Astrocytes Modulate Neural Network Activity by Ca
            <sup>2+</sup>
            -Dependent Uptake of Extracellular K
            <sup>+</sup>

Wang, Fushun; Smith, Nathan A.; Xu, Qiwu; Fujita, Takumi; Baba, Akemichi; Matsuda, Takehisa; Takano, Takahiro; Bekar, Lane K.

doi:10.1126/scisignal.2002334

Cited by 257 publications

(268 citation statements)

References 72 publications

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“…In all, although a reduction in extracellular K + results in membrane hyperpolarization at up states and depolarization at down states, the net effect is a stabilization and prolongation of up state combined with depolarization and destabilization of down state. (14). We speculate that a similar mechanism exists in cerebellum and that the transient reduction of extracellular K + hyperpolarized Purkinje cells, which paradoxically prolonged up states.…”

Section: Discussionmentioning

confidence: 99%

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Bergmann glia modulate cerebellar Purkinje cell bistability via Ca ²⁺ -dependent K ⁺ uptake

Wang

Xu²,

Wang³

et al. 2012

Proc. Natl. Acad. Sci. U.S.A.

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106

104

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Recent studies have shown that cerebellar Bergmann glia display coordinated Ca 2+ transients in live mice. However, the functional significance of Bergmann glial Ca 2+ signaling remains poorly understood. Using transgenic mice that allow selective stimulation of glial cells, we report here that cytosolic Ca 2+ regulates uptake of K + by Bergmann glia, thus providing a powerful mechanism for control of Purkinje cell-membrane potential. The decline in extracellular K + evoked by agonist-induced Ca 2+ in Bergmann glia transiently increased spike activity of Purkinje cells in cerebellar slices as well as in live anesthetized mice. Thus, Bergmann glia play a previously unappreciated role in controlling the membrane potential and thereby the activity of adjacent Purkinje cells.two-photon laser scanning microscopy | ion-sensitive microelectrode B ergmann glial cells in cerebellum are electrically nonexcitable cells that in many ways serve the same functions as protoplasmic astrocytes in forebrain. Bergmann glia are chiefly responsible for glutamate uptake and extracellular K + homeostasis (1). Their highly negative resting membrane potential of −80 to −85 mV combined with a large number of inwardly rectifying K + channels helps maintain a tight control of extracellular K + concentration (2). Bergmann glial cells also display Ca 2+ transients in response to glutamate or stimulation of climbing and parallel fibers in slices and to motor activity in vivo (3). However, although glial Ca 2+ signaling has been shown to regulate synaptic transmission in several brain regions, it is presently not established whether Bergmann glia can modulate the activity of Purkinje cells.Membrane potentials of almost all neurons in mammalian brain fluctuate between a hyperpolarized state (down state) and depolarized state (up state) during sleep/anesthesia and quiet wakefulness (4, 5). These fluctuations of the membrane potentials are synchronized between neighboring cells and detected as slow (∼0.5-1 Hz), large-amplitude delta waves (4). Even though the existence of bistability of Purkinje cells in awake mice has been questioned, it is generally agreed that bistability is a common phenomenon in both anesthetized and sleeping animals (5). The bistability of the resting membrane potential in Purkinje cells was first discovered by Llinás and Sugimori in cerebellar slices (6, 7). The current model predicts that bistability of Purkinje cells, similar to thalamic neurons, relies on the balance between noninactivating inward currents (persistent Na + currents and/or T-type Ca 2+ currents) (4, 8, 9) and an outward K + leak current (5-7, 10). However, Purkinje cell bistability is not simply an expression of intrinsic membrane properties because complex spikes generated by climbing fiber activation can toggle the membrane potential between up and down states in vivo (5). Recently, glutamate uncaging on distal dendrites of striate spiny neurons was shown to induce up states that lasted hundreds of milliseconds (11), and small hyperpolarization current...

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Section: Discussionmentioning

confidence: 99%

“…Our earlier studies have shown that astrocytes in hippocampus and cortex increase K + uptake in response to agonist-induced Ca 2+ signaling (14). Fig.…”

mentioning

confidence: 99%

Bergmann glia modulate cerebellar Purkinje cell bistability via Ca ²⁺ -dependent K ⁺ uptake

Wang

Xu²,

Wang³

et al. 2012

Proc. Natl. Acad. Sci. U.S.A.

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106

104

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“…[55][56][57][58][59][60]). Astrocytes can also influence neuronal function and synaptic plasticity through active control of extracellular ion concentrations, re-uptake of neurotransmitters from the synaptic cleft and release of gliotransmitters ( [56,[61][62][63][64], but see also [65,66]). This notion of a synapse containing not only pre-and postsynaptic elements but also astrocytic elements is referred to as the 'tripartite synapse' [67][68][69].…”

Section: Intercellular Pathwaysmentioning

confidence: 99%

Mechanisms of heterosynaptic metaplasticity

Hulme

Jones

Raymond³

et al. 2014

Phil. Trans. R. Soc. B

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Synaptic plasticity is fundamental to the neural processes underlying learning and memory. Interestingly, synaptic plasticity itself can be dynamically regulated by prior activity, in a process termed ‘metaplasticity’, which can be expressed both homosynaptically and heterosynaptically. Here, we focus on heterosynaptic metaplasticity, particularly long-range interactions between synapses spread across dendritic compartments, and review evidence for intra cellular versus inter cellular signalling pathways leading to this effect. Of particular interest is our previously reported finding that priming stimulation in stratum oriens of area CA1 in the hippocampal slice heterosynaptically inhibits subsequent long-term potentiation and facilitates long-term depression in stratum radiatum. As we have excluded the most likely intracellular signalling pathways that might mediate this long-range heterosynaptic effect, we consider the hypothesis that intercellular communication may be critically involved. This hypothesis is supported by the finding that extracellular ATP hydrolysis, and activation of adenosine A2 receptors are required to induce the metaplastic state. Moreover, delivery of the priming stimulation in stratum oriens elicited astrocytic calcium responses in stratum radiatum. Both the astrocytic responses and the metaplasticity were blocked by gap junction inhibitors. Taken together, these findings support a novel intercellular communication system, possibly involving astrocytes, being required for this type of heterosynaptic metaplasticity.

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“…Astrocytes are located adjacent to neurons and are involved in a broad range of functions including synaptic plasticity, neuronal excitability and regulation of the strength of synaptic transmission through the release of glutamic acid, D-serine and adenosine triphosphate [4][5][6][7][8][9]. An elevation in astrocytic calcium concentration has been reported to actively reduce concentration of extracellular potassium ions, which has an impact on neuronal activity [10,11]. The fact that neurons and astrocytes respond synchronously to sensory stimuli, for example stimulation of whiskers in the barrel cortex of mice, also implicates astrocytes in the processing of sensory information [12].…”

Section: Introductionmentioning

confidence: 99%

Computational simulation: astrocyte-induced depolarization of neighboring neurons mediates synchronous UP states in a neural network

2015

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Although recent reports have suggested that synchronous neuronal UP states are mediated by astrocytic activity, the mechanism responsible for this remains unknown. Astrocytic glutamate release synchronously depolarizes adjacent neurons, while synaptic transmissions are blocked. The purpose of this study was to confirm that astrocytic depolarization, propagated through synaptic connections, can lead to synchronous neuronal UP states. We applied astrocytic currents to local neurons in a neural network consisting of model cortical neurons. Our results show that astrocytic depolarization may generate synchronous UP states for hundreds of milliseconds in neurons even if they do not directly receive glutamate release from the activated astrocyte.Keywords Astrocyte · Synchronous UP state · Slow inward current · Release of glutamic acid · Neural network model · Adaptive exponential integrate-and-fire model

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Astrocytes Modulate Neural Network Activity by Ca ²⁺ -Dependent Uptake of Extracellular K ⁺

Cited by 257 publications

References 72 publications

Bergmann glia modulate cerebellar Purkinje cell bistability via Ca ²⁺ -dependent K ⁺ uptake

Bergmann glia modulate cerebellar Purkinje cell bistability via Ca ²⁺ -dependent K ⁺ uptake

Mechanisms of heterosynaptic metaplasticity

Computational simulation: astrocyte-induced depolarization of neighboring neurons mediates synchronous UP states in a neural network

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Astrocytes Modulate Neural Network Activity by Ca 2+ -Dependent Uptake of Extracellular K +

Cited by 257 publications

References 72 publications

Bergmann glia modulate cerebellar Purkinje cell bistability via Ca 2+ -dependent K + uptake

Bergmann glia modulate cerebellar Purkinje cell bistability via Ca 2+ -dependent K + uptake

Mechanisms of heterosynaptic metaplasticity

Computational simulation: astrocyte-induced depolarization of neighboring neurons mediates synchronous UP states in a neural network

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Astrocytes Modulate Neural Network Activity by Ca ²⁺ -Dependent Uptake of Extracellular K ⁺

Bergmann glia modulate cerebellar Purkinje cell bistability via Ca ²⁺ -dependent K ⁺ uptake

Bergmann glia modulate cerebellar Purkinje cell bistability via Ca ²⁺ -dependent K ⁺ uptake