The DOI matches its Crossref record; 41 of the 41 references it cites were found in a registry or an index.
Gamma frequency entrainment attenuates amyloid load and modifies microglia
Open accessAbstract
Changes in gamma oscillations (20-50 Hz) have been observed in several neurological disorders. However, the relationship between gamma oscillations and cellular pathologies is unclear. Here we show reduced, behaviourally driven gamma oscillations before the onset of plaque formation or cognitive decline in a mouse model of Alzheimer's disease. Optogenetically driving fast-spiking parvalbumin-positive (FS-PV)-interneurons at gamma (40 Hz), but not other frequencies, reduces levels of amyloid-β (Aβ)1-40 and Aβ 1-42 isoforms. Gene expression profiling revealed induction of genes associated with morphological transformation of microglia, and histological analysis confirmed increased microglia co-localization with Aβ. Subsequently, we designed a non-invasive 40 Hz light-flickering regime that reduced Aβ 1-40 and Aβ 1-42 levels in the visual cortex of pre-depositing mice and mitigated plaque load in aged, depositing mice. Our findings uncover a previously unappreciated function of gamma rhythms in recruiting both neuronal and glial responses to attenuate Alzheimer's-disease-associated pathology.
Overview
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Verification
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
The source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“By genetically engineering these proteins into target neurons and controlling the light around them, these neurons can be activated or inhibited, which is particularly important for sensory and motor recovery and rehabilitation.[555]”
From Flexible Electronics and Devices as Human–Machine Interfaces for Medical Robotics (2022) · cites this paper as [555]
Experimental — accuracy not yet measuredThe cited source says what the claim attributes to it.
In the citing paper
“Optogenetic stimulation is based on opsins that are sensitive to light signals and only expressed in certain types of cells.”
From Flexible Electronics and Devices as Human–Machine Interfaces for Medical Robotics (2022) · cites this paper as [555]
The cited source says what the claim attributes to it.
In the citing paper
“Indeed, gamma frequency modulation was beneficial in models with amyloid and/or tau pathology54.”
From The R136S mutation in the APOE3 gene confers resilience against tau pathology via inhibition of the cGAS-STING-IFN pathway (2025) · cites this paper as [54]
The cited source says what the claim attributes to it.
In the citing paper
“Indeed, gamma frequency modulation was found to be beneficial in models with either amyloid and/or tau pathology52”
From APOE3 - R136S mutation confers resilience against tau pathology via cGAS-STING-IFN inhibition (2024) · cites this paper as [52]
The cited source says what the claim attributes to it.
In the citing paper
“our sample sizes are similar to those reported in previous publications.15,24,86”
From TERT activation targets DNA methylation and multiple aging hallmarks (2024) · cites this paper as [86]
In the citing paper
“Interestingly, entraining gamma oscillation at 40 Hz in 5xFAD mice induced amyloid reductions that were associated with an increase in microglial numbers and morphological changes such as soma enlargement and shortening of processes loaded with Aβ.”
From Microglia in Alzheimer's disease (2017) · cites this paper as [158]
In the citing paper
“Interestingly, entraining gamma oscillation at 40 Hz in 5xFAD mice induced amyloid reductions that were associated with an increase in microglial numbers and morphological changes such as soma enlargement and shortening of processes loaded with Aβ.”
From Microglia in Alzheimer's disease (2017) · cites this paper as [158]
In the citing paper
“Gamma oscillations arise from the activation of local circuits of excitatory and fast-spiking inhibitory neurons resonating at 20-50 Hz, and changes in gamma oscillation have been observed in neurological diseases (158).”
From Microglia in Alzheimer's disease (2017) · cites this paper as [158]
In the citing paper
“Gamma oscillations arise from the activation of local circuits of excitatory and fast-spiking inhibitory neurons resonating at 20-50 Hz, and changes in gamma oscillation have been observed in neurological diseases (158).”
From Microglia in Alzheimer's disease (2017) · cites this paper as [158]
In the citing paper
“Interestingly, entraining gamma oscillation at 40 Hz in 5xFAD mice induced amyloid reductions that were associated with an increase in microglial numbers and morphological changes such as soma enlargement and shortening of processes loaded with Aβ.”
From Microglia in Alzheimer's disease (2017) · cites this paper as [158]
In the citing paper
“Notably, levels of proinflammatory genes (Il1b, Il6, Cd11b) and antiinflammatory genes (Igf1) were not changed (158), suggesting that it is possible to use immunomodulation to polarize microglia toward a beneficial activation state that is characterized by increased phagocytic activity without the induction of sustained inflammatory responses.”
From Microglia in Alzheimer's disease (2017) · cites this paper as [158]
In the citing paper
“Notably, levels of proinflammatory genes (Il1b, Il6, Cd11b) and antiinflammatory genes (Igf1) were not changed (158), suggesting that it is possible to use immunomodulation to polarize microglia toward a beneficial activation state that is characterized by increased phagocytic activity without the induction of sustained inflammatory responses.”
From Microglia in Alzheimer's disease (2017) · cites this paper as [158]
In the citing paper
“RNA sequencing analysis showed an increase in phagocytic genes, such as Cd68, β 2 -microglobulin (B2m), Icam, and lysozyme 2 (Lyz2), and in the proliferation markers Csf1, Csf1r, and Csf2ra.”
From Microglia in Alzheimer's disease (2017) · cites this paper as [158]
In the citing paper
“RNA sequencing analysis showed an increase in phagocytic genes, such as Cd68, β 2 -microglobulin (B2m), Icam, and lysozyme 2 (Lyz2), and in the proliferation markers Csf1, Csf1r, and Csf2ra.”
From Microglia in Alzheimer's disease (2017) · cites this paper as [158]
In the citing paper
“In mice, slow gamma frequency visual or audio input entrains neural firing to this frequency in the cortex and hippocampus and reduces Aβ pathology and microglial abnormalities [204, 205].”
From Apolipoprotein E4, inhibitory network dysfunction, and Alzheimer’s disease (2019) · cites this paper as [204]
In the citing paper
“Transgenic mice with AD-like pathology were found to have reduced gamma power that, in one model, precedes cognitive impairment and amyloid plaque formation [21,22].”
From Parvalbumin interneuron vulnerability and brain disorders (2021) · cites this paper as [21]
In the citing paper
“Interestingly, amyloid plaques were reduced when hippocampal PV-INs artificially produced gamma oscillations in optogenetics paradigms [21].”
From Parvalbumin interneuron vulnerability and brain disorders (2021) · cites this paper as [21]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Citations
Cites
Zhang, Y., Chen, K., Sloan, S. A., Bennett, M. L., Scholze, A. R., O'Keeffe, S., Phatnani, H. P., Guarnieri, P., Caneda, C., Ruderisch, N., et al. (2014) · The Journal of Neuroscience · doi:10.1523/jneurosci.1860-14.2014 · Cited by 4,875 · cited 1×
“To understand the cellular and molecular mechanisms from our RNA-seq data, 14 of publicly available RNA-seq datasets 35 were processed for cell-type-specific analysis.”
Buzsáki, G. (2006) · doi:10.1093/acprof:oso/9780195301069.001.0001 · Cited by 4,873
Gray, C. M., König, P., Engel, A. K., & Singer, W. (1989) · Nature · doi:10.1038/338334a0 · Cited by 4,183
Host microbiota constantly control maturation and function of microglia in the CNS
Erny, D., Hrabě de Angelis, A. L., Jaitin, D., Wieghofer, P., Staszewski, O., David, E., Keren-Shaul, H., Mahlakoiv, T., Jakobshagen, K., Buch, T., et al. (2015) · Nature Neuroscience · doi:10.1038/nn.4030 · Cited by 3,569
Oakley, H., Cole, S. L., Logan, S., Maus, E., Shao, P., Craft, J., Guillozet-Bongaarts, A., Ohno, M., Disterhoft, J., Van Eldik, L., et al. (2006) · The Journal of Neuroscience · doi:10.1523/jneurosci.1202-06.2006 · Cited by 3,530
Theta oscillations in the hippocampus
Buzsáki, G. (2002) · Neuron · doi:10.1016/s0896-6273(02)00586-x · Cited by 3,332
Driving fast-spiking cells induces gamma rhythm and controls sensory responses
Cardin, J. A., Carlén, M., Meletis, K., Knoblich, U., Zhang, F., Deisseroth, K., Tsai, L.-H., & Moore, C. I. (2009) · Nature · doi:10.1038/nature08002 · Cited by 2,603
Self-citationCoherent oscillations: A mechanism of feature linking in the visual cortex?
Eckhorn, R., Bauer, R., Jordan, W., Brosch, M., Kruse, W., Munk, M., & Reitboeck, H. J. (1988) · Biological Cybernetics · doi:10.1007/bf00202899 · Cited by 2,329
Synapse Loss and Microglial Activation Precede Tangles in a P301S Tauopathy Mouse Model
Yoshiyama, Y., Higuchi, M., Zhang, B., Huang, S.-M., Iwata, N., Saido, T. C., Maeda, J., Suhara, T., Trojanowski, J. Q., & Lee, V. M.-Y. (2007) · Neuron · doi:10.1016/j.neuron.2007.01.010 · Cited by 2,208
Synaptic mechanisms of synchronized gamma oscillations in inhibitory interneuron networks
Bartos, M., Vida, I., & Jonas, P. (2007) · Nature Reviews Neuroscience · doi:10.1038/nrn2044 · Cited by 2,070
Flagged first, then by citations
Cited by
Sorted by citations
Microglia emerge as central players in brain disease
Salter, M. W., & Stevens, B. (2017) · Nature Medicine · doi:10.1038/nm.4397 · Cited by 1,767
Fang, E. F., Hou, Y., Palikaras, K., Adriaanse, B. A., Kerr, J. S., Yang, B., Lautrup, S., Hasan-Olive, M. M., Caponio, D., Dan, X., et al. (2019) · Nature Neuroscience · doi:10.1038/s41593-018-0332-9 · Cited by 1,740
Microglia in neurodegenerative diseases: mechanism and potential therapeutic targets
Gao, C., Jiang, J., Tan, Y., & Chen, S. (2023) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-023-01588-0 · Cited by 1,616
Coupled electrophysiological, hemodynamic, and cerebrospinal fluid oscillations in human sleep
Fultz, N. E., Bonmassar, G., Setsompop, K., Stickgold, R. A., Rosen, B. R., Polimeni, J. R., & Lewis, L. D. (2019) · Science · doi:10.1126/science.aax5440 · Cited by 1,197
Lin, Y.-T., Seo, J., Gao, F., Feldman, H. M., Wen, H.-L., Penney, J., Cam, H. P., Gjoneska, E., Raja, W. K., Cheng, J., et al. (2018) · Neuron · doi:10.1016/j.neuron.2018.05.008 · Cited by 1,125
Self-citation
Metadata
- Authors
- Iaccarino, H. F., Singer, A. C., Martorell, A. J., Rudenko, A., Gao, F., Gillingham, T. Z., Mathys, H., Seo, J., Kritskiy, O., Abdurrob, F., Adaikkan, C., Canter, R. G., Rueda, R., Brown, E. N., Boyden, E. S., & Tsai, L.-H.
- Affiliations
- McGovern Institute for Brain Research (US)
- Massachusetts Institute of Technology (US)
- Massachusetts General Hospital (US)
- Broad Institute (US)
- Corresponding author
- Tsai, Li-Huei
- ORCID
- Venue
- Nature
- Published
- 2016-12-07
- Volume
- 540
- Issue
- 7632
- Pages
- 230-235
- ISSN
- 0028-0836 (ISSN-L)
- 1476-4687
- PMC
- PMC5656389
- OpenAlex
- W2560234750
- Cited by
- 1,328
- References
- 41
- Citations by year
- 2026: 169 · 2025: 191 · 2024: 172 · 2023: 160 · 2022: 147 · 2021: 150 · 2020: 131 · 2019: 85 · 2018: 76 · 2017: 42 · 2016: 2
- FWCI
- 54.95
- Type
- journal article
- Language
- en
- Update notices
- Open access
- green
- www.ncbi.nlm.nih.gov
- Licence
- Locations
- Nature (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- RePEc: Research Papers in Economics (submittedVersion)
- DSpace@MIT (Massachusetts Institute of Technology) (submittedVersion, cc-by-nc)
- DSpace@MIT (Massachusetts Institute of Technology) (submittedVersion)
- PMC
- Funders
- National Institute on Aging (RF1AG047661)
- National Eye Institute (R01EY023173)
- National Institute of General Medical Sciences (R01GM104948)
- National Institute of Neurological Disorders and Stroke (DP1NS087724)
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Alzheimer's disease research and treatments
- Life Sciences › Neuroscience › Cognitive Neuroscience › Neural dynamics and brain function
- Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
- Keywords
- gamma oscillations, Alzheimer's disease, amyloid-beta, microglia, parvalbumin interneurons, optogenetics, amyloid plaques, 5xFAD mice, APP/PS1 mice, visual cortex, neurodegeneration
- MeSH terms
- Alzheimer Disease, Amyloid, Animals, Disease Models, Animal, Female, Interneurons, Light, Male, Parvalbumins, Peptide Fragments, Visual Cortex, Amyloid beta-Peptides, Microglia, Cell Shape, Mice, CA1 Region, Hippocampal, Plaque, Amyloid, Transcriptome, Optogenetics, Gamma Rhythm
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
