@article{pmid41765195,

title = {Serotonergic psychedelics as epigenetic modulators: A paradigm shift in Alzheimer's disease therapeutics},

author = {Esmaeel G Gojani and Houman Farzin and Robert J Sutherland and Majid H Mohajerani},

doi = {10.1016/j.neubiorev.2026.106619},

issn = {1873-7528},

year  = {2026},

date = {2026-05-01},

journal = {Neurosci Biobehav Rev},

volume = {184},

pages = {106619},

abstract = {Alzheimer's disease (AD) is a multifactorial neurodegenerative disorder characterized by amyloid-β (Aβ) accumulation, tau pathology, synaptic dysfunction, and neuroinflammation, which collectively drive progressive memory loss, cognitive decline, and behavioral changes. Increasing evidence implicates epigenetic dysregulation as a key contributor to these pathological processes by altering gene expression programs. Serotonergic psychedelics, which primarily act as agonists of the serotonin 2 A receptor (5-HT₂AR), have recently attracted attention for their ability to robustly promote neuroplasticity and induce sustained transcriptional changes in the brain. Preclinical studies indicate that these compounds can modulate epigenetic mechanisms, including histone modifications and DNA methylation (DNAm). This review examines the emerging intersection between psychedelic-induced epigenetic modulation and AD pathology, and proposes that targeted engagement of 5-HT₂Ars may help counteract epigenetic abnormalities that contribute to AD pathogenesis.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid41736228,

title = {The effects of chronic cannabidiol administration on brain pathology and behavioral deficits found in the tau P301s-line PS19 mouse model of Alzheimer's disease},

author = {Abigail G Nixon and Nancy S Hong and Behroo Mirza Agha and Jackson R Ham and Merrin Monteith and Tina Kaloa and Angela Kyriazopolus and Matt Nielsen and David R Robertson and Andrey Golubov and Robert J Sutherland and Igor Kovalchuk and Andrew Iwaniuk and Majid H Mohajerani and Robert J McDonald},

doi = {10.1177/13872877261421654},

issn = {1875-8908},

year  = {2026},

date = {2026-04-01},

journal = {J Alzheimers Dis},

volume = {110},

number = {3},

pages = {1099--1126},

abstract = {BackgroundCompounds derived from the plant  demonstrate many therapeutic properties suggesting that they could delay the onset and progression of Alzheimer's disease (AD).ObjectiveThe goal of the present experiment was to observe the effects of chronic cannabidiol (CBD) administration on the behavior and brain pathology of an AD tauopathy mouse model, Tau P301S-Line PS19 mice.MethodsMice were orally given CBD (20 mg/kg) or vehicle, daily, beginning around 3 months of age. At 6 months old, mice were tested on a battery of tasks to assess object recognition, motor function, and spatial learning and memory. The mice were retested at 9 months old on the behavioral tasks and the fear conditioning paradigm was added. Following completion of behavioral testing, the mice were perfused for histological analysis.ResultsChronic CBD treatments did not appear to affect the behavior nor restore the reduced hippocampal volume of Tau P301S mice. However, a deeper assessment of the changes in inflammatory markers showed a treatment effect on a measure of microglia reactivity. Robust sex differences were revealed with Tau P301S males showing more severe pathology relative to females. Finally, daily treatments of CBD did not negatively impact the behavior or brain of any of the experimental groups suggesting that its chronic administration was relatively safe.ConclusionsTaken together, the results suggested that CBD can have beneficial effects on some of the pathology associated with AD, even in an aggressive model of this neurodegenerative disease, but the impacts on impaired behavior were minimal.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid41884593,

title = {Pyruvate kinase M2 in Alzheimer's disease: from dysregulation to therapeutic inhibition},

author = {Esmaeel G Gojani and Robert J Sutherland and Majid H Mohajerani},

doi = {10.1093/braincomms/fcag054},

issn = {2632-1297},

year  = {2026},

date = {2026-01-01},

journal = {Brain Commun},

volume = {8},

number = {2},

pages = {fcag054},

abstract = {Pyruvate kinase M2 (PKM2) has emerged as a critical regulator of Alzheimer's disease pathophysiology. This review synthesizes current evidence demonstrating how PKM2 dysregulation contributes to cognitive decline by driving Warburg-like metabolic reprogramming, altering post-translational modifications and modulating protein-protein interactions. These processes collectively impair cell-cycle control, transcriptional regulation and cytoskeletal stability in neuronal cells. We further examine the impact of PKM2 on neuroinflammation, highlighting its context-dependent roles in microglia and astrocytes. In addition, we provide a comprehensive evaluation of natural and synthetic PKM2 modulators with therapeutic potential in Alzheimer's disease, summarizing their mechanisms and reported outcomes. Clarifying the molecular basis of PKM2-mediated neurodegeneration and rigorously testing these modulators in preclinical models will be essential steps towards developing PKM2-targeted strategies for Alzheimer's disease intervention.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid40460395,

title = {Reaction Time, Speech Recognition, and Verbal Memory Performance: Nonnative Versus Native English Speakers},

author = {Zahra Jafari and Hardeep Ryait and Mohammad Habibnezhad and Claire Niehaus and Erin Cantwell and Jordan Dudley and Bryan Kolb and Majid Mohajerani},

doi = {10.1044/2025_JSLHR-24-00580},

issn = {1558-9102},

year  = {2025},

date = {2025-06-01},

journal = {J Speech Lang Hear Res},

pages = {1--13},

abstract = {PURPOSE: Previous studies have debated differences in spoken language processing between nonnative and native English speakers, often yielding varying and sometimes contradictory results. To address these discrepancies, we employed a comprehensive battery of tasks to compare auditory, speech, and memory processing between nonnative and native English language speakers (NELS).nnMETHOD: The study included 70 university students aged 18-35 years, comprising 29 nonnative and 41 native monolingual NELS of both genders. Participants were assessed on auditory and visual reaction time (RT), speech recognition, and verbal memory tasks under two conditions: quiet and multitalker babble noise (0 dB).nnRESULTS: In sentence recognition ( < .001) and word memory tests, the nonnative group performed worse than the native group under both quiet ( = .001) and noisy ( = .002) conditions. Both groups demonstrated a significant reduction in word recognition scores and slower RTs for auditory and visual modules in noise compared to quiet conditions ( < .001).nnCONCLUSIONS: The study yielded two primary findings. First, background noise negatively impacts all levels of auditory processing, from RT to speech recognition and memory recall. Second, nonnative students experience more difficulty in speech perception and memory performance in their second language, English, in both quiet and noisy conditions. These findings underscore the importance of providing additional support to facilitate learning and academic growth for nonnative English language students.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid40325514,

title = {Machine Learning Models Can Predict Tinnitus and Noise-Induced Hearing Loss},

author = {Zahra Jafari and Ryan E Harari and Glenn Hole and Bryan E Kolb and Majid H Mohajerani},

doi = {10.1097/AUD.0000000000001670},

issn = {1538-4667},

year  = {2025},

date = {2025-05-01},

journal = {Ear Hear},

abstract = {OBJECTIVES: Despite the extensive use of machine learning (ML) models in health sciences for outcome prediction and condition classification, their application in differentiating various types of auditory disorders remains limited. This study aimed to address this gap by evaluating the efficacy of five ML models in distinguishing (a) individuals with tinnitus from those without tinnitus and (b) noise-induced hearing loss (NIHL) from age-related hearing loss (ARHL).nnDESIGN: We used data from a cross-sectional study of the Canadian population, which included audiologic and demographic information from 928 adults aged 30 to 100 years, diagnosed with either ARHL or NIHL due to long-term occupational noise exposure. The ML models applied in this study were artificial neural networks (ANNs), K-nearest neighbors, logistic regression, random forest (RF), and support vector machines.nnRESULTS: The study revealed that tinnitus prevalence was over twice as high in the NIHL group compared with the ARHL group, with a frequency of 27.85% versus 8.85% in constant tinnitus and 18.55% versus 10.86% in intermittent tinnitus. In pattern recognition, significantly greater hearing loss was found at medium- and high-band frequencies in NIHL versus ARHL. In both NIHL and ARHL, individuals with tinnitus showed better pure-tone sensitivity than those without tinnitus. Among the ML models, ANN achieved the highest overall accuracy (70%), precision (60%), and F1-score (87%) for predicting tinnitus, with an area under the curve of 0.71. RF outperformed other models in differentiating NIHL from ARHL, with the highest precision (79% for NIHL, 85% for ARHL), recall (85% for NIHL), F1-score (81% for NIHL), and area under the curve (0.90).nnCONCLUSIONS: Our findings highlight the application of ML models, particularly ANN and RF, in advancing diagnostic precision for tinnitus and NIHL, potentially providing a framework for integrating ML techniques into clinical audiology for improved diagnostic precision. Future research is suggested to expand datasets to include diverse populations and integrate longitudinal data.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid40017733,

title = {Assessing cognitive flexibility in mice using a custom-built touchscreen chamber},

author = {Rui C Pais and Ali Goldani and Jayden Hutchison and Amirhossein Mazrouei and Mostafa Khavaninzadeh and Leonardo A Molina and Robert J Sutherland and Majid H Mohajerani},

doi = {10.3389/fnbeh.2025.1536458},

issn = {1662-5153},

year  = {2025},

date = {2025-01-01},

journal = {Front Behav Neurosci},

volume = {19},

pages = {1536458},

abstract = {Automated touchscreen systems have become increasingly prevalent in rodent model screening. This technology has significantly enhanced cognitive and behavioral assessments in mice and has bridged the translational gap between basic research using rodent models and human clinical research. Our study introduces a custom-built touchscreen operant conditioning chamber powered by a Raspberry Pi and a commercially available computer tablet, which effectively addresses the significant cost barriers traditionally associated with this technology. In order to test our prototype, we decided to train C57BL/6 mice on a visual discrimination serial-reversal task, and both C57BL/6 and Appstrain - an Alzheimer's Disease (AD) mouse model - on a new location discrimination serial-reversal task. The results demonstrated a clear progression toward asymptotic performance, particularly in the location discrimination task, which also revealed potential genotype-specific deficits, with App mice displaying an increase in the average number of errors in the first reversal as well as in perseverative errors, compared to wild-type mice. These results validate the practical utility of our touchscreen apparatus and underline its potential to provide insights into the behavioral and cognitive markers of neurobiological disorders.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid40416734,

title = {Effects of cannabidiol (CBD) treatment on age-related cognitive decline in C57 mice},

author = {Behroo Mirza Agha and Merrin Monteith and Jarem Earl and Keona Ganske and Tina Kaloa and Kelan J McDonald and Abigail G Nixon and Maleeha Panjwani and Danika Robinson and Valeria Rusnak and Majid H Mohajerani and Igor Kovalchuk and Robert J Sutherland and Nancy S Hong and Robert J McDonald},

doi = {10.3389/fnagi.2025.1567650},

issn = {1663-4365},

year  = {2025},

date = {2025-01-01},

journal = {Front Aging Neurosci},

volume = {17},

pages = {1567650},

abstract = {Aging is associated with cognitive decline, and currently, there are no approved medications that can prevent these impairments. Recently, cannabinoids derived from  have emerged as promising therapeutic compounds with neuroprotective, anti-inflammatory, and cognitive-enhancing properties. Despite their benefits, further research is needed to fully understand their efficacy across various conditions. This study investigates the effects of cannabidiol (CBD) on memory impairment and brain inflammation in aging mice. Fourteen-month-old C57 mice were administered CBD orally for 7 months and subsequently evaluated between 19 and 21 months of age using behavioral tasks that are sensitive to dysfunction of the perirhinal cortex, hippocampus, amygdala, and various brain regions that are crucial for motor control and coordination. The findings of this study indicate that CBD reduces inflammatory response in the brain and improves cognitive decline associated with aging.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid39364682,

title = {Psilocybin reduces functional correlation and the encoding of spatial information by neurons in mouse retrosplenial cortex},

author = {Victorita E Ivan and David P Tomàs-Cuesta and Ingrid M Esteves and Artur Luczak and Majid Mohajerani and Bruce L McNaughton and Aaron J Gruber},

doi = {10.1111/ejn.16558},

issn = {1460-9568},

year  = {2024},

date = {2024-11-01},

journal = {Eur J Neurosci},

volume = {60},

number = {10},

pages = {6395--6407},

abstract = {Psychedelic drugs have profound effects on perception, cognition and mood. How psychedelics affect neural signaling to produce these effects remains poorly understood. We investigated the effect of the classic psychedelic psilocybin on neural activity patterns and spatial encoding in the retrosplenial cortex of head-fixed mice navigating on a treadmill. The place specificity of neurons to distinct locations along the belt was reduced by psilocybin. Moreover, the stability of place-related activity across trials decreased. Psilocybin also reduced the functional correlation among simultaneously recorded neurons. The 5-HTR (serotonin 2A receptor) antagonist ketanserin blocked these effects. These data are consistent with proposals that psychedelics increase the entropy of neural signaling and provide a potential neural mechanism contributing to disorientation frequently reported by humans after taking psychedelics.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid39255789,

title = {Spatiotemporal resonance in mouse primary visual cortex},

author = {Rasa Gulbinaite and Mojtaba Nazari and Michael E Rule and Edgar J Bermudez-Contreras and Michael X Cohen and Majid H Mohajerani and J Alexander Heimel},

doi = {10.1016/j.cub.2024.07.091},

issn = {1879-0445},

year  = {2024},

date = {2024-09-01},

journal = {Curr Biol},

volume = {34},

number = {18},

pages = {4184--4196.e7},

abstract = {Human primary visual cortex (V1) responds more strongly, or resonates, when exposed to ∼10, ∼15-20, and ∼40-50 Hz rhythmic flickering light. Full-field flicker also evokes the perception of hallucinatory geometric patterns, which mathematical models explain as standing-wave formations emerging from periodic forcing at resonant frequencies of the simulated neural network. However, empirical evidence for such flicker-induced standing waves in the visual cortex was missing. We recorded cortical responses to flicker in awake mice using high-spatial-resolution widefield imaging in combination with high-temporal-resolution glutamate-sensing fluorescent reporter (iGluSnFR). The temporal frequency tuning curves in the mouse V1 were similar to those observed in humans, showing a banded structure with multiple resonance peaks (8, 15, and 33 Hz). Spatially, all flicker frequencies evoked responses in V1 corresponding to retinotopic stimulus location, but some evoked additional peaks. These flicker-induced cortical patterns displayed standing-wave characteristics and matched linear wave equation solutions in an area restricted to the visual cortex. Taken together, the interaction of periodic traveling waves with cortical area boundaries leads to spatiotemporal activity patterns that may affect perception.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid38856286,

title = {Spatial-Temporal Analysis of Neural Desynchronization in Sleeplike States Reveals Critical Dynamics},

author = {Davor Curic and Surjeet Singh and Mojtaba Nazari and Majid H Mohajerani and Jörn Davidsen},

doi = {10.1103/PhysRevLett.132.218403},

issn = {1079-7114},

year  = {2024},

date = {2024-05-01},

journal = {Phys Rev Lett},

volume = {132},

number = {21},

pages = {218403},

abstract = {Sleep is characterized by nonrapid eye movement sleep, originating from widespread neuronal synchrony, and rapid eye movement sleep, with neuronal desynchronization akin to waking behavior. While these were thought to be global brain states, recent research suggests otherwise. Using time-frequency analysis of mesoscopic voltage-sensitive dye recordings of mice in a urethane-anesthetized model of sleep, we find transient neural desynchronization occurring heterogeneously across the cortex within a background of synchronized neural activity, in a manner reminiscent of a critical spreading process and indicative of an "edge-of-synchronization" phase transition.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid38441248,

title = {A systematic review of altered resting-state networks in early deafness and implications for cochlear implantation outcomes},

author = {Zahra Jafari and Bryan E Kolb and Majid H Mohajerani},

doi = {10.1111/ejn.16295},

issn = {1460-9568},

year  = {2024},

date = {2024-05-01},

journal = {Eur J Neurosci},

volume = {59},

number = {10},

pages = {2596--2615},

abstract = {Auditory deprivation following congenital/pre-lingual deafness (C/PD) can drastically affect brain development and its functional organisation. This systematic review intends to extend current knowledge of the impact of C/PD and deafness duration on brain resting-state networks (RSNs), review changes in RSNs and spoken language outcomes post-cochlear implant (CI) and draw conclusions for future research. The systematic literature search followed the PRISMA guideline. Two independent reviewers searched four electronic databases using combined keywords: 'auditory deprivation', 'congenital/prelingual deafness', 'resting-state functional connectivity' (RSFC), 'resting-state fMRI' and 'cochlear implant'. Seventeen studies (16 cross-sectional and one longitudinal) met the inclusion criteria. Using the Crowe Critical Appraisal Tool, the publications' quality was rated between 65.0% and 92.5% (mean: 84.10%), ≥80% in 13 out of 17 studies. A few studies were deficient in sampling and/or ethical considerations. According to the findings, early auditory deprivation results in enhanced RSFC between the auditory network and brain networks involved in non-verbal communication, and high levels of spontaneous neural activity in the auditory cortex before CI are evidence of occupied auditory cortical areas with other sensory modalities (cross-modal plasticity) and sub-optimal CI outcomes. Overall, current evidence supports the idea that moreover intramodal and cross-modal plasticity, the entire brain adaptation following auditory deprivation contributes to spoken language development and compensatory behaviours.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid38494417,

title = {Hippocampal ripples coincide with "up-state" and spindles in retrosplenial cortex},

author = {Rafael Pedrosa and Mojtaba Nazari and Loig Kergoat and Christophe Bernard and Majid Mohajerani and Federico Stella and Francesco Battaglia},

doi = {10.1093/cercor/bhae083},

issn = {1460-2199},

year  = {2024},

date = {2024-03-01},

journal = {Cereb Cortex},

volume = {34},

number = {3},

abstract = {During NREM sleep, hippocampal sharp-wave ripple (SWR) events are thought to stabilize memory traces for long-term storage in downstream neocortical structures. Within the neocortex, a set of distributed networks organized around retrosplenial cortex (RS-network) interact preferentially with the hippocampus purportedly to consolidate those traces. Transient bouts of slow oscillations and sleep spindles in this RS-network are often observed around SWRs, suggesting that these two activities are related and that their interplay possibly contributes to memory consolidation. To investigate how SWRs interact with the RS-network and spindles, we combined cortical wide-field voltage imaging, Electrocorticography, and hippocampal LFP recordings in anesthetized and sleeping mice. Here, we show that, during SWR, "up-states" and spindles reliably co-occur in a cortical subnetwork centered around the retrosplenial cortex. Furthermore, retrosplenial transient activations and spindles predict slow gamma oscillations in CA1 during SWRs. Together, our results suggest that retrosplenial-hippocampal interaction may be a critical pathway of information exchange between the cortex and hippocampus.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid37838246,

title = {Information-theory analysis of mouse string-pulling agrees with Fitts's Law: Increasing task difficulty engages multiple sensorimotor modalities in a dual oscillator behavior},

author = {Pardeepak S Sandhu and Behroo Mirza Agha and Samsoon Inayat and Surjeet Singh and Hardeep S Ryait and Majid H Mohajerani and Ian Q Whishaw},

doi = {10.1016/j.bbr.2023.114705},

issn = {1872-7549},

year  = {2024},

date = {2024-01-01},

journal = {Behav Brain Res},

volume = {456},

pages = {114705},

abstract = {Mouse string pulling, in which a mouse reels in a string with hand-over-hand movements, can provide insights into skilled motor behavior, neurological status, and cognitive function. The task involves two oscillatory movements connected by a string. The snout oscillates to track the pendulum movement of the string produced by hand-over-hand oscillations of pulling, and so the snout guides the hands to grasp the string. The present study examines the allocation of time required to pull strings of varying diameter. Movement is also described with end-point measures, string-pulling topography with 2D markerless pose estimates based on transfer learning with deep neural networks, and Mat-lab image-segmentation and heuristic algorithms for object tracking. With reduced string diameter, mice took longer to pull 60 cm long strings. They also made more pulling cycles, misses, and mouth engagements, and displayed changes in the amplitude and frequency of pull cycles. The time measures agree with Fitts's law in showing that increased task difficulty slows behavior and engages multiple compensatory sensorimotor modalities. The analysis reveals that time is a valuable resource in skilled motor behavior and information-theory can serve as a measure of its effective use.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid38298796,

title = {The Nonclassic Psychedelic Ibogaine Disrupts Cognitive Maps},

author = {Victorita E Ivan and David P Tomàs-Cuesta and Ingrid M Esteves and Davor Curic and Majid Mohajerani and Bruce L McNaughton and Joern Davidsen and Aaron J Gruber},

doi = {10.1016/j.bpsgos.2023.07.008},

issn = {2667-1743},

year  = {2024},

date = {2024-01-01},

journal = {Biol Psychiatry Glob Open Sci},

volume = {4},

number = {1},

pages = {275--283},

abstract = {BACKGROUND: The ability of psychedelic compounds to profoundly alter mental function has been long known, but the underlying changes in cellular-level information encoding remain poorly understood.nnMETHODS: We used two-photon microscopy to record from the retrosplenial cortex in head-fixed mice running on a treadmill before and after injection of the nonclassic psychedelic ibogaine (40 mg/kg intraperitoneally).nnRESULTS: We found that the cognitive map, formed by the representation of position encoded by ensembles of individual neurons in the retrosplenial cortex, was destabilized by ibogaine when mice had to infer position between tactile landmarks. This corresponded with increased neural activity rates, loss of correlation structure, and increased responses to cues. Ibogaine had surprisingly little effect on the size-frequency distribution of network activity events, suggesting that signal propagation within the retrosplenial cortex was largely unaffected.nnCONCLUSIONS: Taken together, these data support proposals that compounds with psychedelic properties disrupt representations that are important for constraining neocortical activity, thereby increasing the entropy of neural signaling. Furthermore, the loss of expected position encoding between landmarks recapitulated effects of hippocampal impairment, suggesting that disruption of cognitive maps or other hippocampal processing may be a contributing mechanism of discoordinated neocortical activity in psychedelic states.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid37551444,

title = {Restoring neuronal chloride extrusion reverses cognitive decline linked to Alzheimer's disease mutations},

author = {Iason Keramidis and Brendan B McAllister and Julien Bourbonnais and Feng Wang and Dominique Isabel and Edris Rezaei and Romain Sansonetti and Phil Degagne and Justin P Hamel and Mojtaba Nazari and Samsoon Inayat and Jordan C Dudley and Annie Barbeau and Lionel Froux and Marie-Eve Paquet and Antoine G Godin and Majid H Mohajerani and Yves De Koninck},

doi = {10.1093/brain/awad250},

issn = {1460-2156},

year  = {2023},

date = {2023-12-01},

journal = {Brain},

volume = {146},

number = {12},

pages = {4903--4915},

abstract = {Disinhibition during early stages of Alzheimer's disease is postulated to cause network dysfunction and hyperexcitability leading to cognitive deficits. However, the underlying molecular mechanism remains unknown. Here we show that, in mouse lines carrying Alzheimer's disease-related mutations, a loss of neuronal membrane potassium-chloride cotransporter KCC2, responsible for maintaining the robustness of GABAA-mediated inhibition, occurs pre-symptomatically in the hippocampus and prefrontal cortex. KCC2 downregulation was inversely correlated with the age-dependent increase in amyloid-β 42 (Aβ42). Acute administration of Aβ42 caused a downregulation of membrane KCC2. Loss of KCC2 resulted in impaired chloride homeostasis. Preventing the decrease in KCC2 using long term treatment with CLP290 protected against deterioration of learning and cortical hyperactivity. In addition, restoring KCC2, using short term CLP290 treatment, following the transporter reduction effectively reversed spatial memory deficits and social dysfunction, linking chloride dysregulation with Alzheimer's disease-related cognitive decline. These results reveal KCC2 hypofunction as a viable target for treatment of Alzheimer's disease-related cognitive decline; they confirm target engagement, where the therapeutic intervention takes place, and its effectiveness.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid38012135,

title = {Cortical reactivation of spatial and non-spatial features coordinates with hippocampus to form a memory dialogue},

author = {HaoRan Chang and Ingrid M Esteves and Adam R Neumann and Majid H Mohajerani and Bruce L McNaughton},

doi = {10.1038/s41467-023-43254-7},

issn = {2041-1723},

year  = {2023},

date = {2023-11-01},

journal = {Nat Commun},

volume = {14},

number = {1},

pages = {7748},

abstract = {Episodic memories comprise diverse attributes of experience distributed across neocortical areas. The hippocampus is integral to rapidly binding these diffuse representations, as they occur, to be later reinstated. However, the nature of the information exchanged during this hippocampal-cortical dialogue remains poorly understood. A recent study has shown that the secondary motor cortex carries two types of representations: place cell-like activity, which were impaired by hippocampal lesions, and responses tied to visuo-tactile cues, which became more pronounced following hippocampal lesions. Using two-photon Ca imaging to record neuronal activities in the secondary motor cortex of male Thy1-GCaMP6s mice, we assessed the cortical retrieval of spatial and non-spatial attributes from previous explorations in a virtual environment. We show that, following navigation, spontaneous resting state reactivations convey varying degrees of spatial (trajectory sequences) and non-spatial (visuo-tactile attributes) information, while reactivations of non-spatial attributes tend to precede reactivations of spatial representations surrounding hippocampal sharp-wave ripples.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid37950055,

title = {Repeated multi-domain cognitive training prevents cognitive decline, anxiety and amyloid pathology found in a mouse model of Alzheimer disease},

author = {Jogender Mehla and Scott H Deibel and Hadil Karem and Nancy S Hong and Shakhawat R Hossain and Sean G Lacoursiere and Robert J Sutherland and Majid H Mohajerani and Robert J McDonald},

doi = {10.1038/s42003-023-05506-6},

issn = {2399-3642},

year  = {2023},

date = {2023-11-01},

journal = {Commun Biol},

volume = {6},

number = {1},

pages = {1145},

abstract = {Education, occupation, and an active lifestyle, comprising enhanced social, physical, and mental components are associated with improved cognitive functions in aged people and may delay the progression of various neurodegenerative diseases including Alzheimer's disease. To investigate this protective effect, 3-month-old APP mice were exposed to repeated single- or multi-domain cognitive training. Cognitive training was given at the age of 3, 6, & 9 months. Single-domain cognitive training was limited to a spatial navigation task. Multi-domain cognitive training consisted of a spatial navigation task, object recognition, and fear conditioning. At the age of 12 months, behavioral tests were completed for all groups. Then, mice were sacrificed, and their brains were assessed for pathology. APP mice given multi-domain cognitive training compared to APP control group showed an improvement in cognitive functions, reductions in amyloid load and microgliosis, and a preservation of cholinergic function. Additionally, multi-domain cognitive training improved anxiety in APP mice as evidenced by measuring thigmotaxis behavior in the Morris water maze. There were mild reductions in microgliosis in the brain of APP mice with single-domain cognitive training. These findings provide causal evidence for the potential of certain forms of cognitive training to mitigate the cognitive deficits in Alzheimer disease.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid37531809,

title = {Weak-hyperactive hippocampal CA1 neurons in the prodromal stage of Alzheimer's disease in hybrid App × Thy1-GCaMP6s mice suggest disrupted plasticity},

author = {Samsoon Inayat and Brendan B McAllister and HaoRan Chang and Sean G Lacoursiere and Ian Q Whishaw and Robert J Sutherland and Majid H Mohajerani},

doi = {10.1016/j.neurobiolaging.2023.06.002},

issn = {1558-1497},

year  = {2023},

date = {2023-10-01},

journal = {Neurobiol Aging},

volume = {130},

pages = {154--171},

abstract = {This study investigated the impact of familial Alzheimer's disease (AD)-linked amyloid precursor protein (App) mutations on hippocampal CA1 neuronal activity and function at an early disease stage in App × Thy1-GCaMP6s (A-TG) mice using calcium imaging. Longitudinal assessment of spatial behavior at 12 and 18 months of age identified an early disease stage at 12 months when there was significant amyloid beta pathology with mild behavioral deficits. Hippocampal CA1 neuronal activity and event-related encoding of distance and time were therefore assessed at 12 months of age in several configurations of an air-induced running task to assess the dynamics of cellular activity. Neurons in A-TG mice displayed diminished (weaker) and more frequent (hyperactive) neuronal firing that was more pronounced during movement compared to immobility. Responsive neurons showed configuration-specific deficits in distance and time encoding with impairment in adapting their responses to changing configurations. These results suggest that at an early stage of AD in the absence of full-blown behavioral deficits, weak-hyperactive neuronal activity may induce impairments in sensory perception of changing environments.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid37536439,

title = {Early tactile stimulation influences the development of Alzheimer's disease in gestationally stressed APP  adult offspring  mice},

author = {Shakhawat R Hossain and Hadil Karem and Zahra Jafari and Bryan E Kolb and Majid H Mohajerani},

doi = {10.1016/j.expneurol.2023.114498},

issn = {1090-2430},

year  = {2023},

date = {2023-10-01},

journal = {Exp Neurol},

volume = {368},

pages = {114498},

abstract = {Alzheimer's disease (AD) is associated with cerebral plaques and tangles, reduced synapse number, and shrinkage in several brain areas and these morphological effects are associated with the onset of compromised cognitive, motor, and anxiety-like behaviours. The appearance of both anatomical and behavioural symptoms is worsened by stress. The focus of this study was to examine the effect of neonatal tactile stimulation on AD-like behavioural and neurological symptoms on APP  mice, a mouse model of AD, who have been gestationally stressed. Our findings indicate that neonatal tactile stimulation improves cognition, motor skills, and anxiety-like symptoms in both gestationally stressed and non-stressed adult APP mice and that these alterations are associated with reduced Aβ plaque formation. Thus, tactile stimulation appears to be a promising non-invasive preventative strategy for slowing the onset of dementia in aging animals.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}