Retrograde Synaptic Signaling Mediated by K+ Efflux through Postsynaptic NMDA Receptors

Shih, Pei‐Yu; Savtchenko, Leonid P.; Kamasawa, Naomi; Dembitskaya, Yulia; McHugh, Thomas J.; Rusakov, Dmitri A.; Shigemoto, Ryuichi; Semyanov, Alexey

doi:10.1016/j.celrep.2013.10.026

Cited by 67 publications

(97 citation statements)

References 48 publications

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“…To investigate whether the reduced expression of the α 2 NKA in W887R/+ KI mice causes a reduced rate of K + clearance by astrocytes during neuronal activity, we took advantage of the fact that (i) as a consequence of the very high expression of K + channels that are open at negative resting voltages, the astrocyte passive conductance is essentially K + selective and the astrocyte membrane potential behaves as a good K + electrode, rendering astrocytes useful [K + ] e biosensors (Meeks & Mennerick, ; Zhou et al , ; Hwang et al , ); (ii) the slowly decaying inward current elicited in astrocytes upon extracellular neuronal stimulation in acute brain slices is largely a K + current that reflects [K + ] e accumulation due to neuronal K + efflux and the accompanying change in driving force through glial K + channels (mainly inward rectifier Kir channels judging from the sensitivity of the slow current to low Ba 2+ concentrations and to Kir4.1 knockout) (De Saint & Westbrook, ; Djukic et al , ; Meeks & Mennerick, ; Bernardinelli & Chatton, ; Shih et al , ; Sibille et al , ). The time constant of decay of this slow current (hereafter called I K ) provides a measure of the rate of K + clearance, which has been shown to be equivalent to that obtained with [K + ] e ‐sensitive microelectrodes (Meeks & Mennerick, ).…”

Section: Resultsmentioning

confidence: 99%

“…Therefore, to investigate the effect of the FHM2 mutation on K + clearance, we recorded the current evoked in layer 1 astrocytes by extracellular stimulation in layer 1, a protocol similar to that used for the STC. However, the recordings were performed in the absence of synaptic receptor blockers because postsynaptic Glu receptors, in particular the NMDA receptors (NMDARs), represent a major source of K + efflux during neuronal activity (Poolos et al , ; De Saint & Westbrook, ; Shih et al , ; Sibille et al , ). The I K current elicited by repetitive stimulation (10 pulses at 50 Hz) in WT astrocytes decayed with a time constant of 2.36 ± 0.10 s, more than two orders of magnitude more slowly than the STC (Fig ).…”

Section: Resultsmentioning

confidence: 99%

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Defective glutamate and K ⁺ clearance by cortical astrocytes in familial hemiplegic migraine type 2

et al. 2016

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Migraine is a common disabling brain disorder. A subtype of migraine with aura (familial hemiplegic migraine type 2: FHM2) is caused by loss‐of‐function mutations in α2 Na+,K+ ATPase (α2 NKA), an isoform almost exclusively expressed in astrocytes in adult brain. Cortical spreading depression (CSD), the phenomenon that underlies migraine aura and activates migraine headache mechanisms, is facilitated in heterozygous FHM2‐knockin mice with reduced expression of α2 NKA. The mechanisms underlying an increased susceptibility to CSD in FHM2 are unknown. Here, we show reduced rates of glutamate and K+ clearance by cortical astrocytes during neuronal activity and reduced density of GLT‐1a glutamate transporters in cortical perisynaptic astrocytic processes in heterozygous FHM2‐knockin mice, demonstrating key physiological roles of α2 NKA and supporting tight coupling with GLT‐1a. Using ceftriaxone treatment of FHM2 mutants and partial inhibition of glutamate transporters in wild‐type mice, we obtain evidence that defective glutamate clearance can account for most of the facilitation of CSD initiation in FHM2‐knockin mice, pointing to excessive glutamatergic transmission as a key mechanism underlying the vulnerability to CSD ignition in migraine.

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Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Defective glutamate and K ⁺ clearance by cortical astrocytes in familial hemiplegic migraine type 2

et al. 2016

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“…Recently, K + released from postsynaptic neurons due to synaptic activation has been shown to influence presynaptic activity by acting as a retrograde messenger (Shih et al . ). Bursts of action potentials can cause considerable change in the extracellular K + due to the limited volume of the interstitial space and low baseline levels of extracellular K + (Kume‐Kick et al .…”

Section: Discussionmentioning

confidence: 97%

Depression biased non‐Hebbian spike‐timing‐dependent synaptic plasticity in the rat subiculum

Pandey

Sikdar

2014

The Journal of Physiology

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Key pointsr Spike-timing-dependent plasticity (STDP) is the induction of synaptic plasticity by coincident activity of pre-and postsynaptic neurons.r In most of the excitatory synapses, an EPSP immediately followed by a back-propagating action potential (bAP) enhances the synaptic efficacy, whereas the reverse weakens it.r Contrary to the above observation, we demonstrate that, at the proximal excitatory synapses on the subicular pyramidal neurons, an EPSP immediately followed by a burst of bAPs weakens the synaptic strength, whereas the reverse strengthens the synapse in both bursting and regular firing neurons.r This reverse STDP rule may have strong implications in synaptic integration and information outflow from the hippocampus.r Interestingly, the mechanisms associated with synaptic depression using the same induction protocol were different in the two neuronal subtypes, being postsynaptic in the bursting neurons requiring NMDA receptor activity, but presynaptic in the regular firing neurons involving L-type calcium channels.Abstract The subiculum is a structure that forms a bridge between the hippocampus and the entorhinal cortex (EC), and plays a major role in the memory consolidation process. Here, we demonstrate spike-timing-dependent plasticity (STDP) at the proximal excitatory inputs on the subicular pyramidal neurons of juvenile rat. Causal (positive) pairing of a single EPSP with a single back-propagating action potential (bAP) after a time interval of 10 ms (+10 ms) failed to induce plasticity. However, increasing the number of bAPs in a burst to three, at two different frequencies of 50 Hz (bAP burst) and 150 Hz, induced long-term depression (LTD) after a time interval of +10 ms in both the regular-firing (RF), and the weak burst firing (WBF) neurons. The LTD amplitude decreased with increasing time interval between the EPSP and the bAP burst. Reversing the order of the pairing of the EPSP and the bAP burst induced LTP at a time interval of −10 ms. This finding is in contrast with reports at other synapses, wherein prebefore postsynaptic (causal) pairing induced LTP and vice versa. Our results reaffirm the earlier observations that the relative timing of the pre-and postsynaptic activities can lead to multiple types of plasticity profiles. The induction of timing-dependent LTD (t-LTD) was dependent on postsynaptic calcium change via NMDA receptors in the WBF neurons, while it was independent of postsynaptic calcium change, but required active L-type calcium channels in the RF neurons. Thus the mechanism of synaptic plasticity may vary within a hippocampal subfield depending on the postsynaptic neuron involved. This study also reports a novel mechanism of LTD induction, where L-type calcium channels are involved in a presynaptically induced synaptic plasticity. The findings may have strong implications in the memory consolidation process owing to the central role of the subiculum and LTD in this process.

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“…Increased VF of perisynaptic astrocytic leaflets may modify major homeostatic functions including K + clearance. During synaptic transmission, K + is mostly released through postsynaptic ionotropic glutamate receptors, predominantly of NMDA type (Ge and Duan, 2007;Shih et al, 2013;Sibille et al, 2014). Thus, astrocytic K + current (IK) in astrocyte can provide a readout of both postsynaptic response (the IK amplitude) and astrocytic K + clearance (the IK decay time [τdecay IK], Fig.…”

Section: Cr Enhances Activity-dependent K + Release But Reduces K + Smentioning

confidence: 99%

“…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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Retrograde Synaptic Signaling Mediated by K+ Efflux through Postsynaptic NMDA Receptors

Cited by 67 publications

References 48 publications

Defective glutamate and K ⁺ clearance by cortical astrocytes in familial hemiplegic migraine type 2

Defective glutamate and K ⁺ clearance by cortical astrocytes in familial hemiplegic migraine type 2

Depression biased non‐Hebbian spike‐timing‐dependent synaptic plasticity in the rat subiculum

An astrocytic basis of caloric restriction action on the brain plasticity

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Retrograde Synaptic Signaling Mediated by K+ Efflux through Postsynaptic NMDA Receptors

Cited by 67 publications

References 48 publications

Defective glutamate and K + clearance by cortical astrocytes in familial hemiplegic migraine type 2

Defective glutamate and K + clearance by cortical astrocytes in familial hemiplegic migraine type 2

Depression biased non‐Hebbian spike‐timing‐dependent synaptic plasticity in the rat subiculum

An astrocytic basis of caloric restriction action on the brain plasticity

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Product

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Defective glutamate and K ⁺ clearance by cortical astrocytes in familial hemiplegic migraine type 2

Defective glutamate and K ⁺ clearance by cortical astrocytes in familial hemiplegic migraine type 2