MicroRNA-218 instructs proper assembly of hippocampal networks.
GABAergic interneurons
development
miR-218
microRNA
mouse
network stability
neuroscience
Journal
eLife
ISSN: 2050-084X
Titre abrégé: Elife
Pays: England
ID NLM: 101579614
Informations de publication
Date de publication:
20 10 2023
20 10 2023
Historique:
received:
16
08
2022
accepted:
10
10
2023
medline:
13
11
2023
pubmed:
20
10
2023
entrez:
20
10
2023
Statut:
epublish
Résumé
The assembly of the mammalian brain is orchestrated by temporally coordinated waves of gene expression. Post-transcriptional regulation by microRNAs (miRNAs) is a key aspect of this program. Indeed, deletion of neuron-enriched miRNAs induces strong developmental phenotypes, and miRNA levels are altered in patients with neurodevelopmental disorders. However, the mechanisms used by miRNAs to instruct brain development remain largely unexplored. Here, we identified miR-218 as a critical regulator of hippocampal assembly. MiR-218 is highly expressed in the hippocampus and enriched in both excitatory principal neurons (PNs) and GABAergic inhibitory interneurons (INs). Early life inhibition of miR-218 results in an adult brain with a predisposition to seizures. Changes in gene expression in the absence of miR-218 suggest that network assembly is impaired. Indeed, we find that miR-218 inhibition results in the disruption of early depolarizing GABAergic signaling, structural defects in dendritic spines, and altered intrinsic membrane excitability. Conditional knockout of
Identifiants
pubmed: 37862092
doi: 10.7554/eLife.82729
pii: 82729
pmc: PMC10637775
doi:
pii:
Substances chimiques
MicroRNAs
0
MIRN218 microRNA, human
0
Banques de données
GEO
['GSE241245']
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Research Support, N.I.H., Extramural
Langues
eng
Sous-ensembles de citation
IM
Subventions
Organisme : NINDS NIH HHS
ID : R01 NS012601
Pays : United States
Organisme : NINDS NIH HHS
ID : R21 NS087342
Pays : United States
Organisme : NIH HHS
ID : S10 OD026817
Pays : United States
Organisme : NINDS NIH HHS
ID : R01 NS092705
Pays : United States
Organisme : NINDS NIH HHS
ID : R01 NS121223
Pays : United States
Informations de copyright
© 2023, Taylor et al.
Déclaration de conflit d'intérêts
ST, MK, AV, DT, NZ, JD, KS, AH, CG, YA, YS, CD, GB, RD, CG, MZ, DB, GL No competing interests declared
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