Loose coupling between Ca2+ channels and sensors enables endogenous buffer control of release probability and short-term dynamics at a cortical synapse

2013 ◽  
Vol 1 (Suppl. 1) ◽  
pp. A1.49
Author(s):  
Nicholas P. Vyleta
Keyword(s):  
Loose Coupling ◽  
Short Term ◽  
Release Probability ◽  
Buffer Control ◽  
Ca2 Channels

scholarly journals VGluT1 Deficiency Impairs Visual Attention and Reduces the Dynamic Range of Short-Term Plasticity at Corticothalamic Synapses

2019 ◽  
Vol 30 (3) ◽  
pp. 1813-1829
Author(s):  
Sarah H Lindström ◽  
Sofie C Sundberg ◽  
Max Larsson ◽  
Fredrik K Andersson ◽  
Jonas Broman ◽  
...  
Keyword(s):  
Visual Processing ◽  
Dynamic Range ◽  
Sensorimotor Gating ◽  
Short Term ◽  
Attention Task ◽  
Attentional Processing ◽  
Excitatory Neurotransmitter ◽  
Release Probability ◽  
Visual Spatial

Abstract The most common excitatory neurotransmitter in the central nervous system, glutamate, is loaded into synaptic vesicles by vesicular glutamate transporters (VGluTs). The primary isoforms, VGluT1 and 2, are expressed in complementary patterns throughout the brain and correlate with short-term synaptic plasticity. VGluT1 deficiency is observed in certain neurological disorders, and hemizygous (VGluT1+/−) mice display increased anxiety and depression, altered sensorimotor gating, and impairments in learning and memory. The synaptic mechanisms underlying these behavioral deficits are unknown. Here, we show that VGluT1+/− mice had decreased visual processing speeds during a sustained visual-spatial attention task. Furthermore, in vitro recordings of corticothalamic (CT) synapses revealed dramatic reductions in short-term facilitation, increased initial release probability, and earlier synaptic depression in VGluT1+/− mice. Our electron microscopy results show that VGluT1 concentration is reduced at CT synapses of hemizygous mice, but other features (such as vesicle number and active zone size) are unchanged. We conclude that VGluT1-haploinsuficiency decreases the dynamic range of gain modulation provided by CT feedback to the thalamus, and this deficiency contributes to the observed attentional processing deficit. We further hypothesize that VGluT1 concentration regulates release probability by applying a “brake” to an unidentified presynaptic protein that typically acts as a positive regulator of release.

scholarly journals Short-term potentiation of mEPSCs requires N-, P/Q- and L-type Ca2+channels and mitochondria in the supraoptic nucleus

2008 ◽  
Vol 586 (13) ◽  
pp. 3147-3161 ◽  
Author(s):  
Michelle E. Quinlan ◽  
Christian O. Alberto ◽  
Michiru Hirasawa
Keyword(s):  
Supraoptic Nucleus ◽  
Short Term ◽  
Term Potentiation ◽  
Ca2 Channels

scholarly journals RIM-binding protein 2 regulates release probability by fine-tuning calcium channel localization at murine hippocampal synapses

2016 ◽  
Vol 113 (41) ◽  
pp. 11615-11620 ◽  
Author(s):  
M. Katharina Grauel ◽  
Marta Maglione ◽  
Suneel Reddy-Alla ◽  
Claudia G. Willmes ◽  
Marisa M. Brockmann ◽  
...  
Keyword(s):  
Hippocampal Neurons ◽  
Autism Spectrum ◽  
Fine Tuning ◽  
Model Systems ◽  
Short Term ◽  
Superresolution Microscopy ◽  
Release Probability ◽  
Spatial Coupling ◽  
Hippocampal Synapses ◽  
Initial Release

The tight spatial coupling of synaptic vesicles and voltage-gated Ca2+ channels (CaVs) ensures efficient action potential-triggered neurotransmitter release from presynaptic active zones (AZs). Rab-interacting molecule-binding proteins (RIM-BPs) interact with Ca2+ channels and via RIM with other components of the release machinery. Although human RIM-BPs have been implicated in autism spectrum disorders, little is known about the role of mammalian RIM-BPs in synaptic transmission. We investigated RIM-BP2–deficient murine hippocampal neurons in cultures and slices. Short-term facilitation is significantly enhanced in both model systems. Detailed analysis in culture revealed a reduction in initial release probability, which presumably underlies the increased short-term facilitation. Superresolution microscopy revealed an impairment in CaV2.1 clustering at AZs, which likely alters Ca2+ nanodomains at release sites and thereby affects release probability. Additional deletion of RIM-BP1 does not exacerbate the phenotype, indicating that RIM-BP2 is the dominating RIM-BP isoform at these synapses.

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 Local design principles at hippocampal synapses revealed by an energy-information trade-off

2019 ◽  
Author(s):  
Gaurang Mahajan ◽  
Suhita Nadkarni
Keyword(s):  
Information Transfer ◽  
Design Principles ◽  
Short Term ◽  
Vesicle Release ◽  
Efficient Manner ◽  
Heterogeneous Distribution ◽  
Trade Off ◽  
Release Probability ◽  
Wide Range ◽  
Hippocampal Synapses

AbstractSynapses across different brain regions display distinct structure-function relationships. We investigate the interplay of fundamental design principles that shape the transmission properties of the excitatory CA3-CA1 pyramidal cell connection, a prototypic synapse for studying the mechanisms of learning in the hippocampus. This small synapse is characterized by probabilistic release of transmitter, which is markedly facilitated in response to naturally occurring trains of action potentials. Based on a physiologically realistic computational model of the CA3 presynaptic terminal, we show how unreliability and short-term dynamics of vesicle release work together to regulate the trade-off of information transfer versus energy use. We propose that individual CA3-CA1 synapses are designed to operate at close to maximum possible capacity of information transfer in an efficient manner. Experimental measurements reveal a wide range of vesicle release probabilities at hippocampal synapses, which may be a necessary consequence of long-term plasticity and homeostatic mechanisms that manifest as presynaptic modifications of release probability. We show that the timescales and magnitude of short-term plasticity render synaptic information transfer nearly independent of differences in release probability. Thus, individual synapses transmit optimally while maintaining a heterogeneous distribution of presynaptic strengths indicative of synaptically-encoded memory representations. Our results support the view that organizing principles that are evident on higher scales of neural organization percolate down to the design of an individual synapse.

scholarly journals Molecular moieties masking Ca2+-dependent facilitation of voltage-gated Cav2.2 Ca2+ channels

2017 ◽  
Vol 150 (1) ◽  
pp. 83-94 ◽  
Author(s):  
Jessica R. Thomas ◽  
Jussara Hagen ◽  
Daniel Soh ◽  
Amy Lee
Keyword(s):  
Functional Divergence ◽  
Short Term ◽  
Voltage Gated ◽  
Regulatory Domains ◽  
Dependent Inactivation ◽  
Weak Binding ◽  
Ef Hand ◽  
Molecular Determinants ◽  
Ca2 Channels ◽  
Α1 Subunit

Voltage-gated Cav2.1 (P/Q-type) Ca2+ channels undergo Ca2+-dependent inactivation (CDI) and facilitation (CDF), both of which contribute to short-term synaptic plasticity. Both CDI and CDF are mediated by calmodulin (CaM) binding to sites in the C-terminal domain of the Cav2.1 α1 subunit, most notably to a consensus CaM-binding IQ-like (IQ) domain. Closely related Cav2.2 (N-type) channels display CDI but not CDF, despite overall conservation of the IQ and additional sites (pre-IQ, EF-hand–like [EF] domain, and CaM-binding domain) that regulate CDF of Cav2.1. Here we investigate the molecular determinants that prevent Cav2.2 channels from undergoing CDF. Although alternative splicing of C-terminal exons regulates CDF of Cav2.1, the splicing of analogous exons in Cav2.2 does not reveal CDF. Transfer of sequences encoding the Cav2.1 EF, pre-IQ, and IQ together (EF-pre-IQ-IQ), but not individually, are sufficient to support CDF in chimeric Cav2.2 channels; Cav2.1 chimeras containing the corresponding domains of Cav2.2, either alone or together, fail to undergo CDF. In contrast to the weak binding of CaM to just the pre-IQ and IQ of Cav2.2, CaM binds to the EF-pre-IQ-IQ of Cav2.2 as well as to the corresponding domains of Cav2.1. Therefore, the lack of CDF in Cav2.2 likely arises from an inability of its EF-pre-IQ-IQ to transduce the effects of CaM rather than weak binding to CaM per se. Our results reveal a functional divergence in the CDF regulatory domains of Cav2 channels, which may help to diversify the modes by which Cav2.1 and Cav2.2 can modify synaptic transmission.

Loose Coupling Between Ca2+ Channels and Release Sensors at a Plastic Hippocampal Synapse

Science ◽  
2014 ◽  
Vol 343 (6171) ◽  
pp. 665-670 ◽  
Author(s):  
N. P. Vyleta ◽  
P. Jonas
Keyword(s):  
Loose Coupling ◽  
Ca2 Channels
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