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Title

Astrocytic p38α MAPK drives NMDA receptor-dependent long-term depression and modulates long-term memory

AuthorsNavarrete, Marta ; Cuartero, María Isabel; Palenzuela, Rocío ; Draffin, Jonathan E. ; Konomi, Ainoa.; Serra, Irene; Colié, Sandra; Castaño-Castaño, Sergio; Hasan, Mazahir.T.; Nebreda, Angel R.; Esteban, José A.
Issue Date2019
PublisherNature Publishing Group
CitationNature Communications 10 (2019)
AbstractNMDA receptor-dependent long-term depression (LTD) in the hippocampus is a well-known form of synaptic plasticity that has been linked to different cognitive functions. The core mechanism for this form of plasticity is thought to be entirely neuronal. However, we now demonstrate that astrocytic activity drives LTD at CA3-CA1 synapses. We have found that LTD induction enhances astrocyte-to-neuron communication mediated by glutamate, and that Ca signaling and SNARE-dependent vesicular release from the astrocyte are required for LTD expression. In addition, using optogenetic techniques, we show that low-frequency astrocytic activation, in the absence of presynaptic activity, is sufficient to induce postsynaptic AMPA receptor removal and LTD expression. Using cell-type-specific gene deletion, we show that astrocytic p38α MAPK is required for the increased astrocytic glutamate release and astrocyte-to-neuron communication during low-frequency stimulation. Accordingly, removal of astrocytic (but not neuronal) p38α abolishes LTD expression. Finally, this mechanism modulates long-term memory in vivo.
Publisher version (URL)http://dx.doi.org/10.1038/s41467-019-10830-9
URIhttp://hdl.handle.net/10261/213971
Identifiersdoi: 10.1038/s41467-019-10830-9
issn: 2041-1723
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