Theta and gamma oscillatory dynamics in mouse models of Alzheimer’s disease: A path to prospective therapeutic intervention

Mehak, Sonam Fathima; Shivakumar, Apoorva Bettagere; Kumari, Sparsha; Muralidharan, Bhadra; Gangadharan, Gireesh

doi:10.1016/j.neubiorev.2022.104628

Cited by 21 publications

(17 citation statements)

References 301 publications

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“…Previous studies have reported altered physiological patterns in aged rodents and especially in AD mouse models (Radulescu et al, 2021; Palop & Mucke 2016; Wang et al, 2020; Mehak et al, 2022). AD pathology has been reported to correlate with impaired cognitive performance of the animals in various tasks (Lesné et al, 2008; Hsiao et al, 1996; Cramer et al, 2012; Zhang et al, 2011).…”

Section: Discussionmentioning

confidence: 99%

“…AD pathology has been reported to correlate with impaired cognitive performance of the animals in various tasks (Lesné et al, 2008; Hsiao et al, 1996; Cramer et al, 2012; Zhang et al, 2011). The relationship between cognitive deterioration and physiological changes, however, is much less clear (Palop & Mucke 2016; Verret et al, 2012; Villette et al, 2010; Mehak et al, 2022; Wang et al, 2020; Bakker et al, 2012). It is possible that several overlapping and interrelated changes in neuronal dynamics contribute to decreased memory and other cognitive deficits.…”

Section: Discussionmentioning

confidence: 99%

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Interictal epileptiform discharges affect memory in an Alzheimer’s Disease mouse model

Soula

Maslarova

Harvey

et al. 2023

Preprint

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Interictal epileptiform discharges (IEDs) are transient abnormal electrophysiological events commonly observed in epilepsy patients but are also present in other neurological disease, such as Alzheimer's disease (AD). Understanding the role IEDs have on the hippocampal circuit is important for our understanding of the cognitive deficits seen in epilepsy and AD. We characterize and compare the IEDs of human epilepsy patients from microwire hippocampal recording with those of AD transgenic mice with implanted multi-layer hippocampal silicon probes. Both the local field potential features and firing patterns of pyramidal cells and interneurons were similar in mouse and human. We found that as IEDs emerged from the CA3-1 circuits, they recruited pyramidal cells and silenced interneurons, followed by post-IED suppression. IEDs suppressed the incidence and altered the properties of physiological sharp-wave ripples (SPW-Rs), altered their physiological properties, and interfered with the replay of place field sequences in a maze. In addition, IEDs in AD mice inversely correlated with daily memory performance. Together, our work implicates that IEDs may present a common and epilepsy-independent phenomenon in neurodegenerative diseases that perturbs hippocampal-cortical communication and interferes with memory.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Interictal epileptiform discharges affect memory in an Alzheimer’s Disease mouse model

Soula

Maslarova

Harvey

et al. 2023

Preprint

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“…Power of LFP signals serves as a reflection of brain activity patterns during cognitive tasks. 34 Alteration in the power of brain regions oscillations, particularly in higher frequency bands, has been documented in both patients and animal models of AD. 35 In this analysis, our primary objective was to examine the potential influence of OB stimulation on brain rhythms while engaged in a working memory task.…”

Section: Ob Stimulation Augmented the Brain Regions Activity In Ad-li...mentioning

confidence: 99%

Olfactory bulb stimulation mitigates Alzheimer’s-like disease progression

Salimi,

Nazari,

Shahsavar

et al. 2024

Preprint

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Background: Deep brain stimulation (DBS) has demonstrated potential in mitigating Alzheimer's disease (AD). However, the invasive nature of DBS presents challenges for its application. The olfactory bulb (OB), showing early AD-related changes and extensive connections with memory regions, offers an attractive entry point for intervention, potentially restoring normal activity in deteriorating memory circuits. Aims: Our study examined the impact of electrically stimulating the OB on working memory as well as pathological and electrophysiological alterations in the OB, medial prefrontal cortex, hippocampus, and entorhinal cortex in amyloid beta (Aβ) AD model rats. Methods: Male Wistar rats underwent surgery for electrode implantation in brain regions, inducing Alzheimer's-like disease. Bilateral olfactory bulb (OB) electrical stimulation was performed for 1 hour daily to the OB of stimulation group animals for 18 consecutive days, followed by evaluations of histological, behavioral, and local field potential signal processing. Results: OB stimulation counteracted Aβ plaque accumulation and prevented AD-induced working memory impairments. Furthermore, it prompted an increase in power across diverse frequency bands and enhanced functional connectivity, particularly in the gamma band, within the investigated regions during a working memory task. Conclusion: This preclinical investigation highlights the potential of olfactory pathway-based brain stimulation to modulate the activity of deep-seated memory networks for AD treatment. Importantly, the accessibility of this pathway via the nasal cavity lays the groundwork for the development of minimally invasive approaches targeting the olfactory pathway for brain modulation.

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“…There is evidence for oscillatory disruption across all of the frequency bands specified, with disruption dependent on the model or pathological burden. One common phenotype across animal models of amyloidopathy is a reduction in gamma activity and a slowing of theta, along with alterations in cross-frequency coupling ( Mehak et al, 2022 ). In addition, animal models of amyloidopathy have increased susceptibility to seizures ( Palop et al, 2007 ).…”

Section: The Role Of Amyloid In Synaptic Dysfunction In Alzheimer’s D...mentioning

confidence: 99%

Alzheimer’s disease as a synaptopathy: Evidence for dysfunction of synapses during disease progression

Meftah

Gan

2023

Front. Synaptic Neurosci.

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The synapse has consistently been considered a vulnerable and critical target within Alzheimer’s disease, and synapse loss is, to date, one of the main biological correlates of cognitive decline within Alzheimer’s disease. This occurs prior to neuronal loss with ample evidence that synaptic dysfunction precedes this, in support of the idea that synaptic failure is a crucial stage within disease pathogenesis. The two main pathological hallmarks of Alzheimer’s disease, abnormal aggregates of amyloid or tau proteins, have had demonstrable effects on synaptic physiology in animal and cellular models of Alzheimer’s disease. There is also growing evidence that these two proteins may have a synergistic effect on neurophysiological dysfunction. Here, we review some of the main findings of synaptic alterations in Alzheimer’s disease, and what we know from Alzheimer’s disease animal and cellular models. First, we briefly summarize some of the human evidence to suggest that synapses are altered, including how this relates to network activity. Subsequently, animal and cellular models of Alzheimer’s disease are considered, highlighting mouse models of amyloid and tau pathology and the role these proteins may play in synaptic dysfunction, either in isolation or examining how the two pathologies may interact in dysfunction. This specifically focuses on neurophysiological function and dysfunction observed within these animal models, typically measured using electrophysiology or calcium imaging. Following synaptic dysfunction and loss, it would be impossible to imagine that this would not alter oscillatory activity within the brain. Therefore, this review also discusses how this may underpin some of the aberrant oscillatory patterns seen in animal models of Alzheimer’s disease and human patients. Finally, an overview of some key directions and considerations in the field of synaptic dysfunction in Alzheimer’s disease is covered. This includes current therapeutics that are targeted specifically at synaptic dysfunction, but also methods that modulate activity to rescue aberrant oscillatory patterns. Other important future avenues of note in this field include the role of non-neuronal cell types such as astrocytes and microglia, and mechanisms of dysfunction independent of amyloid and tau in Alzheimer’s disease. The synapse will certainly continue to be an important target within Alzheimer’s disease for the foreseeable future.

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Theta and gamma oscillatory dynamics in mouse models of Alzheimer’s disease: A path to prospective therapeutic intervention

Cited by 21 publications

References 301 publications

Interictal epileptiform discharges affect memory in an Alzheimer’s Disease mouse model

Interictal epileptiform discharges affect memory in an Alzheimer’s Disease mouse model

Olfactory bulb stimulation mitigates Alzheimer’s-like disease progression

Alzheimer’s disease as a synaptopathy: Evidence for dysfunction of synapses during disease progression

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