A Late Phase of Long-Term Synaptic Depression in Cerebellar Purkinje Cells Requires Activation of MEF2.
Arc
MRE
autism
cerebellum
memory
motor learning
Journal
Cell reports
ISSN: 2211-1247
Titre abrégé: Cell Rep
Pays: United States
ID NLM: 101573691
Informations de publication
Date de publication:
29 01 2019
29 01 2019
Historique:
received:
08
03
2016
revised:
06
09
2018
accepted:
28
12
2018
entrez:
31
1
2019
pubmed:
31
1
2019
medline:
14
3
2020
Statut:
ppublish
Résumé
The MEF2 family of transcription factors restricts excitatory synapse number in an activity-dependent fashion during development, yet MEF2 has not been implicated in long-term synaptic depression (LTD), which is thought to initiate synapse elimination. Mutations in MEF2 pathways are implicated in autism spectrum disorders, which include cerebellar dysfunction. Here, we test the hypothesis that cerebellar LTD requires postsynaptic activation of MEF2. Knockdown of MEF2D produces suppression of the transcription-dependent late phase of LTD in cultured Purkinje cells. The late phase of LTD is also completely blocked in Purkinje cells derived from MEF2A+MEF2D null mice and rescued with plasmids that drive expression of MEF2D but not phosphatase-resistant mutant MEF2D S444D. Wild-type Purkinje cells transfected with a constitutively active form of MEF2 show no alterations of synaptic strength. Thus, postsynaptic activation of MEF2 by S444 dephosphorylation is necessary, but not sufficient, for the late phase of cerebellar LTD.
Identifiants
pubmed: 30699340
pii: S2211-1247(19)30004-X
doi: 10.1016/j.celrep.2019.01.004
pmc: PMC6433166
mid: NIHMS1519901
pii:
doi:
Substances chimiques
MEF2 Transcription Factors
0
Mef2a protein, mouse
0
Mef2d protein, mouse
0
RNA, Small Interfering
0
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
1089-1097.e3Subventions
Organisme : NINDS NIH HHS
ID : R01 NS095907
Pays : United States
Organisme : NIGMS NIH HHS
ID : T32 GM007753
Pays : United States
Organisme : NIMH NIH HHS
ID : P50 MH084020
Pays : United States
Informations de copyright
Copyright © 2019 The Author(s). Published by Elsevier Inc. All rights reserved.
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