Neuroscience and Neurobiology Commons^™

Focal Augmentation Of Somatostatin Interneuron Function And Subsequent Circuit Effects In Developmentally Malformed, Epileptogenic Cortex, Nicole Ekanem

Theses and Dissertations

Drug-resistant epilepsy (DRE) is a common clinical sequela of developmental cortical malformations such as polymicrogyria. Unfortunately, much remains unknown about the aberrant GABA-mediated circuit alterations that underlie DRE's onset and persistence in this context. To address this knowledge gap, we utilized the transcranial freeze lesion model in optogenetic mice lines (Somatostatin (SST)-Cre or Parvalbumin (PV)-Cre x floxed channelrhodopsin-2) to dissect features of the SST, PV, and pyramidal neuron microcircuit that are potentially associated with DRE. Investigations took place within developmental microgyria’s known pathological substrate, the adjoined and epileptogenic paramicrogyral region (PMR). As well, microcircuit relationships within the previously unexplored range …

Diverse Autonomic Nervous System Stress Response Patterns In Childhood Sensory Modulation, Jacquelyn Christensen, Heather Wild, Erin S. Kenzie, Wayne Wakeland, Deborah Budding, Connie Lillas

Complex Systems Faculty Publications and Presentations

The specific role of the autonomic nervous system (ANS) in emotional and behavioral regulation—particularly in relation to automatic processes—has gained increased attention in the sensory modulation literature. This mini-review article summarizes current knowledge about the role of the ANS in sensory modulation, with a focus on the integrated functions of the ANS and the hypothalamic-pituitary-adrenal (HPA) axis and their measurement. Research from the past decade illustrates that sympathetic and parasympathetic interactions are more complex than previously assumed. Patterns of ANS activation vary across individuals, with distinct physiological response profiles influencing the reactivity underlying automatic behavioral responses. This review article advances …

Young African American Men's Conception Of Fatherhood Among Survivors Of Childhood Abuse, Ohan Patricia Carter

Walden Dissertations and Doctoral Studies

Male survivors of abuse who become fathers themselves face challenges different from female survivors, such as conceptualizing their roles as providers and heads of households after the traumatic and often belittling experiences of abuse. However, very few researchers have studied the connection between child abuse and fatherhood, and none specific to young African American fathers. An interpretative phenomenological approach enabled exploration of how African American fathers who were abused as children, conceptualized and perceived their own experiences with fatherhood. The theoretical framework for this study was identity theory, which indicates that how people conceptualize a social role influences their actions …

Toward Automated Region Detection & Parcellation Of Rat Brain Tissue Images, Alexandro Arnal

Open Access Theses & Dissertations

People who analyze images of biological tissue often rely on segmentation of structures as a preliminary step. In particular, laboratories studying the rat brain manually delineate brain regions to position scientific findings on a brain atlas to propose hypotheses about the rat brain, and ultimately, the human brain. Our work intersects with the preliminary step of delineating regions in images of brain tissue via computational methods.

We investigate pixel-wise classification or segmentation of brain regions using ten histological images of brain tissue sections stained for Nissl substance, and two deep learning models: U-Net and Tile2Vec. Our goal is to assess …

The Substantiality Of The Neuroplasticity Hypothesis Of Major Depressive Disorder: The Prospective Use Of Ketamine-Like Drugs As Antidepressants, Roma Kankaria

AUCTUS: The Journal of Undergraduate Research and Creative Scholarship

Abstract

Major depressive disorder (MDD) affects approximately 17.3 million adults in the United States each year. For more than 50 years, the serotonin hypothesis of MDD, which hypothesizes that a deficiency of monoaminergic neurotransmitters results in depression, has been the foundation for neuropsychological research. However, studies reveal that only an estimated 50% of MDD patients respond to traditional, biogenic-amine-based antidepressants (ADs), like selective serotonin reuptake inhibitors (SSRIs). Research has noted that the neuroplasticity hypothesis, which posits that weakened excitatory synaptic transmission results in depression, offers an alternative mechanism by which ketamine-like drugs lacking the abuse liability and psychoactive effects of …

Characterizing The Diverse Cells That Associate With The Developing Commissures Of The Zebrafish Forebrain, Jake Schnabl, M.P.H Litz, Caitlin Schneider, N. Penkofflidbeck, Sarah Bashiruddin, M. S. Schwartz, Kristin Alligood, Michael Barresi

Zebrafish Forebrain Cellular Characterization

During embryonic development of bilateral organisms, neurons send axons across the midline at specific points to connect the two halves of the nervous system with a commissure. Little is known about the cells at the midline that facilitate this tightly regulated process. We exploit the con served process of vertebrate embryonic development in the zebrafish model system to elucidate the identity of cells at the midline that may facilitate postoptic (POC) and anterior commissure (AC) development. We have discovered that three differentgfap+ astroglial cell morphologies persist in contact with pathfinding axons throughout commissure formation. Similarly, olig2+ progenitor cells occupy delineated …

Alterations In Corticotropin-Releasing Factor Receptor Type 1 In The Hypothalamus And Preoptic Area During The Postpartum Period, Rose Ann M. De Guzman

Legacy Theses & Dissertations (2009 - 2024)

Despite the apparent sex difference in prevalence of anxiety in humans, pre-clinical studies that have led to anxiolytic drug discoveries between 1960 and 2012 used male animals and approximately 6% of 10,000 studies used female animals. The generalizability of the efficacy of these drugs to both sexes may be limited if data derived are predominantly based on the male brain. The purpose of this dissertation, therefore, was to investigate potential underlying neuronal mechanisms that could be contributing to the sex differences in stress-related mood disorder prevalence and to focus on shedding light on female brains.

Tfap2e/Ap-2e Is A Transcriptional Regulator Controlling Neuronal Identity And Circuitry Formation In The Mouse Accessory Olfactory System, Jennifer M. Lin

Legacy Theses & Dissertations (2009 - 2024)

Developmental progression is driven by specific spatiotemporal gene expression, which give rise to consistently patterned organisms despite environmental and genetic variation. The specific activation of robust gene regulatory networks that define tissue structure and individual cellular identity are necessary for tissue and cell specific programs to be activated. Cellular specification is guided by the interplay of intrinsic and extrinsic signals at specific developmental timepoints. The molecular mechanisms underlying the acquisition and maintenance of individual cellular identity remains a fundamental question across biological systems. Understanding the regulatory networks controlling the acquisition of neuronal identity, diversity, and connectivity in the formation of …

The Role Of Progesterone Receptor In The Postnatal Development Of The Dentate Gyrus And Episodic-Like Memory, Andrew James Newell

Legacy Theses & Dissertations (2009 - 2024)

The hippocampus is a critical structure for the encoding and retrieval of declarative memories in humans, including episodic-memories. In rodents the steroid hormone receptor progesterone receptor (PR) is expressed in the dentate gyrus (DG) of the hippocampus during the postnatal period, a key stage in development of DG cytoarchitecture and connectivity. During the first postnatal week, the main cortical input to the hippocampal circuit, the perforant path, innervates the molecular layer (MOL) of the DG and forms temporary initial synaptic connections with pioneer neurons. By the third postnatal week, long-term synapses have been established with granule cells, the principle neurons …

Effect Of Draxin Manipulation On Btbr Mouse Brain And Behavior, Adam Blau

Legacy Theses & Dissertations (2009 - 2024)

Autism Spectrum Disorder (ASD) is known for distinct behavioral phenotypes such as a preference for repetitive activities and difficulty in socialization. However, little is known about what might cause ASD. Current evidence implicates genetics as playing a substantial role in ASD. Mouse models, such as BTBR T+ Itpr3tf/J (BTBR) inbred mice, are an invaluable resource for ASD research, as they allow the investigation of both genetics and behavior in parallel. BTBR mice are of interest due to their reduced hippocampal commissure (HC) and absent corpus callosum (CC), along with increased exploratory activity, decreased anxiety, reduced sociability, and increased repetitive self-grooming …

The Brain's Large-Scale Electrophysiological Signals : Fundamental Attributes And Neurosurgical Applications, Mohammad Amin N/A Nourmohammadi

Legacy Theses & Dissertations (2009 - 2024)

Brain’s electrophysiological signals are most certainly the ultimate source for studying the sophisticated neural network inside our cranium. The unparalleled complexity of these biosignalsis the quintessential manifestation of their underlying complicated neurophysiological processes. Studying brain signals on the cellular level provides valuable information regarding the brain’s electrophysiology on the small-scale. However, it is the remarkable network in the large-scale that gives rise to the brain’s extraordinary attributes and exceptional capabilities—perception, cognition, computation, and consciousness are all the emergent byproducts of the dynamic neuronal interactions on the network level. In this sense, the large-scale electrophysiological signals, recorded from the surface of …

The Dysregulation Of Circadian Rhythms And Its Relation To Hippocampal Neurodegenerative Disease, John Patrick Mccauley

Legacy Theses & Dissertations (2009 - 2024)

Circadian rhythms modulate body temperature, sleep-wake cycles and cognitive functions like learning and memory. Interestingly, patients suffering from neurodegenerative disease like Alzheimer’s disease and brain insults like traumatic brain injury experience dysregulated circadian rhythms and learning and memory deficiencies as a symptom. The core molecular machinery that establishes these rhythms relies on the activation of positive and negative transcriptional-translational feedback loops within the hypothalamic suprachiasmatic nucleus (SCN). Subordinate circadian oscillators distributed throughout the peripheral and central nervous system follow the rhythmic activity of the SCN. One of these, the hippocampus, is mostly involved in regulating memory formation and recall. Experimental …

Statistical Methods To Unravel Cortical Mechanism Of Perception And Response To Auditory Stimuli, Ladan Moheimanian

Legacy Theses & Dissertations (2009 - 2024)

Behavioral responses to auditory stimuli have a critical role in our daily activities. The perception of these stimuli and the generation of appropriate behavioral responses requires the interaction of thousands of neurons in the auditory-motor pathways in the brain. Despite their importance, still many neuroscientific questions about these interactions are remained to be answered. This may result from the limitations of brain recordings as well as statistical methods to analyze brain recordings. In this dissertation, I investigated underlying mechanisms that govern these neural interactions in the auditory-motor pathways using novel statistical techniques applied to the brain recordings from the surface …

Role Of Smad4 Dependent Signaling In Controlling The Functioning And Connectivity Of Basal Vomeronasal Sensory Neurons, Ankana S. Naik

Legacy Theses & Dissertations (2009 - 2024)

ABSTRACT

Book Review: Was Yosef On The Spectrum By Samuel J. Levine, Ian Hale, Ph.D.

Touro Law Review

No abstract provided.

Assessing A Two-Hit Model Of Schizophrenia: Prenatal Choline Deficiency And Induced Hypofunction Of Nmda Receptors In Male And Female Long Evans Rats, Samuel Gray, Samuel W. Gray

Honors Theses

Choline is an essential dietary nutrient essential to the development and function of the central nervous system. Prenatal choline deficiency alters hippocampal development as well as acetylcholine metabolism, leading to cognitive impairments and attentional and sensory processing deficits into adulthood. MK-801 is an NMDA receptor antagonist frequently used in rodent models of neuropsychiatric conditions, particularly schizophrenia. Acutely and sub- chronically, it causes hyperlocomotion and social withdrawal. One primary goal of the present study were to investigate prenatal choline deficiency induces a biological vulnerability to the motor deficits, anhedonia, and social impairment precipitated by low-dose sub-chronic MK-801 administration in adulthood. Another …

Executive Function Deficit As A Precursor To Memory Impairments In Hapoe4 Transgenic Rats, Kaitlin Mcmanus

Honors Theses

The hApoE4 allele is one of the strongest genetic risk factors for Alzheimer’s disease (AD). It underlies amyloid-bdeposits and neurofibrillary tangles, the two hallmarks associated with AD pathology, and is subsequently associated with AD symptomology. Despite its importance, no rat animal studies to date use hApoE4 knock-ins. In addition to this deficit in the field of AD literature, the vast majority of AD studies focus on memory, even though executive function deficits may precede memory impairments in AD, and may be a predictor of AD development. Thus, the present study addressed these gaps in AD research by investigating the behavioral …

Cell-Type Specific Extracellular Matrix Signaling In The Opioid-Addicted Synapse, Vivian C. Chioma

MUSC Theses and Dissertations

To date, heroin abuse is a leading cause of drug overdose-related deaths in the United States, highlighting a need for further research elucidating effects of maladaptive neuroadaptations following prolonged heroin use. Activation of the tetrapartite synapse in nucleus accumbens core (NAcore), which comprises of pre- and post-synapse, astrocytic processes, and surrounding extracellular matrix (ECM), has been linked to increased relapse vulnerability. Specifically, degradation of ECM by activated matrix metalloproteinases (MMPs) is involved in extracellular synaptic remodeling both constitutively and transiently in extinguished and drug seeking conditions, respectively. Although increases in MMP-2,9 fluorescence can be localized to soma and dendritic processes …

Effects Of The Abused Inhalant Toluene On Mpfc-Dependent Cognitive Behaviors And Associated Neural Activity, Kevin Michael Braunscheidel

MUSC Theses and Dissertations

Volatile organic solvents like toluene induce euphoria and intoxication when inhaled at high concentrations. Inhalant misuse is linked to behavioral, cognitive, and anatomical deficits in humans leading to a reduced productivity and quality of life. Yet, preclinical studies on the effect of inhalants on executive control in animal models are limited. We address this gap in knowledge using rodent models in two ways: first, by examining the long-lasting effects of repeated toluene inhalation during adolescence on several measures of executive function in adulthood and second, by studying the effects of acute toluene inhalation on risk/reward decision making and related neurocircuitry. …

Polygenic Risk Score Analysis Revealed Shared Genetic Background In Attention Deficit Hyperactivity Disorder And Narcolepsy, Nagahide Takahashi, Tomoko Nishimura, Taeko Harada, Akemi Okumura, Damee Choi, Toshiki Iwabuchi, Hitoshi Kuwabara, Shu Takagi, Yoko Nomura, Jeffrey H. Newcorn, Nori Takei, Kenji J. Tsuchiya

Publications and Research

Attention deficit hyperactive disorder (ADHD) is a highly heritable neurodevelopmental disorder, and excessive daytime sleepiness is frequently observed in ADHD patients. Excessive daytime sleepiness is also a core symptom of narcolepsy and essential hypersomnia (EHS), which are also heritable conditions. Psychostimulants are effective for the symptomatic control of ADHD (primary recommended intervention) and the two sleep disorders (frequent off-label use). However, the common biological mechanism for these disorders has not been well understood. Using a previously collected genome-wide association study of narcolepsy and EHS, we calculated polygenic risk scores (PRS) for each individual. We investigated a possible genetic association between …

Juvenile Fluoxetine Treatment Mediates An Anxiogenic Phenotype That Is Ameliorated By Its Re-Exposure In Adulthood, Francisco Javier Flores Ramirez

Open Access Theses & Dissertations

Accumulating preclinical evidence indicates that early-life exposure to psychotropic medications induce an anxiogenic-like behavioral profile in later life. However, these preclinical approaches have been conducted primarily using male subjects. This is problematic since clinical data indicates that women are more likely to be diagnosed with anxiety disorders than their male counterparts, and thus, women are prescribed with psychotropic medications like fluoxetine (FLX), a selective serotonin reuptake inhibitor (SSRI), at significantly higher rates. Therefore, the goal of this Dissertation is to examine whether alterations in behavioral responses to anxiety-eliciting stimuli are exhibited in adulthood, as a result of early-life FLX exposure. …

Tissue-Specific Regulation Of Pnmt By Intron Retention During Neural Development, Meeti Mehta

Digital Repository: Showcase of Undergraduate Research Excellence

No abstract provided.

The Role Of Melatonin In Biological Rhythms Of Songbirds, Clifford E. Harpole

Theses and Dissertations--Biology

In vertebrates, melatonin is a hormone that is produced and secreted at night and inhibited by light. This unique “darkness-only” expression profile makes it an intellectually appealing candidate for a means of transmitting temporal information to an individual, both time of day and time of year.

In passerine birds, “time of day” information is certainly transmitted via melatonin secretion. The primary producer of systemic melatonin in this family of birds is the pineal gland, and surgical removal of it causes a bird to become arrhythmic in constant conditions. I find that as pinealectomized house sparrows (Passer domesticus) become …

Involvement Of The Sigma-1 Receptor In Methamphetamine-Mediated Changes To Astrocyte Structure And Function, Richik Neogi

Theses and Dissertations--Medical Sciences

Methamphetamine is a highly addictive psychostimulant drug. There are currently no FDA-approved pharmacological treatments for methamphetamine addiction. Pharmacologically, (+)-methamphetamine is a dopamine releasing agent and dopamine transporter substrate that redistributes dopamine from intracellular vesicles via the vesicular monoamine transporter 2 (VMAT2) and reverses the direction of dopamine transport in the dopamine transporter. Methamphetamine, cocaine, and other drugs of abuse are also sigma-1 receptor ligands, and previous studies have demonstrated the role of the sigma-1 receptor in modulating the behavioral and cellular effects of these drugs. However, almost all these studies were conducted in cell culture systems or with emphasis on …

Combination Of Investigational Cell-Based Therapy And Deep Brain Stimulation To Alter The Progression Of Parkinson’S Disease, Nader El Seblani

Theses and Dissertations--Pharmacy

Parkinson’s disease (PD) is the second most common neurodegenerative disorder and the motor symptoms are caused by progressive loss of midbrain dopamine neurons. There is no current treatment that can slow or reverse PD. Our current “DBS-Plus” clinical trial (NCT02369003) features the implantation in vivo of autologous Schwann cells (SCs) derived from a patient’s sural nerve into the substantia nigra pars compacta (SNpc) in combination with Deep Brain Stimulation (DBS) therapy for treating patients with advanced PD.

The central hypothesis of our research is that transdifferentiated SCs within conditioned nerve tissue will deliver pro-regenerative factors to enhance the survival of …

Divergence In Neuronal Calcium Dysregulation In Brain Aging And Animal Models Of Ad, Adam Ghoweri

Theses and Dissertations--Pharmacology and Nutritional Sciences

Neuronal calcium dysregulation first garnered attention during the mid-1980’s as a key factor in brain aging, which led to the formulation of the Ca²⁺ hypothesis of brain aging and dementia. Indeed, many Ca²⁺-dependent cellular processes that change with age, including an increase in the afterhyperpolarization, a decrease in long-term potentiation, an increased susceptibility to long-term depression, and a reduction in short-term synaptic plasticity, have been identified. It was later determined that increased intracellular Ca²⁺ with age was due to increased Ca²⁺ channel density, elevated release from intracellular Ca²⁺ stores, and decreased Ca²⁺ buffering …

Apoe As A Metabolic Regulator In Humans, Mice, And Astrocytes, Brandon C. Farmer

Theses and Dissertations--Physiology

Altered metabolic pathways appear to play central roles in the pathophysiology of late-onset Alzheimer’s disease (AD). Carrier status of the E4 allele of the APOE gene is the strongest genetic risk factor for late-onset AD, and increasing evidence suggests that E4 carriers may be at an increased risk for neurodegeneration based on inherent metabolic impairments. A new appreciation is forming for the role of APOE in cerebral metabolism, and how nutritional factors may impact this role. In chapter 1, the literature on nutritional interventions in E4 carriers aimed at mitigating disease risk is reviewed. Studies investigating the mechanism by which …

Ceramide-Enriched Extracellular Vesicles: A Role In Enhancing Amyloid-Beta Neurotoxicity And Mitochondrial Damage In Alzheimer’S Disease, Ahmed Elsherbini

Theses and Dissertations--Physiology

Alzheimer’s disease (AD) is an age-dependent, progressive, neurodegenerative disorder that is characterized clinically by the impairment of cognitive functions concomitant with behavioral and personality changes. AD is associated with distinct pathological hallmarks, namely, intracellular neurofibrillary tangles comprised of hyperphosphorylated tau protein, extracellular amyloid beta (Aβ) plaques, and marked brain atrophy. Besides their main role as the core component of amyloid plaques, oligomeric Aβ have been shown to be neurotoxic. The exact mechanism of Aβ neurotoxicity is yet to be elucidated.

Recently, a pathogenic function of small extracellular vesicles- also known as exosomes- has been proposed, suggesting that exosomes can transfer …

Intracellular Localization Of The Novel Polyq Protein Fam171b, Dulanjani Rajaguru

All Graduate Theses, Dissertations, and Other Capstone Projects

FAM171B is a relatively uncharacterized protein that contains fourteen consecutive glutamine residues within its primary amino acid sequence; thus it is a polyglutamine (polyQ) protein. PolyQ proteins are interesting because mutations within the polyQ tract have been linked to a number of severe neurodegenerative diseases including Huntingtons Disease (HD). To date, there are minimal published data regarding FAM171B and its molecular function, such that both expression levels and intracellular localization have yet to be definitively determined. Using immunohistochemical and in situ hybridization analyses, our lab has recently found that FAM171B is expressed throughout the mouse brain. This current study attempts …

Covid-19, Evolution, Brains And Psychology, Frederick Toates

Animal Sentience

Attention needs to be directed to the processes that control behavior in humans and the adaptive problems that they solved in our early evolutionary environment. The evolutionary mismatch between the current environment and the human brain can yield important insights into the problems that beset us in the context of environmental degradation and nonhuman animal welfare.