| First Author | Guyon N | Year | 2021 |
| Journal | J Neurosci | Volume | 41 |
| Issue | 13 | Pages | 2944-2963 |
| PubMed ID | 33593859 | Mgi Jnum | J:313257 |
| Mgi Id | MGI:6681953 | Doi | 10.1523/JNEUROSCI.2250-20.2021 |
| Citation | Guyon N, et al. (2021) Network Asynchrony Underlying Increased Broadband Gamma Power. J Neurosci 41(13):2944-2963 |
| abstractText | Synchronous activity of cortical inhibitory interneurons expressing parvalbumin (PV) underlies expression of cortical gamma rhythms. Paradoxically, deficient PV inhibition is associated with increased broadband gamma power in the local field potential. Increased baseline broadband gamma is also a prominent characteristic in schizophrenia and a hallmark of network alterations induced by NMDAR antagonists, such as ketamine. Whether enhanced broadband gamma is a true rhythm, and if so, whether rhythmic PV inhibition is involved or not, is debated. Asynchronous and increased firing activities are thought to contribute to broadband power increases spanning the gamma band. Using male and female mice lacking NMDAR activity specifically in PV neurons to model deficient PV inhibition, we here show that neuronal activity with decreased synchronicity is associated with increased prefrontal broadband gamma power. Specifically, reduced spike time precision and spectral leakage of spiking activity because of higher firing rates (spike "contamination") affect the broadband gamma band. Desynchronization was evident at multiple time scales, with reduced spike entrainment to the local field potential, reduced cross-frequency coupling, and fragmentation of brain states. Local application of S(+)-ketamine in (control) mice with intact NMDAR activity in PV neurons triggered network desynchronization and enhanced broadband gamma power. However, our investigations suggest that disparate mechanisms underlie increased broadband gamma power caused by genetic alteration of PV interneurons and ketamine-induced power increases in broadband gamma. Our study confirms that enhanced broadband gamma power can arise from asynchronous activities and demonstrates that long-term deficiency of PV inhibition can be a contributor.SIGNIFICANCE STATEMENT Brain oscillations are fundamental to the coordination of neuronal activity across neurons and structures. gamma oscillations (30-80 Hz) have received particular attention through their association with perceptual and cognitive processes. Synchronous activity of inhibitory parvalbumin (PV) interneurons generates cortical gamma oscillation, but, paradoxically, PV neuron deficiency is associated with increases in gamma oscillations. We here reconcile this conundrum and show how deficient PV inhibition can lead to increased and asynchronous excitatory firing, contaminating the local field potential and manifesting as increased gamma power. Thus, increased gamma power does not always reflect a genuine rhythm. Further, we show that ketamine-induced gamma increases are caused by separate network mechanisms. |
