Parvalbumin cell ablation of NMDA-R1 leads to altered phase, but not amplitude, of gamma-band cross frequency coupling.

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, though the direction of change remains unresolved. It also remains unclear if murine models relevant to ASD recapitulate this altered gamma-band CFC. As such, this study examined if mice with parvalbumin (PV) cell-specific ablation of NMDA-R1 (PVcre/NR1fl/fl) demonstrated altered gamma-band CFC as compared to their control littermates (PVcre/NR1+/+). Ten mice of each genotype had four minutes of "resting" electroencephalography (EEG) 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 to PVcre/NR1+/+. CFC analyses then examined both the standard magnitude (strength) of CFC, as well as 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 cross frequency coupling as compared to PVcre/NR1+/+ mice. As such, this study suggests a potential novel metric to explore when studying neuropsychiatric disorders.