Neurosciences Commons^™

Synaptic Development In Diverse Olfactory Neuron Classes Uses Distinct Temporal And Activity-Related Programs, Michael A. Aimino, Alison T. Depew, Lucas Restrepo, Timothy J. Mosca

Farber Institute for Neuroscience Faculty Papers

Developing neurons must meet core molecular, cellular, and temporal requirements to ensure the correct formation of synapses, resulting in functional circuits. However, because of the vast diversity in neuronal class and function, it is unclear whether or not all neurons use the same organizational mechanisms to form synaptic connections and achieve functional and morphologic maturation. Moreover, it remains unknown whether neurons united in a common goal and comprising the same sensory circuit develop on similar timescales and use identical molecular approaches to ensure the formation of the correct number of synapses. To begin to answer these questions, we took advantage …

A Multiple Input Multiple Output Framework For The Automatic Optical Fractionator-Based Cell Counting In Z-Stacks Using Deep Learning, Palak Dave

USF Tampa Graduate Theses and Dissertations

Quantifying cells in a defined region of biological tissue is critical for many clinical and preclinical studies, especially in pathology, toxicology, cancer, and behavior. Unbiased stereology is the state-of-art method for quantification of the total number and other morphometric parameters of stained objects in a defined region of biological tissue. As part of a program to develop accurate, precise, and more efficient automatic approaches for quantifying morphometric changes in biological tissue, our group has shown that both deep learning-based and hand-crafted algorithms can estimate the total number of histologically stained cells at their maximal profile of focus in extended depth …

The Association Of Gabapentin Initiation And Neurocognitive Changes In Older Adults With Normal Cognition, Gyeon Oh, Daniela Claudia Moga, David W. Fardo, Erin L. Abner

Sanders-Brown Center on Aging Faculty Publications

Background: Gabapentin is increasingly prescribed to older adults, which raises concerns about its potential to cause neurocognitive changes. Therefore, we aimed to examine the association of gabapentin use with neurocognitive changes (i.e., cognitive decline, functional status decline, and motor function change) in older adults.

Methods: We conducted a retrospective cohort study using the National Alzheimer’s Coordinating Center Uniform Data Set (UDS; September 2005-March 2021 data freeze). From the eligible sample (≥age 65 years), we identified cognitively normal new-users of gabapentin and the visit they initiated gabapentin (i.e., index visit). Initiators were matched to randomly selected nonusers on year …

Notch Missense Mutations In Drosophila Reveal Functions Of Specific Egf-Like Repeats In Notch Folding, Trafficking, And Signaling, Hilman Nurmahdi, Mao Hasegawa, Elzava Yuslimatin Mujizah, Takeshi Sasamura, Mikiko Inaki, Shinya Yamamoto, Tomoko Yamakawa, Kenji Matsuno

Duncan NRI Faculty and Staff Publications

Notch signaling plays various roles in cell-fate specification through direct cell–cell interactions. Notch receptors are evolutionarily conserved transmembrane proteins with multiple epidermal growth factor (EGF)-like repeats. Drosophila Notch has 36 EGF-like repeats, and while some play a role in Notch signaling, the specific functions of most remain unclear. To investigate the role of each EGF-like repeat, we used 19 previously identified missense mutations of Notch with unique amino acid substitutions in various EGF-like repeats and a transmembrane domain; 17 of these were identified through a single genetic screen. We assessed these mutants’ phenotypes in the nervous system and hindgut during …

Single Nuclei Analyses Reveal Transcriptional Profiles And Marker Genes For Diverse Supraspinal Populations, Zachary Beine, Zimei Wang, Pantelis Tsoulfas, Murray G. Blackmore

Biomedical Sciences Faculty Research and Publications

The mammalian brain contains numerous neurons distributed across forebrain, midbrain, and hindbrain that project axons to the lower spinal cord and work in concert to control movement and achieve homeostasis. Extensive work has mapped the anatomic location of supraspinal cell types and continues to establish specific physiological functions. The patterns of gene expression that typify and distinguish these disparate populations, however, are mostly unknown. Here, using adult mice of mixed sex, we combined retrograde labeling of supraspinal cell nuclei with fluorescence-activated nuclei sorting and single-nuclei RNA sequencing analyses to transcriptionally profile neurons that project axons from the brain to lumbar …

Influence Of Data Sampling Methods On The Representation Of Neural Spiking Activity In Vivo, Meike E Van Der Heijden, Amanda M Brown, Roy V Sillitoe

Duncan NRI Faculty and Staff Publications

No abstract provided.

Satisfaction With Alemtuzumab In Relapsing Multiple Sclerosis Patients: Results From The Real-World Pro-Act Study., Sibyl Wray, Francois Jacques, Tamara A Miller, Jacqueline A Nicholas, Rafael Arroyo, Lori Travis, Bhupendra Khatri, Magdalena Chirieac, Roopali Gandhi, Nora Roesch, Amelie Rodrigues, Lydie Melas-Melt, Andreea M Rawlings, Samuel F Hunter

Ambulatory and Primary Care Articles

BACKGROUND: Patient-reported outcomes are increasingly used in the management of patients with multiple sclerosis to understand the patient's perspective of disease and treatment. These measures provide insights into important factors including treatment satisfaction, physical and psychological function, and quality of life.

OBJECTIVE: To present results from the real-world PRO-ACT study in patients with multiple sclerosis who switched to alemtuzumab from another disease-modifying therapy.

METHODS: This 24-month, prospective, multicenter, observational study had a primary endpoint of change in overall satisfaction, measured using the Treatment Satisfaction Questionnaire for Medication (TSQM) version 1.4. Secondary endpoints included the Multiple Sclerosis Impact Scale-29 (MSIS-29), Modified …

Region-Specific Denoising Identifies Spatial Co-Expression Patterns And Intra-Tissue Heterogeneity In Spatially Resolved Transcriptomics Data, Linhua Wang, Mirjana Maletic-Savatic, Zhandong Liu

Duncan NRI Faculty and Staff Publications

Spatially resolved transcriptomics is a relatively new technique that maps transcriptional information within a tissue. Analysis of these datasets is challenging because gene expression values are highly sparse due to dropout events, and there is a lack of tools to facilitate in silico detection and annotation of regions based on their molecular content. Therefore, we develop a computational tool for detecting molecular regions and region-based Missing value Imputation for Spatially Transcriptomics (MIST). We validate MIST-identified regions across multiple datasets produced by 10x Visium Spatial Transcriptomics, using manually annotated histological images as references. We benchmark MIST against a spatial k-nearest neighboring …

Uncovering The Biological Basis Of Control Energy: Structural And Metabolic Correlates Of Energy Inefficiency In Temporal Lobe Epilepsy, Xiaosong He, Lorenzo Caciagli, Linden Parkes, Jennifer Stiso, Teresa M. Karrer, Jason Z. Kim, Zhixin Lu, Tommaso Menara, Fabio Pasqualetti, Michael R. Sperling, Joseph I. Tracy, Dani S. Bassett

Department of Neurology Faculty Papers

Network control theory is increasingly used to profile the brain's energy landscape via simulations of neural dynamics. This approach estimates the control energy required to simulate the activation of brain circuits based on structural connectome measured using diffusion magnetic resonance imaging, thereby quantifying those circuits' energetic efficiency. The biological basis of control energy, however, remains unknown, hampering its further application. To fill this gap, investigating temporal lobe epilepsy as a lesion model, we show that patients require higher control energy to activate the limbic network than healthy volunteers, especially ipsilateral to the seizure focus. The energetic imbalance between ipsilateral and …

Two Neuronal Peptides Encoded From A Single Transcript Regulate Mitochondrial Complex Iii In Drosophila, Justin A Bosch, Berrak Ugur, Israel Pichardo-Casas, Jordan Rabasco, Felipe Escobedo, Zhongyuan Zuo, Ben Brown, Susan Celniker, David A Sinclair, Hugo J Bellen, Norbert Perrimon

Duncan NRI Faculty and Staff Publications

Naturally produced peptides (<100 amino acids) are important regulators of physiology, development, and metabolism. Recent studies have predicted that thousands of peptides may be translated from transcripts containing small open-reading frames (smORFs). Here, we describe two peptides in Drosophila encoded by conserved smORFs, Sloth1 and Sloth2. These peptides are translated from the same bicistronic transcript and share sequence similarities, suggesting that they encode paralogs. Yet, Sloth1 and Sloth2 are not functionally redundant, and loss of either peptide causes animal lethality, reduced neuronal function, impaired mitochondrial function, and neurodegeneration. We provide evidence that Sloth1/2 are highly expressed in neurons, imported to mitochondria, and regulate mitochondrial complex III assembly. These results suggest that phenotypic analysis of smORF genes in Drosophila can provide a wealth of information on the biological functions of this poorly characterized class of …

Deep Learning Algorithm Reveals Probabilities Of Stage-Specific Time To Conversion In Individuals With Neurodegenerative Disease Late, Xinxing Wu, Chong Peng, Peter T. Nelson, Qiang Cheng

Sanders-Brown Center on Aging Faculty Publications

Introduction: Limbic-predominant age-related TAR DNA-binding protein 43 (TDP-43) encephalopathy (LATE) is a recently defined neurodegenerative disease. Currently, there is no effective way to make a prognosis of time to stage-specific future conversions at an individual level.

Methods: After using the Kaplan–Meier estimation and log-rank test to confirm the heterogeneity of LATE progression, we developed a deep learning–based approach to assess the stage-specific probabilities of time to LATE conversions for different subjects.

Results: Our approach could accurately estimate the disease incidence and transition to next stages: the concordance index was at least 82% and the integrated Brier score …

Living With Brain Cancer: From Researcher To Patient, Stephen P. Chelko, Daniel L. Fay Ph.D.

Patient Experience Journal

As an academic researcher, my work-life revolves around testing the efficaciousness of pharmaceutical drugs on the prevention of cardiac dysfunction, arrhythmias, and sudden cardiac death in animal models of heart disease. I never thought I would go from someone studying a life-threatening disease to a patient living with one in twenty-four hours. Yet, that transformation occurred October 8, 2019. I was just appointed to Assistant Professor at Johns Hopkins University School of Medicine (JHUSOM), yet after sitting for my professional headshot I had a grand mal seizure. I cannot recall this event, but I bit the tip of my tongue …

All The Brain's A Stage For Serotonin: The Forgotten Story Of Serotonin Diffusion Across Cell Membranes, Paul W. Andrews, Catherine Bosyj, Luke Brenton, Laura Green, Paul J. Gasser, Christopher A. Lowry, Virginia M. Pickel

Biomedical Sciences Faculty Research and Publications

In the conventional model of serotonin neurotransmission, serotonin released by neurons in the midbrain raphe nuclei exerts its actions on forebrain neurons by interacting with a large family of post-synaptic receptors. The actions of serotonin are terminated by active transport of serotonin back into the releasing neuron, which is mediated by the serotonin reuptake transporter (SERT). Because SERT is expressed pre-synaptically and is widely thought to be the only serotonin transporter in the forebrain, the conventional model does not include serotonin transport into post-synaptic neurons. However, a large body of evidence accumulating since the 1970s has shown that serotonin, despite …

Possibilities Of Using Neuromarketing Tools In The Hospitality Industry, Serdar Bulbul

University of South Florida (USF) M3 Publishing

Usage of neurosciences in social sciences has emerged new perspectives and methods for marketing and tourism marketing. Neuro-marketing and Neuro-tourism are some of those concepts. In the hospitality industry, marketing is in a complex state because the decision-making processes of the guests are unpredictable. For this reason, hotel managements are unable to satisfy guest’s requests and demands with traditional methods. Therefore, Neuro-marketing has importance because this new way of marketing has a high chance to replace currently used methods. Usage of Neuro-marketing in the hospitality industry could satisfy the guest requests while generating new marketing perspectives on hotel management. This …

Examining The Effects Of Formal Education Level On The Montreal Cognitive Assessment, Renee S. White, Justin M. Barber, Jordan P. Harp, Gregory A. Jicha

Sanders-Brown Center on Aging Faculty Publications

Background: Brief, global assessments such as the Montreal Cognitive Assessment (MoCA) are widely used in primary care for assessing cognition in older adults. Like other neuropsychological instruments, lower formal education can influence MoCA interpretation.

Methods: Data from 2 large studies of cognitive aging were used—Alzheimer’s Disease Neuroimaging Initiative (ADNI) and National Alzheimer’s Coordinating Center (NACC). Both use comprehensive examinations to determine cognitive status and have brain amyloid status for many participants. Mixed models were used to account for random variation due to data source.

Results: Cognitively intact participants with lower education (≤12 years) were more likely than …

Multiple Gene Variants Linked To Alzheimer's-Type Clinical Dementia Via Gwas Are Also Associated With Non-Alzheimer's Neuropathologic Entities, Yuriko Katsumata, Lincoln M. P. Shade, Timothy J. Hohman, Julie A. Schneider, David A. Bennett, Jose M. Farfel, Walter A. Kukull, David W. Fardo, Peter T. Nelson

Sanders-Brown Center on Aging Faculty Publications

The classic pathologic hallmarks of Alzheimer’s disease (AD) are amyloid plaques and neurofibrillary tangles (AD neuropathologic changes, or ADNC). However, brains from individuals clinically diagnosed with “AD-type” (amnestic) dementia usually harbor heterogeneous neuropathologies in addition to, or other than, ADNC. We hypothesized that some AD-type dementia associated genetic single nucleotide variants (SNVs) identified from large genomewide association studies (GWAS) were associated with non-ADNC neuropathologies. To test this hypothesis, we analyzed data from multiple studies with available genotype and neuropathologic phenotype information. Clinical AD/dementia risk alleles of interest were derived from the very large GWAS by Bellenguez et al. (2022) who …

Cerebellar Coordination Of Neuronal And Behavioral Rhythms, Brittany Correia Chapman

Theses and Dissertations (ETD)

Long known for its role in motor control, it is increasingly clear that the cerebellum is also involved in numerous cognitive and affective behaviors. Though the neuronal mechanism for the role of the cerebellum in cognition is still unclear, there is a consensus that it involves cerebellar interactions with the cerebral cortex. Recent studies suggest that the cerebellum monitors, and possibly coordinates, the precise phase alignment or coherence of neuronal oscillations in cerebral cortical areas. Here, we asked how loss of cerebellar function affects respiratory rhythms and the interactions of local field potential (LFP) oscillations between the lobulus simplex (LS) …

Olfactory Processing In The Piriform Cortex Of Awake, Freely Moving Mice, Ian F. Chapman

Theses and Dissertations (ETD)

The piriform cortex (PC) has long been established as the primary cortical recipient of olfactory information in the mammalian brain. In rodents, information extracted from recordings of PC neurons can accurately decode the identity of odors, leading to delineation of PC as the primary cortical region involved in the formation of odor perception. Unfortunately, due to technical limitations, many of the prior studies establishing these coding principles were performed without the ability to track the responses of the same cells over time. Additionally, recordings have often relied on head-fixation to minimize diffusion of odor stimuli, limiting movement range and natural …

Clinical Significance And Potential Role Of Trimethylamine N-Oxide In Neurological And Neuropsychiatric Disorders, Sowjanya Mudimela, Narahari Koppa Vishwanath, Anilkumar Pillai, Rodrigo Morales, Sean P Marrelli, Tatiana Barichello, Vijayasree V Giridharan

Faculty, Staff and Student Publications

Research in the last three decades has attracted the attention of many scientists and industrialists on the gut microbiome and its metabolites. Among many of these metabolites, trimethylamine oxide. Dietary choline, phosphatidylcholine, carnitine, and betaine produces TMAO that with other gut metabolites such as TMA (trimethylamine), and short-chain fatty acids (SCFA) enter the circulation. Finally they reach the brain through the blood-brain barrier (BBB) where they are involved in several physiological functions such as brain development, neurogenesis, and behavior. Gut-microbiota composition is influenced by diet, lifestyle, antibiotics, and age resulting in dysbiosis. Several studies have confirmed that altered TMAO levels …

Assessing Naming Errors Using An Automated Machine Learning Approach, Tatiana T Schnur, Chia-Ming Lei

Faculty, Staff and Student Publications

OBJECTIVE: After left hemisphere stroke, 20%-50% of people experience language deficits, including difficulties in naming. Naming errors that are semantically related to the intended target (e.g., producing "violin" for picture HARP) indicate a potential impairment in accessing knowledge of word forms and their meanings. Understanding the cause of naming impairments is crucial to better modeling of language production as well as for tailoring individualized rehabilitation. However, evaluation of naming errors is typically by subjective and laborious dichotomous classification. As a result, these evaluations do not capture the degree of semantic similarity and are susceptible to lower interrater reliability because of …