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Darby, F.

Publications and source records attributed to Darby, F..

2 recordsLinked to original sources

Auditory Perception Induces Cortical and Thalamic Event-Related Desynchronization in the Mouse

Studies of human perception have shown early cortical signals for primary information encoding, and later signals for higher order processing. An important late signal is the cortical event-related desynchronization (ERD) in the alpha (8-12Hz) and beta (12-30Hz) frequency band, which has been linked to human perceptual awareness. Detailed mechanistic investigation of the ERD would be greatly facilitated by availability of a suitable animal model. We conducted local field potential recordings in the mouse frontal association cortex (FrA), thalamic intralaminar centrolateral nucleus (Cl), primary auditory cortex (A1), and primary visual cortex (V1) during two auditory tasks. Fully audible brief 50 ms stimuli with both tasks produced early broadband gamma (30-100Hz) frequency activity at 0-250ms, followed by a late cortical alpha/beta ERD 250 - 750 ms after stimulus onset. The ERD was statistically significant in FrA and A1, but not in V1. Interestingly, a significant ERD was also observed in thalamic Cl. The magnitude of the ERD at full stimulus intensity, and the slope of the relationship between stimulus intensity versus ERD magnitude, were both largest in FrA, and smaller in Cl and A1. Conversely, for early broadband gamma activity the magnitude at full intensity and slopes were largest in A1, smaller in Cl and smaller still in FrA. These findings suggest that mice, like humans, process perceptual signals in hierarchically organized corticothalamic networks, and strongly support mice as a promising platform for further investigation of the ERD to better understand the origin and function of this robust yet understudied electrophysiological phenomenon. Significance StatementAuditory-induced alpha/beta event-related desynchronizations (ERDs), decreases in cortical activity between 8 and 30Hz following auditory stimulus presentation, are thought to represent systems underlying higher perception and cognition. However, fundamental mechanistic studies are difficult in humans, the dominant organism for studying this phenomenon. In this study we assess mice as a potential alternative model organism. Our results demonstrate that mice exhibit auditory-induced alpha/beta ERDs, that this response is also present in subcortical regions of the mouse brain, and that the cortical ERD is largest and most strongly related to auditory stimulus amplitude in association cortex rather than in primary auditory cortex. These results support the efficacy of mice as an ideal model organism for further examination of alpha/beta ERDs.

neuroscience↗

Daily glucocorticoids promote glioblastoma growth and circadian synchrony to the host

Glioblastoma (GBM) is the most common primary brain tumor in adults with a poor prognosis despite aggressive therapy. A recent, retrospective clinical study found that administering Temozolomide in the morning increased patient overall survival by 6 months compared to evening. Here, we tested the hypothesis that daily host signaling regulates tumor growth and synchronizes circadian rhythms in GBM. We found daily Dexamethasone promoted or suppressed GBM growth depending on time of day of administration and on the clock gene, Bmal1. Blocking circadian signals, like VIP or glucocorticoids, dramatically slowed GBM growth and disease progression. Finally, mouse and human GBM models have intrinsic circadian rhythms in clock gene expression in vitro and in vivo that entrain to the host through glucocorticoid signaling, regardless of tumor type or host immune status. We conclude that GBM entrains to the circadian circuit of the brain, which modulates its growth through clock-controlled cues, like glucocorticoids.

neuroscience↗