GSK3β modulates timing-dependent long-term depression through direct phosphorylation of Kv4.2 channels

Giuseppe Aceto, Agnese Re, Andrea Mattera, Lucia Leone, Claudia Colussi, Marco Rinaudo, Federico Scala, Katia Gironi, Saviana Antonella Barbati, Salvatore Fusco, Thomas Green, Fernanda Laezza, Marcello D'Ascenzo, Claudio Grassi

Research output: Contribution to journalArticle

1 Citation (Scopus)

Abstract

Spike timing-dependent plasticity (STDP) is a form of activity-dependent remodeling of synaptic strength that underlies memory formation. Despite its key role in dictating learning rules in the brain circuits, the molecular mechanisms mediating STDP are still poorly understood. Here, we show that spike timing-dependent long-term depression (tLTD) and A-type K+ currents are modulated by pharmacological agents affecting the levels of active glycogen-synthase kinase 3 (GSK3) and by GSK3β knockdown in layer 2/3 of the mouse somatosensory cortex. Moreover, the blockade of A-type K+ currents mimics the effects of GSK3 up-regulation on tLTD and occludes further changes in synaptic strength. Pharmacological, immunohistochemical and biochemical experiments revealed that GSK3β influence over tLTD induction is mediated by direct phosphorylation at Ser-616 of the Kv4.2 subunit, a molecular determinant of A-type K+ currents. Collectively, these results identify the functional interaction between GSK3β and Kv4.2 channel as a novel mechanism for tLTD modulation providing exciting insight into the understanding of GSK3β role in synaptic plasticity.

Original languageEnglish (US)
Pages (from-to)1851-1865
Number of pages15
JournalCerebral Cortex
Volume29
Issue number5
DOIs
StatePublished - May 1 2019

Fingerprint

Glycogen Synthase Kinase 3
Phosphorylation
Depression
Pharmacology
Neuronal Plasticity
Somatosensory Cortex
Up-Regulation
Learning
Brain

Keywords

  • A-type K current
  • GSK3β
  • Kv4.2
  • Personalized medicine
  • Somatosensory cortex
  • Spike timing-dependent plasticity

ASJC Scopus subject areas

  • Cognitive Neuroscience
  • Cellular and Molecular Neuroscience

Cite this

Aceto, G., Re, A., Mattera, A., Leone, L., Colussi, C., Rinaudo, M., ... Grassi, C. (2019). GSK3β modulates timing-dependent long-term depression through direct phosphorylation of Kv4.2 channels. Cerebral Cortex, 29(5), 1851-1865. https://doi.org/10.1093/cercor/bhy042

GSK3β modulates timing-dependent long-term depression through direct phosphorylation of Kv4.2 channels. / Aceto, Giuseppe; Re, Agnese; Mattera, Andrea; Leone, Lucia; Colussi, Claudia; Rinaudo, Marco; Scala, Federico; Gironi, Katia; Barbati, Saviana Antonella; Fusco, Salvatore; Green, Thomas; Laezza, Fernanda; D'Ascenzo, Marcello; Grassi, Claudio.

In: Cerebral Cortex, Vol. 29, No. 5, 01.05.2019, p. 1851-1865.

Research output: Contribution to journalArticle

Aceto, G, Re, A, Mattera, A, Leone, L, Colussi, C, Rinaudo, M, Scala, F, Gironi, K, Barbati, SA, Fusco, S, Green, T, Laezza, F, D'Ascenzo, M & Grassi, C 2019, 'GSK3β modulates timing-dependent long-term depression through direct phosphorylation of Kv4.2 channels', Cerebral Cortex, vol. 29, no. 5, pp. 1851-1865. https://doi.org/10.1093/cercor/bhy042
Aceto, Giuseppe ; Re, Agnese ; Mattera, Andrea ; Leone, Lucia ; Colussi, Claudia ; Rinaudo, Marco ; Scala, Federico ; Gironi, Katia ; Barbati, Saviana Antonella ; Fusco, Salvatore ; Green, Thomas ; Laezza, Fernanda ; D'Ascenzo, Marcello ; Grassi, Claudio. / GSK3β modulates timing-dependent long-term depression through direct phosphorylation of Kv4.2 channels. In: Cerebral Cortex. 2019 ; Vol. 29, No. 5. pp. 1851-1865.
@article{8da58cd61b4e4cba876dbe4026db5bcc,
title = "GSK3β modulates timing-dependent long-term depression through direct phosphorylation of Kv4.2 channels",
abstract = "Spike timing-dependent plasticity (STDP) is a form of activity-dependent remodeling of synaptic strength that underlies memory formation. Despite its key role in dictating learning rules in the brain circuits, the molecular mechanisms mediating STDP are still poorly understood. Here, we show that spike timing-dependent long-term depression (tLTD) and A-type K+ currents are modulated by pharmacological agents affecting the levels of active glycogen-synthase kinase 3 (GSK3) and by GSK3β knockdown in layer 2/3 of the mouse somatosensory cortex. Moreover, the blockade of A-type K+ currents mimics the effects of GSK3 up-regulation on tLTD and occludes further changes in synaptic strength. Pharmacological, immunohistochemical and biochemical experiments revealed that GSK3β influence over tLTD induction is mediated by direct phosphorylation at Ser-616 of the Kv4.2 subunit, a molecular determinant of A-type K+ currents. Collectively, these results identify the functional interaction between GSK3β and Kv4.2 channel as a novel mechanism for tLTD modulation providing exciting insight into the understanding of GSK3β role in synaptic plasticity.",
keywords = "A-type K current, GSK3β, Kv4.2, Personalized medicine, Somatosensory cortex, Spike timing-dependent plasticity",
author = "Giuseppe Aceto and Agnese Re and Andrea Mattera and Lucia Leone and Claudia Colussi and Marco Rinaudo and Federico Scala and Katia Gironi and Barbati, {Saviana Antonella} and Salvatore Fusco and Thomas Green and Fernanda Laezza and Marcello D'Ascenzo and Claudio Grassi",
year = "2019",
month = "5",
day = "1",
doi = "10.1093/cercor/bhy042",
language = "English (US)",
volume = "29",
pages = "1851--1865",
journal = "Cerebral Cortex",
issn = "1047-3211",
publisher = "Oxford University Press",
number = "5",

}

TY - JOUR

T1 - GSK3β modulates timing-dependent long-term depression through direct phosphorylation of Kv4.2 channels

AU - Aceto, Giuseppe

AU - Re, Agnese

AU - Mattera, Andrea

AU - Leone, Lucia

AU - Colussi, Claudia

AU - Rinaudo, Marco

AU - Scala, Federico

AU - Gironi, Katia

AU - Barbati, Saviana Antonella

AU - Fusco, Salvatore

AU - Green, Thomas

AU - Laezza, Fernanda

AU - D'Ascenzo, Marcello

AU - Grassi, Claudio

PY - 2019/5/1

Y1 - 2019/5/1

N2 - Spike timing-dependent plasticity (STDP) is a form of activity-dependent remodeling of synaptic strength that underlies memory formation. Despite its key role in dictating learning rules in the brain circuits, the molecular mechanisms mediating STDP are still poorly understood. Here, we show that spike timing-dependent long-term depression (tLTD) and A-type K+ currents are modulated by pharmacological agents affecting the levels of active glycogen-synthase kinase 3 (GSK3) and by GSK3β knockdown in layer 2/3 of the mouse somatosensory cortex. Moreover, the blockade of A-type K+ currents mimics the effects of GSK3 up-regulation on tLTD and occludes further changes in synaptic strength. Pharmacological, immunohistochemical and biochemical experiments revealed that GSK3β influence over tLTD induction is mediated by direct phosphorylation at Ser-616 of the Kv4.2 subunit, a molecular determinant of A-type K+ currents. Collectively, these results identify the functional interaction between GSK3β and Kv4.2 channel as a novel mechanism for tLTD modulation providing exciting insight into the understanding of GSK3β role in synaptic plasticity.

AB - Spike timing-dependent plasticity (STDP) is a form of activity-dependent remodeling of synaptic strength that underlies memory formation. Despite its key role in dictating learning rules in the brain circuits, the molecular mechanisms mediating STDP are still poorly understood. Here, we show that spike timing-dependent long-term depression (tLTD) and A-type K+ currents are modulated by pharmacological agents affecting the levels of active glycogen-synthase kinase 3 (GSK3) and by GSK3β knockdown in layer 2/3 of the mouse somatosensory cortex. Moreover, the blockade of A-type K+ currents mimics the effects of GSK3 up-regulation on tLTD and occludes further changes in synaptic strength. Pharmacological, immunohistochemical and biochemical experiments revealed that GSK3β influence over tLTD induction is mediated by direct phosphorylation at Ser-616 of the Kv4.2 subunit, a molecular determinant of A-type K+ currents. Collectively, these results identify the functional interaction between GSK3β and Kv4.2 channel as a novel mechanism for tLTD modulation providing exciting insight into the understanding of GSK3β role in synaptic plasticity.

KW - A-type K current

KW - GSK3β

KW - Kv4.2

KW - Personalized medicine

KW - Somatosensory cortex

KW - Spike timing-dependent plasticity

UR - http://www.scopus.com/inward/record.url?scp=85061034919&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85061034919&partnerID=8YFLogxK

U2 - 10.1093/cercor/bhy042

DO - 10.1093/cercor/bhy042

M3 - Article

VL - 29

SP - 1851

EP - 1865

JO - Cerebral Cortex

JF - Cerebral Cortex

SN - 1047-3211

IS - 5

ER -