4.7 Article

Unraveling cognitive traits using the Morris water maze unbiased strategy classification (MUST-C) algorithm

Journal

BRAIN BEHAVIOR AND IMMUNITY
Volume 52, Issue -, Pages 132-144

Publisher

ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1016/j.bbi.2015.10.013

Keywords

Morris water maze; Learning and memory; Spatial learning; Hippocampus; SVM; Machine learning; Strategy; Spatial resolution; Cognitive score

Funding

  1. Alzheimer's Association Foundation
  2. Feder Family Fund

Ask authors/readers for more resources

The assessment of spatial cognitive learning in rodents is a central approach in neuroscience, as it enables one to assess and quantify the effects of treatments and genetic manipulations from a broad perspective. Although the Morris water maze (MWM) is a well-validated paradigm for testing spatial learning abilities, manual categorization of performance in the MWM into behavioral strategies is subject to individual interpretation, and thus to biases. Here we offer a support vector machine (SVM) - based, automated, MWM unbiased strategy classification (MUST-C) algorithm, as well as a cognitive score scale. This model was examined and validated by analyzing data obtained from five MWM experiments with changing platform sizes, revealing a limitation in the spatial capacity of the hippocampus. We have further employed this algorithm to extract novel mechanistic insights on the impact of members of the Toll-like receptor pathway on cognitive spatial learning and memory. The MUST-C algorithm can greatly benefit MWM users as it provides a standardized method of strategy classification as well as a cognitive scoring scale, which cannot be derived from typical analysis of MWM data. (C) 2015 The Authors. Published by Elsevier Inc.

Authors

I am an author on this paper
Click your name to claim this paper and add it to your profile.

Reviews

Primary Rating

4.7
Not enough ratings

Secondary Ratings

Novelty
-
Significance
-
Scientific rigor
-
Rate this paper

Recommended

Article Biochemical Research Methods

A modified Barnes maze for an accurate assessment of spatial learning in mice

Tomer Illouz, Ravit Madar, Eitan Okun

JOURNAL OF NEUROSCIENCE METHODS (2020)

Article Neurosciences

A Tellurium-Based Small Immunomodulatory Molecule Ameliorates Depression-Like Behavior in Two Distinct Rat Models

Moshe Hagar, Gersner Roman, Okun Eitan, Barnea-Ygael Noam, Zangen Abrham, Sredni Benjamin

NEUROMOLECULAR MEDICINE (2020)

Editorial Material Geriatrics & Gerontology

Food and Age: It Takes Two to Degenerate

Raneen Nicola, Eitan Okun

FRONTIERS IN AGING NEUROSCIENCE (2020)

Article Biochemistry & Molecular Biology

Proteinoid Nanocapsules as Drug Delivery System for Improving Antipsychotic Activity of Risperidone

Liroy Lugasi, Igor Grinberg, Rivka Sabag, Ravit Madar, Haim Einat, Shlomo Margel

MOLECULES (2020)

Review Neurosciences

High-Intensity Functional Training: Molecular Mechanisms and Benefits

Tavor Ben-Zeev, Eitan Okun

Summary: High-intensity interval training (HIIT) and strength exercise are beneficial for improving health markers such as cardiovascular health, metabolic health, and cognitive function, reducing all-cause mortality. High-Intensity Functional Training (HIFT) combines HIIT and strength exercise to enhance muscle recruitment, improving both cardiovascular fitness and strength parameters. This review focuses on the molecular mechanisms underlying the positive effects of HIFT on cardiovascular, metabolic, and cognitive functions.

NEUROMOLECULAR MEDICINE (2021)

Article Biology

Maternal antibodies facilitate Amyloid-β clearance by activating Fc-receptor-Syk-mediated phagocytosis

Tomer Illouz, Raneen Nicola, Linoy Ben-Shushan, Ravit Madar, Arya Biragyn, Eitan Okun

Summary: A study by Illouz et al. demonstrated that maternal immunization with anti-A beta antibodies in wildtype female mice bred with 5xFAD males led to reduced cortical A beta levels and alleviated memory deficits in the offspring, even 4 months after the antibodies were undetectable. This long-term effect was attributed to a shift in microglial phenotype. The findings suggest that maternal immunization could potentially alleviate cognitive decline and pathology associated with early A beta deposition in diseases like AD and DS.

COMMUNICATIONS BIOLOGY (2021)

Review Neurosciences

Adult Hippocampal Neurogenesis: One Lactate to Rule Them All

Raneen Nicola, Eitan Okun

Summary: Adult hippocampal neurogenesis is a dynamic process involving cognitive functions such as learning and memory, regulated by numerous intrinsic and extrinsic factors. Physical exercise, particularly the impact of lactate, plays a beneficial role in neural plasticity. Lactate, considered a potent factor in health and disease, influences most cells in the CNS and affects different cell types within the neurogenic niche, regulating adult hippocampal neurogenesis.

NEUROMOLECULAR MEDICINE (2021)

Article Multidisciplinary Sciences

Therapeutic B-cell depletion reverses progression of Alzheimer's disease

Ki Kim, Xin Wang, Emeline Ragonnaud, Monica Bodogai, Tomer Illouz, Marisa DeLuca, Ross A. McDevitt, Fedor Gusev, Eitan Okun, Evgeny Rogaev, Arya Biragyn

Summary: The study demonstrates that accumulation of activated B cells is crucial to the pathology of AD in three relevant transgenic animal models, and depletion of B cells interferes with both histological and behavioral manifestations of the disease.

NATURE COMMUNICATIONS (2021)

Article Immunology

Induction of an effective anti-Amyloid-β humoral response in aged mice

Tomer Illouz, Ravit Madar, Tamir Hirsh, Arya Biragyn, Eitan Okun

Summary: The decline in immune functions related to aging, known as immunosenescence, leads to reduced protective responses to vaccines in the elderly. Developing vaccination strategies that harness memory-based immunity can overcome this age-related decline in immune responses and have potential implications for aging-related diseases such as Alzheimer's disease.

VACCINE (2021)

Article Neurosciences

HCAR1-Mediated l-Lactate Signaling Suppresses Microglial Phagocytosis

Raneen Nicola, Ravit Madar, Eitan Okun

Summary: A recent study found that extracellular lactate can reduce the phagocytic ability of microglial cells by binding to a specific receptor, potentially impacting brain homeostasis and inflammatory conditions.

NEUROMOLECULAR MEDICINE (2022)

Letter Immunology

Reply to letter by Dr. Fu and Dr. Chu: Risk factors for poor COVID-19 outcomes in patients with psychiatric disorders

Wan-Ju Cheng, Hong-Mo Shih, Kuan-Pin Su, Po-Ren Hsueh

BRAIN BEHAVIOR AND IMMUNITY (2024)

Article Immunology

Cognitive, behavioral, neuroimaging and inflammatory biomarkers after hospitalization for COVID-19 in Brazil

Felipe Kenji Sudo, Talita P. Pinto, Fernanda G. Q. Barros-Aragao, Ivanei Bramati, Theo F. Marins, Marina Monteiro, Fernanda Meireles, Rejane Soares, Pilar Erthal, Victor Calil, Naima Assuncao, Natalia Oliveira, Joana Bondarovsky, Camila Lima, Beatriz Chagas, Alana Batista, Julia Lins, Thais L. Pinheiro, Felippe Mendonca, Andrea Silveira de Souza, Fernanda C. Rodrigues, Gabriel R. de Freitas, Pedro Kurtz, Paulo Mattos, Erika C. Rodrigues, Fernanda G. De Felice, Fernanda Tovar-Moll

Summary: Post-COVID-19 Condition (PCC) is a multisystemic syndrome that persists for months after SARS-CoV-2 infection, affecting cognitive function and neuropsychiatric features. A study on COVID-19 survivors in Brazil found that these patients experienced significant difficulties in overall cognition, memory, working memory, and inhibitory control, as well as fatigue, anxiety, and depressive symptoms. In addition, elevated levels of inflammatory markers in the blood were associated with brain microstructural damage and cognitive impairments.

BRAIN BEHAVIOR AND IMMUNITY (2024)

Article Immunology

Chemogenetic approaches reveal dual functions of microglia in seizures

Aastha Dheer, Dale B. Bosco, Jiaying Zheng, Lingxiao Wang, Shunyi Zhao, Koichiro Haruwaka, Min-Hee Yi, Abhijeet Barath, Dai-Shi Tian, Long-Jun Wu

Summary: Microglial activation plays a crucial role in the pathology of epilepsy, with both acute and prolonged activation affecting seizure severity and neuronal loss.

BRAIN BEHAVIOR AND IMMUNITY (2024)

Article Immunology

Maternal inflammation during pregnancy is associated with risk of ADHD in children at age 10

Julie B. Rosenberg, Jens Richardt Mollegaard Jepsen, Parisa Mohammadzadeh, Astrid Sevelsted, Rebecca Vinding, Mikkel E. Sorensen, David Horner, Kristina Aagaard, Birgitte Fagerlund, Susanne Brix, Nilofar Folsgaard, Ann -Marie M. Schoos, Jakob Stokholm, Bo Chawes, Christos Pantelis, Soren Dalsgaard, Birte Y. Glenthoj, Niels Bilenberg, Klaus Bonnelykke, Bjorn H. Ebdrup

Summary: Clinical data demonstrates a strong association between prenatal maternal inflammation assessed by hs-CRP and a diagnosis of ADHD by age 10. Maternal inflammation is also associated with ADHD symptom load in the entire cohort.

BRAIN BEHAVIOR AND IMMUNITY (2024)

Article Immunology

Voluntary wheel running prevents formation of membrane attack complexes and myelin degradation after peripheral nerve injury

Suzanne M. Green-Fulgham, Michael J. Lacagnina, Kendal F. Willcox, Jiahe Li, Michael E. Harland, Adriano Polican Ciena, Igor R. Correia Rocha, Jayson B. Ball, Renee A. Dreher, Younus A. Zuberi, Joseph M. Dragavon, Marucia Chacur, Steven F. Maier, Linda R. Watkins, Peter M. Grace

Summary: Regular aerobic activity, specifically voluntary wheel running, can reduce the risk of chronic pain by inhibiting MAC and preserving myelin integrity at the site of peripheral nerve injury.

BRAIN BEHAVIOR AND IMMUNITY (2024)

Article Immunology

Neuronanomedicine for Alzheimer's and Parkinson's disease: Current progress and a guide to improve clinical translation

India Boyton, Stella M. Valenzuela, Lyndsey E. Collins-Praino, Andrew Care

Summary: Neuronanomedicine is a multidisciplinary field that aims to develop innovative nanotechnologies for the treatment of neurodegenerative disorders. Nanoparticles are an important component of neuronanomedicine, as they can improve drug properties and enhance safety and delivery across the blood-brain barrier. However, a major challenge for neuronanomedicine translation is the poor understanding of bio-nano interactions, partly due to inconsistent reporting in published works. This review provides specific recommendations to guide researchers in harnessing the unique properties of nanoparticles for breakthrough treatments of Alzheimer's and Parkinson's disease.

BRAIN BEHAVIOR AND IMMUNITY (2024)

Article Immunology

Mind versus body: Perceived stress and biological stress are independently related to cognitive decline

Celine De Looze, Cathal McCrory, Aisling O'Halloran, Silvia Polidoro, Rose Anne Kenny, Joanne Feeney

Summary: Our study found that subjective measures of stress and biological metrics may be independently associated with cognitive function over time in older adults, hinting at potential different underlying mechanisms.

BRAIN BEHAVIOR AND IMMUNITY (2024)

Article Immunology

Choroid plexus volume is increased in mood disorders and associates with circulating inflammatory cytokines

Beatrice Bravi, Elisa Maria Teresa Melloni, Marco Paolini, Mariagrazia Palladini, Federico Calesella, Laura Servidio, Elena Agnoletto, Sara Poletti, Cristina Lorenzi, Cristina Colombo, Francesco Benedetti

Summary: Depressed patients show changes in immune-inflammatory markers in their blood and cerebrospinal fluid. The Choroid Plexus, located at the base of the brain ventricles, plays a key role in regulating the exchange of substances between the brain and immune cells. Patients with bipolar disorder or major depressive disorder have larger Choroid Plexus volumes compared to healthy controls. Age and levels of circulating cytokines are associated with Choroid Plexus volumes in the clinical groups.

BRAIN BEHAVIOR AND IMMUNITY (2024)

Article Immunology

Probiotic Clostridium butyricum ameliorates cognitive impairment in obesity via the microbiota-gut-brain axis

Mingxuan Zheng, Huaiyu Ye, Xiaoying Yang, Lijun Shen, Xuemei Dang, Xiaoli Liu, Yuying Gong, Qingyuan Wu, Li Wang, Xing Ge, Xiaoli Fang, Benchi Hou, Peng Zhang, Renxian Tang, Kuiyang Zheng, Xu-Feng Huang, Yinghua Yu

Summary: Obesity is linked to cognitive dysfunction and neurodegenerative disease. The connection between the gut microbiota and the brain is altered in obesity. The probiotic Clostridium butyricum can improve cognitive impairment caused by obesity and prevent gut microbiota dysbiosis and inflammation.

BRAIN BEHAVIOR AND IMMUNITY (2024)

Article Immunology

Stem-cell derived neurosphere assay highlights the effects of viral infection on human cortical development

Edward Drydale, Phalguni Rath, Katie Holden, Gregory Holt, Laurissa Havins, Thomas Johnson, James Bancroft, Lahiru Handunnetthi

Summary: This study created a novel three-dimensional neurosphere assay using induced pluripotent stem cell differentiation and live cell imaging techniques to investigate the effect of a simulated viral infection on cortical development. The findings demonstrated that the infection led to reduced radial glial growth and neural migration.

BRAIN BEHAVIOR AND IMMUNITY (2024)

Article Immunology

An integral blood-brain barrier in adulthood relies on microglia-derived PDGFB

Yuancheng Weng, Ningting Chen, Rui Zhang, Jian He, Xukai Ding, Guo Cheng, Qianqian Bi, Ying-mei Lu, Xiao Z. Shen, Shu Wan, Peng Shi

Summary: This study reveals that microglia is the primary cellular source of PDGFB in adults, and microglial PDGFB is crucial for maintaining BBB integrity in adult mice.

BRAIN BEHAVIOR AND IMMUNITY (2024)

Article Immunology

Gonadal hormones impart male-biased behavioral vulnerabilities to immune activation via microglial mitochondrial function

Evan A. Bordt, Haley A. Moya, Young Chan Jo, Caitlin T. Ravichandran, Izabella M. Bankowski, Alexis M. Ceasrine, Christopher J. Mcdougle, William A. Carlezon Jr, Staci D. Bilbo

Summary: There is a strong male bias in many neurodevelopmental disorders such as autism spectrum disorder, but the mechanisms behind this bias are unknown. Infection during the perinatal period increases the risk of neurodevelopmental disorders. Using a mouse model, researchers found that early-life immune activation only induced deficits in social behaviors in male mice. These behavioral changes were associated with alterations in microglial immune signaling, mitochondrial morphology, gene expression, and function specifically in microglia, the brain's innate immune cells. Furthermore, the vulnerability to early-life immune activation and its effects on behavior and microglial mitochondria were programmed by the male-typical perinatal gonadal hormone surge. These findings highlight the role of microglia-specific mechanisms shaped by early developmental events in regulating male social behavior throughout lifespan.

BRAIN BEHAVIOR AND IMMUNITY (2024)

Article Immunology

Interleukin-15 alters hippocampal synaptic transmission and impairs episodic memory formation in mice

Maria Amalia Di Castro, Stefano Garofalo, Alessandro Mormino, Laura Carbonari, Erika Di Pietro, Eleonora De Felice, Myriam Catalano, Laura Maggi, Cristina Limatola

Summary: Cytokines, such as interleukin-15 (IL-15), play important roles in modulating the central nervous system (CNS). In this study, the authors found that exposure to IL-15 enhances GABA release and reduces glutamatergic currents in hippocampal slices. Chronic treatment with IL-15 has negative effects on memory formation. Serotonin is involved in mediating these effects, as a selective 5-HT3A receptor antagonist prevents the effects on inhibitory neurotransmission and improves performance in a memory test.

BRAIN BEHAVIOR AND IMMUNITY (2024)

Article Immunology

Comprehensive immunoprofiling of neurodevelopmental disorders suggests three distinct classes based on increased neurogenesis, Th-1 polarization or IL-1 signaling

Nikhitha Sreenivas, Michael Maes, Hansashree Padmanabha, Apoorva Dharmendra, Priyanka Chakkera, Saptamita Paul Choudhury, Fazal Abdul, Thrinath Mullapudi, Vykuntaraju K. Gowda, Michael Berk, John Vijay Sagar Kommu, Monojit Debnath

Summary: Neurodevelopmental disorders (NDDs) are a spectrum of conditions with both common and differing characteristics in terms of phenome, symptomatome, neuropathology, risk factors and underlying mechanisms. This study investigates the possibility of a shared immune etiology among three early-onset NDDs, namely Autism Spectrum Disorder (ASD), Attention Deficit Hyperactivity Disorder (ADHD) and Intellectual Disability Disorder (IDD).

BRAIN BEHAVIOR AND IMMUNITY (2024)