Activity-dependent changes in transporter and potassium currents in hippocampal astrocytes

Лебедева, А.В.; Plata, Alex; Nosova, Olga; Tyurikova, Olga; Semyanov, Alexey

doi:10.1016/j.brainresbull.2017.08.015

Cited by 20 publications

(23 citation statements)

References 51 publications

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“…Astrocytes do not generate action potentials; therefore, they have a more extensive range of gradual ('analog') changes in the membrane potential than neurons. Astrocyte depolarization produced by extracellular K + elevations may affect voltagedependent processes in these cells, e.g., reduce uptake of neurotransmitters and even reverse some antiporters such as GABA transporter or Na + /Ca 2+ exchanger 22,31,61 . Thus, astrocyte input resistance affects astrocyte function and can be tuned by changes in the expression of connexins.…”

Section: Discussionmentioning

confidence: 99%

“…However, the absence of voltage-gated Na + channels permits larger spike-free fluctuations of membrane potential in astrocytes than in neurons. The changes in astrocyte membrane potential can affect electrochemical gradients and modulate voltagedependent neurotransmitters uptake 31 . Hence, the electrical properties of the cell membrane play an essential physiological role in astrocytes.…”

Section: A Decrease In Cx43 Expression Compensates For Astrocyte Vf Imentioning

confidence: 99%

“…Therefore, we recorded I GluT to estimate the time course of glutamate clearance. Because K + accumulation in the synaptic cleft affects both presynaptic release probability and efficiency of glutamate uptake [31][32][33] , further recordings were performed in the presence of synaptic receptor blockers (Fig. 5a).…”

Section: Cr Reduces Glutamate Spillovermentioning

confidence: 99%

“…5a). The residual nonsynaptic I K was pharmacologically isolated by glutamate transporter blocker and subtracted from the synaptically induced current to reveal net I GluT 31,35 . The response to the fifth stimulus (I GluT (5)) in the 5 × 50 Hz stimulation was compared with the response to a single stimulus (I GluT (1), Fig.…”

Section: Cr Reduces Glutamate Spillovermentioning

confidence: 99%

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Caloric restriction triggers morphofunctional remodeling of astrocytes and enhances synaptic plasticity in the mouse hippocampus

Popov

Denisov²,

Bychkov

et al. 2020

Cell Death Dis

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Calorie-restricted (CR) diet has multiple beneficial effects on brain function. Here we report morphological and functional changes in hippocampal astrocytes in 3-months-old mice subjected to 1 month of the diet. Whole-cell patch-clamp recordings were performed in the CA1 stratum (str.) radiatum astrocytes of hippocampal slices. The cells were also loaded with fluorescent dye through the patch pipette. CR did not affect the number of astrocytic branches but increased the volume fraction (VF) of distal perisynaptic astrocytic leaflets. The astrocyte growth did not lead to a decrease in the cell input resistance, which may be attributed to a decrease in astrocyte coupling through the gap junctions. Western blotting revealed a decrease in the expression of Cx43 but not Cx30. Immunocytochemical analysis demonstrated a decrease in the density and size of Cx43 clusters. Cx30 cluster density did not change, while their size increased in the vicinity of astrocytic soma. CR shortened K + and glutamate transporter currents in astrocytes in response to 5 × 50 Hz Schaffer collateral stimulation. However, no change in the expression of astrocytic glutamate transporter 1 (GLT-1) was observed, while the level of glutamine synthetase (GS) decreased. These findings suggest that enhanced enwrapping of synapses by the astrocytic leaflets reduces glutamate and K + spillover. Reduced spillover led to a decreased contribution of extrasynaptic N2B containing N-methyl-D-aspartate receptors (NMDARs) to the tail of burst-induced EPSCs. The magnitude of long-term potentiation (LTP) in the glutamatergic CA3-CA1 synapses was significantly enhanced after CR. This enhancement was abolished by N2B-NMDARs antagonist. Our findings suggest that astrocytic morphofunctional remodeling is responsible for enhanced synaptic plasticity, which provides a basis for improved learning and memory reported after CR.

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Section: Discussionmentioning

confidence: 99%

Section: A Decrease In Cx43 Expression Compensates For Astrocyte Vf Imentioning

confidence: 99%

Section: Cr Reduces Glutamate Spillovermentioning

confidence: 99%

Section: Cr Reduces Glutamate Spillovermentioning

confidence: 99%

See 2 more Smart Citations

Caloric restriction triggers morphofunctional remodeling of astrocytes and enhances synaptic plasticity in the mouse hippocampus

Popov

Denisov²,

Bychkov

et al. 2020

Cell Death Dis

Self Cite

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show abstract

“…Next, we recorded IGluT in astrocytes. Because K + accumulation in the synaptic cleft affects both presynaptic release probability and glutamate uptake efficiency (Ge and Duan, 2007;Lebedeva et al, 2018;Shih et al, 2013), further recordings were performed in the presence of NMDA, AMPA and GABAA receptor blockers (Fig. 5a).…”

Section: Cr Reduces Glutamate Spillovermentioning

confidence: 99%

An astrocytic basis of caloric restriction action on the brain plasticity

Plata¹,

Popov

Denisov³

et al. 2019

Preprint

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One month of calorically restricted diet (CR) induced morphological plasticity of astrocytes in the stratum (str.) radiatum of hippocampal CA1 in three-months old mice: the volume fraction of distal perisynaptic astrocytic processes increased whereas the number of gapjunction coupled astrocytes decreased. The uncoupling was not associated with a decrease in the expression of connexin 43. Uncoupling and morphological remodeling affected spontaneous Ca 2+ activity in the astrocytic network: Ca 2+ events became longer, whereas their spread was reduced. The change in the pattern of astrocytic Ca 2+ activity may increase the spatial resolution of the information encoding in the astroglial network. Consistent with expanded synaptic enwrapping by the astroglial processes, the spillover of synaptically released K + and glutamate was diminished after CR. However, no significant changes in the expression of astrocytic glutamate transporter (GLT-1/EAAT2) were observed, although the level of glutamine synthetase was decreased. Glutamate uptake is known to regulate the synaptic plasticity. Indeed, the magnitude of long-term potentiation (LTP) in the glutamatergic CA3-CA1 synapses was significantly enhanced after CR. Our findings highlight an astroglial basis for improved learning and memory reported in various species subjected to CR.

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K⁺ efflux through postsynaptic NMDA receptors suppresses local astrocytic glutamate uptake

Tyurikova

Shih

Dembitskaya

et al. 2022

Glia

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Glutamatergic transmission prompts K + efflux through postsynaptic NMDA receptors. The ensuing hotspot of extracellular K + elevation depolarizes presynaptic terminal, boosting glutamate release, but whether this also affects glutamate uptake in local astroglia has remained an intriguing question. Here, we find that the pharmacological blockade, or conditional knockout, of postsynaptic NMDA receptors suppresses use-dependent increase in the amplitude and duration of the astrocytic glutamate transporter current (I GluT ), whereas blocking astrocytic K + channels prevents the duration increase only. Glutamate spot-uncaging reveals that astrocyte depolarization, rather than extracellular K + rises per se, is required to reduce the amplitude and duration of I GluT . Biophysical simulations confirm that local transient elevations of extracellular K + can inhibit local glutamate uptake in fine astrocytic processes. Optical glutamate sensor imaging and a two-pathway test relate postsynaptic K + efflux to enhanced extrasynaptic glutamate signaling. Thus, repetitive glutamatergic transmission triggers a feedback loop in which postsynaptic K + efflux can transiently facilitate presynaptic release while reducing local glutamate uptake.

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Activity-dependent changes in transporter and potassium currents in hippocampal astrocytes

Cited by 20 publications

References 51 publications

Caloric restriction triggers morphofunctional remodeling of astrocytes and enhances synaptic plasticity in the mouse hippocampus

Caloric restriction triggers morphofunctional remodeling of astrocytes and enhances synaptic plasticity in the mouse hippocampus

An astrocytic basis of caloric restriction action on the brain plasticity

K⁺ efflux through postsynaptic NMDA receptors suppresses local astrocytic glutamate uptake

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Activity-dependent changes in transporter and potassium currents in hippocampal astrocytes

Cited by 20 publications

References 51 publications

Caloric restriction triggers morphofunctional remodeling of astrocytes and enhances synaptic plasticity in the mouse hippocampus

Caloric restriction triggers morphofunctional remodeling of astrocytes and enhances synaptic plasticity in the mouse hippocampus

An astrocytic basis of caloric restriction action on the brain plasticity

K+ efflux through postsynaptic NMDA receptors suppresses local astrocytic glutamate uptake

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Product

Resources

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K⁺ efflux through postsynaptic NMDA receptors suppresses local astrocytic glutamate uptake