Parvalbumin Cell Ablation of NMDA-R1 Leads to Altered Phase, But Not Amplitude, of Gamma-Band Cross-Frequency Coupling

Brain Connect. 2019 Apr;9(3):263-272. doi: 10.1089/brain.2018.0639. Epub 2019 Mar 15.


Altered gamma-band electrophysiological activity in individuals with autism spectrum disorder (ASD) is well documented, and analogous gamma-band alterations are recapitulated in several preclinical murine models relevant to ASD. Such gamma-band activity is hypothesized to underlie local circuit processes. Gamma-band cross-frequency coupling (CFC), a related though distinct metric, interrogates local neural circuit signal integration. Several recent studies have observed perturbed gamma-band CFC in individuals with ASD, although the direction of change remains unresolved. It also remains unclear whether murine models relevant to ASD recapitulate this altered gamma-band CFC. As such, this study examined whether mice with parvalbumin (PV) cell-specific ablation of NMDA-R1 (PVcre/NR1fl/fl) demonstrated altered gamma-band CFC as compared with their control littermates (PVcre/NR1+/+-mice that do not have the PV cell-specific ablation of NMDA-R1). Ten mice of each genotype had 4 min of "resting" electroencephalography recorded and analyzed. First, resting electrophysiological power was parsed into the canonical frequency bands and genotype-related differences were subsequently explored so as to provide context for the subsequent CFC analyses. PVcre/NR1fl/fl mice exhibited an increase in resting power specific to the high gamma-band, but not other frequency bands, as compared with PVcre/NR1+/+. CFC analyses then examined both the standard magnitude (strength) of CFC and the novel metric PhaseMax-which denotes the phase of the lower frequency signal at which the peak higher frequency signal power occurred. PVcre/NR1fl/fl mice exhibited altered PhaseMax, but not strength, of gamma-band CFC as compared with PVcre/NR1+/+ mice. As such, this study suggests a potential novel metric to explore when studying neuropsychiatric disorders.

Keywords: ASD; cross-frequency coupling; gamma; phase; phase-amplitude coupling.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Autism Spectrum Disorder / physiopathology
  • Disease Models, Animal
  • Electroencephalography / methods
  • Electrophysiological Phenomena / physiology
  • Gamma Rhythm / physiology*
  • Magnetic Resonance Imaging / methods
  • Male
  • Mice
  • Mice, Inbred Strains
  • Parvalbumins / pharmacology
  • Receptors, N-Methyl-D-Aspartate / metabolism*
  • Receptors, N-Methyl-D-Aspartate / physiology*
  • Rest / physiology


  • NMDA receptor A1
  • Parvalbumins
  • Receptors, N-Methyl-D-Aspartate