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

Abstract

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 (PV_cre/NR1_fl/fl) demonstrated altered gamma-band CFC as compared with their control littermates (PV_cre/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. PV_cre/NR1_fl/fl mice exhibited an increase in resting power specific to the high gamma-band, but not other frequency bands, as compared with PV_cre/NR1_+/+. CFC analyses then examined both the standard magnitude (strength) of CFC and the novel metric Phase_Max—which denotes the phase of the lower frequency signal at which the peak higher frequency signal power occurred. PV_cre/NR1_fl/fl mice exhibited altered Phase_Max, but not strength, of gamma-band CFC as compared with PV_cre/NR1_+/+ mice. As such, this study suggests a potential novel metric to explore when studying neuropsychiatric disorders.