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Gamma Entrainment Binds Higher-Order Brain Regions and Offers Neuroprotection.

ABSTRACT: Neuronal and synaptic loss is characteristic in many neurodegenerative diseases, such as frontotemporal dementia and Alzheimer's disease. Recently, we showed that inducing gamma oscillations with visual stimulation (gamma entrainment using sensory stimuli, or GENUS) reduced amyloid plaques and phosphorylated tau in multiple mouse models. Whether GENUS can affect neurodegeneration or cognitive performance remains unknown. Here, we demonstrate that GENUS can entrain gamma oscillations in the visual cortex, hippocampus, and prefrontal cortex in Tau P301S and CK-p25 mouse models of neurodegeneration. Tau P301S and CK-p25 mice subjected to chronic, daily GENUS from the early stages of neurodegeneration showed a preservation of neuronal and synaptic density across multiple brain areas and modified cognitive performance. Our transcriptomic and phosphoproteomic data suggest that chronic GENUS shifts neurons to a less degenerative state, improving synaptic function, enhancing neuroprotective factors, and reducing DNA damage in neurons while also reducing inflammatory response in microglia.

SUBMITTER: Adaikkan C

PROVIDER: S-EPMC6697125 | biostudies-literature | 2019 Jun

REPOSITORIES: biostudies-literature

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Gamma Entrainment Binds Higher-Order Brain Regions and Offers Neuroprotection.

Adaikkan Chinnakkaruppan C Middleton Steven J SJ Marco Asaf A Pao Ping-Chieh PC Mathys Hansruedi H Kim David Nam-Woo DN Gao Fan F Young Jennie Z JZ Suk Ho-Jun HJ Boyden Edward S ES McHugh Thomas J TJ Tsai Li-Huei LH

Neuron 20190507 5

Neuronal and synaptic loss is characteristic in many neurodegenerative diseases, such as frontotemporal dementia and Alzheimer's disease. Recently, we showed that inducing gamma oscillations with visual stimulation (gamma entrainment using sensory stimuli, or GENUS) reduced amyloid plaques and phosphorylated tau in multiple mouse models. Whether GENUS can affect neurodegeneration or cognitive performance remains unknown. Here, we demonstrate that GENUS can entrain gamma oscillations in the visua ...[more]

PMID: 31076275

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Project description:IntroductionThe relationship between oscillatory activity in hippocampus and cognitive impairment in traumatic brain injury (TBI) remains unclear. Although TBI decreases gamma oscillations and 40 Hz light flicker improves TBI prognosis, the effects and mechanism of rhythmic flicker on TBI remain unclear.AimsIn this study, we aimed to explore whether light flicker could reverse cognitive deficits, and further explore its potential mechanisms in TBI mouse model.MethodsThe Morris water maze test (MWM), step-down test (SDT), and novel object recognition test (NOR) were applied to evaluate the cognitive ability. The local field potential (LFP) recording was applied to measure low gamma reduction of CA1 in hippocampus after TBI. And electrophysiological experiments were applied to explore effects of the gamma frequency entrainment on long-term potentiation (LTP), postsynaptic transmission, and intrinsic excitability of CA1 pyramidal cells (PCs) in TBI mice. Immunofluorescence staining and western blotting were applied to explore the effects of 40 Hz light flicker on the expression of PSD95 in hippocampus of TBI mice.ResultsWe found that 40 Hz light flicker restored low gamma reduction of CA1 in hippocampus after TBI. And 40 Hz, but not random or 80 Hz light flicker, reversed cognitive impairment after TBI in behavioral tests. Moreover, 40 Hz light flicker improved N-methyl-D-aspartate (NMDA) receptor-dependent LTP (LTPNMDAR ) and L-type voltage-gated calcium channel-dependent LTP (LTPL-VGCC ) after TBI treatment. And gamma frequency entrainment decreased excitatory postsynaptic currents (EPSCs) of CA1 PCs in TBI mice. Our results have illustrated that 40 Hz light flicker could decrease intrinsic excitability of PCs after TBI treatment in mice. Furthermore, 40 Hz light flicker decreased the expression of PSD95 in hippocampus of TBI mice.ConclusionThese results demonstrated that 40 Hz light flicker rescues cognitive impairment by decreasing postsynaptic transmission in PCs after TBI treatment in mice.

Dataset Information

Gamma Entrainment Binds Higher-Order Brain Regions and Offers Neuroprotection.

Publications

Gamma Entrainment Binds Higher-Order Brain Regions and Offers Neuroprotection.

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