Neuroscience and Neurobiology Commons^™

A Cross-Species Meta-Analysis Of Environmental Enrichment Effects On Cognition, Greg S. Fitzgerald

Electronic Theses & Dissertations (2024 - present)

Environmental enrichment --providing animals or people with stimulating, complex surroundings --consistently improves cognitive performance in laboratory rodents. But when similar interventions are tested in humans, the benefits are much smaller. Understanding why matters: if researchers overestimate how well rodent findings will translate, it can mislead expectations for human cognitive interventions.

This dissertation presents the first cross-species meta-analysis comparing environmental enrichment effects on cognition between rodent and human studies. Drawing on 121 studies (71 rodent, 50 human) contributing 478 effect sizes, the analysis used multilevel models with variance correction to account for the statistical dependence created when studies report multiple outcomes. …

The Multifaceted Role Of Glutamate At Excitatory And Inhibitory Synapses, Maurice A. Petroccione

Electronic Theses & Dissertations (2024 - present)

Our thoughts, memories, and actions are finely controlled by the coordinated activity of neural circuits in the brain. Prior work has identified a multitude of molecular mechanisms that contribute to the generation of these higher order functions, yet we know very little about how our ability to learn and perform habitual actions change depending on how far neurotransmitters released from neurons can travel away from their point of release. This is the main focus of my work, which I carried out using a diverse toolbox and focusing on two brain regions: the hippocampus and the striatum. The hippocampus controls learning …

Characterization Of Corticotropin Releasing Factor Receptor 2 In Stress-Regulating Regions Of The Mouse Brain, Jennifer J. Lafrican

Electronic Theses & Dissertations (2024 - present)

Sex differences in the morphology of the brain are thought to underlie the sex differences we see in anxiety and depression, where women are twice as likely to be diagnosed when compared to men. Stress, or a disruption to homeostasis, can exacerbate these mood disorders. Corticotropin releasing factor (CRF), and its receptors, play an important role in regulating the stress response. Binding of CRF with CRFR2 has been shown to reduce behavioral and neuroendocrine stress responses, yet whether there are sex differences in CRFR2 expressing neurons and stress-induced activation of these neurons in mice is unknown, in part due to …

The Role Of The Nasal Migratory Mass In Olfactory Bulb Formation And Fertility, Charisse Martin

Electronic Theses & Dissertations (2024 - present)

The olfactory migratory mass plays an essential role in the development of the olfactory bulb by facilitating the migration of the gonadotropin-releasing hormone neurons from the olfactory placode to the pre-optic hypothalamic area in the brain. In mammals, the migration of GnRH neurons is critical for establishing the hypothalamic-pituitary-gonadal axis (HPG axis), which regulates reproductive function through the production and secretion of gonadotropins. Luteinizing hormone (LH) and Follicle-stimulating hormone (FSH) instruct the gonads to function appropriately, ensuring sexual maturation and fertility. Disruptions in this migratory pathway have been linked with Kallmann syndrome, a condition characterized by low levels of GnRH, …

Technological Development Of In-Cell Nmr: Microfluidic, Metabolomic, And Fluxomic Approaches, Nicholas Sciolino

Electronic Theses & Dissertations (2024 - present)

In the fields of structural biology, metabolomics, and fluxomics, there is a driving, technique-based concern when it comes to high-resolution spectrometry and its marriage to biological and physiological relevance. Sample preparation often involves cellular perturbation, lysate separation schemes, combinations with non-biological reagents, and timeline slack. Conceptually, the farther we get from the cell, the greater the potential disparity between what exists in vivo and our in vitro manipulations. This is particularly true when seeking to collect data on transfected targets of interest, and on sensitive metabolic equilibria that occur on the order of minutes. The question remains: if we are …

Hippocampal Insulin Exists! In Vivo Sampling Methods, Basal Concentrations, Recurrent Hypoglycemia, And Behavioral Extracellular Insulin Responses, Starlette R. Douglass

Electronic Theses & Dissertations (2024 - present)

Insulin has widespread actions within the brain, including energy homeostasis, modulation of feeding, and as a key component of memory processes. Further, brain insulin dysfunction correlates with Alzheimer's disease and other neurodegenerative disorders. To this point, measurement of hippocampal insulin has been limited. Determining in vivo hippocampal insulin levels both at a healthy baseline and after, e.g., induction of a disease state or in response to cognitive challenge, is essential to advance our understanding of both insulin's procognitive actions and to guide potential therapeutic interventions.

We first sought to establish a sampling technique for insulin within awake and moving rats …

Maternal Experience-Driven Changes In Oxytocin Neuron Co-Localization With Crf Receptors In The Hypothalamus Of Mice, Katherine Parra

Legacy Theses & Dissertations (2009 - 2024)

The postpartum period is a time of adaptiveness for new mothers who have to not only maintain their own health and well-being, but also that of a brand-new life. In both humans and across various common laboratory species like rats, mice, and non-human primates, priorities must shift greatly for a new mother to now include initiation and maintenance of offspring-focused behaviors regardless of her circumstances.The neurobiology of this adaptivity includes a complex sequence of changes that amount to suppression of hypothalamic-pituitary-adrenal (HPA) axis activity. Corticotropin-releasing factor receptor 1 (CRFR1) is a receptor involved with initiating the physiological stress response and …

Androgen Regulation Of The Hpa Axis And Stress-Related Behaviors In Mice: The Role Of Crf And Crf Receptor 1, Krystyna Ann Rybka

Electronic Theses & Dissertations (2024 - present)

Mood disorders such as anxiety and depression are nearly twice as prevalent in women when compared to men, with potential contributing factors involving sex-dependent exposure to gonadal hormones and dysregulation of the hypothalamic-pituitary-adrenal (HPA) axis. Androgen actions through androgen receptors (AR) or actions at estrogen receptors such as ERα, following the conversion of androgens to estradiol, have been shown to regulate stress-related behaviors as well as HPA axis responsiveness. Where androgen actions at AR appear to decrease the stress response and subsequent stress-related behaviors, actions at ERα seem to do the opposite and increase HPA axis reactivity. When the HPA …

Effects Of Aerobic Exercise On Rage And Lrp1 In Stz And Hfd Models Of Diabetes: Relationship With Cognitive Function And Aβ Clearance, Corey Joseph Frank

Legacy Theses & Dissertations (2009 - 2024)

The number of individuals with diabetes worldwide has quadrupled since 1980, making diabetes the 4th most common cause of death from non-communicable disease. Since 1975, the number of individuals classified as obese has tripled to 650 million adults, or 13% of the global population (World Health Organization, 2018). Obesity rates in the United States are three times the global average, with 39.8% of adults having a body-mass index of 30 or greater (Hales, 2017). At the same time, in the United States, AD is the sixth most common cause of death, with 5.8 million currently diagnosed, a number that may …

Neural Correlates And Neuroanatomy Of Juvenile And Adult Contextual Fear Memory Retention, Natalie Odynocki

Legacy Theses & Dissertations (2009 - 2024)

AbstractFear is an evolutionarily conserved mechanism that allows an organism to discern potential harm and act accordingly by engaging in defensive behaviors. While fear is an adaptive response, dysregulation of fear by means of a traumatic event can lead to psychiatric conditions such as post-traumatic stress disorder (PTSD). Animal research using rodents in Pavlovian context fear conditioning experiments allows for the ability to study the underlying neural circuitry of threat-appropriate and aberrant fear learning and memory that may contribute to PTSD. However, despite reports that women are more than two times more likely to develop PTSD compared to men, the …

Mechanisms Underlying Pre- And Postnatal Development Of The Mouse Vomeronasal Organ, Raghu Ram Katreddi

Legacy Theses & Dissertations (2009 - 2024)

The Vomeronasal organ (VNO) is a specialized olfactory sensory organ located in the ventral region of the nasal cavity in rodents. The vomeronasal epithelium (VNE) of rodents is composed of 2 major types of vomeronasal sensory neurons (VSNs): 1) VSNs distributed in the apical VNE regions that express vomeronasal type-1 receptors (V1Rs) and the G protein subunit Gi2, and 2) VSNs in the basal territories of the VNE that express vomeronasal type-2 receptors (V2Rs) and the G subunit Go. Besides these two neuronal types, VNE also accommodate a third non-neuronal cell type called Sustentacular cells that lie anatomically above apical …

Ab42 Alters Glutamatergic Transmission In The Ca1 Region Of The Mouse Hippocampus, Patrick Harry Wehrle

Legacy Theses & Dissertations (2009 - 2024)

Alzheimer’s disease (AD) is a neurodegenerative disease affecting 4.5 million people in the US, a number expected to increase 3-fold over the next 30 years. One of the hallmarks of AD is the extracellular accumulation of the protein Aß₄₂ throughout in the brain, particularly in limbic structures like the temporal cortex and hippocampus, key regions for learning and memory. Currently available animal models for AD aim to reproduce key genetic traits of the familial variant of the disease, but >90% of AD patients are affected by idiopathic AD. To overcome this potential limitation, we use a different approach to study …

Exploring The Roles Of Stress, Codon Usage, And Rna Modifications In Myotonic Dystrophy Type 1, Afrooz Golestanian

Legacy Theses & Dissertations (2009 - 2024)

Myotonic dystrophy (DM), the most common form of muscular dystrophy, is a neuromuscular disease caused by microsatellite repeat expansions. It can represent a multi-systemic autosomal dominant disease with DM1 and DM2 subtypes. A cytosine-thymine-guanine (CTG) triplet repeat in the 3’ untranslated region (3’UTR) of myotonic dystrophy protein kinase (DMPK) gene causes DM1 disease, which leads to the production of a longer, abnormal and toxic mRNA. The toxic DMPK mRNA sequester the splicing proteins such as Muscle blind-like (MBNL) and rbFOX which leads to gene expression alteration. Repeat associated non-AUG (RAN) translation also occurs in DM1. Mitochondrial dysregulation has also been …

Sex Differences In Context Fear Neural Circuitry And Behavior Across Development, Lorianna Marie Colon

Legacy Theses & Dissertations (2009 - 2024)

Over the span of five decades, staggering progress has been made in elucidating the neural circuits involved in fear learning. Research focused on rodents and healthy individuals has been instrumental in elucidating how abnormalities in this circuitry may lend to increased prevalence of various fear and anxiety disorders. However, many of the key findings concerning the acquisition, storage, and retrieval of fear memories have been established in the adult male rodent, leaving a gap in knowledge as to whether females and developing animals process fear and stress inducing information in a similar fashion. Compared to men, women are twice as …

Ampa And Kainate Receptor-Potentiating Rna Aptamers, Janet L. Lynch

Legacy Theses & Dissertations (2009 - 2024)

Glutamate receptors act to bring about excitatory transmission in the central nervous system. The receptors are divided into two groups: ionotropic and metabotropic glutamate receptors. Ionotropic glutamate receptors are ion channels which are activated by an agonist such as glutamate or kainate. The main receptors in the ionotropic glutamate receptor family are the α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA), kainate and N-methyl-D-aspartate (NMDA) receptors. In the central nervous system ionotropic glutamate receptors are found both pre- and postsynaptically. It has been found that most AMPA and NMDA receptors are postsynaptic receptors while the kainate receptors can be pre- or postsynaptic. Underactivity of these …

Mapping Of Auditory Cortical Functions Using Electrocorticography, James Robert Swift

Legacy Theses & Dissertations (2009 - 2024)

Communication is a dynamic process through which we translate our inner thoughts in such a way that they can be shared with another person. This complex neurological phenomenon is a key predictor of our productivity and health. When our ability to communicate is compromised, our quality of life suffers. Although numerous methods to investigate the neuroscientific underpinnings of human language exist, our understanding of this process remains incomplete. Improving our understanding of where, when, and how auditory cortical activity occurs can enhance diagnostic techniques and improve treatment methods for neurological conditions that can impact auditory processing, such as epilepsy, or …

Behavioral, Endocrine, And Neural Responses To Stress In Postpartum And Nulliparous Rats : Potential Mechanisms Of Postpartum Stress Resilience, Joanna Medina

Legacy Theses & Dissertations (2009 - 2024)

Major depressive disorder is one of the most pervasive psychiatric illnesses in the United States. Women are at greater risk for developing depression, particularly during their childbearing years. Approximately 17% of new mothers develop postpartum depression within 4 weeks after parturition. The risk for postpartum depression is even greater in women who do not breastfeed or stop breastfeeding early. Major depressive disorder and postpartum depression share the same symptomology and common etiological bases. Dysregulated stress responses, dopamine activity, and neuroinflammation are recognized mechanisms for depression. The transition to motherhood encompasses physiological and behavioral adaptations in the brain essential for ensuring …

The Effects Of 17alpha-Hydroxyprogesterone Caproate On The Development Of The Mesocortical Dopamine Pathway And Cognitive Behavior, Melanie Lolier

Legacy Theses & Dissertations (2009 - 2024)

This dissertation examined the complex developmental impact of the clinically relevant synthetic progestin 17α-hydroxyprogesterone caproate (17-OHPC) on medial prefrontal cortex (mPFC) development. In rodents, the effects of 17-OHPC are subtle, but significant. In the Chapter II, we observed that 17-OHPC abolishes sex differences in dopaminergic fiber innervation and alters microglia phenotype in the prelimbic and infralimbic areas by the end of the first postnatal week. In the third chapter, the overall effect of 17-OHPC on the ontogeny of dopaminergic fiber innervation and synaptic bouton density were used to characterize the timing and duration of treatment effects in the mPFC. In …

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

The Role Of Progesterone Receptor In The Developing Medial Preoptic Nucleus, Diana Lalitsasivimol

Legacy Theses & Dissertations (2009 - 2024)

Numerous neurodevelopmental and neuropsychiatric diseases have a distinct sex bias in

The Role Of Progesterone Receptor In The Development Of The Mesocortical Serotonergic Pathway, Allyssa Phillips

Legacy Theses & Dissertations (2009 - 2024)

The mesocortical serotonergic pathway, consisting of serotonergic fibers projecting from the dorsal raphe nucleus (DRN) to the prefrontal cortex (PFC), regulates higher order executive functions and complex cognitive behaviors. Disruptions in this pathway lead to dysfunction in behavior and have been linked to several clinical disorders, including anxiety and ADHD. While this pathway continues to change throughout the lifespan, it is during early development that this pathway undergoes a rapid period of maturation, with the greatest rate of fiber innervation and synaptogenesis occurring in the mesocortical serotonergic pathway at this time. The development of a properly functioning circuit is directed …

Characterization Of A Novel, Stress-Responsive Sexually Dimorphic Corticotropin-Releasing Factor Receptor 1 (Crfr1) Nucleus In The Rostral Anteroventral Periventricular Nucleus Of The Mouse, Zachary Julius Rosinger

Legacy Theses & Dissertations (2009 - 2024)

Within the United States, women are at double the risk of men to develop a stress-related mood disorder (e.g., anxiety or depression) during their reproductive years (Kornstein et al., 2000; Kessler et al., 2005). Many factors contribute to the potential sex difference in such disorders, including gonadal hormones (hypothalamic-pituitary-gonadal axis; HPG) and how they interact with the stress response system, or hypothalamic-pituitary-adrenal (HPA) axis. Corticotropin-releasing factor (CRF) signals through binding the GS-coupled receptor, CRF receptor 1 (CRFR1), and activity between CRF/CRFR1 regulates the hormonal and behavioral stress response (Chen et al., 1993; Bale and Vale, 2004; Heinrichs et al., 1995; …

Developmental Changes In The Activation And Structure Of The Contextual Fear Neural Circuit From Infancy To Adulthood, Anthony John Santarelli

Legacy Theses & Dissertations (2009 - 2024)

The contextual fear circuit, centered on the basolateral nucleus of the amygdala (BLA), is comprised of projections from the hippocampal formation and prefrontal cortex, and mediates an animals ability to learn and predict associations between the environment and biologically relevant stimuli. While the function and structure of this circuit has been well characterized in adult species, relatively little is known about its development as an animal transitions from infancy to adulthood. Recent evidence has begun to suggest that infants, juveniles, and adolescents may show remarkable heterogeneity in the behavioral, activational, and structural properties of the circuit. In this thesis, I …