GSK3β Modulates Timing-Dependent Long-Term Depression Through Direct Phosphorylation of Kv4.2 Channels

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

Risultato della ricerca: Contributo in rivistaArticolo in rivistapeer review

6 Citazioni (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.
Lingua originaleEnglish
pagine (da-a)1851-1865
Numero di pagine15
RivistaCerebral Cortex
Volume2019
DOI
Stato di pubblicazionePubblicato - 2019

Keywords

  • A-type K+ current
  • GSK3
  • Kv4.2
  • Synaptic Plasticity
  • somatosensory cortex
  • spike timing-dependent plasticity

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