Type

Journal Article

Authors

Gerhard Schratt
Christoph Dieterich
David C Henshall
Felix Rosenow
Jørgen Kjems
Thomas Braun
Marcus Krüger
Morten T Veno
Braxton Norwood
Sebastian Bauer
and 12 others

Subjects

Biochemistry

Topics
animals gene expression regulation hippocampus micrornas proteome metabolism picrotoxin gene expression profiling doublecortin protein plasma membrane calcium transporting atpases mice rbfox1 protein mouse synapses microtubule associated proteins drug effects rna splicing factors mirn129 microrna mouse neuropeptides computational biology physiology

A microRNA-129-5p/Rbfox crosstalk coordinates homeostatic downscaling of excitatory synapses. (2016)

Abstract Synaptic downscaling is a homeostatic mechanism that allows neurons to reduce firing rates during chronically elevated network activity. Although synaptic downscaling is important in neural circuit development and epilepsy, the underlying mechanisms are poorly described. We performed small RNA profiling in picrotoxin (PTX)-treated hippocampal neurons, a model of synaptic downscaling. Thereby, we identified eight microRNAs (miRNAs) that were increased in response to PTX, including miR-129-5p, whose inhibition blocked synaptic downscaling in vitro and reduced epileptic seizure severity in vivo Using transcriptome, proteome, and bioinformatic analysis, we identified the calcium pump Atp2b4 and doublecortin (Dcx) as miR-129-5p targets. Restoring Atp2b4 and Dcx expression was sufficient to prevent synaptic downscaling in PTX-treated neurons. Furthermore, we characterized a functional crosstalk between miR-129-5p and the RNA-binding protein (RBP) Rbfox1. In the absence of PTX, Rbfox1 promoted the expression of Atp2b4 and Dcx. Upon PTX treatment, Rbfox1 expression was downregulated by miR-129-5p, thereby allowing the repression of Atp2b4 and Dcx. We therefore identified a novel activity-dependent miRNA/RBP crosstalk during synaptic scaling, with potential implications for neural network homeostasis and epileptogenesis.
Collections Ireland -> Royal College of Surgeons in Ireland -> PubMed

Full list of authors on original publication

Gerhard Schratt, Christoph Dieterich, David C Henshall, Felix Rosenow, Jørgen Kjems, Thomas Braun, Marcus Krüger, Morten T Veno, Braxton Norwood, Sebastian Bauer and 12 others

Experts in our system

1
David C Henshall
Royal College of Surgeons in Ireland
Total Publications: 127
 
2
Felix Rosenow
Royal College of Surgeons in Ireland
Total Publications: 8
 
3
Braxton A Norwood
Royal College of Surgeons in Ireland
Total Publications: 4
 
4
Sebastian Bauer
Royal College of Surgeons in Ireland
Total Publications: 7