Dataset Information

MicroRNA-101 Regulates Multiple Developmental Programs to Constrain Excitation in Adult Neural Networks.

ABSTRACT: A critical feature of neural networks is that they balance excitation and inhibition to prevent pathological dysfunction. How this is achieved is largely unknown, although deficits in the balance contribute to many neurological disorders. We show here that a microRNA (miR-101) is a key orchestrator of this essential feature, shaping the developing network to constrain excitation in the adult. Transient early blockade of miR-101 induces long-lasting hyper-excitability and persistent memory deficits. Using target site blockers in vivo, we identify multiple developmental programs regulated in parallel by miR-101 to achieve balanced networks. Repression of one target, NKCC1, initiates the switch in ?-aminobutyric acid (GABA) signaling, limits early spontaneous activity, and constrains dendritic growth. Kif1a and Ank2 are targeted to prevent excessive synapse formation. Simultaneous de-repression of these three targets completely phenocopies major dysfunctions produced by miR-101 blockade. Our results provide new mechanistic insight into brain development and suggest novel candidates for therapeutic intervention.

SUBMITTER: Lippi G

PROVIDER: S-EPMC5182124 | biostudies-literature | 2016 Dec

REPOSITORIES: biostudies-literature

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Publications

MicroRNA-101 Regulates Multiple Developmental Programs to Constrain Excitation in Adult Neural Networks.

Lippi Giordano G Fernandes Catarina C CC Ewell Laura A LA John Danielle D Romoli Benedetto B Curia Giulia G Taylor Seth R SR Frady E Paxon EP Jensen Anne B AB Liu Jerry C JC Chaabane Melanie M MM Belal Cherine C Nathanson Jason L JL Zoli Michele M Leutgeb Jill K JK Biagini Giuseppe G Yeo Gene W GW Berg Darwin K DK

Neuron 20161208 6

A critical feature of neural networks is that they balance excitation and inhibition to prevent pathological dysfunction. How this is achieved is largely unknown, although deficits in the balance contribute to many neurological disorders. We show here that a microRNA (miR-101) is a key orchestrator of this essential feature, shaping the developing network to constrain excitation in the adult. Transient early blockade of miR-101 induces long-lasting hyper-excitability and persistent memory defici ...[more]

PMID: 27939580

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Dataset Information

MicroRNA-101 Regulates Multiple Developmental Programs to Constrain Excitation in Adult Neural Networks.

Publications

MicroRNA-101 Regulates Multiple Developmental Programs to Constrain Excitation in Adult Neural Networks.

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