Network Asynchrony Underlying Increased Broadband Gamma Power

Abstract

Synchronous activity of cortical inhibitory interneurons expressing parvalbumin (PV) underlies the expression of cortical gamma rhythms. Paradoxically, deficient PV inhibition is associated with increased broadband gamma power. Increased baseline broadband gamma is also a prominent characteristic in schizophrenia, and a hallmark of network alterations induced by N-methyl-D-aspartate receptor (NMDAR) antagonists such as ketamine. It has been questioned if enhanced broadband gamma power is a true rhythm, and if rhythmic PV inhibition is involved or not. It has been suggested that asynchronous and increased firing activities underlie broadband power increases spanning the gamma band. Using mice lacking NMDAR activity specifically in PV neurons to model deficient PV inhibition, we here show that local LFP (local field potential) oscillations and neuronal activity with decreased synchronicity generate increases in prefrontal broadband gamma power. Specifically, reduced spike time precision of both local PV interneurons and wide-spiking (WS) excitatory neurons contribute to increased firing rates, and spectral leakage of spiking activity (spike "contamination") affecting the broadband gamma band. Desynchronization was evident at multiple time scales, with reduced spike-LFP entrainment, reduced cross-frequency coupling, and fragmentation of brain states. While local application of S(+)-ketamine in wildtype mice triggered network desynchronization and increases in broadband gamma power, our investigations suggest that disparate mechanisms underlie increased power of broadband gamma caused by genetic alteration of PV interneurons, and ketamine-induced power increases in broadband gamma. Our studies, thus, confirm that broadband gamma increases can arise from asynchronous activities, and demonstrate that long-term deficiency of PV inhibition can be a contributor..

Impact of Perineuronal Nets on Electrophysiology of Parvalbumin Interneurons, Principal Neurons, and Brain Oscillations: A Review

“…Some observed discrepancies are likely due to differences in recording preparations in which optogenetic suppression of PV interneurons in anesthetized animals (Sohal et al, 2009 ) may decrease gamma power, whereas PV suppression in awake and behaving animals may show different changes in the power spectrum that depend on the behavior. Overall, these results are consistent with the idea that decreased inhibitory function can lead to broadband increases in spontaneous gamma power but deficits in narrowband, evoked gamma oscillatory activity (Cho et al, 2015 ; Sohal and Rubenstein, 2019 ; Guyon et al, 2021 ). While a few studies show increases in gamma power after PNN removal, it is still unclear whether increases are reflective of aberrant network instability or true oscillations.…”

“…Optogenetic activation of PV interneurons is known to create stable network oscillations in a narrow gamma frequency range ~40 Hz (Cardin et al, 2009 ; Sohal et al, 2009 ; Chen et al, 2017 ). Inhibition of PV interneurons has been shown to cause both increases in spectral power over a broad gamma frequency range and decreases in narrowband gamma activity (Cho et al, 2015 ; Chen et al, 2017 ; Abbas et al, 2018 ; Sohal and Rubenstein, 2019 ; Guyon et al, 2021 ). These findings are seemingly contradictory, as both activation and inhibition of PV interneurons can cause gamma power activity.…”

Hippocampal gamma-band oscillopathy in a mouse model of Fragile X Syndrome

“…On the other hand, a reduction in cellular firing was evident, when gamma oscillations were induced by KA. Thus, increased CCh-induced gamma oscillations might reflect such an aberrant increase in cellular firing leading to an enhanced broadband gamma power as observed in vivo (Arbab et al, 2018;Guyon et al, 2021;Talbot et al, 2018). On the other hand, reduced synchronization of gamma oscillations induced by KA might be associated with the desynchronization of underlying cellular activities (reduced unit firing) together with a potentially reduced KAR function in the hippocampus as reported in the cortex of the FMR1 KO mice (Qiu et al, 2018).…”

“…PV+ interneuron dysfunction and reduction in their number have been reported in the FMR1 KO mice (Lee et al, 2019;Lovelace et al, 2020;Steullet et al, 2017;Wen et al, 2018) and in postmortem neocortical tissue of autistic individuals (Hashemi et al, 2017). Paradoxically, deficient PV+ neuron function can lead to increased broadband gamma power, however, with a desynchronized cellular activity to the ongoing LFP oscillations (Guyon et al, 2021). Indeed, despite the overall increase in the pyramidal cell firing (Boone et al, 2018), such desynchronization of cellular activity within the CA1 network and to the ongoing LFP oscillations have been demonstrated in the FMR1 KO mice (Arbab et al, 2018;Talbot et al, 2018).…”

Neocortical localization and thalamocortical modulation of neuronal hyperexcitability contribute to Fragile X Syndrome

“…The role of gamma oscillations is increasingly nuanced, such that precise synchrony in gamma activity is contributory to higher-order cognition 61 , 73 , and that a modest degree of asynchrony or noise represents physiological processes 74 – 76 . Nevertheless, asynchronous (usually broadband) gamma power, above what is typically expected, has been associated with disease states 72 as well as with reduced spike precision and spectral leakage of spiking activities in microcircuit preparations 77 .…”