Assessment of the excitation–inhibition ratio in the Fmr1 KO2 mouse using neuronal oscillation dynamics

Kat, Renate; Linkenkaer-Hansen, Klaus; Koopmans, Marthe A; Houtman, Simon J; Bruining, Hilgo; Kas, Martien J H

doi:10.1093/cercor/bhae201

Cited by 2 publications

(1 citation statement)

References 55 publications

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“…There have been numerous recent studies, in human and rodent models of FXS, identifying EEG biomarkers [ 57 , 58 , 59 , 60 , 61 , 62 , 63 , 64 , 65 , 66 , 67 , 68 , 69 , 70 , 71 , 72 , 73 , 74 , 75 , 76 , 77 ]. To our knowledge, our study was the first published work conducting 24 h polysomnography recordings in Fmr1 KO mice [ 43 ].…”

Section: Discussionmentioning

confidence: 99%

Adult Inception of Ketogenic Diet Therapy Increases Sleep during the Dark Cycle in C57BL/6J Wild Type and Fragile X Mice

Westmark,

Swietlik,

Runde

et al. 2024

IJMS

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Sleep problems are a significant phenotype in children with fragile X syndrome. Our prior work assessed sleep–wake cycles in Fmr1KO male mice and wild type (WT) littermate controls in response to ketogenic diet therapy where mice were treated from weaning (postnatal day 18) through study completion (5–6 months of age). A potentially confounding issue with commencing treatment during an active period of growth is the significant reduction in weight gain in response to the ketogenic diet. The aim here was to employ sleep electroencephalography (EEG) to assess sleep–wake cycles in mice in response to the Fmr1 genotype and a ketogenic diet, with treatment starting at postnatal day 95. EEG results were compared with prior sleep outcomes to determine if the later intervention was efficacious, as well as with published rest-activity patterns to determine if actigraphy is a viable surrogate for sleep EEG. The data replicated findings that Fmr1KO mice exhibit sleep–wake patterns similar to wild type littermates during the dark cycle when maintained on a control purified-ingredient diet but revealed a genotype-specific difference during hours 4–6 of the light cycle of the increased wake (decreased sleep and NREM) state in Fmr1KO mice. Treatment with a high-fat, low-carbohydrate ketogenic diet increased the percentage of NREM sleep in both wild type and Fmr1KO mice during the dark cycle. Differences in sleep microstructure (length of wake bouts) supported the altered sleep states in response to ketogenic diet. Commencing ketogenic diet treatment in adulthood resulted in a 15% (WT) and 8.6% (Fmr1KO) decrease in body weight after 28 days of treatment, but not the severe reduction in body weight associated with starting treatment at weaning. We conclude that the lack of evidence for improved sleep during the light cycle (mouse sleep time) in Fmr1KO mice in response to ketogenic diet therapy in two studies suggests that ketogenic diet may not be beneficial in treating sleep problems associated with fragile X and that actigraphy is not a reliable surrogate for sleep EEG in mice.

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Section: Discussionmentioning

confidence: 99%

Adult Inception of Ketogenic Diet Therapy Increases Sleep during the Dark Cycle in C57BL/6J Wild Type and Fragile X Mice

Westmark,

Swietlik,

Runde

et al. 2024

IJMS

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Functional excitation-inhibition ratio indicates near-critical oscillations across frequencies

Diachenko,

Sharma,

Smit

et al. 2024

Imaging Neuroscience

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The concept of excitation/inhibition (E/I) balance plays an important role in understanding brain function in health and disease. We recently introduced an algorithm to determine a functional E/I ratio based on the critical brain dynamics that emerge in neuronal networks balancing between order and disorder. Little, however, is known about the frequency specificity of E/I regulation and how to measure it. Here, we optimized the algorithm for measuring functional excitation-inhibition ratio (fE/I) in narrow frequency ranges and validated it on a computational model of critical oscillations and EEG data. In the computational model, we confirmed that fE/I discriminated E/I connectivity differences across a wide range of frequencies (1–150 Hz). Twin EEG data revealed significant genetic influences on fE/I across frequencies, whereas contrasting eyes-open and -closed EEG indicated functional changes of fE/I restricted to a subset of alpha and beta oscillations and brain regions. We propose that assessing fE/I with finer frequency resolution will prove useful for understanding the functional role of E/I regulation in a spectrally refined fashion in health and disease.

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Assessment of the excitation–inhibition ratio in the Fmr1 KO2 mouse using neuronal oscillation dynamics

Cited by 2 publications

References 55 publications

Adult Inception of Ketogenic Diet Therapy Increases Sleep during the Dark Cycle in C57BL/6J Wild Type and Fragile X Mice

Adult Inception of Ketogenic Diet Therapy Increases Sleep during the Dark Cycle in C57BL/6J Wild Type and Fragile X Mice

Functional excitation-inhibition ratio indicates near-critical oscillations across frequencies

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