Role of glutamine and neuronal glutamate uptake in glutamate homeostasis and synthesis during vesicular release in cultured glutamatergic neurons

Thin basal dendrites can strongly influence neuronal output via generation of dendritic spikes. It was recently postulated that glial processes actively support dendritic spikes by either ceasing glutamate uptake or by actively releasing glutamate and adenosine triphosphate (ATP). We used calcium imaging to study the role of NR2C/D-containing N -methyl- d -aspartate (NMDA) receptors and adenosine A1 receptors in the generation of dendritic NMDA spikes and plateau potentials in basal dendrites of layer 5 pyramidal neurons in the mouse prefrontal cortex. We found that NR2C/D glutamate receptor subunits contribute to the amplitude of synaptically evoked NMDA spikes. Dendritic calcium signals associated with glutamate-evoked dendritic plateau potentials were significantly shortened upon application of the NR2C/D receptor antagonist PPDA, suggesting that NR2C/D receptors prolong the duration of calcium influx during dendritic spiking. In contrast to NR2C/D receptors, adenosine A1 receptors act to abbreviate dendritic and somatic signals via the activation of dendritic K + current. This current is characterized as a slow-activating outward-rectifying voltage- and adenosine-gated current, insensitive to 4-aminopyridine but sensitive to TEA. Our data support the hypothesis that the release of glutamate and ATP from neurons or glia contribute to initiation, maintenance and termination of local dendritic glutamate-mediated regenerative potentials.

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Pedunculopontine glutamatergic neurons control spike patterning in substantia nigra dopaminergic neurons

eLife ◽

10.7554/elife.30352 ◽

2017 ◽

Vol 6 ◽

Cited By ~ 13

Author(s):

Daniel J Galtieri ◽

Chad M Estep ◽

David L Wokosin ◽

Stephen Traynelis ◽

D James Surmeier

Keyword(s):

Substantia Nigra ◽

Dopaminergic Neurons ◽

Substantia Nigra Pars Compacta ◽

Glutamatergic Synapses ◽

Glutamatergic Neurons ◽

Oscillatory Mechanisms ◽

Goal Directed Behavior ◽

Stimulation Of

Burst spiking in substantia nigra pars compacta (SNc) dopaminergic neurons is a key signaling event in the circuitry controlling goal-directed behavior. It is widely believed that this spiking mode depends upon an interaction between synaptic activation of N-methyl-D-aspartate receptors (NMDARs) and intrinsic oscillatory mechanisms. However, the role of specific neural networks in burst generation has not been defined. To begin filling this gap, SNc glutamatergic synapses arising from pedunculopotine nucleus (PPN) neurons were characterized using optical and electrophysiological approaches. These synapses were localized exclusively on the soma and proximal dendrites, placing them in a good location to influence spike generation. Indeed, optogenetic stimulation of PPN axons reliably evoked spiking in SNc dopaminergic neurons. Moreover, burst stimulation of PPN axons was faithfully followed, even in the presence of NMDAR antagonists. Thus, PPN-evoked burst spiking of SNc dopaminergic neurons in vivo may not only be extrinsically triggered, but extrinsically patterned as well.

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Role of presynaptic metabotropic glutamate receptors in the induction of long-term synaptic plasticity of vesicular release

Neuropharmacology ◽

10.1016/j.neuropharm.2012.05.004 ◽

2013 ◽

Vol 66 ◽

pp. 31-39 ◽

Cited By ~ 14

Author(s):

Chirag Upreti ◽

Xiao-lei Zhang ◽

Simon Alford ◽

Patric K. Stanton

Keyword(s):

Synaptic Plasticity ◽

Glutamate Receptors ◽

Metabotropic Glutamate Receptors ◽

Metabotropic Glutamate ◽

Vesicular Release

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T117 THE ROLE OF SPINAL GLUTAMATE UPTAKE VIA GLUTAMATE TRANSPORTER FOR INCISION-INDUCED PAIN BEHAVIORS IN RATS

European Journal of Pain Supplements ◽

10.1016/s1754-3207(11)70062-1 ◽

2011 ◽

Vol 5 (S1) ◽

pp. 19-20

Author(s):

S. Reichl ◽

A. Boecker ◽

V. Keller ◽

P.K. Zahn ◽

E.M. Pogatzki-Zahn

Keyword(s):

Glutamate Uptake ◽

Glutamate Transporter ◽

Pain Behaviors

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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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Role of Na,K-ATPase α1 and α2 Isoforms in the Support of Astrocyte Glutamate Uptake

PLoS ONE ◽

10.1371/journal.pone.0098469 ◽

2014 ◽

Vol 9 (6) ◽

pp. e98469 ◽

Cited By ~ 38

Author(s):

Nina B. Illarionava ◽

Hjalmar Brismar ◽

Anita Aperia ◽

Eli Gunnarson

Keyword(s):

Glutamate Uptake

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Neuronal control of suppression, initiation and completion of egg deposition in Drosophila melanogaster

10.1101/2021.08.23.457359 ◽

2021 ◽

Author(s):

Cristina Oliveira-Ferreira ◽

Miguel Gaspar ◽

Maria Luisa Vasconcelos

Keyword(s):

Cholinergic Neurons ◽

Egg Laying ◽

Glutamatergic Neurons ◽

Neuronal Populations ◽

Motor Circuits ◽

Neuronal Control ◽

Egg Deposition ◽

Complex Motor ◽

A Site

Egg-laying in Drosophila is the product of post-mating physiological and behavioural changes that culminate in a stereotyped sequence of actions. While egg-laying behaviour has been mostly used as a system to understand the neuronal basis of decision making in the context of site selection, it harbours a great potential as a paradigm to uncover how, once a site is selected, the appropriate motor circuits are organized and activated to deposit an egg. To study this programme, we first describe the different stages of the egg-laying programme and the specific actions associated with each stage. Using a combination of neuronal activation and silencing experiments we characterize the role of three distinct neuronal populations in the abdominal ganglion with different contributions to the egg deposition motor elements. Specifically, we identify a subset of glutamatergic neurons and a subset of cholinergic neurons that promote the initiation and completion of egg expulsion respectively, while a subset of GABAergic neurons suppresses egg-laying. This study provides insight into the organization of neuronal circuits underlying complex motor behaviour.

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Electro-acupuncture Alleviates METH Withdrawal-induced Spatial Memory Deficits by Restoring Astrocyte-drived Glutamate Uptake in dCA1

10.1101/2020.05.20.106153 ◽

2020 ◽

Author(s):

Pengbo Shi ◽

Zhaosu Li ◽

Xing Xu ◽

Jiaxun Nie ◽

Dekang Liu ◽

...

Keyword(s):

Spatial Memory ◽

Cognitive Deficits ◽

Glutamate Uptake ◽

Cognitive Disorders ◽

Memory Deficits ◽

Therapeutic Interventions ◽

Therapeutic Effects ◽

Non Invasive ◽

The Brain

ABSTRACTMethamphetamine (METH) is frequently abused drug and produces cognitive deficits. METH could induce hyper-glutamatergic state in the brain, which could partially explain METH-related cognitive deficits, but the synaptic etiology remains incompletely understood. To address this issue, we explored the role of dCA1 tripartite synapses and the potential therapeutic effects of electro-acupuncture (EA) in the development of METH withdrawal-induced spatial memory deficits in mice. We found that METH withdrawal weakened astrocytic capacity of glutamate (Glu) uptake, but failed to change Glu release from dCA3, which lead to hyper-glutamatergic excitotoxicity at dCA1 tripartite synapses. By restoring the astrocytic capacity of Glu uptake, EA treatments suppressed the hyper-glutamatergic state and normalized the excitability of postsynaptic neuron in dCA1, finally alleviated spatial memory deficits in METH withdrawal mice. These findings indicate that astrocyte at tripartite synapses might be a key target for developing therapeutic interventions against METH-associated cognitive disorders, and EA represent a promising non-invasive therapeutic strategy for the management of drugs-caused neurotoxicity.

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