terminal

2000 ◽  
Vol 524 (2) ◽  
pp. 513-523 ◽  
Author(s):  
Sharon Oleskevich ◽  
John Clements ◽  
Bruce Walmsley
Keyword(s):  
Short Term ◽  
Short Term Plasticity ◽  
Release Probability

scholarly journals Peroxisomes contribute to intracellular calcium dynamics in cardiomyocytes and non-excitable cells

2021 ◽  
Vol 4 (9) ◽  
pp. e202000987
Author(s):  
Yelena Sargsyan ◽  
Uta Bickmeyer ◽  
Christine S Gibhardt ◽  
Katrin Streckfuss-Bömeke ◽  
Ivan Bogeski ◽  
...  
Keyword(s):  
Intracellular Calcium ◽  
Hela Cells ◽  
Calcium Influx ◽  
Induced Pluripotent Stem Cell ◽  
Cytosolic Calcium ◽  
Neonatal Rat ◽  
Calcium Handling ◽  
Calcium Stores ◽  
Calcium Dynamics ◽  
Rat Cardiomyocytes

Peroxisomes communicate with other cellular compartments by transfer of various metabolites. However, whether peroxisomes are sites for calcium handling and exchange has remained contentious. Here we generated sensors for assessment of peroxisomal calcium and applied them for single cell-based calcium imaging in HeLa cells and cardiomyocytes. We found that peroxisomes in HeLa cells take up calcium upon depletion of intracellular calcium stores and upon calcium influx across the plasma membrane. Furthermore, we show that peroxisomes of neonatal rat cardiomyocytes and human induced pluripotent stem cell–derived cardiomyocytes can take up calcium. Our results indicate that peroxisomal and cytosolic calcium signals are tightly interconnected both in HeLa cells and in cardiomyocytes. Cardiac peroxisomes take up calcium on beat-to-beat basis. Hence, peroxisomes may play an important role in shaping cellular calcium dynamics of cardiomyocytes.

Sign in / Sign up

Export Citation Format

Share Document