title: Astrocytes mediate in vivo cholinergic-induced synaptic plasticity.
abstract: Long-term potentiation (LTP) of synaptic transmission represents the cellular basis of learning and memory. Astrocytes have been shown to regulate synaptic transmission and plasticity. However, their involvement in specific physiological processes that induce LTP in vivo remains unknown. Here we show that in vivo cholinergic activity evoked by sensory stimulation or electrical stimulation of the septal nucleus increases Ca²⁺ in hippocampal astrocytes and induces LTP of CA3-CA1 synapses, which requires cholinergic muscarinic (mAChR) and metabotropic glutamate receptor (mGluR) activation. Stimulation of cholinergic pathways in hippocampal slices evokes astrocyte Ca²⁺ elevations, postsynaptic depolarizations of CA1 pyramidal neurons, and LTP of transmitter release at single CA3-CA1 synapses. Like in vivo, these effects are mediated by mAChRs, and this cholinergic-induced LTP (c-LTP) also involves mGluR activation. Astrocyte Ca²⁺ elevations and LTP are absent in IP₃R2 knock-out mice. Downregulating astrocyte Ca²⁺ signal by loading astrocytes with BAPTA or GDPβS also prevents LTP, which is restored by simultaneous astrocyte Ca²⁺ uncaging and postsynaptic depolarization. Therefore, cholinergic-induced LTP requires astrocyte Ca²⁺ elevations, which stimulate astrocyte glutamate release that activates mGluRs. The cholinergic-induced LTP results from the temporal coincidence of the postsynaptic activity and the astrocyte Ca²⁺ signal simultaneously evoked by cholinergic activity. Therefore, the astrocyte Ca²⁺ signal is necessary for cholinergic-induced synaptic plasticity, indicating that astrocytes are directly involved in brain storage information.
authors.affiliation: Instituto Cajal, Consejo Superior de Investigaciones Científicas. Madrid, Spain.
authors.forename: Marta
authors.initials: M
authors.lastname: Navarrete
authors.forename: Gertrudis
authors.initials: G
authors.lastname: Perea
authors.forename: David
authors.initials: D
authors.lastname: Fernandez de Sevilla
authors.forename: Marta
authors.initials: M
authors.lastname: Gómez-Gonzalo
authors.forename: Angel
authors.initials: A
authors.lastname: Núñez
authors.forename: Eduardo D
authors.initials: ED
authors.lastname: Martín
authors.forename: Alfonso
authors.initials: A
authors.lastname: Araque
mesh_terms: D000818:Animals; D001253:Astrocytes / Q000187:drug effects / Q000378:metabolism / Q000502:physiology*; D001285:Atropine / Q000494:pharmacology; D020013:Calcium Signaling; D059329:Cholinergic Neurons / Q000187:drug effects / Q000378:metabolism / Q000502:physiology*; D018698:Glutamic Acid / Q000378:metabolism; D005998:Glycine / Q000031:analogs & derivatives / Q000494:pharmacology; D006624:Hippocampus / Q000166:cytology / Q000187:drug effects / Q000502:physiology; D053496:Inositol 1,4,5-Trisphosphate Receptors / Q000235:genetics / Q000378:metabolism; D017774:Long-Term Potentiation; D008564:Membrane Potentials / Q000187:drug effects; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D018727:Muscarinic Antagonists / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D018094:Receptors, Metabotropic Glutamate / Q000037:antagonists & inhibitors / Q000378:metabolism; D013569:Synapses / Q000187:drug effects / Q000378:metabolism / Q000502:physiology*; D009435:Synaptic Transmission / Q000187:drug effects
chemical_list: D053496:Inositol 1,4,5-Trisphosphate Receptors; D018727:Muscarinic Antagonists; D018094:Receptors, Metabotropic Glutamate; C474696:methyl-(4-carboxyphenyl)glycine; D018698:Glutamic Acid; D001285:Atropine; D005998:Glycine