Astrocyte signaling controls spike timing-dependent depression at neocortical synapses

Rogier Min, Thomas Nevian

Research output: Contribution to journalArticleAcademicpeer-review

Abstract

Endocannabinoid mediated spike timing-dependent depression (t-LTD) is crucially involved in the development of the sensory neocortex. t-LTD at excitatory synapses in the developing rat barrel cortex requires cannabinoid CB(1) receptor (CB(1)R) activation, as well as activation of NMDA receptors located on the presynaptic terminal, but the exact signaling cascade leading to t-LTD remains unclear. We found that astrocytes are critically involved in t-LTD. Astrocytes gradually increased their Ca(2+) signaling specifically during the induction of t-LTD in a CB(1)R-dependent manner. In this way, astrocytes might act as a memory buffer for previous coincident neuronal activity. Following activation, astrocytes released glutamate, which activated presynaptic NMDA receptors to induce t-LTD. Astrocyte stimulation coincident with afferent activity resulted in long-term depression, indicating that astrocyte activation is sufficient for the induction of synaptic depression. Taken together, our findings describe the retrograde signaling cascade underlying neocortical t-LTD. The critical involvement of astrocytes in this process highlights their importance for experience-dependent sensory remodeling.

Original languageEnglish
Pages (from-to)746-53
Number of pages8
JournalNature Neuroscience
Volume15
Issue number5
DOIs
Publication statusPublished - 25 Mar 2012

Cite this

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abstract = "Endocannabinoid mediated spike timing-dependent depression (t-LTD) is crucially involved in the development of the sensory neocortex. t-LTD at excitatory synapses in the developing rat barrel cortex requires cannabinoid CB(1) receptor (CB(1)R) activation, as well as activation of NMDA receptors located on the presynaptic terminal, but the exact signaling cascade leading to t-LTD remains unclear. We found that astrocytes are critically involved in t-LTD. Astrocytes gradually increased their Ca(2+) signaling specifically during the induction of t-LTD in a CB(1)R-dependent manner. In this way, astrocytes might act as a memory buffer for previous coincident neuronal activity. Following activation, astrocytes released glutamate, which activated presynaptic NMDA receptors to induce t-LTD. Astrocyte stimulation coincident with afferent activity resulted in long-term depression, indicating that astrocyte activation is sufficient for the induction of synaptic depression. Taken together, our findings describe the retrograde signaling cascade underlying neocortical t-LTD. The critical involvement of astrocytes in this process highlights their importance for experience-dependent sensory remodeling.",
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Astrocyte signaling controls spike timing-dependent depression at neocortical synapses. / Min, Rogier; Nevian, Thomas.

In: Nature Neuroscience, Vol. 15, No. 5, 25.03.2012, p. 746-53.

Research output: Contribution to journalArticleAcademicpeer-review

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T1 - Astrocyte signaling controls spike timing-dependent depression at neocortical synapses

AU - Min, Rogier

AU - Nevian, Thomas

PY - 2012/3/25

Y1 - 2012/3/25

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AB - Endocannabinoid mediated spike timing-dependent depression (t-LTD) is crucially involved in the development of the sensory neocortex. t-LTD at excitatory synapses in the developing rat barrel cortex requires cannabinoid CB(1) receptor (CB(1)R) activation, as well as activation of NMDA receptors located on the presynaptic terminal, but the exact signaling cascade leading to t-LTD remains unclear. We found that astrocytes are critically involved in t-LTD. Astrocytes gradually increased their Ca(2+) signaling specifically during the induction of t-LTD in a CB(1)R-dependent manner. In this way, astrocytes might act as a memory buffer for previous coincident neuronal activity. Following activation, astrocytes released glutamate, which activated presynaptic NMDA receptors to induce t-LTD. Astrocyte stimulation coincident with afferent activity resulted in long-term depression, indicating that astrocyte activation is sufficient for the induction of synaptic depression. Taken together, our findings describe the retrograde signaling cascade underlying neocortical t-LTD. The critical involvement of astrocytes in this process highlights their importance for experience-dependent sensory remodeling.

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KW - Calcium Channel Blockers/pharmacology

KW - Dizocilpine Maleate/pharmacology

KW - Electric Stimulation

KW - Excitatory Amino Acid Antagonists/pharmacology

KW - Excitatory Postsynaptic Potentials/drug effects

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KW - Morpholines/pharmacology

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KW - Pyrazoles/pharmacology

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KW - Receptor, Cannabinoid, CB1/antagonists & inhibitors

KW - Signal Transduction/drug effects

KW - Sodium Channel Blockers/pharmacology

KW - Synapses/drug effects

KW - Tetrodotoxin/pharmacology

KW - Thalamus/cytology

KW - Time Factors

U2 - 10.1038/nn.3075

DO - 10.1038/nn.3075

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VL - 15

SP - 746

EP - 753

JO - Nature Neuroscience

JF - Nature Neuroscience

SN - 1097-6256

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