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Articles 31 - 60 of 119
Full-Text Articles in Neurosciences
Neuronal Alpha-Synuclein Disease Integrated Staging System Performance In Ppmi, Pasadena, And Spark Baseline Cohorts, Tien Dam, Gennaro Pagano, Michael C Brumm, Caroline Gochanour, Kathleen L Poston, Daniel Weintraub, Lana M Chahine, Christopher Coffey, Caroline M Tanner, Catherine M Kopil, Yuge Xiao, Sohini Chowdhury, Luis Concha-Marambio, Peter Dibiaso, Tatiana Foroud, Mark Frasier, Danna Jennings, Karl Kieburtz, Kalpana Merchant, Brit Mollenhauer, Thomas J Montine, Kelly Nudelman, John Seibyl, Todd Sherer, Andrew Singleton, Diane Stephenson, Matthew Stern, Claudio Soto, Eduardo Tolosa, Andrew Siderowf, Billy Dunn, Tanya Simuni, Kenneth Marek, Parkinson’S Progression Markers Initiative Collaborators
Neuronal Alpha-Synuclein Disease Integrated Staging System Performance In Ppmi, Pasadena, And Spark Baseline Cohorts, Tien Dam, Gennaro Pagano, Michael C Brumm, Caroline Gochanour, Kathleen L Poston, Daniel Weintraub, Lana M Chahine, Christopher Coffey, Caroline M Tanner, Catherine M Kopil, Yuge Xiao, Sohini Chowdhury, Luis Concha-Marambio, Peter Dibiaso, Tatiana Foroud, Mark Frasier, Danna Jennings, Karl Kieburtz, Kalpana Merchant, Brit Mollenhauer, Thomas J Montine, Kelly Nudelman, John Seibyl, Todd Sherer, Andrew Singleton, Diane Stephenson, Matthew Stern, Claudio Soto, Eduardo Tolosa, Andrew Siderowf, Billy Dunn, Tanya Simuni, Kenneth Marek, Parkinson’S Progression Markers Initiative Collaborators
Faculty, Staff and Student Publications
The Neuronal alpha-Synuclein Disease (NSD) biological definition and Integrated Staging System (NSD-ISS) provide a research framework to identify individuals with Lewy body pathology and stage them based on underlying biology and increasing degree of functional impairment. Utilizing data from the PPMI, PASADENA, and SPARK studies, we developed and applied biologic and clinical data-informed definitions for the NSD-ISS across the disease continuum. Individuals enrolled as Parkinson's disease, Prodromal, or Healthy Controls were defined and staged based on biological, clinical, and functional anchors at baseline. Across the three studies 1741 participants had SAA data and of these 1030 (59%) were S+ consistent …
Investigating Neuropsychiatric Symptoms In Asian Subgroups With Dementia Using The National Alzheimer's Coordinating Center (Nacc) Database, Maria Sophia Zaraspe Malbas, Luis A. Peña Marquez, Ramya Kunta, Astrid-Ines Foamkom, Ney Alliey-Rodriguez
Investigating Neuropsychiatric Symptoms In Asian Subgroups With Dementia Using The National Alzheimer's Coordinating Center (Nacc) Database, Maria Sophia Zaraspe Malbas, Luis A. Peña Marquez, Ramya Kunta, Astrid-Ines Foamkom, Ney Alliey-Rodriguez
Research Colloquium
Background: The incidence of neuropsychiatric symptoms (NPS), such as agitation, depression, anxiety, irritability, and sleeping disturbances, is common among patients with dementia. These symptoms are commonly evaluated with the Neuropsychiatric Inventory Questionnaire (NPI-Q), a useful tool for studying changes in behavior associated with neurodegenerative disorders for the past couple of decades. Another database utilizing the NPI-Q to assess NPS is the National Alzheimer’s Coordinating Center (NACC) Database. This uniform data set aims to store participant information, including neuropsychological tests, demographic information, and medical health history, collected from Alzheimer’s Disease Centers across the United States. To date, no studies using the …
Pre-Hospital Stroke Time Intervals In The Rio Grande Valley, Kelsey Baker, Elio E. Garcia Sosa
Pre-Hospital Stroke Time Intervals In The Rio Grande Valley, Kelsey Baker, Elio E. Garcia Sosa
Research Colloquium
Background and Introduction: Stroke continues to be a significant cause of mortality in the United States. Despite advancements in acute stroke treatments such as thrombolytic therapy and endovascular procedures, many patients remain unable to benefit from these interventions due to delays in receiving treatment. Healthcare professionals have made substantial efforts to improve 'door to needle' times, the interval between a patient's arrival at the hospital and the administration of thrombolytic therapy, yielding promising outcomes. However, a critical gap persists: the time interval from the onset of stroke symptoms to when patients actually present at a healthcare facility. This study aims …
Proximity Analysis Of Native Proteomes Reveals Phenotypic Modifiers In A Mouse Model Of Autism And Related Neurodevelopmental Conditions, Yudong Gao, Daichi Shonai, Matthew Trn, Jieqing Zhao, Erik J Soderblom, S Alexandra Garcia-Moreno, Charles A Gersbach, William C Wetsel, Geraldine Dawson, Dmitry Velmeshev, Yong-Hui Jiang, Laura G Sloofman, Joseph D Buxbaum, Scott H Soderling
Proximity Analysis Of Native Proteomes Reveals Phenotypic Modifiers In A Mouse Model Of Autism And Related Neurodevelopmental Conditions, Yudong Gao, Daichi Shonai, Matthew Trn, Jieqing Zhao, Erik J Soderblom, S Alexandra Garcia-Moreno, Charles A Gersbach, William C Wetsel, Geraldine Dawson, Dmitry Velmeshev, Yong-Hui Jiang, Laura G Sloofman, Joseph D Buxbaum, Scott H Soderling
Faculty, Staff and Students Publications
One of the main drivers of autism spectrum disorder is risk alleles within hundreds of genes, which may interact within shared but unknown protein complexes. Here we develop a scalable genome-editing-mediated approach to target 14 high-confidence autism risk genes within the mouse brain for proximity-based endogenous proteomics, achieving the identification of high-specificity spatial proteomes. The resulting native proximity proteomes are enriched for human genes dysregulated in the brain of autistic individuals, and reveal proximity interactions between proteins from high-confidence risk genes with those of lower-confidence that may provide new avenues to prioritize genetic risk. Importantly, the datasets are enriched for …
Regulation And Mechanisms Of Ocular Dominance Plasticity At Cellular Resolution., Thomas Christopher Brown
Regulation And Mechanisms Of Ocular Dominance Plasticity At Cellular Resolution., Thomas Christopher Brown
Electronic Theses and Dissertations
Sensory systems throughout the brain require experience to aid in proper wiring during development. While forming, many sensory systems have periods of heightened sensitivity where alterations in the quality of experience can have a profound impact on cortical responses throughout life. These periods of heightened sensitivity have been coined critical periods. In the visual system of mice a critical period for ocular dominance has been well studied and defined between postnatal days nineteen and thirty-six. During this critical period, altering visual experience by suturing one eye closed called monocular deprivation (MD) shifts responses in cortex towards the non-deprived eye. Similar …
Cerebellar Nuclei Cells Produce Distinct Pathogenic Spike Signatures In Mouse Models Of Ataxia, Dystonia, And Tremor, Meike E Van Der Heijden, Amanda M Brown, Dominic J Kizek, Roy V Sillitoe
Cerebellar Nuclei Cells Produce Distinct Pathogenic Spike Signatures In Mouse Models Of Ataxia, Dystonia, And Tremor, Meike E Van Der Heijden, Amanda M Brown, Dominic J Kizek, Roy V Sillitoe
Duncan NRI Faculty and Staff Publications
The cerebellum contributes to a diverse array of motor conditions, including ataxia, dystonia, and tremor. The neural substrates that encode this diversity are unclear. Here, we tested whether the neural spike activity of cerebellar output neurons is distinct between movement disorders with different impairments, generalizable across movement disorders with similar impairments, and capable of causing distinct movement impairments. Using in vivo awake recordings as input data, we trained a supervised classifier model to differentiate the spike parameters between mouse models for ataxia, dystonia, and tremor. The classifier model correctly assigned mouse phenotypes based on single-neuron signatures. Spike signatures were shared …
Comprehensive Single-Cell Atlas Of The Mouse Retina, Jin Li, Jongsu Choi, Xuesen Cheng, Justin Ma, Shahil Pema, Joshua R Sanes, Graeme Mardon, Benjamin J Frankfort, Nicholas M Tran, Yumei Li, Rui Chen
Comprehensive Single-Cell Atlas Of The Mouse Retina, Jin Li, Jongsu Choi, Xuesen Cheng, Justin Ma, Shahil Pema, Joshua R Sanes, Graeme Mardon, Benjamin J Frankfort, Nicholas M Tran, Yumei Li, Rui Chen
Faculty, Staff and Students Publications
Single-cell RNA sequencing (scRNA-seq) has advanced our understanding of cellular heterogeneity by characterizing cell types across tissues and species. While several mouse retinal scRNA-seq datasets exist, each dataset is either limited in cell numbers or focused on specific cell classes, thereby hindering comprehensive gene expression analysis across all retina types. To fill the gap, we generated the largest retinal scRNA-seq dataset to date, comprising approximately 190,000 single cells from C57BL/6J mouse retinas, enriched for rare population cells via antibody-based magnetic cell sorting. Integrating this dataset with public datasets, we constructed the Mouse Retina Cell Atlas (MRCA) for wild-type mice, encompassing …
Alzheimer's Disease Risk Gene Cd2ap Is A Dose-Sensitive Determinant Of Synaptic Structure And Plasticity, Taeyong Ahn, Gabrielle E Largoza, Julia Younis, Mary E Dickinson, Chih-Wei Hsu, Joshua D Wythe
Alzheimer's Disease Risk Gene Cd2ap Is A Dose-Sensitive Determinant Of Synaptic Structure And Plasticity, Taeyong Ahn, Gabrielle E Largoza, Julia Younis, Mary E Dickinson, Chih-Wei Hsu, Joshua D Wythe
Faculty, Staff and Students Publications
Tissue clearing is an essential prerequisite for 3D volumetric imaging of larger tissues or organs. Here, we present a detailed protocol for optical, aqueous-based clearing of adult murine tissues using EZ Clear. We describe steps to ensure successful perfusion and fixation of organs from the adult mouse and supply guidelines for optimal lipid removal, refractive index matching, and tissue clearing. Finally, we provide imaging parameters for visualizing both exogenous perfused fluorescent dyes and endogenous fluorescence reporters in the adult mouse. For complete details on the use and execution of this protocol, please refer to Hsu et al.
Cognitive And Neuroscientific Perspectives Of Healthy Ageing, Jon B. Prince, Helen L. Davis, Jane Tan, Katrina Muller-Townsend, Shaun Markovic, David M. G. Lewis, Brianne Hastie, Matthew B. Thompson, Peter D. Drummond, Hakuei Fujiyama, Hamid R. Sohrabi
Cognitive And Neuroscientific Perspectives Of Healthy Ageing, Jon B. Prince, Helen L. Davis, Jane Tan, Katrina Muller-Townsend, Shaun Markovic, David M. G. Lewis, Brianne Hastie, Matthew B. Thompson, Peter D. Drummond, Hakuei Fujiyama, Hamid R. Sohrabi
Research outputs 2022 to 2026
With dementia incidence projected to escalate significantly within the next 25 years, the United Nations declared 2021–2030 the Decade of Healthy Ageing, emphasising cognition as a crucial element. As a leading discipline in cognition and ageing research, psychology is well-equipped to offer insights for translational research, clinical practice, and policy-making. In this comprehensive review, we discuss the current state of knowledge on age-related changes in cognition and psychological health. We discuss cognitive changes during ageing, including (a) heterogeneity in the rate, trajectory, and characteristics of decline experienced by older adults, (b) the role of cognitive reserve in age-related cognitive decline, …
The Role Of Spreading Depolarizations In Mild Traumatic Brain Injuries, Natalie J. Pinkowski
The Role Of Spreading Depolarizations In Mild Traumatic Brain Injuries, Natalie J. Pinkowski
Biomedical Sciences ETDs
Mild traumatic brain injuries (mTBIs) often lead to acute symptoms like disorientation and discoordination, but the underlying mechanisms are unknown. Although most patients recover quickly from a single mTBI, repeated injuries can be debilitating. After an mTBI, a neurometabolic cascade produces metabolic burden and vulnerability. Spreading depolarizations (SDs) have been observed after mTBIs. Here we investigated SDs’ role in short-term motor behavioral deficits post-mTBI. We hypothesized that SDs contribute to the deficits, and exacerbated symptoms after repeated mTBIs. To test this, we used acute motor behavioral tests and long-term behavioral and cognitive tests after initiating SDs by mTBI, chemical, or …
Consensus On Best Practices In Neuroscience-Informed Treatment Of Combat-Related Posttraumatic Stress In Military Veterans: A Delphi Study Of Experts In The Field Of Mental Health, Danielle Lauren Winters
Consensus On Best Practices In Neuroscience-Informed Treatment Of Combat-Related Posttraumatic Stress In Military Veterans: A Delphi Study Of Experts In The Field Of Mental Health, Danielle Lauren Winters
Counseling & Human Services Theses & Dissertations
The purpose of this study was to capture consensus among mental health professionals who work with combat trauma-afflicted veterans and/or utilize a neuroscience-informed counseling approach, about a set of best practices for uniting neuroscience-informed treatment modalities with the treatment of veterans who present with Post Traumatic Stress (PTS). A multi-round Delphi study was used to elicit information from mental health professionals, which led to the proposition of ways in which mental health professionals may more efficiently work with combat veterans while utilizing neuroscience-informed treatments such as Prolonged Exposure Therapy, Eye Movement Desensitization and Reprocessing (EMDR) neuro-informed Cognitive Behavioral therapy (nCBT), …
Tumor Treating Fields Suppress Tumor Cell Growth And Neurologic Decline In Models Of Spinal Metastases, Daniel Ledbetter, Romulo Augusto Andrade De Almeida, Xizi Wu, Ariel Naveh, Chirag B Patel, Queena Gonzalez, Thomas H Beckham, Robert North, Laurence Rhines, Jing Li, Amol Ghia, David Aten, Claudio Tatsui, Christopher Alvarez-Breckenridge
Tumor Treating Fields Suppress Tumor Cell Growth And Neurologic Decline In Models Of Spinal Metastases, Daniel Ledbetter, Romulo Augusto Andrade De Almeida, Xizi Wu, Ariel Naveh, Chirag B Patel, Queena Gonzalez, Thomas H Beckham, Robert North, Laurence Rhines, Jing Li, Amol Ghia, David Aten, Claudio Tatsui, Christopher Alvarez-Breckenridge
Faculty, Staff and Student Publications
Spinal metastases can result in severe neurologic compromise and decreased overall survival. Despite treatment advances, local disease progression is frequent, highlighting the need for novel therapies. Tumor treating fields (TTFields) impair tumor cell replication and are influenced by properties of surrounding tissue. We hypothesized that bone's dielectric properties will enhance TTFields-mediated suppression of tumor growth in spinal metastasis models. Computational modeling of TTFields intensity was performed following surgical resection of a spinal metastasis and demonstrated enhanced TTFields intensity within the resected vertebral body. Additionally, luciferase-tagged human KRIB osteosarcoma and A549 lung adenocarcinoma cell lines were cultured in demineralized bone grafts …
Mapping Sca1 Regional Vulnerabilities Reveals Neural And Skeletal Muscle Contributions To Disease, Lisa Duvick, W Michael Southern, Kellie A Benzow, Zoe N Burch, Hillary P Handler, Jason S Mitchell, Hannah Kuivinen, Udaya Gadiparthi, Praseuth Yang, Alyssa Soles, Carrie A Sheeler, Orion Rainwater, Shannah Serres, Erin B Lind, Tessa Nichols-Meade, Yun You, Brennon O'Callaghan, Huda Y Zoghbi, Marija Cvetanovic, Vanessa C Wheeler, James M Ervasti, Michael D Koob, Harry T Orr
Mapping Sca1 Regional Vulnerabilities Reveals Neural And Skeletal Muscle Contributions To Disease, Lisa Duvick, W Michael Southern, Kellie A Benzow, Zoe N Burch, Hillary P Handler, Jason S Mitchell, Hannah Kuivinen, Udaya Gadiparthi, Praseuth Yang, Alyssa Soles, Carrie A Sheeler, Orion Rainwater, Shannah Serres, Erin B Lind, Tessa Nichols-Meade, Yun You, Brennon O'Callaghan, Huda Y Zoghbi, Marija Cvetanovic, Vanessa C Wheeler, James M Ervasti, Michael D Koob, Harry T Orr
Duncan NRI Faculty and Staff Publications
Spinocerebellar ataxia type 1 (SCA1) is a fatal neurodegenerative disease caused by an expanded polyglutamine tract in the widely expressed ataxin-1 (ATXN1) protein. To elucidate anatomical regions and cell types that underlie mutant ATXN1-induced disease phenotypes, we developed a floxed conditional knockin mouse (f-ATXN1146Q/2Q) with mouse Atxn1 coding exons replaced by human ATXN1 exons encoding 146 glutamines. f-ATXN1146Q/2Q mice manifested SCA1-like phenotypes including motor and cognitive deficits, wasting, and decreased survival. Central nervous system (CNS) contributions to disease were revealed using f-ATXN1146Q/2Q;Nestin-Cre mice, which showed improved rotarod, open field, and Barnes maze performance by 6-12 weeks of age. In contrast, …
Estrogen Signaling In The Dorsal Raphe Regulates Binge-Like Drinking In Mice, Valeria C Torres Irizarry, Bing Feng, Xiaohua Yang, Nirali Patel, Sarah Schaul, Lucas Ibrahimi, Hui Ye, Pei Luo, Leslie Carrillo-Sáenz, Penghua Lai, Maya Kota, Devin Dixit, Chunmei Wang, Amy W Lasek, Yanlin He, Pingwen Xu
Estrogen Signaling In The Dorsal Raphe Regulates Binge-Like Drinking In Mice, Valeria C Torres Irizarry, Bing Feng, Xiaohua Yang, Nirali Patel, Sarah Schaul, Lucas Ibrahimi, Hui Ye, Pei Luo, Leslie Carrillo-Sáenz, Penghua Lai, Maya Kota, Devin Dixit, Chunmei Wang, Amy W Lasek, Yanlin He, Pingwen Xu
Faculty, Staff and Students Publications
Estrogens promote binge alcohol drinking and contribute to sex differences in alcohol use disorder. However, the mechanisms are largely unknown. This study aims to test if estrogens act on 5-hydroxytryptamine neurons in the dorsal raphe nucleus (5-HTDRN) to promote binge drinking. We found that female mice drank more alcohol than male mice in chronic drinking in the dark (DID) tests. This sex difference was associated with distinct alterations in mRNA expression of estrogen receptor α (ERα) and 5-HT-related genes in the DRN, suggesting a potential role of estrogen/ERs/5-HT signaling. In supporting this view, 5-HTDRN neurons from naïve male mice had …
The Ddhd2-Stxbp1 Interaction Mediates Long-Term Memory Via Generation Of Saturated Free Fatty Acids, Isaac O Akefe, Saber H Saber, Benjamin Matthews, Bharat G Venkatesh, Rachel S Gormal, Daniel G Blackmore, Suzy Alexander, Emma Sieriecki, Yann Gambin, Jesus Bertran-Gonzalez, Nicolas Vitale, Yann Humeau, Arnaud Gaudin, Sevannah A Ellis, Alysee A Michaels, Mingshan Xue, Benjamin Cravatt, Merja Joensuu, Tristan P Wallis, Frédéric A Meunier
The Ddhd2-Stxbp1 Interaction Mediates Long-Term Memory Via Generation Of Saturated Free Fatty Acids, Isaac O Akefe, Saber H Saber, Benjamin Matthews, Bharat G Venkatesh, Rachel S Gormal, Daniel G Blackmore, Suzy Alexander, Emma Sieriecki, Yann Gambin, Jesus Bertran-Gonzalez, Nicolas Vitale, Yann Humeau, Arnaud Gaudin, Sevannah A Ellis, Alysee A Michaels, Mingshan Xue, Benjamin Cravatt, Merja Joensuu, Tristan P Wallis, Frédéric A Meunier
Faculty, Staff and Students Publications
The phospholipid and free fatty acid (FFA) composition of neuronal membranes plays a crucial role in learning and memory, but the mechanisms through which neuronal activity affects the brain's lipid landscape remain largely unexplored. The levels of saturated FFAs, particularly of myristic acid (C14:0), strongly increase during neuronal stimulation and memory acquisition, suggesting the involvement of phospholipase A1 (PLA1) activity in synaptic plasticity. Here, we show that genetic ablation of the PLA1 isoform DDHD2 in mice dramatically reduces saturated FFA responses to memory acquisition across the brain. Furthermore, DDHD2 loss also decreases memory performance in reward-based learning and spatial memory …
Risk For Diagnosis Or Treatment Of Mood Or Anxiety Disorders In Adults After Sars-Cov-2 Infection, 2020–2022, Christina X. Wang, Rhea Kohli, Veronica R. Olaker, Pauline Terebuh, Rong Xu, David C. Kaelber, Pamela B. Davis
Risk For Diagnosis Or Treatment Of Mood Or Anxiety Disorders In Adults After Sars-Cov-2 Infection, 2020–2022, Christina X. Wang, Rhea Kohli, Veronica R. Olaker, Pauline Terebuh, Rong Xu, David C. Kaelber, Pamela B. Davis
Faculty Scholarship
COVID-19 is associated with increased risks for mood or anxiety disorders, but it remains uncertain how the association evolves over time or which patient groups are most affected. We conducted a retrospective cohort study using a nationwide database of electronic health records to determine the risk of depressive or anxiety disorder diagnoses after SARS-CoV-2 infection by 3-month blocks from January 2020 to April 2022. The study population comprised 822,756 patients (51.8% female; mean age 42.8 years) with COVID-19 and 2,034,353 patients with other respiratory tract infections (RTIs) (53.5% female, mean age 30.6 years). First time diagnoses of depressive or anxiety …
Aging Fly Cell Atlas Identifies Exhaustive Aging Features At Cellular Resolution, Kenneth A Wilson, Sudipta Bar, Eric B Dammer, Enrique M Carrera, Brian A Hodge, Tyler A U Hilsabeck, Joanna Bons, George W Brownridge, Jennifer N Beck, Jacob Rose, Melia Granath-Panelo, Christopher S Nelson, Grace Qi, Akos A Gerencser, Jianfeng Lan, Alexandra Afenjar, Geetanjali Chawla, Rachel B Brem, Philippe M Campeau, Hugo J Bellen, Birgit Schilling, Nicholas T Seyfried, Lisa M Ellerby, Pankaj Kapahi
Aging Fly Cell Atlas Identifies Exhaustive Aging Features At Cellular Resolution, Kenneth A Wilson, Sudipta Bar, Eric B Dammer, Enrique M Carrera, Brian A Hodge, Tyler A U Hilsabeck, Joanna Bons, George W Brownridge, Jennifer N Beck, Jacob Rose, Melia Granath-Panelo, Christopher S Nelson, Grace Qi, Akos A Gerencser, Jianfeng Lan, Alexandra Afenjar, Geetanjali Chawla, Rachel B Brem, Philippe M Campeau, Hugo J Bellen, Birgit Schilling, Nicholas T Seyfried, Lisa M Ellerby, Pankaj Kapahi
Faculty, Staff and Students Publications
Dietary restriction (DR) delays aging, but the mechanism remains unclear. We identified polymorphisms in mtd, the fly homolog of OXR1, which influenced lifespan and mtd expression in response to DR. Knockdown in adulthood inhibited DR-mediated lifespan extension in female flies. We found that mtd/OXR1 expression declines with age and it interacts with the retromer, which regulates trafficking of proteins and lipids. Loss of mtd/OXR1 destabilized the retromer, causing improper protein trafficking and endolysosomal defects. Overexpression of retromer genes or pharmacological restabilization with R55 rescued lifespan and neurodegeneration in mtd-deficient flies and endolysosomal defects in fibroblasts from patients with lethal loss-of-function …
Examining The Impact Of Firearm Recoil During A Round Of Trap Shooting On Neurometabolic Changes Associated With Traumatic Brain Injury, Lakota Jones
Theses, Dissertations and Capstones
The CDC identifies concussion as a blunt, blow, or jolt to the head resulting in brain injury. Shooting sports do not impose a direct blow to the head but instead inflict rapid acceleration to the brain via recoil transfer. Exposure to rapid, repetitive recoil may cause physiological disturbances in the brain, therefore resulting in mild traumatic brain injury (TBI). Chronic recoil transfer and overpressure exposure influencing neurometabolic changes of TBI have yet to be measured. The objective of this study was to examine kinetic energy experienced in trap and skeet shooters following one round of shooting in comparison to neurometabolic …
Abnormal Patterns Of Sleep And Waking Behaviors Are Accompanied By Neocortical Oscillation Disturbances In An Ank3 Mouse Model Of Epilepsy-Bipolar Disorder Comorbidity, Juan E Villacres, Nicholas Riveira, Sohmee Kim, Laura L Colgin, Jeffrey L Noebels, Angel Y Lopez
Abnormal Patterns Of Sleep And Waking Behaviors Are Accompanied By Neocortical Oscillation Disturbances In An Ank3 Mouse Model Of Epilepsy-Bipolar Disorder Comorbidity, Juan E Villacres, Nicholas Riveira, Sohmee Kim, Laura L Colgin, Jeffrey L Noebels, Angel Y Lopez
Faculty, Staff and Students Publications
ANK3 is a leading bipolar disorder (BD) candidate gene in humans and provides a unique opportunity for studying epilepsy-BD comorbidity. Previous studies showed that deletion of Ank3-1b, a BD-associated variant of Ank3 in mice leads to increased firing threshold and diminished action potential dynamic range of parvalbumin (PV) interneurons and absence epilepsy, thus providing a biological mechanism linking epilepsy and BD. To explore the behavioral overlap of these disorders, we characterized behavioral patterns of Ank3-1b KO mice during overnight home-cage activity and examined network activity during these behaviors using paired video and EEG recordings. Since PV interneurons contribute to the …
A Transcriptomic Taxonomy Of Mouse Brain-Wide Spinal Projecting Neurons, Carla C Winter, Anne Jacobi, Junfeng Su, Leeyup Chung, Cindy T J Van Velthoven, Zizhen Yao, Changkyu Lee, Zicong Zhang, Shuguang Yu, Kun Gao, Geraldine Duque Salazar, Evgenii Kegeles, Yu Zhang, Makenzie C Tomihiro, Yiming Zhang, Zhiyun Yang, Junjie Zhu, Jing Tang, Xuan Song, Ryan J Donahue, Qing Wang, Delissa Mcmillen, Michael Kunst, Ning Wang, Kimberly A Smith, Gabriel E Romero, Michelle M Frank, Alexandra Krol, Riki Kawaguchi, Daniel H Geschwind, Guoping Feng, Lisa V Goodrich, Yuanyuan Liu, Bosiljka Tasic, Hongkui Zeng, Zhigang He
A Transcriptomic Taxonomy Of Mouse Brain-Wide Spinal Projecting Neurons, Carla C Winter, Anne Jacobi, Junfeng Su, Leeyup Chung, Cindy T J Van Velthoven, Zizhen Yao, Changkyu Lee, Zicong Zhang, Shuguang Yu, Kun Gao, Geraldine Duque Salazar, Evgenii Kegeles, Yu Zhang, Makenzie C Tomihiro, Yiming Zhang, Zhiyun Yang, Junjie Zhu, Jing Tang, Xuan Song, Ryan J Donahue, Qing Wang, Delissa Mcmillen, Michael Kunst, Ning Wang, Kimberly A Smith, Gabriel E Romero, Michelle M Frank, Alexandra Krol, Riki Kawaguchi, Daniel H Geschwind, Guoping Feng, Lisa V Goodrich, Yuanyuan Liu, Bosiljka Tasic, Hongkui Zeng, Zhigang He
Faculty, Staff and Student Publications
The brain controls nearly all bodily functions via spinal projecting neurons (SPNs) that carry command signals from the brain to the spinal cord. However, a comprehensive molecular characterization of brain-wide SPNs is still lacking. Here we transcriptionally profiled a total of 65,002 SPNs, identified 76 region-specific SPN types, and mapped these types into a companion atlas of the whole mouse brain1. This taxonomy reveals a three-component organization of SPNs: (1) molecularly homogeneous excitatory SPNs from the cortex, red nucleus and cerebellum with somatotopic spinal terminations suitable for point-to-point communication; (2) heterogeneous populations in the reticular formation with broad …
Widefield Imaging Of Rapid Pan-Cortical Voltage Dynamics With An Indicator Evolved For One-Photon Microscopy, Xiaoyu Lu, Yunmiao Wang, Zhuohe Liu, Yueyang Gou, Dieter Jaeger, François St-Pierre
Widefield Imaging Of Rapid Pan-Cortical Voltage Dynamics With An Indicator Evolved For One-Photon Microscopy, Xiaoyu Lu, Yunmiao Wang, Zhuohe Liu, Yueyang Gou, Dieter Jaeger, François St-Pierre
Faculty, Staff and Students Publications
Widefield imaging with genetically encoded voltage indicators (GEVIs) is a promising approach for understanding the role of large cortical networks in the neural coding of behavior. However, the limited performance of current GEVIs restricts their deployment for single-trial imaging of rapid neuronal voltage dynamics. Here, we developed a high-throughput platform to screen for GEVIs that combine fast kinetics with high brightness, sensitivity, and photostability under widefield one-photon illumination. Rounds of directed evolution produced JEDI-1P, a green-emitting fluorescent indicator with enhanced performance across all metrics. Next, we optimized a neonatal intracerebroventricular delivery method to achieve cost-effective and wide-spread JEDI-1P expression in …
Computational Modeling And Minimization Of Unintended Neuronal Excitation In A Lifu Stimulation, Boqiang Fan, Wayne Goodman, Raymond Y Cho, Sameer A Sheth, Richard R Bouchard, Behnaam Aazhang
Computational Modeling And Minimization Of Unintended Neuronal Excitation In A Lifu Stimulation, Boqiang Fan, Wayne Goodman, Raymond Y Cho, Sameer A Sheth, Richard R Bouchard, Behnaam Aazhang
Faculty, Staff and Student Publications
The neuromodulation effect of low-intensity focused ultrasound (LIFU) is highly target-specific. Unintended off-target neuronal excitation can be elicited when the beam focusing accuracy and resolution are limited, whereas the resulted side effect has not been evaluated quantitatively. There is also a lack of methods addressing the minimization of such side effects. Therefore, this work introduces a computational model of unintended neuronal excitation during LIFU neuromodulation, which evaluates the off-target activation area (OTAA) by integrating an ultrasound field model with the neuronal spiking model. In addition, a phased array beam focusing scheme called constrained optimal resolution beamforming (CORB) is proposed to …
Two Structurally Defined Aβ Polymorphs Promote Different Pathological Changes In Susceptible Mice, Ruben Gomez-Gutierrez, Ujjayini Ghosh, Wai-Ming Yau, Nazaret Gamez, Katherine Do, Carlos Kramm, Hamid Shirani, Laura Vegas-Gomez, Jonathan Schulz, Ines Moreno-Gonzalez, Antonia Gutierrez, K Peter R Nilsson, Robert Tycko, Claudio Soto, Rodrigo Morales
Two Structurally Defined Aβ Polymorphs Promote Different Pathological Changes In Susceptible Mice, Ruben Gomez-Gutierrez, Ujjayini Ghosh, Wai-Ming Yau, Nazaret Gamez, Katherine Do, Carlos Kramm, Hamid Shirani, Laura Vegas-Gomez, Jonathan Schulz, Ines Moreno-Gonzalez, Antonia Gutierrez, K Peter R Nilsson, Robert Tycko, Claudio Soto, Rodrigo Morales
Faculty, Staff and Student Publications
Misfolded Aβ is involved in the progression of Alzheimer's disease (AD). However, the role of its polymorphic variants or conformational strains in AD pathogenesis is not fully understood. Here, we study the seeding properties of two structurally defined synthetic misfolded Aβ strains (termed 2F and 3F) using in vitro and in vivo assays. We show that 2F and 3F strains differ in their biochemical properties, including resistance to proteolysis, binding to strain-specific dyes, and in vitro seeding. Injection of these strains into a transgenic mouse model produces different pathological features, namely different rates of aggregation, formation of different plaque types, …
Neuro-Immune Interactions And Immuno-Oncology, Narmina Khanmammadova, Shajedul Islam, Padmanee Sharma, Moran Amit
Neuro-Immune Interactions And Immuno-Oncology, Narmina Khanmammadova, Shajedul Islam, Padmanee Sharma, Moran Amit
Faculty, Staff and Student Publications
The nervous system is an important component of the tumor microenvironment (TME), driving tumorigenesis and tumor progression. Neuronal cues (e.g., neurotransmitters and neuropeptides) in the TME cause phenotypic changes in immune cells, such as increased exhaustion and inhibition of effector cells, which promote immune evasion and cancer progression. Two types of immune regulation by tumor-associated nerves are discussed in this review: regulation via neuronal stimuli (i.e., by neural transmission) and checkpoint-mediated neuronal immune regulation. The latter occurs via the expression of immune checkpoints on the membranes of intratumoral nerves and glial cells. Here, we summarize novel findings regarding the neuroimmune …
Intraoperative Cortical Localization Of Music And Language Reveals Signatures Of Structural Complexity In Posterior Temporal Cortex, Meredith J Mccarty, Elliot Murphy, Xavier Scherschligt, Oscar Woolnough, Cale W Morse, Kathryn Snyder, Bradford Z Mahon, Nitin Tandon
Intraoperative Cortical Localization Of Music And Language Reveals Signatures Of Structural Complexity In Posterior Temporal Cortex, Meredith J Mccarty, Elliot Murphy, Xavier Scherschligt, Oscar Woolnough, Cale W Morse, Kathryn Snyder, Bradford Z Mahon, Nitin Tandon
Faculty, Staff and Student Publications
Language and music involve the productive combination of basic units into structures. It remains unclear whether brain regions sensitive to linguistic and musical structure are co-localized. We report an intraoperative awake craniotomy in which a left-hemispheric language-dominant professional musician underwent cortical stimulation mapping (CSM) and electrocorticography of music and language perception and production during repetition tasks. Musical sequences were melodic or amelodic, and differed in algorithmic compressibility (Lempel-Ziv complexity). Auditory recordings of sentences differed in syntactic complexity (single vs. multiple phrasal embeddings). CSM of posterior superior temporal gyrus (pSTG) disrupted music perception and production, along with speech production. pSTG and …
Memory Rescue And Learning In Synaptic Impaired Neuronal Circuits, Kwan Tung Li, Daoyun Ji, Changsong Zhou
Memory Rescue And Learning In Synaptic Impaired Neuronal Circuits, Kwan Tung Li, Daoyun Ji, Changsong Zhou
Faculty, Staff and Students Publications
Neuronal impairment is a characteristic of Alzheimer's disease (AD), but its effect on neural activity dynamics underlying memory deficits is unclear. Here, we studied the effects of synaptic impairment on neural activities associated with memory recall, memory rescue, and learning a new memory, in an integrate-and-fire neuronal network. Our results showed that reducing connectivity decreases the neuronal synchronization of memory neurons and impairs memory recall performance. Although, slow-gamma stimulation rescued memory recall and slow-gamma oscillations, the rescue caused a side effect of activating mixed memories. During the learning of a new memory, reducing connectivity caused impairment in storing the new …
Anoctamin 4 Channel Currents Activate Glucose-Inhibited Neurons In The Mouse Ventromedial Hypothalamus During Hypoglycemia, Longlong Tu, Jonathan C Bean, Yang He, Hailan Liu, Meng Yu, Hesong Liu, Nan Zhang, Na Yin, Junying Han, Nikolas A Scarcelli, Kristine M Conde, Mengjie Wang, Yongxiang Li, Bing Feng, Peiyu Gao, Zhao-Lin Cai, Makoto Fukuda, Mingshan Xue, Qingchun Tong, Yongjie Yang, Lan Liao, Jianming Xu, Chunmei Wang, Yanlin He, Yong Xu
Anoctamin 4 Channel Currents Activate Glucose-Inhibited Neurons In The Mouse Ventromedial Hypothalamus During Hypoglycemia, Longlong Tu, Jonathan C Bean, Yang He, Hailan Liu, Meng Yu, Hesong Liu, Nan Zhang, Na Yin, Junying Han, Nikolas A Scarcelli, Kristine M Conde, Mengjie Wang, Yongxiang Li, Bing Feng, Peiyu Gao, Zhao-Lin Cai, Makoto Fukuda, Mingshan Xue, Qingchun Tong, Yongjie Yang, Lan Liao, Jianming Xu, Chunmei Wang, Yanlin He, Yong Xu
Faculty, Staff and Student Publications
Glucose is the basic fuel essential for maintenance of viability and functionality of all cells. However, some neurons - namely, glucose-inhibited (GI) neurons - paradoxically increase their firing activity in low-glucose conditions and decrease that activity in high-glucose conditions. The ionic mechanisms mediating electric responses of GI neurons to glucose fluctuations remain unclear. Here, we showed that currents mediated by the anoctamin 4 (Ano4) channel are only detected in GI neurons in the ventromedial hypothalamic nucleus (VMH) and are functionally required for their activation in response to low glucose. Genetic disruption of the Ano4 gene in VMH neurons reduced blood …
Complement C3ar Depletion Reverses Hif-1Α-Induced Metabolic Impairment And Enhances Microglial Response To Aβ Pathology, Manasee Gedam, Michele M Comerota, Nicholas E Propson, Tao Chen, Feng Jin, Meng C Wang, Hui Zheng
Complement C3ar Depletion Reverses Hif-1Α-Induced Metabolic Impairment And Enhances Microglial Response To Aβ Pathology, Manasee Gedam, Michele M Comerota, Nicholas E Propson, Tao Chen, Feng Jin, Meng C Wang, Hui Zheng
Faculty, Staff and Students Publications
Microglia are the major cell type expressing complement C3a receptor (C3aR) in the brain. Using a knockin mouse line in which a Td-tomato reporter is incorporated into the endogenous C3ar1 locus, we identified 2 major subpopulations of microglia with differential C3aR expression. Expressing the Td-tomato reporter on the APPNL-G-F-knockin (APP-KI) background revealed a significant shift of microglia to a high-C3aR-expressing subpopulation and they were enriched around amyloid β (Aβ) plaques. Transcriptomic analysis of C3aR-positive microglia documented dysfunctional metabolic signatures, including upregulation of hypoxia-inducible factor 1 (HIF-1) signaling and abnormal lipid metabolism in APP-KI mice compared with wild-type controls. Using primary …
Effects Of Spaceflight On The Eeg Alpha Power And Functional Connectivity, Sandra Pusil, Jonathan Zegarra-Valdivia, Pablo Cuesta, Christopher Laohathai, Ana Maria Cebolla, Jens Haueisen, Patrique Fiedler, Michael Funke, Fernando Maestú, Guy Cheron
Effects Of Spaceflight On The Eeg Alpha Power And Functional Connectivity, Sandra Pusil, Jonathan Zegarra-Valdivia, Pablo Cuesta, Christopher Laohathai, Ana Maria Cebolla, Jens Haueisen, Patrique Fiedler, Michael Funke, Fernando Maestú, Guy Cheron
Faculty, Staff and Student Publications
Electroencephalography (EEG) can detect changes in cerebral activity during spaceflight. This study evaluates the effect of spaceflight on brain networks through analysis of the Default Mode Network (DMN)'s alpha frequency band power and functional connectivity (FC), and the persistence of these changes. Five astronauts' resting state EEGs under three conditions were analyzed (pre-flight, in-flight, and post-flight). DMN's alpha band power and FC were computed using eLORETA and phase-locking value. Eyes-opened (EO) and eyes-closed (EC) conditions were differentiated. We found a DMN alpha band power reduction during in-flight (EC: p < 0.001; EO: p < 0.05) and post-flight (EC: p < 0.001; EO: p < 0.01) when compared to pre-flight condition. FC strength decreased during in-flight (EC: p < 0.01; EO: p < 0.01) and post-flight (EC: ns; EO: p < 0.01) compared to pre-flight condition. The DMN alpha band power and FC strength reduction persisted until 20 days after landing. Spaceflight caused electrocerebral alterations that persisted after return to earth. Periodic assessment by EEG-derived DMN analysis has the potential to become a neurophysiologic marker of cerebral functional integrity during exploration missions to space.
Effects Of Concussion And Visuomotor Metrics On Nhl Performance: An Explainable Ai Approach, Michael T. Moschitto
Effects Of Concussion And Visuomotor Metrics On Nhl Performance: An Explainable Ai Approach, Michael T. Moschitto
Master's Theses
Cognitive motor integration (CMI), the simultaneous coordination between cerebral function and motor output, is known to deteriorate following a mild traumatic brain injury (mTBI). This thesis explores the relationship between mTBI, CMI, and the performance of elite athletes in the National Hockey League (NHL). The approach focuses on examining the predictive value of various supervised Machine Learning (ML) models with an emphasis on Explainable Artificial Intelligence (XAI) models. Since the ML solution is intended to complement human scouting decisions, we evaluate the experiments based on both interpretability and accuracy on a limited class imbalanced dataset. The contributions of this research …