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 γ-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.

journal_name

Neuron

journal_title

Neuron

authors

Lippi G,Fernandes CC,Ewell LA,John D,Romoli B,Curia G,Taylor SR,Frady EP,Jensen AB,Liu JC,Chaabane MM,Belal C,Nathanson JL,Zoli M,Leutgeb JK,Biagini G,Yeo GW,Berg DK

doi

10.1016/j.neuron.2016.11.017

subject

Has Abstract

pub_date

2016-12-21 00:00:00

pages

1337-1351

issue

6

eissn

0896-6273

issn

1097-4199

pii

S0896-6273(16)30855-8

journal_volume

92

pub_type

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