Neuroscience and Neurobiology Commons^™

Voltage Set Points For Sodium Channel Inactivation: Intrinsic And Modulatory Mechanisms, Akshay Sharma

Dissertations, Theses, and Capstone Projects

During an action potential, voltage-gated sodium channels (VGSC) control sodium ion flow into the cytoplasm of cells by using membrane voltage to alter channel conformation. These membrane proteins exhibit three main functional conformations: closed, open, and fast-inactivated, with transitions between these states dependent on membrane voltage and kinetics. The channels open within 1 millisecond and swiftly transition from open to fast-inactivated within 1-2 milliseconds following membrane depolarization. Subsequent membrane repolarization resets the channels to the closed state. Notably, even at mildly depolarized potentials that preclude channel opening, VGSCs can undergo transitions between the closed and inactivated states, known as closed-state …

The Seattle Amyotrophic Lateral Sclerosis (Als) Patient Project Database: Observational, Longitudinal, Dyadic Characterization Of People With Als And Their Partners, Suzanne C. Segerstrom, Edward J. Kasarskis

Neurology Faculty Publications

Introduction: The median survival time in ALS is approximately 3 years, but survival times range from less than a year to more than 10 years and much variance in disease course remains to be explained. As is true for physical outcomes, there is considerable variance in QOL, which is influenced by psychological health, coping, and social support, among other psychosocial factors. The Seattle ALS Patient Project Database (SALSPPD) provides a unique opportunity for researchers to address established and novel hypotheses about disease progression and QOL in ALS.

Methods: The SALSPPD is a longitudinal dataset of people with ALS (n = …

Novel Psychoplastogen Dm506 Reduces Cue-Induced Heroin-Seeking And Inhibits Tonic Gaba Currents In The Prelimbic Cortex, Kassandra Looschen, Shailesh N. Khatri, Malabika Maulik, Colin Salisbury, Alaina F. Carman, Katilyn Corriveau, Colton Smith, Dina Manetti, Maria Novella Romanelli, Hugo R. Arias, Cassandra D. Gipson, Swarup Mitra

Markey Cancer Center Faculty Publications

Opioid use disorder is a major public health crisis that is manifested by persistent drug-seeking behavior and high relapse frequency. Most of the available treatments rely on targeting opioid receptors using small molecules that do not provide sustained symptom alleviation. Psychoplastogens are a novel class of non-opioid drugs that produce rapid and sustained effects on neuronal plasticity, intended to produce therapeutic benefits. Ibogalogs are synthetic derivatives of iboga alkaloids that lack hallucinogenic or adverse side effects. In the current study, we examine the therapeutic potential of DM506, a novel ibogalog lacking any cardiotoxic or hallucinogenic effects, in cue-induced seeking behavior …

Resting-State Eeg Microstate Features For Major Depressive Disorder Classification, George M. V. Quinn

Dissertations, Theses, and Capstone Projects

Neuroimaging studies have revealed consistent abnormalities in functional connectivity within specific neural networks that may serve as biomarkers for major depressive disorder (MDD). It is important to find inexpensive, non-invasive techniques that target these biomarkers to make diagnosis easier and more objective. EEG microstates are quasi-stable potential topographies that are thought to reflect the quasi-stable network activity of the underlying neural generators. MDD has been shown to alter features of the four canonical EEG microstates (A, B, C, D) with some conflicting results. The most consistent network abnormalities in MDD are found in the anterior default mode network, and this …

Repurposing Bt-11 To Treat Alzheimer’S Disease: Exploring The Glutathione-S-Transferase Lancl2 As A Target, Emily Birnbaum

Dissertations, Theses, and Capstone Projects

Approximately 99.6% of potential Alzheimer’s drugs fail, thus developing successful drugs is a high priority. The failure at developing successful drugs relates to the complex nature of the disease itself. Many components act together to trigger a cascade that ultimately results in neurodegeneration and cognitive dysfunction associated with the disease. In building a multiplex model of Alzheimer’s it is important to understand its specific biological mechanisms. One of these key pathological mechanisms is neuroinflammation. Understanding the pathways involved in neuroinflammation in Alzheimer’s is an urgent need, as it poses a promising avenue for future effective therapeutics. Specifically, as many investigational …

Meconium: A Potential Means To Predicting Later-Life Cognition, Leah Duran

Dissertations, Theses, and Capstone Projects

Maternal perinatal stress is a commonly experienced, yet chronically undiagnosed condition (CDC, 2010). Literature has suggested that perinatal stress exposure has long lasting implications of the developing child both physically and mentally (Behrman et al., 2007; Hobel et al., 2008; Bowman et al., 2004; Polanska et al., 2017; Van de Bergh et. al, 2020). The use of meconium in the clinical setting has become one that serves a purpose of detection in medical conditions like in utero drug exposure. Using meconium as a predictor for brain behavior, however, is still an emerging concept in the literature. It is quickly gaining …

Large Deviation Theory In Stochastic Processes: Applications To Biological Modeling, Moshe C. Silverstein

Dissertations

This dissertation delves into developing and applying stochastic models to analyze complex biological systems. It leverages Large Deviation Theory (LDT) to gain insights into these systems, focusing on two key examples: neural networks and calcium signaling dynamics. Traditional deterministic methods frequently fail to capture biological processes' randomness and inherent variability. Meanwhile, many stochastic approaches struggle to be mathematically tractable or provide accessible insights. The approach introduced in this study provides rigorous mathematical frameworks to enhance understanding of these stochastic behaviors while remaining tractable and insightful.

A stochastic model for a random biological neural network is constructed that addresses the dependencies …

The Neuroscience Of Mindfulness Based Art Therapy: A Literature Review, Elizabeth Strasser

Expressive Therapies Capstone Theses

Art therapy and neuroscience are two fields which are currently growing and expanding with the development of new technology which allows for therapists and scientists to advance their understanding of how the brain and the body respond to the world around us. The interaction between the brain, body, and environment is complex, and for the sake of clarity for this thesis this interaction will be conceptualized through the lens of the body-mind model, polyvagal theory, neuroaesthetics, the flow state, mindfulness, sensory engagement, and art as therapy. Neuroscience in relation to psychology can be used to develop a deeper understanding of …

Unraveling The Role Of Hid-1: Insights Into Sgii Regulation, Breanna L. Sellers

Electronic Theses and Dissertations

The regulated secretory pathway is important for the secretion of hormones and neuropeptides from large dense core vesicles (LDCVs). Dysregulation of the biogenesis of LDCVs can result in metabolic and neurological diseases. Recent studies have suggested that the peripheral membrane protein HID-1 plays a role in the sorting and storage of granins which contribute to LDCV biogenesis. To further understand how HID-1 influences the regulation of granins, we investigated potential HID-1 interactors. We determined that while HID-1 is likely functioning in the same pathway as USP25, a deubiquitinating enzyme (DUB), the cause of reduced cellular SgII levels is likely not …

Slow Ramping Emerges From Spontaneous Fluctuations In Spiking Neural Networks, Jake Gavenas, Ueli Rutishauer, Aaron Schurger, Uri Maoz

Psychology Faculty Articles and Research

The capacity to initiate actions endogenously is critical for goal-directed behavior. Spontaneous voluntary actions are typically preceded by slow-ramping activity in medial frontal cortex that begins around two seconds before movement, which may reflect spontaneous fluctuations that influence action timing. However, the mechanisms by which these slow ramping signals emerge from single-neuron and network dynamics remain poorly understood. Here, we developed a spiking neural-network model that produces spontaneous slow ramping activity in single neurons and population activity with onsets ~2 s before threshold crossings. A key prediction of our model is that neurons that ramp together have correlated firing patterns …

Multiple Guidance Mechanisms Control Axon Growth To Generate Precise T-Shaped Bifurcation During Dorsal Funiculus Development In The Spinal Cord, Bridget M. Curran, Kelsey R. Nickerson, Andrea R. Yung, Lisa V. Goodrich, Alexander Jaworski, Marc Tessier-Lavigne, Le Ma

Farber Institute for Neuroscience Faculty Papers

The dorsal funiculus in the spinal cord relays somatosensory information to the brain. It is made of T-shaped bifurcation of dorsal root ganglion (DRG) sensory axons. Our previous study has shown that Slit signaling is required for proper guidance during bifurcation, but loss of Slit does not affect all DRG axons. Here, we examined the role of the extracellular molecule Netrin-1 (Ntn1). Using wholemount staining with tissue clearing, we showed that mice lacking Ntn1 had axons escaping from the dorsal funiculus at the time of bifurcation. Genetic labeling confirmed that these misprojecting axons come from DRG neurons. Single axon analysis …

Long-Term Neurodevelopmental Outcomes Post-Chronic Midazolam Exposure During Early Life, Nghi M. Nguyen

Theses & Dissertations

In recent decades, the rising number of neonates born in the Neonatal Intensive Care Unit (NICU) due to prematurity has raised concerns about their overall well-being and development. Premature neonates are at higher risk of health complications and often require invasive procedures. These invasive procedures often induce stress and agitation, prompting physicians and healthcare providers to provide sedation or general anesthesia to manage discomfort. Epidemiological studies of human patients have revealed a correlation between childhood exposure to general anesthetic and sedative agents and subsequent cognitive deficits. This association is also supported in animal models, which shows that exposure to anesthetics …

The Effect Of Acute Social Isolation On Neural Molecular Responses In Components Of The Social Decision-Making Network, Patricia C. Lopes, Madeleine Chang, Faith Holloway, Biola Fatusin, Sachin Patel, Chandler Siemonsma, Morgan Kindel

Biology, Chemistry, and Environmental Sciences Faculty Articles and Research

Prolonged or chronic social isolation has pronounced effects on animals, ranging from altered stress responses, increased anxiety and aggressive behaviour, and even increased mortality. The effects of shorter periods of isolation are much less well researched; however, short periods of isolation are used routinely for testing animal behaviour and physiology. Here, we studied how a 3 h period of isolation from a cagemate affected neural gene expression in three brain regions that contain important components of the social decision-making network, the hypothalamus, the nucleus taeniae of the amygdala, and the bed nucleus of the stria terminalis, using a gregarious bird …

Prelimbic Neuronal Ensembles In Natural Reward Seeking, Roger Ian Grant

MUSC Theses and Dissertations

External cues can become powerful motivators of behavior when paired with rewarding stimuli, such as natural rewards or drugs of abuse, as is the case in individuals with substance use disorder (SUD). The dorsomedial prefrontal cortex (dmPFC) has been implicated as a neural substrate which encodes cue-reward associations and has been shown to exert top-down control over both natural and drug reward seeking. We and others have shown that activity within the dmPFC is heterogeneous during reward seeking, with some neurons displaying excitatory responses to reward-predictive cues, and others showing inhibitory responses to the same cues. Furthermore, this response heterogeneity …

Emotional Content In Working Memory Processes: An Fmri Study., Manal Zafar

Electronic Theses and Dissertations

Working memory (WM) is a dynamic system that processes and manipulates both goal-relevant and goal-irrelevant information, integral to higher-level cognition and executive control (Fujii, 2001; Nyberg & Erikkson, 2016). The processing and manipulation of representations is modulated by the affective nature of the information (Pessoa, 2009) such that negative information can either impair or enhance WM processing. WM impairments are seen commonly across clinical disorders such as depression, anxiety, PTSD and schizophrenia (Levens & Gotlib, 2010; Joorman et a., 2011; Brodziak et al., 2015). Specifically, negative information is known to have differential processing in WM compared to neutral and positive …

Epidural Stimulation For Urogenital Dysfunction In The Spinal Cord Injured Rat., Natasha Lorraine Wilkins

Electronic Theses and Dissertations

Spinal cord injury (SCI) is a devastating, life changing event that greatly impacts quality of life. SCI can have body-wide, multi-system consequences including dysfunction within the urogenital system. Challenges with the urinary system include urinary incontinence, urine retention, and detrusor-sphincter dyssynergia all of which require maintenance through the regular use of catheters. Sexual dysfunction in men, who comprise nearly 80% of the SCI population, includes erectile dysfunction, anejaculation, retrograde ejaculation, poor expulsive force during ejaculation, and poor sperm quality. The treatment for sexual function in SCI men is focused more on fertility through the collection of sperm for insemination procedures …

Establishing A Mouse Model Of Cerebral/Cortical Visual Impairment., Dana K. Oakes

Electronic Theses and Dissertations

Cerebral/cortical visual impairment (CVI) is a disorder most often caused by perinatal hypoxic injury to the developing brain. CVI is the leading cause of childhood visual impairment in developed nations, encompassing deficits in many aspects of vision including visual acuity, contrast sensitivity, and object recognition. The pathophysiology of CVI is not well understood because no animal model currently exists to study this disorder. Because there is no animal model, the pathophysiology of CVI is poorly understood. Here, we developed a murine early postnatal hypoxic model of CVI by exposing mice to 9.5% O₂ at postnatal day (P)3 for a …

Investigating The Role Of Insulin-Like Signaling In Paclitaxel-Induced Nociceptive Hypersensitivity Using Drosophila Melanogaster, Sreepradha Sridharan

Dissertations and Theses (Open Access)

Paclitaxel (PTX), a chemotherapeutic that alters microtubule dynamics, is known to induce nociceptive hypersensitivity and sensory neuron damage in human patients and in Drosophila larvae. We used a modified feeding protocol to establish a genetically tractable Drosophila model of PTX-induced hypersensitivity. Larvae fed PTX exhibited hypersensitivity to thermal and mechanical stimuli. Thermal hypersensitivity was observed at low concentrations of PTX (even below 1 μM per ml of food), begins within 8 hours of PTX feeding, and did not completely resolve at the larval stage. Live imaging of peripheral thermal nociceptors showed that this hypersensitivity precedes observable neuronal damage. At low …

The Role Of The Circadian Clock In The Paraventricular Nucleus Of The Hypothalamus In Diurnal Energy Balance, Rachel Van Drunen

Dissertations and Theses (Open Access)

Circadian rhythms are internal biological rhythms that drive oscillations in physiology and metabolism. Maintained at the level of individual cells throughout the body, the circadian clock is necessary for driving tissue-specific temporal programs of energy balance. Though loss of the circadian transcription factor, BMAL1, in the paraventricular nucleus (PVN) of the hypothalamus has revealed its importance in driving rhythms in energy intake and metabolism, its transcriptional functions across time and in individual cell types in the PVN are not well understood. In this study, we show that loss of BMAL1 in the PVN not only results in arrhythmicity in processes …

Cerebrovascular Reactivity Mri As A Biomarker For Cerebral Small Vessel Disease–Related Cognitive Decline: Multi-Site Validation In The Markvcid Consortium, Peiying Liu, Zixuan Lin, Kaisha Hazel, George Pottanat, Cuimei Xu, Dengrong Jiang, Jay J. Pillai, Emma Lucke, Christopher E. Bauer, Brian T. Gold, Steven M. Greenburg, Karl G. Helmer, Kay Jann, Gregory Jicha, Joel Kramer, Pauline Maillard, Rachel M. Mulavelil, Pavel Rodriguez, Claudia L. Satizabal, Kristin Schwab, Sudha Seshadri, Herpreet Singh, Ángel G. Velarde Dediós, Danny J. J. Wang, Rita R. Kalyani, Abhay Moghekar, Paul B. Rosenberg, Sevil Yasar, Marilyn Albert, Hanzhang Lu

Neurology Faculty Publications

INTRODUCTION: Vascular contributions to cognitive impairment and dementia (VCID) represent a major factor in cognitive decline in older adults. The present study examined the relationship between cerebrovascular reactivity (CVR) measured by magnetic resonance imaging (MRI) and cognitive function in a multi-site study, using a predefined hypothesis.

METHODS: We conducted the study in a total of three analysis sites and 263 subjects. Each site performed an identical CVR MRI procedure using 5% carbon dioxide inhalation. A global cognitive measure of Montreal Cognitive Assessment (MoCA) and an executive function measure of item response theory (IRT) score were used as outcomes.

RESULTS: CVR …