REST/NRSF drives homeostatic plasticity of inhibitory synapses in a target-dependent fashion

The repressor-element 1-silencing transcription/neuron-restrictive silencer factor (REST/NRSF) controls hundreds of neuron-specific genes. We showed that REST/NRSF downregulates glutamatergic transmission in response to hyperactivity, thus contributing to neuronal homeostasis. However, whether GABAe...

Descripción completa

Guardado en:

Detalles Bibliográficos
Autores principales:	Cosimo Prestigio, Daniele Ferrante, Antonella Marte, Alessandra Romei, Gabriele Lignani, Franco Onofri, Pierluigi Valente, Fabio Benfenati, Pietro Baldelli
Formato:	article
Lenguaje:	EN
Publicado:	eLife Sciences Publications Ltd 2021
Materias:	REST/NRSF GABAergic synapses BDNF synaptic homeostasis neural hyperactivity homeostatic plasticity Medicine R Science Q Biology (General) QH301-705.5
Acceso en línea:	https://doaj.org/article/14914593879644449fe8f7f3e92e6cdc
Etiquetas:	Agregar Etiqueta Sin Etiquetas, Sea el primero en etiquetar este registro!

id	oai:doaj.org-article:14914593879644449fe8f7f3e92e6cdc
record_format	dspace
spelling	oai:doaj.org-article:14914593879644449fe8f7f3e92e6cdc2021-12-02T17:05:17ZREST/NRSF drives homeostatic plasticity of inhibitory synapses in a target-dependent fashion10.7554/eLife.690582050-084Xe69058https://doaj.org/article/14914593879644449fe8f7f3e92e6cdc2021-12-01T00:00:00Zhttps://elifesciences.org/articles/69058https://doaj.org/toc/2050-084XThe repressor-element 1-silencing transcription/neuron-restrictive silencer factor (REST/NRSF) controls hundreds of neuron-specific genes. We showed that REST/NRSF downregulates glutamatergic transmission in response to hyperactivity, thus contributing to neuronal homeostasis. However, whether GABAergic transmission is also implicated in the homeostatic action of REST/NRSF is unknown. Here, we show that hyperactivity-induced REST/NRSF activation, triggers a homeostatic rearrangement of GABAergic inhibition, with increased frequency of miniature inhibitory postsynaptic currents (IPSCs) and amplitude of evoked IPSCs in mouse cultured hippocampal neurons. Notably, this effect is limited to inhibitory-onto-excitatory neuron synapses, whose density increases at somatic level and decreases in dendritic regions, demonstrating a complex target- and area-selectivity. The upscaling of perisomatic inhibition was occluded by TrkB receptor inhibition and resulted from a coordinated and sequential activation of the Npas4 and Bdnf gene programs. On the opposite, the downscaling of dendritic inhibition was REST-dependent, but BDNF-independent. The findings highlight the central role of REST/NRSF in the complex transcriptional responses aimed at rescuing physiological levels of network activity in front of the ever-changing environment.Cosimo PrestigioDaniele FerranteAntonella MarteAlessandra RomeiGabriele LignaniFranco OnofriPierluigi ValenteFabio BenfenatiPietro BaldellieLife Sciences Publications LtdarticleREST/NRSFGABAergic synapsesBDNFsynaptic homeostasisneural hyperactivityhomeostatic plasticityMedicineRScienceQBiology (General)QH301-705.5ENeLife, Vol 10 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	REST/NRSF GABAergic synapses BDNF synaptic homeostasis neural hyperactivity homeostatic plasticity Medicine R Science Q Biology (General) QH301-705.5
spellingShingle	REST/NRSF GABAergic synapses BDNF synaptic homeostasis neural hyperactivity homeostatic plasticity Medicine R Science Q Biology (General) QH301-705.5 Cosimo Prestigio Daniele Ferrante Antonella Marte Alessandra Romei Gabriele Lignani Franco Onofri Pierluigi Valente Fabio Benfenati Pietro Baldelli REST/NRSF drives homeostatic plasticity of inhibitory synapses in a target-dependent fashion
description	The repressor-element 1-silencing transcription/neuron-restrictive silencer factor (REST/NRSF) controls hundreds of neuron-specific genes. We showed that REST/NRSF downregulates glutamatergic transmission in response to hyperactivity, thus contributing to neuronal homeostasis. However, whether GABAergic transmission is also implicated in the homeostatic action of REST/NRSF is unknown. Here, we show that hyperactivity-induced REST/NRSF activation, triggers a homeostatic rearrangement of GABAergic inhibition, with increased frequency of miniature inhibitory postsynaptic currents (IPSCs) and amplitude of evoked IPSCs in mouse cultured hippocampal neurons. Notably, this effect is limited to inhibitory-onto-excitatory neuron synapses, whose density increases at somatic level and decreases in dendritic regions, demonstrating a complex target- and area-selectivity. The upscaling of perisomatic inhibition was occluded by TrkB receptor inhibition and resulted from a coordinated and sequential activation of the Npas4 and Bdnf gene programs. On the opposite, the downscaling of dendritic inhibition was REST-dependent, but BDNF-independent. The findings highlight the central role of REST/NRSF in the complex transcriptional responses aimed at rescuing physiological levels of network activity in front of the ever-changing environment.
format	article
author	Cosimo Prestigio Daniele Ferrante Antonella Marte Alessandra Romei Gabriele Lignani Franco Onofri Pierluigi Valente Fabio Benfenati Pietro Baldelli
author_facet	Cosimo Prestigio Daniele Ferrante Antonella Marte Alessandra Romei Gabriele Lignani Franco Onofri Pierluigi Valente Fabio Benfenati Pietro Baldelli
author_sort	Cosimo Prestigio
title	REST/NRSF drives homeostatic plasticity of inhibitory synapses in a target-dependent fashion
title_short	REST/NRSF drives homeostatic plasticity of inhibitory synapses in a target-dependent fashion
title_full	REST/NRSF drives homeostatic plasticity of inhibitory synapses in a target-dependent fashion
title_fullStr	REST/NRSF drives homeostatic plasticity of inhibitory synapses in a target-dependent fashion
title_full_unstemmed	REST/NRSF drives homeostatic plasticity of inhibitory synapses in a target-dependent fashion
title_sort	rest/nrsf drives homeostatic plasticity of inhibitory synapses in a target-dependent fashion
publisher	eLife Sciences Publications Ltd
publishDate	2021
url	https://doaj.org/article/14914593879644449fe8f7f3e92e6cdc
work_keys_str_mv	AT cosimoprestigio restnrsfdriveshomeostaticplasticityofinhibitorysynapsesinatargetdependentfashion AT danieleferrante restnrsfdriveshomeostaticplasticityofinhibitorysynapsesinatargetdependentfashion AT antonellamarte restnrsfdriveshomeostaticplasticityofinhibitorysynapsesinatargetdependentfashion AT alessandraromei restnrsfdriveshomeostaticplasticityofinhibitorysynapsesinatargetdependentfashion AT gabrielelignani restnrsfdriveshomeostaticplasticityofinhibitorysynapsesinatargetdependentfashion AT francoonofri restnrsfdriveshomeostaticplasticityofinhibitorysynapsesinatargetdependentfashion AT pierluigivalente restnrsfdriveshomeostaticplasticityofinhibitorysynapsesinatargetdependentfashion AT fabiobenfenati restnrsfdriveshomeostaticplasticityofinhibitorysynapsesinatargetdependentfashion AT pietrobaldelli restnrsfdriveshomeostaticplasticityofinhibitorysynapsesinatargetdependentfashion
_version_	1718381775877570560

REST/NRSF drives homeostatic plasticity of inhibitory synapses in a target-dependent fashion

Ejemplares similares