Kainate Receptors Differentially Regulate Release at Two Parallel Fiber Synapses

Delaney, Andrew; Jahr, Craig E.

doi:10.1016/s0896-6273(02)01008-5

Cited by 88 publications

(92 citation statements)

References 32 publications

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“…The KA2 subunit is highly expressed in cerebellar granule cells, where they likely form heteromeric receptors with GluR6 subunits and modulate excitatory synaptic transmission at parallel fiber synapses (17). Membrane protein lysates were prepared from homogenized cerebella from 129SvEv mice as well as KA2…”

Section: Resultsmentioning

confidence: 99%

Intracellular Trafficking of KA2 Kainate Receptors Mediated by Interactions with Coatomer Protein Complex I (COPI) and 14-3-3 Chaperone Systems

Vivithanaporn

Yan

Swanson

2006

Journal of Biological Chemistry

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Assembly and trafficking of neurotransmitter receptors are processes contingent upon interactions between intracellular chaperone systems and discrete determinants in the receptor proteins. Kainate receptor subunits, which form ionotropic glutamate receptors with diverse roles in the central nervous system, contain a variety of trafficking determinants that promote either membrane expression or intracellular sequestration. In this report, we identify the coatomer protein complex I (COPI) vesicle coat as a critical mechanism for retention of the kainate receptor subunit KA2 in the endoplasmic reticulum. COPI subunits immunoprecipitated with KA2 subunits from both cerebellum and COS-7 cells, and ␤-COP protein interacted directly with immobilized KA2 peptides containing the arginine-rich retention/retrieval determinant. Association between COPI proteins and KA2 subunits was significantly reduced upon alanine substitution of this signal in the cytoplasmic tail of KA2. Temperature-sensitive degradation of COPI complex proteins was correlated with an increase in plasma membrane localization of the homologous KA2 receptor. Assembly of heteromeric GluR6a/KA2 receptors markedly reduced association of KA2 and COPI. Finally, the reduction in COPI binding was correlated with an increased association with 14-3-3 proteins, which mediate forward trafficking of other integral signaling proteins. These interactions therefore represent a critical early checkpoint for biosynthesis of functional KARs. Kainate receptors (KARs)2 play a variety of roles in the mammalian central nervous system that include contributions to postsynaptic neurotransmission at a subset of excitatory synapses and presynaptic modulation of both excitatory and inhibitory transmission (1, 2). These diverse physiological roles of KARs require selective assembly, subcellular trafficking, and targeting of these proteins to their functional sites. Elucidating the cellular mechanisms that control these processes is important for understanding the full spectrum of KAR-mediated signaling in the brain.Oligomerization and intracellular trafficking of KARs are controlled in part through interactions with chaperone proteins that bind to discrete cytoplasmic domains on the receptor proteins themselves. For example, GluR6a KAR subunits contain a forward trafficking determinant in their cytoplasmic tail and therefore are highly expressed as homomeric receptors on the plasma membrane of heterologous cell lines (3), whereas the KA2 subunit has an endoplasmic reticulum (ER) retention/retrieval signal and consequently does not reach the plasma membrane in the absence of other KAR subunits (4). The KA2 ER retention/retrieval signal consists primarily of an arginine-rich domain similar to that characterized on several other ionotropic glutamate receptor subunits, including NR1 (5) and GluR5-2c (6), as well as other signaling proteins such as ATP-sensitive potassium channels (K ATP ) (7) and GABA B receptors (8). Although a number of trafficking motifs in KAR subunits have been id...

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Section: Resultsmentioning

confidence: 99%

Intracellular Trafficking of KA2 Kainate Receptors Mediated by Interactions with Coatomer Protein Complex I (COPI) and 14-3-3 Chaperone Systems

Vivithanaporn

Yan

Swanson

2006

Journal of Biological Chemistry

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“…Our results do not support a role of BG calcium signals in modulating transmitter release at PF synapses, at least on the time scale of seconds to tens of seconds. PF express kainate (Delaney and Jahr, 2002), group III metabotropic glutamate (Kreitzer and Regehr, 2001;Neale et al, 2001), and adenosine (Dittman and Regehr, 1996) receptors and should therefore be able to respond to glutamate or adenosine released by glia.…”

Section: Glial Control Of Transmitter Releasementioning

confidence: 99%

Brief Bursts of Parallel Fiber Activity Trigger Calcium Signals in Bergmann Glia

Beierlein

Regehr

2006

J. Neurosci.

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Changes in synaptic strength during ongoing activity are often mediated by neuromodulators. At the synapse between cerebellar granule cell parallel fibers (PFs) and Purkinje cells (PCs), brief bursts of stimuli can evoke endocannabinoid release from PCs and GABA release from interneurons that both inhibit transmission by activating presynaptic G-protein-coupled receptors. Studies in several brain regions suggest that synaptic activity can also evoke calcium signals in astrocytes, thereby causing them to release a transmitter, which acts presynaptically to regulate neurotransmitter release. In the cerebellum, Bergmann glia cells (BGs) are intimately associated with PF synapses. However, the mechanisms leading to calcium signals in BGs under physiological conditions and the role of BGs in regulating ongoing synaptic transmission are poorly understood. We found that brief bursts of PF activity evoke calcium signals in BGs that are triggered by the activation of metabotropic glutamate receptor 1 and purinergic receptors and mediated by calcium release from IP 3 -sensitive internal stores. We found no evidence for modulation of release from PFs mediated by BGs, even when endocannabinoid-and GABA-mediated presynaptic modulation was prominent. Thus, despite the fact that PF activation can reliably evoke calcium transients within BGs, it appears that BGs do not regulate synaptic transmission on the time scale of seconds to tens of seconds. Instead, endocannabinoid release from PCs and GABA release from molecular layer interneurons provide the primary means of feedback that dynamically regulate release from PF synapses.

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“…In our implementation, both E f s and I f s are modeled using (1)-(5), when f is below f 1 or f 2 , (1)-(5) are used, and above f 1 or f 2 , (1)-(4) are used. Experimental evidence has been reported [32] that shows synaptic switching in the hippocampus occurs at 1 Hz, while other publications [29]- [31] have reported the switching from facilitation to depression is possible over the frequency range 10-100 Hz. Therefore, we can make the approximation that this switching activity occurs at different frequencies for different synapses and we use this concept to implement frequency filtering as follows.…”

Section: A Snn Topologymentioning

confidence: 95%

SWAT: A Spiking Neural Network Training Algorithm for Classification Problems

Wade

McDaid

Santos

et al. 2010

IEEE Trans. Neural Netw.

171

128

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Abstract-This paper presents a synaptic weight association training (SWAT) algorithm for spiking neural networks (SNNs). SWAT merges the Bienenstock-Cooper-Munro (BCM) learning rule with spike timing dependent plasticity (STDP). The STDP/BCM rule yields a unimodal weight distribution where the height of the plasticity window associated with STDP is modulated causing stability after a period of training. The SNN uses a single training neuron in the training phase where data associated with all classes is passed to this neuron. The rule then maps weights to the classifying output neurons to reflect similarities in the data across the classes. The SNN also includes both excitatory and inhibitory facilitating synapses which create a frequency routing capability allowing the information presented to the network to be routed to different hidden layer neurons. A variable neuron threshold level simulates the refractory period. SWAT is initially benchmarked against the nonlinearly separable Iris and Wisconsin Breast Cancer datasets. Results presented show that the proposed training algorithm exhibits a convergence accuracy of 95.5% and 96.2% for the Iris and Wisconsin training sets, respectively, and 95.3% and 96.7% for the testing sets, noise experiments show that SWAT has a good generalization capability. SWAT is also benchmarked using an isolated digit automatic speech recognition (ASR) system where a subset of the TI46 speech corpus is used. Results show that with SWAT as the classifier, the ASR system provides an accuracy of 98.875% for training and 95.25% for testing.Index Terms-Automatic speech recognition, BienenstockCooper-Munro, dynamic synapses, spike timing dependent plasticity, spiking neural networks.

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Kainate Receptors Differentially Regulate Release at Two Parallel Fiber Synapses

Cited by 88 publications

References 32 publications

Intracellular Trafficking of KA2 Kainate Receptors Mediated by Interactions with Coatomer Protein Complex I (COPI) and 14-3-3 Chaperone Systems

Intracellular Trafficking of KA2 Kainate Receptors Mediated by Interactions with Coatomer Protein Complex I (COPI) and 14-3-3 Chaperone Systems

Brief Bursts of Parallel Fiber Activity Trigger Calcium Signals in Bergmann Glia

SWAT: A Spiking Neural Network Training Algorithm for Classification Problems

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