Regulation of brain proteolytic activity is necessary for the in vivo function of NMDA receptors

Mirna Kvajo, Hugo Albrecht, Marita Meins, Ulrich Hengst, Edgardo Troncoso, Sandrine Lefort, J. Kiss, Carl C H Petersen, Denis Monard

Research output: Contribution to journalArticle

42 Citations (Scopus)

Abstract

Serine proteases are considered to be involved in plasticity-related events in the nervous system, but their in vivo targets and the importance of their control by endogenous inhibitors are still not clarified. Here, we demonstrate the crucial role of a potent serine protease inhibitor, protease nexin-1 (PN-1), in the regulation of activity-dependent brain proteolytic activity and the functioning of sensory pathways. Neuronal activity regulates the expression of PN-1, which in turn controls brain proteolytic activity. In PN-1-/- mice, absence of PN-1 leads to increased brain proteolytic activity, which is correlated with an activity-dependent decrease in the NR1 subunit of the NMDA receptor. Correspondingly, reduced NMDA receptor signaling is detected in their barrel cortex. This is coupled to decreased sensory evoked potentials in the barrel cortex and impaired whisker-dependent sensory motor function. Thus, a tight control of serine protease activity is critical for the in vivo function of the NMDA receptors and the proper function of sensory pathways.

Original languageEnglish
Pages (from-to)9734-9743
Number of pages10
JournalJournal of Neuroscience
Volume24
Issue number43
DOIs
Publication statusPublished - Oct 27 2004

Fingerprint

Protease Nexins
N-Methyl-D-Aspartate Receptors
Serine Proteases
Brain
Vibrissae
Serine Proteinase Inhibitors
Evoked Potentials
Nervous System

Keywords

  • Barrel cortex
  • NMDA receptors
  • Plasticity
  • Protease nexin-1
  • Serine protease inhibitors
  • Serine proteases

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

Kvajo, M., Albrecht, H., Meins, M., Hengst, U., Troncoso, E., Lefort, S., ... Monard, D. (2004). Regulation of brain proteolytic activity is necessary for the in vivo function of NMDA receptors. Journal of Neuroscience, 24(43), 9734-9743. https://doi.org/10.1523/JNEUROSCI.3306-04.2004

Regulation of brain proteolytic activity is necessary for the in vivo function of NMDA receptors. / Kvajo, Mirna; Albrecht, Hugo; Meins, Marita; Hengst, Ulrich; Troncoso, Edgardo; Lefort, Sandrine; Kiss, J.; Petersen, Carl C H; Monard, Denis.

In: Journal of Neuroscience, Vol. 24, No. 43, 27.10.2004, p. 9734-9743.

Research output: Contribution to journalArticle

Kvajo, M, Albrecht, H, Meins, M, Hengst, U, Troncoso, E, Lefort, S, Kiss, J, Petersen, CCH & Monard, D 2004, 'Regulation of brain proteolytic activity is necessary for the in vivo function of NMDA receptors', Journal of Neuroscience, vol. 24, no. 43, pp. 9734-9743. https://doi.org/10.1523/JNEUROSCI.3306-04.2004
Kvajo, Mirna ; Albrecht, Hugo ; Meins, Marita ; Hengst, Ulrich ; Troncoso, Edgardo ; Lefort, Sandrine ; Kiss, J. ; Petersen, Carl C H ; Monard, Denis. / Regulation of brain proteolytic activity is necessary for the in vivo function of NMDA receptors. In: Journal of Neuroscience. 2004 ; Vol. 24, No. 43. pp. 9734-9743.
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