CP_ForGammaFrequencyEntrainmentAttenuatesAmyloidLoadAndModifiesMicroglia.bib

@article{7fa7dc25f79946c1fe70eed9be8dec2708114532,
title = {Gamma frequency entrainment attenuates amyloid load and modifies microglia.},
year = {2016},
url = {https://www.semanticscholar.org/paper/7fa7dc25f79946c1fe70eed9be8dec2708114532},
abstract = {S2 TL;DR: Reduced, behaviourally driven gamma oscillations before the onset of plaque formation or cognitive decline in a mouse model of Alzheimer's disease uncover a previously unappreciated function of gamma rhythms in recruiting both neuronal and glial responses to attenuate Alzheimer's-disease-associated pathology.},
author = {Hannah F. Iaccarino and A. Singer and Anthony J. Martorell and A. Rudenko and Fan Gao and Tyler Z. Gillingham and Hansruedi Mathys and Jinsoo Seo and Oleg Kritskiy and F. Abdurrob and C. Adaikkan and R. Canter and Richard Rueda and E. Brown and E. Boyden and L. Tsai},
doi = {10.1038/nature20587},
pmid = {27929004},
}

@article{13a260b0b4962532013ef2f69fbe905dc92c844e,
title = {Response of the medial temporal lobe network in amnestic mild cognitive impairment to therapeutic intervention assessed by fMRI and memory task performance},
year = {2015},
url = {https://www.semanticscholar.org/paper/13a260b0b4962532013ef2f69fbe905dc92c844e},
abstract = {S2 TL;DR: Data support a dysfunctional encoding mechanism detected by fMRI in individuals with aMCI and therapeutic intervention using fMRI to detect target engagement in response to treatment, as well as predictions based on the computational functions of the DG/CA3 elucidated in basic animal research.},
author = {A. Bakker and M. Albert and G. Krauss and Caroline L. Speck and M. Gallagher},
doi = {10.1016/j.nicl.2015.02.009},
pmid = {25844322},
}

@article{0ecf3b3aed951e583cc0e3fe9cee92c57840539b,
title = {Seizures in Alzheimer’s disease},
year = {2015},
url = {https://www.semanticscholar.org/paper/0ecf3b3aed951e583cc0e3fe9cee92c57840539b},
abstract = {S2 TL;DR: A review of recent studies using antiepileptic drugs to rescue cognitive deficits in AD mouse models and human patients and understanding of the connection between neuronal hyperexcitability and Alzheimer's as well as the potential role of epileptiform activity in the progression of AD will be beneficial for improving treatment strategies.},
author = {H. A. Born},
doi = {10.1016/j.neuroscience.2014.11.051},
pmid = {25484360},
}

@article{478c008e1422b46969146ef4fea2d00ab13b5217,
title = {Amyloid β-Induced Neuronal Hyperexcitability Triggers Progressive Epilepsy},
year = {2009},
url = {https://www.semanticscholar.org/paper/478c008e1422b46969146ef4fea2d00ab13b5217},
abstract = {Alzheimer's disease is associated with an increased risk of unprovoked seizures. However, the underlying mechanisms of seizure induction remain elusive. Here, we performed video-EEG recordings in mice carrying mutant human APPswe and PS1dE9 genes (APdE9 mice) and their wild-type littermates to determine the prevalence of unprovoked seizures. In two recording episodes at the onset of amyloid β (Aβ) pathogenesis (3 and 4.5 months of age), at least one unprovoked seizure was detected in 65% of APdE9 mice, of which 46% had multiple seizures and 38% had a generalized seizure. None of the wild-type mice had seizures. In a subset of APdE9 mice, seizure phenotype was associated with a loss of calbindin-D28k immunoreactivity in dentate granular cells and ectopic expression of neuropeptide Y in mossy fibers. In APdE9 mice, persistently decreased resting membrane potential in neocortical layer 2/3 pyramidal cells and dentate granule cells underpinned increased network excitability as identified by patch-clamp electrophysiology. At stimulus strengths evoking single-component EPSPs in wild-type littermates, APdE9 mice exhibited decreased action potential threshold and burst firing of pyramidal cells. Bath application (1 h) of Aβ1–42 or Aβ25–35 (proto-)fibrils but not oligomers induced significant membrane depolarization of pyramidal cells and increased the activity of excitatory cell populations as measured by extracellular field recordings in the juvenile rodent brain, confirming the pathogenic significance of bath-applied Aβ (proto-)fibrils. Overall, these data identify fibrillar Aβ as a pathogenic entity powerfully altering neuronal membrane properties such that hyperexcitability of pyramidal cells culminates in epileptiform activity.},
author = {R. Minkeviciene and S. Rheims and M. Dobszay and M. Zilberter and Jarmo Hartikainen and L. Fülöp and B. Penke and Y. Zilberter and T. Harkany and A. Pitkänen and H. Tanila},
doi = {10.1523/JNEUROSCI.5215-08.2009},
pmid = {19295151},
}

@article{edb041999bbceeafd06ed6e41b61d8be3d966dc9,
title = {Noninvasive 40-Hz light flicker to recruit microglia and reduce amyloid beta load},
year = {2018},
url = {https://www.semanticscholar.org/paper/edb041999bbceeafd06ed6e41b61d8be3d966dc9},
abstract = {S2 TL;DR: This protocol describes a noninvasive approach to evoke microglial engulfment and reduce amyloid levels in mouse brain and should enable further research into the interactions between neural activity, molecular pathology, and the brain’s immune system.},
author = {A. Singer and Anthony J. Martorell and J. M. Douglas and F. Abdurrob and Matthew K. Attokaren and J. Tipton and Hansruedi Mathys and C. Adaikkan and L. Tsai},
doi = {10.1038/s41596-018-0021-x},
pmid = {30072722},
}

@article{233aa01da64ce418115a6bbb843ad0c2d99ceedc,
title = {Hyperactivity Induced by Soluble Amyloid-β Oligomers in the Early Stages of Alzheimer's Disease},
year = {2021},
url = {https://www.semanticscholar.org/paper/233aa01da64ce418115a6bbb843ad0c2d99ceedc},
abstract = {Soluble amyloid-beta oligomers (Aβo) start to accumulate in the human brain one to two decades before any clinical symptoms of Alzheimer's disease (AD) and are implicated in synapse loss, one of the best predictors of memory decline that characterize the illness. Cognitive impairment in AD was traditionally thought to result from a reduction in synaptic activity which ultimately induces neurodegeneration. More recent evidence indicates that in the early stages of AD synaptic failure is, at least partly, induced by neuronal hyperactivity rather than hypoactivity. Here, we review the growing body of evidence supporting the implication of soluble Aβo on the induction of neuronal hyperactivity in AD animal models, in vitro, and in humans. We then discuss the impact of Aβo-induced hyperactivity on memory performance, cell death, epileptiform activity, gamma oscillations, and slow wave activity. We provide an overview of the cellular and molecular mechanisms that are emerging to explain how Aβo induce neuronal hyperactivity. We conclude by providing an outlook on the impact of hyperactivity for the development of disease-modifying interventions at the onset of AD.},
author = {Audrey Hector and J. Brouillette},
doi = {10.3389/fnmol.2020.600084},
pmid = {33488358},
}

@article{a77cbc26ba5fec02d4320225f206dc169a097c97,
title = {Synaptic Depression and Aberrant Excitatory Network Activity in Alzheimer’s Disease: Two Faces of the Same Coin?},
year = {2010},
url = {https://www.semanticscholar.org/paper/a77cbc26ba5fec02d4320225f206dc169a097c97},
abstract = {S2 TL;DR: It remains to be determined if synaptic depression and network dysrhythmias are mechanistically related, which of them is primary or secondary, and whether normalization of one will prevent the other as well as cognitive dysfunction in AD.},
author = {J. Palop and L. Mucke},
doi = {10.1007/s12017-009-8097-7},
pmid = {19838821},
}

@article{bb59607f9520f8e8614a7df2c6c7968486210733,
title = {Modulation of gamma oscillations as a possible therapeutic tool for neuropsychiatric diseases: A review and perspective.},
year = {2020},
url = {https://www.semanticscholar.org/paper/bb59607f9520f8e8614a7df2c6c7968486210733},
abstract = {S2 TL;DR: The present review suggests transcranial alternating current stimulation (tACS) as an alternative brain stimulation technique and discusses several advantages of tACS compared to rhythmic sensory stimulation for the entrainment of gamma oscillations in the human brain.},
author = {D. Strüber and C. Herrmann},
doi = {10.1016/j.ijpsycho.2020.03.003},
pmid = {32240665},
}

@article{8c4af23e7faebdc3729f574f32a484e1fdf45cef,
title = {Neuronal hyperactivity – A key defect in Alzheimer's disease?},
year = {2015},
url = {https://www.semanticscholar.org/paper/8c4af23e7faebdc3729f574f32a484e1fdf45cef},
abstract = {Traditionally, the impairment of cognitive functions in Alzheimeŕs disease (AD) is thought to result from a reduction in neuronal and synaptic activities, and ultimately cell death. Here, we review recent in vivo evidence from mouse models and human patients indicating that, particularly in early stages of AD, neuronal circuits are hyperactive instead of hypoactive. Functional analyses at many levels, from single neurons to neuronal populations to large‐scale networks, with a variety of electrophysiological and imaging techniques have revealed two forms of AD‐related hyperactivity and provided first insights into the synaptic mechanisms. The unexpected finding that hyperactivity is an early neuronal dysfunction represents a major conceptual shift in our understanding of AD that may have important implications for the development of therapeutic approaches.},
author = {M. A. Busche and A. Konnerth},
doi = {10.1002/bies.201500004},
pmid = {25773221},
}

@article{fdc6cd0fb259f674ac7754943b4d52f3ce5655a1,
title = {Gamma Band Neural Stimulation in Humans and the Promise of a New Modality to Prevent and Treat Alzheimer’s Disease},
year = {2018},
url = {https://www.semanticscholar.org/paper/fdc6cd0fb259f674ac7754943b4d52f3ce5655a1},
abstract = {Existing treatments for Alzheimer’s disease (AD) have questionable efficacy with a need for research into new and more effective therapies to both treat and possibly prevent the condition. This review examines a novel therapeutic modality that shows promise for treating AD based on modulating neuronal activity in the gamma frequency band through external brain stimulation. The gamma frequency band is roughly defined as being between 30 Hz-100 Hz, with the 40 Hz point being of particular significance. The epidemiology, diagnostics, existing pathological models, and related current treatment targets are initially briefly reviewed. Next, the concept of external simulation triggering brain activity in the gamma band with potential demonstration of benefit in AD is introduced with reference to a recent important study using a mouse model of the disease. The review then presents a selection of relevant studies that describe the neurophysiology involved in brain stimulation by external sources, followed by studies involving application of the modality to clinical scenarios. A table summarizing the results of clinical studies applied to AD patients is also reported and may aid future development of the modality. The use of a therapy based on modulation of gamma neuronal activity represents a novel non-invasive, non-pharmacological approach to AD. Although use in clinical scenarios is still a relatively recent area of research, the technique shows good signs of efficacy and may represent an important option for treating AD in the future.},
author = {Barry McDermott and E. Porter and Diarmaid Hughes and Brian McGinley and Mark Lang and M. O’halloran and Marggie Jones},
doi = {10.3233/JAD-180391},
pmid = {30040729},
}

@article{3b94208c768118883f375ff569930399eb76d95b,
title = {Silent Hippocampal Seizures and Spikes Identified by Foramen Ovale Electrodes in Alzheimer’s Disease},
year = {2017},
url = {https://www.semanticscholar.org/paper/3b94208c768118883f375ff569930399eb76d95b},
abstract = {S2 TL;DR: The findings in these index cases support a model in which early development of occult hippocampal hyperexcitability may contribute to the pathogenesis of AD.},
author = {Alice D. Lam and G. Deck and A. Goldman and E. Eskandar and J. Noebels and A. Cole},
doi = {10.1038/nm.4330},
pmid = {28459436},
}

@article{aeb49f15ec3ff3a3e625d02db1907380a5aa2520,
title = {Epilepsy and cognitive impairments in Alzheimer disease.},
year = {2009},
url = {https://www.semanticscholar.org/paper/aeb49f15ec3ff3a3e625d02db1907380a5aa2520},
abstract = {Alzheimer disease (AD) is associated with cognitive decline and increased incidence of seizures. Seizure activity in AD has been widely interpreted as a secondary process resulting from advanced stages of neurodegeneration, perhaps in combination with other age-related factors. However, recent findings in animal models of AD have challenged this notion, raising the possibility that aberrant excitatory neuronal activity represents a primary upstream mechanism that may contribute to cognitive deficits in these models. The following observations suggest that such activity may play a similar role in humans with AD: (1) patients with sporadic AD have an increased incidence of seizures that appears to be independent of disease stage and highest in cases with early onset; (2) seizures are part of the natural history of many pedigrees with autosomal dominant early-onset AD, including those with mutations in presenilin-1, presenilin-2, or the amyloid precursor protein, or with duplications of wild-type amyloid precursor protein; (3) inheritance of the major known genetic risk factor for AD, apolipoprotein E4, is associated with subclinical epileptiform activity in carriers without dementia; and (4) some cases of episodic amnestic wandering and disorientation in AD are associated with epileptiform activity and can be prevented with antiepileptic drugs. Here we review recent experimental data demonstrating that high levels of beta-amyloid in the brain can cause epileptiform activity and cognitive deficits in transgenic mouse models of AD. We conclude that beta-amyloid peptides may contribute to cognitive decline in AD by eliciting similar aberrant neuronal activity in humans and discuss potential clinical and therapeutic implications of this hypothesis.},
author = {J. Palop and L. Mucke},
doi = {10.1001/archneurol.2009.15},
pmid = {19204149},
}

@article{e389d100303b9c5f46c7432d5f8c3ee026d900b0,
title = {Seizures and epileptiform activity in the early stages of Alzheimer disease.},
year = {2013},
url = {https://www.semanticscholar.org/paper/e389d100303b9c5f46c7432d5f8c3ee026d900b0},
abstract = {IMPORTANCE
Epileptic activity associated with Alzheimer disease (AD) deserves increased attention because it has a harmful impact on these patients, can easily go unrecognized and untreated, and may reflect pathogenic processes that also contribute to other aspects of the illness. We report key features of AD-related seizures and epileptiform activity that are instructive for clinical practice and highlight similarities between AD and transgenic animal models of the disease.


OBJECTIVE
To describe common clinical characteristics and treatment outcomes of patients with amnestic mild cognitive impairment (aMCI) or early AD who also have epilepsy or subclinical epileptiform activity.


DESIGN
Retrospective observational study from 2007 to 2012. SETTING Memory and Aging Center, University of California, San Francisco.


PATIENTS
We studied 54 patients with a diagnosis of aMCI plus epilepsy (n = 12), AD plus epilepsy (n = 35), and AD plus subclinical epileptiform activity (n = 7).


MAIN OUTCOMES AND MEASURES
Clinical and demographic data, electroencephalogram (EEG) readings, and treatment responses to antiepileptic medications.


RESULTS
Patients with aMCI who had epilepsy presented with symptoms of cognitive decline 6.8 years earlier than patients with aMCI who did not have epilepsy (64.3 vs 71.1 years; P = .02). Patients with AD who had epilepsy presented with cognitive decline 5.5 years earlier than patients with AD who did not have epilepsy (64.8 vs 70.3 years; P = .001). Patients with AD who had subclinical epileptiform activity also had an early onset of cognitive decline (58.9 years). The timing of seizure onset in patients with aMCI and AD was nonuniform (P < .001), clustering near the onset of cognitive decline. Epilepsies were most often complex partial seizures (47%) and more than half were nonconvulsive (55%). Serial or extended EEG monitoring appeared to be more effective than routine EEG at detecting interictal and subclinical epileptiform activity. Epileptic foci were predominantly unilateral and temporal. Of the most commonly prescribed antiepileptics, treatment outcomes appeared to be better for lamotrigine and levetiracetam than for phenytoin.


CONCLUSIONS AND RELEVANCE
Common clinical features of patients with aMCI- or AD-associated epilepsy at our center included early age at onset of cognitive decline, early incidence of seizures in the disease course, unilateral temporal epileptic foci detected by serial/extended EEG, transient cognitive dysfunction, and good seizure control and tolerability with lamotrigine and levetiracetam. Careful identification and treatment of epilepsy in such patients may improve their clinical course.},
author = {K. Vossel and A. Beagle and G. Rabinovici and Huidy Shu and Suzee E Lee and Georges Naasan and Manu Hegde and S. Cornes and M. Henry and Alexandra B Nelson and W. Seeley and M. Geschwind and M. Gorno-Tempini and T. Shih and H. Kirsch and P. Garcia and B. Miller and L. Mucke},
doi = {10.1001/jamaneurol.2013.136},
pmid = {23835471},
}

@article{f9ef370a183036d2aea4d886229253190950cd61,
title = {Amyloid-β–induced neuronal dysfunction in Alzheimer's disease: from synapses toward neural networks},
year = {2010},
url = {https://www.semanticscholar.org/paper/f9ef370a183036d2aea4d886229253190950cd61},
abstract = {S2 TL;DR: Recent evidence that Aβ may be part of a mechanism controlling synaptic activity, acting as a positive regulator presynaptically and a negative regulator postsynaptically is discussed.},
author = {J. Palop and L. Mucke},
doi = {10.1038/nn.2583},
pmid = {20581818},
}

@article{97dccdb90baa2d61b0ceeb0615ba827154e49532,
title = {Clusters of Hyperactive Neurons Near Amyloid Plaques in a Mouse Model of Alzheimer's Disease},
year = {2008},
url = {https://www.semanticscholar.org/paper/97dccdb90baa2d61b0ceeb0615ba827154e49532},
abstract = {The neurodegeneration observed in Alzheimer's disease has been associated with synaptic dismantling and progressive decrease in neuronal activity. We tested this hypothesis in vivo by using two-photon Ca2+ imaging in a mouse model of Alzheimer's disease. Although a decrease in neuronal activity was seen in 29% of layer 2/3 cortical neurons, 21% of neurons displayed an unexpected increase in the frequency of spontaneous Ca2+ transients. These “hyperactive” neurons were found exclusively near the plaques of amyloid β–depositing mice. The hyperactivity appeared to be due to a relative decrease in synaptic inhibition. Thus, we suggest that a redistribution of synaptic drive between silent and hyperactive neurons, rather than an overall decrease in synaptic activity, provides a mechanism for the disturbed cortical function in Alzheimer's disease.},
author = {M. A. Busche and G. Eichhoff and H. Adelsberger and D. Abramowski and K. Wiederhold and C. Haass and M. Staufenbiel and A. Konnerth and O. Garaschuk},
doi = {10.1126/science.1162844},
pmid = {18802001},
}

@article{83dd801362bfea8a89d8ab28f22eb52ef07e5c5e,
title = {Neurotoxicity of amyloid β-protein: synaptic and network dysfunction.},
year = {2012},
url = {https://www.semanticscholar.org/paper/83dd801362bfea8a89d8ab28f22eb52ef07e5c5e},
abstract = {Evidence for an ever-expanding variety of molecular mediators of amyloid β-protein neurotoxicity (membrane lipids, receptor proteins, channel proteins, second messengers and related signaling cascades, cytoskeletal proteins, inflammatory mediators, etc.) has led to the notion that the binding of hydrophobic Aβ assemblies to cellular membranes triggers multiple effects affecting diverse pathways. It appears unlikely that there are only one or two cognate receptors for neurotoxic forms of Aβ and also that there are just one or two assembly forms of the peptide that induce neuronal dysfunction. Rather, various soluble (diffusible) oligomers of Aβ that may be in dynamic equilibrium with insoluble, fibrillar deposits (amyloid plaques) and that can bind to different components of neuronal and non-neuronal plasma membranes appear to induce complex patterns of synaptic dysfunction and network disorganization that underlie the intermittent but gradually progressive cognitive manifestations of the clinical disorder. Modern analyses of this problem utilize electrophysiology coupled with synaptic biochemistry and behavioral phenotyping of animal models to elucidate the affected circuits and assess the effects of potential therapeutic interventions.},
author = {L. Mucke and D. Selkoe},
doi = {10.1101/cshperspect.a006338},
pmid = {22762015},
}

@article{dffe0318b02466fe5f9849eeef369b2e3e7ee694,
title = {Investigation of neuronal activity in a murine model of Alzheimer’s disease using in vivo two-photon calcium imaging},
year = {2019},
url = {https://www.semanticscholar.org/paper/dffe0318b02466fe5f9849eeef369b2e3e7ee694},
abstract = {Alzheimer’s disease (AD) is one of the biggest challenges for biomedical research nowadays as with the growth of life span more and more people are affected by this disorder. Etiology of AD is unknown, yet growing evidence identifies alterations in neuronal activity as of the great importance for pathology. Although several significant studies of neuronal activity alteration in AD were done during the last decade, none of them addressed the question of the time course of these changes over the disease progression. 
Alzheimer’s disease (AD) is characterized by impairments of brain neurons that are responsible for the storage and processing of information. Studies have revealed decrease in the activity of neurons (Silverman et al., 2001; Prvulovic et al., 2005) and it was proposed that generalized hypoactivity and silencing of brain circuits takes place as formulated in the synaptic failure hypothesis (Selkoe, 2002). However, more recent studies also reported opposite effects – hyperexcitability and hyperactivity of neurons in the AD models (Busche et al., 2008; Sanchez et al., 2012; Liebscher et al., 2016). It still remains unclear if these are two sides of the same coin or if these are two stages, that follow each other. Moreover, it is not clear if observed neuronal activity alterations are caused by the dysfunction of individual neurons or if overall circuitry is disturbed because the crucial “activity controllers” (most probably - inhibitory neurons) alter their activity. 
This project aimed to examine spontaneous neuronal activity in the murine model of AD at the early stages of disease progression using chronic in vivo imaging to address the character and the stability of neuronal activity alterations as well relation of the activity alterations to amyloid plaque proximity. Compared to earlier studies the approach of in vivo awake calcium imaging used in the current study has many benefits for brain research. The main advantage is that brain activity can be measured without artifacts generated by anesthesia, which can exaggerate or mitigate experimental readouts. 
In this project, I used genetically encoded calcium indicator GCaMP6 that enables prolonged repetitive imaging of the same neurons in an intact environment. Recording of calcium transients in cell bodies of neurons was accompanied by in vivo imaging of Aβ plaques and followed by immunohistochemical staining of GCaMP6-expressing neurons to investigate how activity changes are correlated with proximity to the plaque. All the experiments were done in awake mice to ensure the absence of anesthesia-derived impact on spontaneous neuronal activity. 
My results support previously published reports of the increased proportion of hyperactive excitatory neurons in the AD mouse model. Importantly, my results also demonstrate that this increased activity is present in the awake state, is stable over a longer period of time (one month) and does not depend on the distance to the closest plaque. These findings support the hypothesis of permanent network alterations driving aberrant activity patterns that appear early in the disease progression, resulting in a chronic excitation/inhibition disbalance. 
Another important finding of my project is that individual neurons do not stay in the silent state and most of them remain functional demonstrating normal activity at the later time points. This finding requires further research as it has important implication for the development of the AD treatment, as in case many neurons remain functional and their normal neuronal activity can be recovered by addressing the cause of the circuit dysfunction with treatment. 
To summarize, the study presented in this PhD thesis is the first longitudinal study of neuronal activity changes in an AD mouse model, and while it provides important insight into pathology, it also emphasizes the importance of chronic in vivo studies to investigate neuronal activity and its role in the disease progression.},
author = {V. Korzhova},
}

@article{51c7030890a4dd26266306ffa7bea096ba2d6fdd,
title = {Incidence and impact of subclinical epileptiform activity in Alzheimer's disease},
year = {2016},
url = {https://www.semanticscholar.org/paper/51c7030890a4dd26266306ffa7bea096ba2d6fdd},
abstract = {Seizures are more frequent in patients with Alzheimer's disease (AD) and can hasten cognitive decline. However, the incidence of subclinical epileptiform activity in AD and its consequences are unknown. Motivated by results from animal studies, we hypothesized higher than expected rates of subclinical epileptiform activity in AD with deleterious effects on cognition.},
author = {K. Vossel and K. Ranasinghe and A. Beagle and D. Mizuiri and S. Honma and Anne F. Dowling and Sonja M. Darwish and V. Van Berlo and D. Barnes and M. Mantle and A. Karydas and G. Coppola and E. Roberson and Bruce L Miller and P. Garcia and H. Kirsch and L. Mucke and S. Nagarajan},
doi = {10.1002/ana.24794},
pmid = {27696483},
}

@article{5953ce4d517f325d2b19cda60534f3c440f35af3,
title = {Inhibitory Interneuron Deficit Links Altered Network Activity and Cognitive Dysfunction in Alzheimer Model},
year = {2012},
url = {https://www.semanticscholar.org/paper/5953ce4d517f325d2b19cda60534f3c440f35af3},
abstract = {S2 TL;DR: It is concluded that reduced Nav1.1 levels and PV cell dysfunction critically contribute to abnormalities in oscillatory rhythms, network synchrony, and memory in hAPP mice and possibly in AD.},
author = {L. Verret and E. Mann and G. B. Hang and A. Barth and I. Cobos and Kaitlyn Ho and N. Devidze and E. Masliah and A. Kreitzer and I. Módy and L. Mucke and J. Palop},
doi = {10.1016/j.cell.2012.02.046},
pmid = {22541439},
}

@article{05bed183c923092f6f32db0fa7470995113d4789,
title = {Critical role of soluble amyloid-β for early hippocampal hyperactivity in a mouse model of Alzheimer’s disease},
year = {2012},
url = {https://www.semanticscholar.org/paper/05bed183c923092f6f32db0fa7470995113d4789},
abstract = {Alzheimer’s disease (AD) is characterized by a progressive dysfunction of central neurons. Recent experimental evidence indicates that in the cortex, in addition to the silencing of a fraction of neurons, other neurons are hyperactive in amyloid-β (Aβ) plaque-enriched regions. However, it has remained unknown what comes first, neuronal silencing or hyperactivity, and what mechanisms might underlie the primary neuronal dysfunction. Here we examine the activity patterns of hippocampal CA1 neurons in a mouse model of AD in vivo using two-photon Ca2+ imaging. We found that neuronal activity in the plaque-bearing CA1 region of older mice is profoundly altered. There was a marked increase in the fractions of both silent and hyperactive neurons, as previously also found in the cortex. Remarkably, in the hippocampus of young mice, we observed a selective increase in hyperactive neurons already before the formation of plaques, suggesting that soluble species of Aβ may underlie this impairment. Indeed, we found that acute treatment with the γ-secretase inhibitor LY-411575 reduces soluble Aβ levels and rescues the neuronal dysfunction. Furthermore, we demonstrate that direct application of soluble Aβ can induce neuronal hyperactivity in wild-type mice. Thus, our study identifies hippocampal hyperactivity as a very early functional impairment in AD transgenic mice and provides direct evidence that soluble Aβ is crucial for hippocampal hyperactivity.},
author = {M. A. Busche and Xiaowei Chen and Horst A. Henning and Julia J. Reichwald and M. Staufenbiel and B. Sakmann and A. Konnerth},
doi = {10.1073/pnas.1206171109},
pmid = {22592800},
}

@article{fb47d67c236ca0b5d062832f4860d4d7eaf30c8a,
title = {What Happens with the Circuit in Alzheimer's Disease in Mice and Humans?},
year = {2018},
url = {https://www.semanticscholar.org/paper/fb47d67c236ca0b5d062832f4860d4d7eaf30c8a},
abstract = {A major mystery of many types of neurological and psychiatric disorders, such as Alzheimer's disease (AD), remains the underlying, disease-specific neuronal damage. Because of the strong interconnectivity of neurons in the brain, neuronal dysfunction necessarily disrupts neuronal circuits. In this article, we review evidence for the disruption of large-scale networks from imaging studies of humans and relate it to studies of cellular dysfunction in mouse models of AD. The emerging picture is that some forms of early network dysfunctions can be explained by excessively increased levels of neuronal activity. The notion of such neuronal hyperactivity receives strong support from in vivo and in vitro cellular imaging and electrophysiological recordings in the mouse, which provide mechanistic insights underlying the change in neuronal excitability. Overall, some key aspects of AD-related neuronal dysfunctions in humans and mice are strikingly similar and support the continuation of such a translational strategy.},
author = {B. Zott and M. A. Busche and R. Sperling and A. Konnerth},
doi = {10.1146/annurev-neuro-080317-061725},
pmid = {29986165},
}

@article{17ad86c8b182f6cefdbabe1a23a09950053555b3,
title = {Levetiracetam suppresses neuronal network dysfunction and reverses synaptic and cognitive deficits in an Alzheimer’s disease model},
year = {2012},
url = {https://www.semanticscholar.org/paper/17ad86c8b182f6cefdbabe1a23a09950053555b3},
abstract = {In light of the rising prevalence of Alzheimer’s disease (AD), new strategies to prevent, halt, and reverse this condition are needed urgently. Perturbations of brain network activity are observed in AD patients and in conditions that increase the risk of developing AD, suggesting that aberrant network activity might contribute to AD-related cognitive decline. Human amyloid precursor protein (hAPP) transgenic mice simulate key aspects of AD, including pathologically elevated levels of amyloid-β peptides in brain, aberrant neural network activity, remodeling of hippocampal circuits, synaptic deficits, and behavioral abnormalities. Whether these alterations are linked in a causal chain remains unknown. To explore whether hAPP/amyloid-β–induced aberrant network activity contributes to synaptic and cognitive deficits, we treated hAPP mice with different antiepileptic drugs. Among the drugs tested, only levetiracetam (LEV) effectively reduced abnormal spike activity detected by electroencephalography. Chronic treatment with LEV also reversed hippocampal remodeling, behavioral abnormalities, synaptic dysfunction, and deficits in learning and memory in hAPP mice. Our findings support the hypothesis that aberrant network activity contributes causally to synaptic and cognitive deficits in hAPP mice. LEV might also help ameliorate related abnormalities in people who have or are at risk for AD.},
author = {Pascal E. Sanchez and Lei Zhu and L. Verret and K. Vossel and Anna G. Orr and J. Cirrito and N. Devidze and Kaitlyn Ho and Gui-qiu Yu and J. Palop and L. Mucke},
doi = {10.1073/pnas.1121081109},
pmid = {22869752},
}

@article{987ba855da54ddad53241eaa71bc34140f86ad4a,
title = {Seizures in Alzheimer disease: who, when, and how common?},
year = {2009},
url = {https://www.semanticscholar.org/paper/987ba855da54ddad53241eaa71bc34140f86ad4a},
abstract = {BACKGROUND
Transient symptoms in Alzheimer disease (AD) are frequent and include seizures, syncope, and episodes of inattention or confusion. The incidence of seizures in AD and predictors of which patients with AD might be more predisposed to them is based primarily on retrospective studies and is not well established.


OBJECTIVE
To determine the incidence and predictors of new-onset unprovoked seizures.


DESIGN
Prospective cohort study.


SETTING
Three academic centers. Patients Four hundred fifty-three patients with probable AD observed prospectively from mild disease stages since 1992. Main Outcome Measure Informant interviews every 6 months included questions about whether the patient had a seizure (convulsion, fainting, or "funny" spell) and whether diagnosis or treatment for epilepsy or seizure was made. Two epileptologists independently retrospectively reviewed all available medical records for 52 patients with positive responses to either of these questions, and using a specific checklist form, events were diagnosed as to whether they were unprovoked seizures (intrarater concordance, kappa = 0.67). Diagnosis of unprovoked seizures constituted the event in survival analyses. Potential predictors included sex, age, race/ethnicity, educational achievement, duration of illness, baseline cognition and function, depression, medical comorbidities, and time-dependent use of cholinesterase inhibitors and neuroleptic agents, apolipoprotein E genotype, and previous electroencephalographic findings.


RESULTS
Over the course of 3518 visit-assessments (per patient: mean, 7.8; maximum, 27), 7 patients (1.5%) developed seizures. Younger age was associated with higher risk (hazard ratio, 1.23; 95% confidence interval, 1.08-1.41; P = .003 for each additional year of age) of seizure incidence. No other predictor was significant. The overall incidence of seizures was low (418 per 100 000 person-years of observation) although significantly higher than expected for idiopathic unprovoked seizures in similar age ranges of the general population (hazard ratio, 8.06; 95% confidence interval, 3.23-16.61).


CONCLUSIONS
Unprovoked seizures are uncommon in AD, but they do occur more frequently than in the general population. Younger age is a risk factor for seizures in AD.},
author = {N. Scarmeas and L. Honig and Hyunmi Choi and Julio Cantero and J. Brandt and D. Blacker and M. Albert and J. Amatniek and K. Marder and K. Bell and W. Hauser and Y. Stern},
doi = {10.1001/archneurol.2009.130},
pmid = {19667221},
}

@article{cde9f9865b6a3d15422b1255d8c8c8c901a1391f,
title = {Aberrant Excitatory Neuronal Activity and Compensatory Remodeling of Inhibitory Hippocampal Circuits in Mouse Models of Alzheimer's Disease},
year = {2007},
url = {https://www.semanticscholar.org/paper/cde9f9865b6a3d15422b1255d8c8c8c901a1391f},
abstract = {S2 TL;DR: It is reported that hAPP mice have spontaneous nonconvulsive seizure activity in cortical and hippocampal networks, which is associated with GABAergic sprouting, enhanced synaptic inhibition, and synaptic plasticity deficits in the dentate gyrus.},
author = {J. Palop and J. Chin and E. Roberson and Jun Wang and Myo T. Thwin and N. Bien-ly and Jong W. Yoo and Kaitlyn Ho and Gui-qiu Yu and A. Kreitzer and S. Finkbeiner and J. Noebels and L. Mucke},
doi = {10.1016/j.neuron.2007.07.025},
pmid = {17785178},
}

@article{0c8e75e4658820f542985ef1ce1aff0968824128,
title = {Network abnormalities and interneuron dysfunction in Alzheimer disease},
year = {2016},
url = {https://www.semanticscholar.org/paper/0c8e75e4658820f542985ef1ce1aff0968824128},
abstract = {S2 TL;DR: The concept that modulating these mechanisms may help to improve brain function in Alzheimer disease and related disorders is explored.},
author = {J. Palop and L. Mucke},
doi = {10.1038/nrn.2016.141},
pmid = {27829687},
}

@article{4728e82116fc01912bb6e7b1060c01f58f96d35b,
title = {Neuronal Network Excitability in Alzheimer’s Disease: The Puzzle of Similar versus Divergent Roles of Amyloid β and Tau},
year = {2021},
url = {https://www.semanticscholar.org/paper/4728e82116fc01912bb6e7b1060c01f58f96d35b},
abstract = {Abstract Alzheimer’s disease (AD) is the most frequent neurodegenerative disorder that commonly causes dementia in the elderly. Recent evidence indicates that network abnormalities, including hypersynchrony, altered oscillatory rhythmic activity, interneuron dysfunction, and synaptic depression, may be key mediators of cognitive decline in AD. In this review, we discuss characteristics of neuronal network excitability in AD, and the role of Aβ and tau in the induction of network hyperexcitability. Many patients harboring genetic mutations that lead to increased Aβ production suffer from seizures and epilepsy before the development of plaques. Similarly, pathologic accumulation of hyperphosphorylated tau has been associated with hyperexcitability in the hippocampus. We present common and divergent roles of tau and Aβ on neuronal hyperexcitability in AD, and hypotheses that could serve as a template for future experiments.},
author = {S. Kazim and Joon ho Seo and R. Bianchi and Chloe S. Larson and Abhijeet Sharma and R. Wong and Kirill Gorbachev and Ana C. Pereira},
doi = {10.1523/ENEURO.0418-20.2020},
pmid = {33741601},
}

@article{91e956790dc173bf5f5a265b0feee40e2707ae93,
title = {Gamma oscillations in cognitive disorders},
year = {2018},
url = {https://www.semanticscholar.org/paper/91e956790dc173bf5f5a265b0feee40e2707ae93},
abstract = {S2 TL;DR: How recent results showing abnormal gamma rhythms in Alzheimer's disease and Fragile X syndrome help reveal links between cellular disturbances and cognitive impairments is reviewed.},
author = {Alexandra J Mably and L. Colgin},
doi = {10.1016/j.conb.2018.07.009},
pmid = {30121451},
}

@article{98d85cb7f2867d466e6ddcd739820ae114ffe1eb,
title = {Gamma Entrainment Binds Higher-Order Brain Regions and Offers Neuroprotection},
year = {2019},
url = {https://www.semanticscholar.org/paper/98d85cb7f2867d466e6ddcd739820ae114ffe1eb},
abstract = {S2 TL;DR: It is demonstrated that GENUS can entrain gamma oscillations in the visual cortex, hippocampus, and prefrontal cortex in Tau P301S and CK-p25 mouse models of neurodegeneration and suggests that chronic GENUS shifts neurons to a less degenerative state.},
author = {C. Adaikkan and Steven J Middleton and A. Marco and P. Pao and Hansruedi Mathys and David Nam-Woo Kim and Fan Gao and Jennie Z. Young and Ho‐Jun Suk and E. Boyden and T. McHugh and L. Tsai},
doi = {10.1016/j.neuron.2019.04.011},
pmid = {31076275},
}

@article{642b0f3d99667010e9889f1941a88669827c669a,
title = {Nav1.1-Overexpressing Interneuron Transplants Restore Brain Rhythms and Cognition in a Mouse Model of Alzheimer’s Disease},
year = {2018},
url = {https://www.semanticscholar.org/paper/642b0f3d99667010e9889f1941a88669827c669a},
abstract = {S2 TL;DR: It is concluded that the efficacy of interneuron transplantation and the function of transplanted cells in an AD-relevant context depend on their Nav1.1 levels, and disease-specific molecular optimization of cell transplants may be required to ensure therapeutic benefits in different conditions.},
author = {M. Martínez-Losa and Tara E. Tracy and K. Ma and L. Verret and Alexandra Clemente-Perez and Abdullah S. Khan and I. Cobos and Kaitlyn Ho and L. Gan and L. Mucke and M. Álvarez-Dolado and J. Palop},
doi = {10.1016/j.neuron.2018.02.029},
pmid = {29551491},
}

@article{52d2c74047d92a3fedffcf24917afcd5275d2db6,
title = {Transient Slow Gamma Synchrony Underlies Hippocampal Memory Replay},
year = {2012},
url = {https://www.semanticscholar.org/paper/52d2c74047d92a3fedffcf24917afcd5275d2db6},
abstract = {S2 TL;DR: It is shown that during SWRs in both awake and quiescent states there are transient increases in slow gamma power and synchrony across dorsal CA3 and CA1 networks of both hemispheres, which indicates that CA3-CA1 gamma synchronization is a central component of awake memory replay and suggests that transient gamma synchronization serves as a clocking mechanism to enable coordinated memory reactivation across the hippocampal network.},
author = {Margaret F. Carr and M. Karlsson and L. Frank},
doi = {10.1016/j.neuron.2012.06.014},
pmid = {22920260},
}

@article{99c6832f89a49867c4ea5dc0d1520b05e175bb61,
title = {p38 MAP kinase-mediated NMDA receptor-dependent suppression of hippocampal hypersynchronicity in a mouse model of Alzheimer’s disease},
year = {2014},
url = {https://www.semanticscholar.org/paper/99c6832f89a49867c4ea5dc0d1520b05e175bb61},
abstract = {S2 TL;DR: Components of hippocampal hypersynchronicity, waveform patterns and cross-frequency coupling in the APP23 mouse model are characterized by pharmacological modulation, furthering the understanding of epileptiform brain activity in AD.},
author = {A. Ittner and A. Gladbach and Josefine Bertz and L. Suh and L. Ittner},
doi = {10.1186/s40478-014-0149-z},
pmid = {25331068},
}

@article{d41325d0f57a899f7d897c35dfb595d5347c22c5,
title = {Amyloid-beta / Fyn – Induced Synaptic , Network , and Cognitive Impairments Depend on Tau Levels in Multiple Mouse Models of Alzheimer ’ s Disease},
year = {2015},
url = {https://www.semanticscholar.org/paper/d41325d0f57a899f7d897c35dfb595d5347c22c5},
abstract = {Part of the Neurology Commons This Article is brought to you for free and open access by the Jefferson Digital Commons. The Jefferson Digital Commons is a service of Thomas Jefferson University's Center for Teaching and Learning (CTL). The Commons is a showcase for Jefferson books and journals, peer-reviewed scholarly publications, unique historical collections from the University archives, and teaching tools. The Jefferson Digital Commons allows researchers and interested readers anywhere in the world to learn about and keep up to date with Jefferson scholarship. Alzheimer's disease (AD), the most common neurodegenerative disorder, is a growing public health problem and still lacks effective treatments. Recent evidence suggests that microtubule-associated protein tau may mediate amyloid-␤ peptide (A␤) toxicity by modulating the tyrosine kinase Fyn. We showed previously that tau reduction prevents, and Fyn overexpression exacerbates, cognitive deficits in human amyloid precursor protein (hAPP) transgenic mice overexpressing A␤. However, the mechanisms by which A␤, tau, and Fyn cooperate in AD-related pathogenesis remain to be fully elucidated. Here we examined the synaptic and network effects of this pathogenic triad. Tau reduction prevented cognitive decline induced by synergistic effects of A␤ and Fyn. Tau reduction also prevented synaptic transmission and plasticity deficits in hAPP mice. Using electroencephalography to examine network effects, we found that tau reduction prevented spontaneous epileptiform activity in multiple lines of hAPP mice. Tau reduction also reduced the severity of spontaneous and chemically induced seizures in mice overexpressing both A␤ and Fyn. To better understand these protective effects, we recorded whole-cell currents in acute hippocampal slices from hAPP mice with and without tau. hAPP mice with tau had increased spontaneous and evoked excitatory currents, reduced inhibitory currents, and NMDA receptor dysfunction. Tau reduction increased inhibitory currents and normalized excitation/inhibition balance and NMDA receptor-mediated currents in hAPP mice. Our results indicate that A␤, tau, and Fyn jointly impair synaptic and network function and suggest that disrupting the copathogenic relationship between these factors could be of therapeutic benefit. Introduction Current treatments for Alzheimer's disease (AD) are only modestly effective and do not appear to alter the underlying disease progression. For good reasons, the search for better AD therapies has focused on amyloid-␤ peptides (A␤), generally thought to drive AD pathogenesis (Hardy and Selkoe, 2002; Tanzi and Ber-tram, 2005). However, disappointing outcomes of initial drug trials targeting A␤ (Gilman et al., 2005; Green et al., 2009) have broadened interest in other, downstream targets, including …},
author = {E. Roberson and B. Halabisky and Jong W. Yoo and J. Yao and J. Chin and F. Yan and Tiffany Wu and Patricia Hamto and N. Devidze and Gui-qiu Yu and J. Palop and J. Noebels and L. Mucke},
}

@article{07283950d3b0ea05d2e17044a2d47fa9448ffb07,
title = {Amyloid-β/Fyn–Induced Synaptic, Network, and Cognitive Impairments Depend on Tau Levels in Multiple Mouse Models of Alzheimer's Disease},
year = {2011},
url = {https://www.semanticscholar.org/paper/07283950d3b0ea05d2e17044a2d47fa9448ffb07},
abstract = {Alzheimer's disease (AD), the most common neurodegenerative disorder, is a growing public health problem and still lacks effective treatments. Recent evidence suggests that microtubule-associated protein tau may mediate amyloid-β peptide (Aβ) toxicity by modulating the tyrosine kinase Fyn. We showed previously that tau reduction prevents, and Fyn overexpression exacerbates, cognitive deficits in human amyloid precursor protein (hAPP) transgenic mice overexpressing Aβ. However, the mechanisms by which Aβ, tau, and Fyn cooperate in AD-related pathogenesis remain to be fully elucidated. Here we examined the synaptic and network effects of this pathogenic triad. Tau reduction prevented cognitive decline induced by synergistic effects of Aβ and Fyn. Tau reduction also prevented synaptic transmission and plasticity deficits in hAPP mice. Using electroencephalography to examine network effects, we found that tau reduction prevented spontaneous epileptiform activity in multiple lines of hAPP mice. Tau reduction also reduced the severity of spontaneous and chemically induced seizures in mice overexpressing both Aβ and Fyn. To better understand these protective effects, we recorded whole-cell currents in acute hippocampal slices from hAPP mice with and without tau. hAPP mice with tau had increased spontaneous and evoked excitatory currents, reduced inhibitory currents, and NMDA receptor dysfunction. Tau reduction increased inhibitory currents and normalized excitation/inhibition balance and NMDA receptor-mediated currents in hAPP mice. Our results indicate that Aβ, tau, and Fyn jointly impair synaptic and network function and suggest that disrupting the copathogenic relationship between these factors could be of therapeutic benefit.},
author = {E. Roberson and B. Halabisky and Jong W. Yoo and J. Yao and J. Chin and F. Yan and Tiffany Wu and Patricia Hamto and N. Devidze and Gui-qiu Yu and J. Palop and J. Noebels and L. Mucke},
doi = {10.1523/JNEUROSCI.4152-10.2011},
pmid = {21228179},
}

@article{0e9b9355b5f471a16cde7206c9c0e34c682359b1,
title = {Multi-sensory Gamma Stimulation Ameliorates Alzheimer’s-Associated Pathology and Improves Cognition},
year = {2019},
url = {https://www.semanticscholar.org/paper/0e9b9355b5f471a16cde7206c9c0e34c682359b1},
abstract = {S2 TL;DR: Auditory tone stimulation that drove gamma frequency neural activity in auditory cortex (AC) and hippocampal CA1 improved spatial and recognition memory and reduced amyloid in AC and hippocampus of 5XFAD mice, suggesting GENUS can be achieved through multiple sensory modalities with wide-ranging effects across multiple brain areas to improve cognitive function.},
author = {Anthony J. Martorell and Abigail L. Paulson and Ho‐Jun Suk and F. Abdurrob and Gabrielle T. Drummond and Webster Guan and Jennie Z. Young and David Nam-Woo Kim and Oleg Kritskiy and Scarlett J. Barker and Vamsi Mangena and S. Prince and E. Brown and K. Chung and E. Boyden and A. Singer and L. Tsai},
doi = {10.1016/j.cell.2019.02.014},
pmid = {30879788},
}

@article{837ee03546c186bede5abf0e2a68914ccc8ef36a,
title = {Inhibitory Neuron and Hippocampal Circuit Dysfunction in an Aged Mouse Model of Alzheimer's Disease},
year = {2013},
url = {https://www.semanticscholar.org/paper/837ee03546c186bede5abf0e2a68914ccc8ef36a},
abstract = {In Alzheimer's disease (AD), a decline in explicit memory is one of the earliest signs of disease and is associated with hippocampal dysfunction. Amyloid protein exerts a disruptive impact on neuronal function, but the specific effects on hippocampal network activity are not well known. In this study, fast voltage-sensitive dye imaging and extracellular and whole-cell electrophysiology were used on entorhinal cortical-hippocampal slice preparations to characterize hippocampal network activity in 12–16 month old female APPswe/PSEN1DeltaE9 (APdE9 mice) mice. Aged APdE9 mice exhibited profound disruptions in dentate gyrus circuit activation. High frequency stimulation of the perforant pathway in the dentate gyrus (DG) area of APdE9 mouse tissue evoked abnormally large field potential responses corresponding to the wider neural activation maps. Whole-cell patch clamp recordings of the identified inhibitory interneurons in the molecular layer of DG revealed that they fail to reliably fire action potentials. Taken together, abnormal DG excitability and an inhibitory neuron failure to generate action potentials are suggested to be important contributors to the underlying cellular mechanisms of early-stage Alzheimer's disease pathophysiology.},
author = {A. Hazra and Feng Gu and Ahmad Aulakh and Casey Berridge and J. Eriksen and J. Ziburkus},
doi = {10.1371/journal.pone.0064318},
pmid = {23691195},
}

@article{0344f212a2bbd46c0229a65dde83a950b50d8843,
title = {Nav 1 . 1-Overexpressing In terneuron Transplants Restore Brain Rhythms and Cognition in a Mouse},
year = {2018},
url = {https://www.semanticscholar.org/paper/0344f212a2bbd46c0229a65dde83a950b50d8843},
abstract = {null},
author = {M. Martínez-Losa and Tara E. Tracy and K. Ma and L. Verret and Alexandra Clemente-Perez and S. Khan and I. Cobos and Kaitlyn Ho and L. Gan and L. Mucke and M. Álvarez-Dolado and J. Palop},
}

@article{88fa15147b33b60ef5c47fbb238e4321b528cb05,
title = {Epileptic activity in Alzheimer's disease: causes and clinical relevance},
year = {2017},
url = {https://www.semanticscholar.org/paper/88fa15147b33b60ef5c47fbb238e4321b528cb05},
abstract = {S2 TL;DR: Clinical trials targeting network hyperexcitability in patients with Alzheimer's disease will identify whether AEDs or related strategies could improve their cognitive symptoms or slow decline.},
author = {K. Vossel and M. Tartaglia and H. Nygaard and A. Zeman and B. Miller},
doi = {10.1016/S1474-4422(17)30044-3},
pmid = {28327340},
}

@article{63217b8adeb18327507714889d22d90e855b0aa1,
title = {Gamma Entrainment: Impact on Neurocircuits, Glia, and Therapeutic Opportunities},
year = {2019},
url = {https://www.semanticscholar.org/paper/63217b8adeb18327507714889d22d90e855b0aa1},
abstract = {S2 TL;DR: Evidence suggests that chronic gamma entrainment offers neuroprotective effects, and techniques such as optogenetics or sensory stimulation appear to engage canonical neurocircuits that encompass excitatory and inhibitory interneurons, similarly to those driven by sensory experience.},
author = {C. Adaikkan and L. Tsai},
doi = {10.1016/j.tins.2019.11.001},
pmid = {31836315},
}

@article{eb3e9a291fca55870abc442c21047f8895aa0632,
title = {Reduction of Hippocampal Hyperactivity Improves Cognition in Amnestic Mild Cognitive Impairment},
year = {2012},
url = {https://www.semanticscholar.org/paper/eb3e9a291fca55870abc442c21047f8895aa0632},
abstract = {S2 TL;DR: The view that increased hippocampal activation in aMCI is a dysfunctional condition and that targeting excess hippocampal activity has therapeutic potential is supported.},
author = {A. Bakker and G. Krauss and M. Albert and Caroline L. Speck and Lauren R. Jones and C. Stark and M. Yassa and S. Bassett and A. Shelton and M. Gallagher},
doi = {10.1016/j.neuron.2012.03.023},
pmid = {22578498},
}

@article{51ee51316d36d0d9e5e8bbf1fae285c45a2c7dde,
title = {Gamma Band Light Stimulation in Human Case Studies: Groundwork for Potential Alzheimer’s Disease Treatment},
year = {2019},
url = {https://www.semanticscholar.org/paper/51ee51316d36d0d9e5e8bbf1fae285c45a2c7dde},
abstract = {Background: It is known that proteins associated with Alzheimer’s disease (AD) pathogenesis are significantly reduced by 40 Hz entrainment in mice. If this were to translate to humans, verifying that such a light stimulus can induce a 40 Hz entrainment response in humans and harnessing insights from these case studies could be one step in the development of a multisensory device to prevent and treat AD. Objective: Verify the inducement of a 40 Hz response in the human brain by a 40 Hz light stimulus and obtain insights that could potentially aid in the development of a multisensory device for the prevention and treatment of AD. Methods: Electroencephalographic brain activity was recorded simultaneously with application of stimulus at different frequencies and intensities. Power spectral densities were analyzed. Results: Entrainment to visual stimuli occurred with the largest response at 40 Hz. The high intensity 40 Hz stimulus caused widespread entrainment. The number of electrodes demonstrating entrainment increased with increasing light intensity. Largest amplitudes for the high intensity 40 Hz stimulus were consistently found at the primary visual cortex. There was a harmonic effect at double the frequency for the 40 Hz stimulus. An eyes-open protocol caused more entrainment than an eyes-closed protocol. Conclusion: It was possible to induce widespread entrainment using a 40 Hz light stimulus in this sample cohort. Insights gleaned from these case studies could potentially aid in the development of a multisensory medical device to prevent and treat AD.},
author = {Marggie Jones and Barry McDermott and B. Oliveira and A. O'Brien and Declan Coogan and Mark Lang and N. Moriarty and E. Dowd and L. Quinlan and B. Mc Ginley and Eoghan Dunne and David Newell and E. Porter and M. A. Elahi and Martin O’ Halloran and A. Shahzad},
doi = {10.3233/JAD-190299},
pmid = {31156180},
}

@article{f8defa30929d1824ac05bd7c3263113a814bcc55,
title = {Apolipoprotein E4 Causes Age-Dependent Disruption of Slow Gamma Oscillations during Hippocampal Sharp-Wave Ripples},
year = {2016},
url = {https://www.semanticscholar.org/paper/f8defa30929d1824ac05bd7c3263113a814bcc55},
abstract = {S2 TL;DR: It is suggested that progressive decline of interneuron-enabled slow gamma activity during SWRs critically contributes to apoE4-mediated learning and memory impairments.},
author = {A. Gillespie and Emily A. Jones and Yuan-Hung Lin and M. Karlsson and K. Kay and Seo Yeon Yoon and Leslie M. Tong and Philip Nova and Jessie S Carr and L. Frank and Yadong Huang},
doi = {10.1016/j.neuron.2016.04.009},
pmid = {27161522},
}