Chondroitinase and Antidepressants Promote Plasticity by Releasing TRKB from Dephosphorylating Control of PTP sigma in Parvalbumin Neurons

Angelina Lesnikova, Plinio Casarotto, Senem Merve Fred, Mikko Voipio, Frederike Winkel, Anna Stenizeig, Hanna Antila, Juzoh Umemori, Caroline Biojone, Eero Castrén

Tutkimustuotos: ArtikkelijulkaisuArtikkelivertaisarvioitu

Abstrakti

Perineuronal nets (PNNs) are an extracellular matrix structure rich in chondroitin sulfate proteoglycans (CSPGs), which preferentially encase parvalbumin-containing (PV+) interneurons. PNNs restrict cortical network plasticity but the molecular mechanisms involved are unclear. We found that reactivation of ocular dominance plasticity in the adult visual cortex induced by chondroitinase ABC (chABC)-mediated PNN removal requires intact signaling by the neurotrophin receptor TRKB in PV+ neurons. Additionally, we demonstrate that chABC increases TRKB phosphorylation (pTRKB), while PNN component aggrecan attenuates brain-derived neurotrophic factor (BDNF)-induced pTRKB in cortical neurons in culture. We further found that protein tyrosine phosphatase sigma (PTP sigma, PTPRS), receptor for CSPGs, interacts with TRKB and restricts TRKB phosphorylation. PTP sigma deletion increases phosphorylation of TRKB in vitro and in vivo in male and female mice, and juvenile-like plasticity is retained in the visual cortex of adult PTP sigma-deficient mice (PTP sigma(+/-)). The antidepressant drug fluoxetine, which is known to promote TRKB phosphorylation and reopen critical period-like plasticity in the adult brain, disrupts the interaction between TRKB and PTP sigma by binding to the transmembrane domain of TRKB. We propose that both chABC and fluoxetine reopen critical period-like plasticity in the adult visual cortex by promoting TRKB signaling in PV+ neurons through inhibition of TRKB dephosphorylation by the PTP sigma-CSPG complex.

Alkuperäiskielienglanti
LehtiJournal of Neuroscience
Vuosikerta41
Numero5
Sivut972-980
Sivumäärä9
ISSN0270-6474
DOI - pysyväislinkit
TilaJulkaistu - 3 helmikuuta 2021
OKM-julkaisutyyppiA1 Alkuperäisartikkeli tieteellisessä aikakauslehdessä, vertaisarvioitu

Tieteenalat

  • 3112 Neurotieteet

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