A translational EEG-based approach to assess modulation of long-lasting NMDAR-dependent synaptic plasticity

Jeffrey S. Burgdorf*, E. P. Christian, L. Sørensen, P. K. Stanton, K. Leaderbrand, T. M. Madsen, M. A. Khan, R. A. Kroes, J. R. Moskal

*Corresponding author for this work

Research output: Contribution to journalArticle

2 Scopus citations

Abstract

Background: NYX-2925 is a novel N-methyl-d-aspartate receptor (NMDAR) modulator that has been shown to facilitate both NMDAR-dependent long-term potentiation (LTP) in vitro and learning and memory in vivo. Objective: The present studies examine the effects of NYX-2925 on NMDAR-dependent auditory LTP (aLTP) in vivo. Methods: NMDAR-dependent aLTP and NMDAR-dependent auditory mismatch negativity (MMN) was measured, as well as changes in resting-state qEEG power. Results: NYX-2925 (1, 10 mg/kg PO) increased aLTP 1 h after auditory tetanus measured by the post- minus pre-tetanus difference waveform 140–180 ms post tone onset. NYX-2925 (0.1, 1 mg/kg PO) facilitated MMN measured by the difference waveform (i.e., deviant minus standard tones). NYX-2925 (0.1, 1, 10 mg/kg PO) also enhanced resting-state alpha qEEG power. Conversely, the NMDAR glutamate site antagonist CPP (10 mg/kg IP) reduces alpha power and MMN and produces an opposite effect as NYX-2925 on aLTP. Conclusions: Together, these data suggest that the activation of the NMDAR by NYX-2925 enhances synaptic plasticity in vivo, which may both reduce symptoms of neurological disorders and serve as a biomarker for drug effects. This is the first demonstration of a long-lasting (1-h post-tetanus) effect of NMDAR modulation on synaptic plasticity processes in vivo using a noninvasive technique in freely behaving animals.

Original languageEnglish (US)
Pages (from-to)3687-3693
Number of pages7
JournalPsychopharmacology
Volume236
Issue number12
DOIs
StatePublished - Dec 1 2019

Keywords

  • Auditory-evoked potentials
  • EEG
  • LTP
  • Mismatch negativity
  • NMDA receptors

ASJC Scopus subject areas

  • Pharmacology

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    Burgdorf, J. S., Christian, E. P., Sørensen, L., Stanton, P. K., Leaderbrand, K., Madsen, T. M., Khan, M. A., Kroes, R. A., & Moskal, J. R. (2019). A translational EEG-based approach to assess modulation of long-lasting NMDAR-dependent synaptic plasticity. Psychopharmacology, 236(12), 3687-3693. https://doi.org/10.1007/s00213-019-05341-w