Pecoraro-Bisogni, F;
Lignani, G;
Contestabile, A;
Castroflorio, E;
Pozzi, D;
Rocchi, A;
Prestigio, C;
... Baldelli, P; + view all
(2018)
REST-Dependent Presynaptic Homeostasis Induced by Chronic Neuronal Hyperactivity.
Molecular Neurobiology
, 55
(6)
pp. 4959-4972.
10.1007/s12035-017-0698-9.
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Abstract
Homeostatic plasticity is a regulatory feedback response in which either synaptic strength or intrinsic excitability can be adjusted up or down to offset sustained changes in neuronal activity. Although a growing number of evidences constantly provide new insights into these two apparently distinct homeostatic processes, a unified molecular model remains unknown. We recently demonstrated that REST is a transcriptional repressor critical for the downscaling of intrinsic excitability in cultured hippocampal neurons subjected to prolonged elevation of electrical activity. Here, we report that, in the same experimental system, REST also participates in synaptic homeostasis by reducing the strength of excitatory synapses by specifically acting at the presynaptic level. Indeed, chronic hyperactivity triggers a REST-dependent decrease of the size of synaptic vesicle pools through the transcriptional and translational repression of specific presynaptic REST target genes. Together with our previous report, the data identify REST as a fundamental molecular player for neuronal homeostasis able to downscale simultaneously both intrinsic excitability and presynaptic efficiency in response to elevated neuronal activity. This experimental evidence adds new insights to the complex activity-dependent transcriptional regulation of the homeostatic plasticity processes mediated by REST.
| Type: | Article |
|---|---|
| Title: | REST-Dependent Presynaptic Homeostasis Induced by Chronic Neuronal Hyperactivity |
| Open access status: | An open access version is available from UCL Discovery |
| DOI: | 10.1007/s12035-017-0698-9 |
| Publisher version: | http://doi.org/10.1007/s12035-017-0698-9 |
| Language: | English |
| Additional information: | This version is the author accepted manuscript. For information on re-use, please refer to the publisher’s terms and conditions. |
| Keywords: | Homeostatic plasticity, REST, Gene transcription, Excitatory synapse, Neuronal excitability, Presynaptic terminals, Synaptic vesicles |
| UCL classification: | UCL UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > UCL Queen Square Institute of Neurology UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > UCL Queen Square Institute of Neurology > Clinical and Experimental Epilepsy |
| URI: | https://discovery.ucl.ac.uk/id/eprint/10057415 |
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