Disruption of NMDAR function prevents normal experience-dependent homeostatic synaptic plasticity in mouse primary visual cortex

Gabriela Rodriguez, Lukas Mesik, Ming Gao, Samuel Parkins, Rinki Saha, Hey Kyoung Lee

Research output: Contribution to journalArticlepeer-review

Abstract

Homeostatic regulation of synaptic strength allows for maintenance of neural activity within a dynamic range for proper circuit function. There are largely two distinct modes of synaptic plasticity that allow for homeostatic adaptation of cortical circuits: synaptic scaling and sliding threshold (BCM theory). Previous findings suggest that the induction of synaptic scaling is not prevented by blocking NMDARs, whereas the sliding threshold model posits that the synaptic modification threshold of LTP and LTD readjusts with activity and thus the outcome of synaptic plasticity is NMDAR dependent. Although synaptic scaling and sliding threshold have been considered two distinct mechanisms, there are indications from recent studies that these two modes of homeostatic plasticity may interact or that they may operate under two distinct activity regimes. Here, we report using both sexes of mouse that acute genetic knock-out of the obligatory subunit of NMDAR or acute pharmacological block of NMDAR prevents experience-dependent homeostatic regulation of AMPARmediated miniature EPSCs in layer 2/3 of visual cortex. This was not due to gross changes in postsynaptic neuronal activity with inhibiting NMDAR function as determine by c-Fos expression and two-photon Ca2+ imaging in awake mice. Our results suggest that experiencedependent homeostatic regulation of intact cortical circuits is mediated by NMDAR-dependent plasticity mechanisms, which supports a sliding threshold model of homeostatic adaptation.

Original languageEnglish (US)
Pages (from-to)7664-7673
Number of pages10
JournalJournal of Neuroscience
Volume39
Issue number39
DOIs
StatePublished - Sep 25 2019

Keywords

  • BCM theory
  • Homeostatic synaptic plasticity
  • NMDAR
  • Sliding threshold
  • Synaptic scaling
  • Visual cortex

ASJC Scopus subject areas

  • Neuroscience(all)

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