Neuroscience and Neurobiology Commons^™

A Framework For Characterizing The Peripheral Immune Isonome Using Long-Read Single-Cell Rna Sequencing And Its Relevance To Neurological Disease, Patricia Hayes Doyle

Theses and Dissertations--Neuroscience

Long-read single-cell RNA sequencing provides an opportunity to understand human health and disease at isoform resolution, revealing cellular diversity and disease mechanisms difficult to resolve with bulk or short-read methodologies.

Using a modified PIPseq workflow and computational pipeline adapted for Oxford Nanopore (ONT) sequencing, we profiled isoform usage across immune cells, integrating marker expression and isoform discovery, generating the largest long-read single-cell dataset of human immune cells from a single individual to date. We identified non-canonical protein-coding variants of GZMB and CD3G enriched in unexpected cell types. We also discovered novel transcripts from CMC1 and LYAR with cell-type-specific signatures that …

Metabolism As A Regulator Of Sleep And Cortical Activity In Health And Alzheimer’S Disease, Nicholas J. Constantino

Theses and Dissertations--Neuroscience

Metabolic flexibility is essential for maintaining normal physiological function, enabling an organism to sense, flux, utilize, and switch fuel sources in response to changing energetic availability, demand, and cellular needs. Energetic demands are state-dependent, with wake and sleep exhibiting distinct metabolic profiles. Sleep is highly sensitive to changes in metabolism and requires metabolic flexibility to both transition into and maintain sleep stability. Alzheimer’s disease (AD) is increasingly recognized as a disease of altered metabolism yet is often framed as a disease of energetic failure. We instead define AD as a disease of metabolic inflexibility, characterized not by insufficient energy availability, …

Design And Advancement Of Analytical Frameworks For In Vivo Single-Photon Calcium Imaging To Characterize Temporal- And Treatment-Dependent Neural Adaptations To Opioid Exposure And Withdrawal In The Medial Prefrontal Cortex, Alexia R. Alsum Dr.

Theses and Dissertations--Pharmacy

Despite the availability of several approved medications for opioid use disorder (OUD), it remains a significant public health concern characterized by persistent neurobiological adaptations that drive relapse and impede successful recovery. The medial prefrontal cortex (mPFC), a region critical for executive control and decision-making, undergoes pronounced functional changes during chronic opioid exposure and withdrawal, yet the cellular mechanisms underlying these adaptations remain poorly understood. This dissertation aims to investigate longitudinal alterations in mPFC neural activity across opioid exposure and withdrawal using in vivo single-photon calcium imaging and newly developed computational frameworks.

Following standard preprocessing to extract and normalize calcium traces, …

Non-Invasive Detection Of Intracranial Pressure, Andrei V. Nesterenko

Honors Undergraduate Theses

Intracranial pressure is a critical metric used when managing tumors, strokes, TBIs, hydrocephalus, and other operative conditions. Traditional methods for continuous ICP monitoring, intraparenchymal catheters, epidural transducers etc., are invasive and carry a high risk of infection. Previous attempts to create accurate, easy to use, and non-invasive ICP monitoring techniques have been unsuccessful. In this study, we investigated the utility of supraorbital and posterior auricular photoplethysmography to monitor changes in ICP during orthostatic tilt and hyperventilation, which increase and decrease ICP respectively.

Through a continuous 5-minute recording on a tilt-table we characterized SOA and PAA waveforms in 12 participants (ages …

The Serotonin 1b Receptor In Psilocybin’S Therapeutic-Like Mechanisms: From Behavior To Network Reorganization, Sixtine Fleury

Dartmouth College Ph.D Dissertations

Mood disorders represent a substantial and growing global health crisis, with ~10 million adults in the US meeting criteria for a major depressive disorder (MDD). Current first-line treatments such as SSRIs require long-term daily administration and fail a significant proportion of patients, driving renewed interest in rapid-acting alternatives. Psilocybin, a serotonergic psychedelic, shows growing clinical evidence of efficacy in treating depressive and anxiety disorders, often producing therapeutic effects persisting weeks to months following a single dose. Yet, the neural mechanisms underlying these enduring effects remain poorly understood and have been largely attributed to the serotonin 2A receptor (5-HT2AR) based on …

Investigating The Effects Of Nucleopore Defects On The Cellular Response To Stress In Als/Ftd Ipsc-Derived Neurons, Alicia Christine Collins

Open Access Dissertations

Amyotrophic lateral sclerosis/frontotemporal dementia (ALS/FTD) is a progressive neurodegenerative disease spectrum characterized by motor dysfunction, cognitive decline, and death within a few years of clinical onset. Hallmark features of ALS/FTD include defects in nucleocytoplasmic transport (NCT) and abnormal cytoplasmic mislocalization and aggregation of the RNA-binding protein TDP-43, both of which have been shown to be exasperated by oxidative stress (OS). It remains unclear how these processes are connected and how they collectively contribute to neurodegeneration. To fill this gap of knowledge, we used human embryonic kidney cells, neuroblastoma cells, and induced pluripotent stem cell-derived cortical neurons harboring the ALS/FTD C9ORF72 …

Bringing The Outdoors In Through Biophilic Design, Gabriela Miotto Leal

Architectural Studies Honors Papers

This thesis investigates the relationship between architecture, human perception, and well-being through the lens of human-centered and biophilic design. Drawing from philosophical traditions, phenomenology, and contemporary neuroscience, this thesis argues that the built environment is an active agent in shaping cognition, emotion, and lived experience. Architecture is understood as multisensory, embodied, and temporally experienced, influencing individuals in both conscious and nonconscious ways. Through a comparative analysis of three case studies, Paimio Sanatorium, AEA House, and the Amazon Spheres, this research examines how biophilic design principles are incorporated into different contexts such as healthcare, residential, and workplace. Each project demonstrates a …

The Effects Of Stress-Related Hormones On Excitatory Synapse Formation, Autumn C. Garvey

Honors Undergraduate Theses

Stress profoundly influences brain function through neuromodulatory hormones that regulate synaptic plasticity, yet how temporal patterns of hormone exposure shape excitatory synapse formation remains poorly understood. This study investigates how exposure to stress hormones, norepinephrine and cortisol, affects excitatory synapse development. While existing research primarily compares concentration models, real-world stress occurs in variable patterns that may produce distinct neural outcomes. To address this gap, differentiated Neuro2A neuronal cells are exposed to norepinephrine or cortisol under a continuous treatment paradigm designed to model chronic stress conditions. Following treatment, immunofluorescence imaging is utilized to quantify excitatory synapse formation through analysis of presynaptic …

Exploring The Effects Of Voluntary Wheel Running On Inhibitory Control, Ava Prieto

Honors Theses and Capstones

Inhibitory control, a central component of executive function, is the ability to suppress unwanted actions in response to a stimulus (Verbruggen et al., 2014; Verbruggen et al., 2019) and is one of the best indicators of executive task management as well as the ability to prevent unwanted prepotent responses. This capacity is essential for goal specific behavior and for responding flexibly to challenges. The present study examined the effects of voluntary wheel running on inhibitory control in two cohorts of Long-Evans rats using a rodent variant of the canonical stop-signal task. We found that rats with access to an active …

Microglial Apoe Across Alzheimer’S Disease-Relevant Pathologies, Georgia Nolt

Theses and Dissertations--Physiology

APOE exists as three common alleles (APOE2, APOE3, APOE4) that encode their corresponding protein isoforms (apoE2, apoE3, apoE4). Despite differing by only one or two single-amino acid substitutions, each APOE allele confers a distinct AD risk profile with APOE4 increasing risk by 28% and APOE2 decreasing risk by 14% compared to the most commonly expressed APOE3 allele. While traditionally considered “neutral,” APOE3 still accounts for ~36% of AD cases while APOE4 contributes ~57%, indicating that the majority of AD cases would not occur in the absence of the APOE3 and APOE4 alleles. Microglia, the resident phagocytic immune cells …

Nonlinear Differences In Postural Sway Across Attentional Focus Conditions In Individuals With And Without Anterior Cruciate Ligament Reconstruction, Natalie L. Ferguson, Brian L. Cone, Christopher K. Rhea, Anne Beethe, Breanna Studenka

Rehabilitation Sciences Faculty Publications

BACKGROUND: The structure of variability in postural sway reflects the adaptability and health of the postural control system. Entropy quantifies this structure by measuring the regularity of repeated fluctuations over time. Although entropy has been used to examine sway in neurological populations, little is known about how sway complexity changes following anterior cruciate ligament reconstruction (ACLR). Attentional focus may also influence postural control, with external focus typically promoting more efficient and automatic regulation than internal focus.

AIM: To examine how attentional focus (internal vs. external) influences the structure of postural sway in individuals with and without ACLR.

METHODS: Forty-three participants …

Temporal Evolution Of Brain Inflammation In The Bilateral Common Carotid Artery Stenosis Model Of Chronic Cerebral Hypoperfusion, Makayla F. Cox, Jill M. Roberts, Ryan K. Shahidehpour, David L. Dornbos Iii, Adam D. Bachstetter

Neuroscience Faculty Publications

Chronic cerebral hypoperfusion is a major contributor to vascular cognitive impairment and dementia, primarily through its disruption of white matter integrity and promotion of neuroinflammatory cascades. The bilateral common carotid artery stenosis (BCAS) model has emerged as the predominant experimental approach for studying the effects of chronic cerebral hypoperfusion, particularly in aging-relevant contexts. This review synthesizes current knowledge of inflammatory responses in the BCAS model, with an emphasis on their temporal progression and functional consequences. We begin by outlining the clinical burden of hypoperfusion, the rationale for BCAS, and the hemodynamic phases it produces. We then examine early neurovascular unit …

Dim Light At Night Impacts Circadian Rhythms And Alzheimer’S Disease-Like Neuroinf Lammation And Neuropathology In Humanized App Saa Knock-In Mice, Marilyn J. Duncan, Margaret R. Hawkins, Leke Bytyqi, Haleigh R. Whitlock, Savannah M. Shepard, Makayla F. Cox, Esther G. Drinkard, Teresa Macheda, Kelly N. Roberts, Katharina Kohler, Mary-Claire Schmidt, Carrie E. Johnson, Sridhar Sunderam, Bruce F. O'Hara, Michael Paul Murphy, Adam D. Bachstetter

Neuroscience Faculty Publications

Artificial light at night (light pollution) is widespread but understudied in the context of Alzheimer’s disease (AD). Sleep and circadian disruption have been linked to amyloid-β (Aβ) accumulation and neuroinflammation, but whether dim light at night (dLAN) modifies these processes remains unclear. We tested whether chronic dLAN exposure (8 lux during the dark phase, 8 weeks) alters circadian rhythms, amyloid pathology, and neuroinflammation in 12–13 month-old humanized APP knock-in (KI) mice. hAPP^SAA KI mice, which develop plaques, were compared with hAPP^WT KI controls carrying only a humanized APP sequence. dLAN reduced circadian rhythm amplitude and stability while increasing …

Eeg Signatures Of Motor Development In Early Childhood: A Systematic Review, Sonia Khurana, Ashwini Kulkarni, Thomas C. Bulea, Hunter J. Bennett

Rehabilitation Sciences Faculty Publications

Background

Early identification of motor developmental disorders is limited due to lack of objective neural markers that characterize typical neurodevelopmental patterns. This systematic review interprets and synthesizes existing evidence to propose a framework of EEG signatures associated with motor development in children aged 0-5 years, which may help inform future benchmarks for early assessment and intervention.

Methods

Following PRISMA guidelines, we searched published and gray literature across five databases between 2000 and 2025 (registered protocol). Included studies examined EEG during task-based, resting-state, or sleep studies linked to motor milestones, task performance, or standardized motor assessments. Study quality was assessed using …

Forcing A Molecule To Switch: Quantifying Mechanical Control At The Atomic Scale, A. M. Shashika D. Wijerathna, Markus Zirnheld, Michael L. Hildebrand, Myles Perry, Marjorie Cenese, Yuan Zhang

Physics Faculty Publications

Mechanically induced conformational switching at the single-molecule level represents a fundamental mechanism for molecular functionality, yet quantitative characterization of the underlying force and energy landscape remains limited. Here, we study individual TBrPP-Co(II) molecules on Au(111) using qPlus atomic force microscopy. By reconstructing interaction potentials from 3D Δf(x,y,z) data, we determine a threshold force of ∼96 ± 8 pN and a tip-induced switching interaction energy of ∼38 ± 4 meV associate with the conformational transition. The isolated tip-molecule force follows a power law (exponent ∼6), indicating dominance of long-range van der Waals interactions. …

Synaptic Connectivity Of Rod Bipolar Cells In The Mouse Retina: A Connectomic Analysis Using Webknossos, Harold F. Eshun

Williams Honors College, Honors Research Projects

Rod bipolar cells (RBCs) are key interneurons in the mouse retina that transmit signals from rod photoreceptors to downstream amacrine and ganglion cells under scotopic (low-light) conditions. Although their general morphology and function are well established, the fine-scale organization of their synaptic inputs and outputs remains incompletely characterized. This project aims to map the pre- and postsynaptic partners of a fully reconstructed rod bipolar cell using the Yu volume, a serial block-face electron microscopy dataset from the ventral retina of an adult wild-type mouse. Using the webKnossos platform, I identify synaptic ribbons in the axon terminals of the rod bipolar …

Manuka Honey Modulates Oxidative Stress In Neuro2-A Cells Through Mitochondrial Regulation, Rachel Abramovici

Honors Undergraduate Theses

Manuka honey is known for its vital usage in wound healing, being an agonist towards fighting infections, and is an acting antioxidant [32]. Its main constituents are flavonoids and phenolic compounds, with methyl syringate (MSYR) being a major active ingredient. The specific compounds responsible for these antioxidant effects, particularly in the CNS, remain unclear. It is hypothesized that pre-treatment of mouse neuroblastoma cells with MSYR followed by hydrogen peroxide exposure will activate the AMPK/SIRT1/PGC-1a pathway, due to MSYR’s phenolic structure, and thus reduce oxidative stress and improve mitochondrial biogenesis. Hydrogen peroxide is a standard reactive oxygen species (ROS) treatment to …

Evaluation Of Tactile Cueing Embedded In An Aviation Headset On Pilot Altitude Control, Nicholas D. Wilson, Jessica Van Bree, Matthew Cleveland, Sunny Charakuru, Thomas Petros, Richard Ferraro, Kouhyar Tavakolian

Journal of Aviation/Aerospace Education & Research

This study evaluated the effectiveness of tactile cueing integrated into a pilot’s headset on pilot altitude control during simulated instrument conditions. Pilots typically rely on visual and auditory inputs to maintain situational awareness, but in high-workload or instrument meteorological conditions (IMC), these channels can become overloaded. One underutilized alternative for alerting is a tactile cueing apparatus. Using an X-Plane simulation of a Piper Archer equipped with a G-1000 avionics suite, 39 FAA-certified pilots flew two precision approaches. The experimental group (n = 20) received haptic cues via ear seal-embedded tactors when deviating from assigned altitude or glideslope. The control group …

Disrupted Circadian Rhythms Affect Hallmark Pathologies In Alzheimer’S Disease-Related Mouse Models, Valeria Buzinova

Theses and Dissertations--Molecular and Cellular Biochemistry

Alzheimer’s Disease (AD) is a complex neurodegenerative disease with two hallmark pathologies: extracellular amyloid-b (Ab) and intracellular neurofibrillary tangles (NFTs). Ab is proteolytically processed from amyloid precursor protein (APP) by b-secretase and g-secretase as a monomeric peptide prone to aggregation. Eventually, the aggregate-prone monomers will form dense plaques that are difficult to break down and remove. These plaques begin to deposit into the cortex decades prior to the formation of NFTs and the onset of cognitive decline. NFTs are comprised of hyper-phosphorylated tau. Tau is a protein that serves to promote and stabilize the formation of microtubules. The formation of …

Exploring Anticholinergic Neurotoxicity: Diphenhydramine's Impact On Neuro-2a Cell Morphology, Expression, And Viability, Jordan B. Mcintyre

Honors Undergraduate Theses

Anticholinergic medications, such as diphenhydramine (commonly known as Benadryl), are increasingly recognized for their association with cognitive impairment and neurodegenerative disease. These medications, which inhibit the action of acetylcholine, a neurotransmitter essential for the formation and utilization of the central and peripheral nervous system, have been implicated in conditions such as dementia and may impact fundamental cellular processes like neurogenesis and cell proliferation. This study investigates the effects of diphenhydramine on neurogenesis when introduced to Neuro-2a cells during differentiation. For all studies cells were plated on coverslips or in 6-well plates with differentiation media containing 0 ng/mL, 50 ng/mL, …

Illusions Of The Brain, Vaso Manakou

Scientific Kenyon: The Neuroscience Edition

No abstract provided.

Scientific Kenyon: Neuroscience Edition (Full Issue)

Scientific Kenyon: The Neuroscience Edition

No abstract provided.

Letter From The Founder And Professor

Scientific Kenyon: The Neuroscience Edition

No abstract provided.

Get The Fruc(Tose) Out Of My Food, Johanna Huelsman

Scientific Kenyon: The Neuroscience Edition

No abstract provided.

My Brain Didn't Get The Memo That It Was Virtual, Samantha Ofori

Scientific Kenyon: The Neuroscience Edition

No abstract provided.

Epigenetic Hangovers: Your Brain On Alcohol, Cindy Chen

Scientific Kenyon: The Neuroscience Edition

No abstract provided.

Ctrl + Alt + Neuron, Stuart Hilton

Scientific Kenyon: The Neuroscience Edition

No abstract provided.

Losing Yourself To Find Yourself: The Neuroscience Ego Dissolution, Mike D'Eletto

Scientific Kenyon: The Neuroscience Edition

No abstract provided.

What The Body Feels, The Mind Reveals: How Inflammation Shapes Emotions, Jamie Murphy

Scientific Kenyon: The Neuroscience Edition

No abstract provided.

Smile! Your Brain Is On Camera, Natalie Stone

Scientific Kenyon: The Neuroscience Edition

No abstract provided.