Life Sciences Commons^™

Rescuing Age-Related Proteolysis Deficits With Methylene Blue, Shane E. Pullins

Theses and Dissertations

The average lifespan is constantly increasing with the advent of new medical techniques, and age-related cognitive decline is becoming a prevalent societal issue. Even during healthy aging, humans and rats exhibit progressive deficits in episodic/declarative memory. In laboratory rats, age-related memory impairment can be assessed with trace fear conditioning (TFC). Recent research implicates ubiquitin proteasome system-mediated protein degradation in the synaptic plasticity supporting memory formation and retrieval. In rats, aging leads to decreased basal proteolytic activity in brain structures known to support the acquisition and retrieval of trace fear memories, and our preliminary data suggests activity-dependent proteasome activity declines in …

The Role Of Hippocampal And Medial Prefrontal Interactions In The Estrogenic Regulation Of Memory, Jennifer Tuscher

Theses and Dissertations

Dendritic spine plasticity is thought to be essential for the formation and storage of memories. The sex-steroid hormone 17-estradiol (E2) increases dendritic spine density in 2 brain regions necessary for memory formation, the dorsal hippocampus (DH) and medial prefrontal cortex (mPFC), but the mechanisms through which it does so remain largely unknown. Further, the extent to which these brain regions interact to mediate E2’s effects on memory is also unclear. Recently, we found that infusion of E2 directly into the DH also increases dendritic spine density in the DH and mPFC, and that these effects depend upon rapid activation of …

Temperature Effects On An Axon’S Ability To Maintain Phasing Of A Rhythmic Motor System, Marissa Elaine Cruz

Theses and Dissertations

The precise timing of action potentials generated in the nervous system is crucial for generating adequate behavior. Once generated, action potentials travel along axons towards the neurons or muscles they innervate. Axons are also responsible for preserving the temporal fidelity of the generated action potentials. One challenge axons face is that they can be of considerable length, and exposed to changes in internal and external conditions. Temperature fluctuations, for example, affect the ion channels that generate and propagate action potentials causing changes in action potential speed. It is unclear if, and how, the timing of action potentials can be preserved …

Sex Differences In Differential Fear Conditioning During The Acquisition And Consolidation Of Learned Safety, David Sylvan Reis

Theses and Dissertations

The ability to distinguish between threatening and non-threatening situations requires careful regulation of behavioral and physiological responses to stress and fear. Deficits in fear regulation are maladaptive and can lead to the development of anxiety disorders such as PTSD. Women are nearly twice as likely to develop PTSD as are men and laboratory animal studies have shown facilitated fear acquisition, resistance to fear extinction, deficits in extinction retention and impaired discrimination between danger and safety cues in females. Taken together this suggests a propensity for reduced inhibitory control over fear responding in females. Here we investigate the mechanisms underlying fear …

Investigating The Functional Connectivity Of The Bed Nucleus Of The Stria Terminalis During Conditions Of Threat And Safety Using High Resolution 7 Tesla Fmri, Walker Scott Pedersen

Theses and Dissertations

An influential model of the extended amygdala defines fear as the immediate response to phasic threat and anxiety as the prolonged response to unpredictable or sustained threat (Davis, Walker, Miles & Grillon, 2010). This model proposes that in response to unpredictable threat, the centromedial amygdala (CeA) activates the bed nucleus of the stria terminalis (BNST), which coordinates the anxiety response, and, in turn, inhibits the CeA. Connectivity between the BNST and both the basolateral amygdala (BLA) and hippocampus may also play an important role in the coordination of the anxiety response (Davis et al., 2010; Herman et al., 2003; Zhu, …

Electrophysiological And Morphological Characterization Of Neurons In The Granular Retrosplenial Cortex, Andrew Nicholas Nye

Theses and Dissertations

The retrosplenial cortex (RSC) is a centrally located brain region that has reciprocal connections with several brain regions important for memory, including the prefrontal cortex, para-hippocampal region, hippocampal formation, and rhinal cortices. The RSC is also well connected with structures important for sensory processing, including the parietal cortex, thalamus, and visual cortices. Due to this connectivity, and early evidence that suggests the RSC plays a critical role in learning and memory, the region has recently gained much more research attention. Early studies found that patients with brain damage that includes the RSC have difficulty with verbal and visual information, retrieving …

Visually-Guided Reaching Under Varying Cognitive And Motor Demand In Young Adult Females With A History Of Concussions, Christopher James Fueger

Theses and Dissertations

Every day, vision guides one’s actions to help one successfully navigate through a complex environment. When our visual and motor systems interact efficiently, we may not fully appreciate how flawless and beneficial this process can be to our daily functioning. Yet, one’s available neural resources needed to successfully perform visually-guided movements do have limits. When an individual suffers a brain injury, such as a concussion, the available resources may be compromised. Examining the extent of this decreased resource pool requires challenging the cognitive abilities enough to observe a behavioral deficit. The purpose of this study was to examine the long-term …

Development Of Mechanosensory Innervation In The Frog, Xenopus Laevis, Peter Andrew Feuk

Theses and Dissertations

ABSTRACT

DEVELOPMENT OF MECHANOSENSORY INNERVATION IN THE FROG, XENOPUS LAEVIS

by

Peter Feuk

The University of Wisconsin-Milwaukee, 2017

Under the Supervision of Dr. R. David Heathcote

This study aims to investigate whether a specific target cell in the epidermis of the African clawed frog, Xenopus laevis, guides the initial outgrowth and pattern of Rohon-Beard (RB) cells and their survival. RB cells are primary mechanosensory neurons present during the early developmental stages of X. laevis. These neurons provide sensory input to the frog throughout embryonic and larval development before initiating apoptosis around the start of metamorphosis. The innervation of embryonic skin …

Characterizing The Role Of Key Planar Cell Polarity Pathway Components In Axon Guidance, Grayland W. Godfrey Ii

Theses and Dissertations

An essential process to the development of the neural network of the nervous system is axon guidance. The noncanonical Wnt/Planar Cell Polarity pathway has been identified as an integral component in controlling the projection of axons during axon guidance. Prickle, ROR1 and ROR2 are PCP related proteins that do not have clearly defined roles in the process. This study aims to use zebrafish CoPA neurons as a model to study the roles of Prickle, ROR1, and ROR2 in axon guidance. Using in situ hybridization, morpholino knockdown, and CRISPR/Cas9 loss of function experiments were able to identify ror1, ror2 and …

Role Of Mitochondrial Beta-Oxidation In Ethanol Response: A Candidate Gene Study Using Caenorhabditis Elegans, Harini Pallikarana Tirumala

Theses and Dissertations

Alcohol use disorder (AUD) is the fourth leading cause of preventable death in the United States, and the fifth leading risk factor for premature death and disability, globally. There are currently very few treatment options for AUD and there is a need for effective preventive and treatment strategies for this condition. AUD risk has a significant hereditary component, with the contribution of genetic factors being estimated to be about 50%. The Davies-Bettinger laboratory uses C. elegans as a model organism to study the contribution of genetic factors in modulating neuronal responses to ethanol. In this project, we examined the role …

Hydrogen Sulfide Regulation Of Kir Channels, Junghoon Ha

Theses and Dissertations

Inwardly rectifying potassium (Kir) channels establish and regulate the resting membrane potential of excitable cells in the heart, brain and other peripheral tissues. Phosphatidylinositol- 4,5-bisphosphate (PIP2) is a key direct activator of ion channels, including Kir channels. Gasotransmitters, such as carbon monoxide (CO), have been reported to regulate the activity of Kir channels by altering channel-PIP2 interactions. We tested, in a model system, the effects and mechanism of action of another important gasotransmitter, hydrogen sulfide (H2S) thought to play a key role in cellular responses under ischemic conditions. Direct administration of sodium hydrogen sulfide (NaHS), as an exogenous H2S source, …

N-Alkyl 4-Methylamphetamine Enantiomers And The Implication For Potential Modulation Of Abuse Liability And Enhancement Of Psychoactive Drug Targeting., Ramsey Sitta

Theses and Dissertations

Drugs of abuse have a long history in humanity. Currently however, a subject of great interest is the phenylalkylamine family of drugs. Not only is the abuse liability of interest but also the potential therapeutic expansion of the capabilities of this family of drugs by utilizing the unique stereospecific effects of the newly discovered hybrid compounds. Based upon prior data of N-Alkyl 4-MA the enantiomers of N-Methyl, N-Ethyl, and N-Propyl were analyzed in hDAT, hNET, and hSERT. It was found that there was a negative correlation between chain length and potency and dopaminergic component. In agreement with the currently established …

Structural And Functional Alterations In Neocortical Circuits After Mild Traumatic Brain Injury, Michal Vascak

Theses and Dissertations

National concern over traumatic brain injury (TBI) is growing rapidly. Recent focus is on mild TBI (mTBI), which is the most prevalent injury level in both civilian and military demographics. A preeminent sequelae of mTBI is cognitive network disruption. Advanced neuroimaging of mTBI victims supports this premise, revealing alterations in activation and structure-function of excitatory and inhibitory neuronal systems, which are essential for network processing. However, clinical neuroimaging cannot resolve the cellular and molecular substrates underlying such changes. Therefore, to understand the full scope of mTBI-induced alterations it is necessary to study cortical networks on the microscopic level, where neurons …

Epigenetic Editing To Validate Findings From Methylome-Wide Association Studies Of Neuropsychiatric Disorders, Robin F. Chan

Theses and Dissertations

DNA methylation is necessary for learning, memory consolidation and has been implicated in a number of neuropsychiatric disorders. Obtaining high quality and comprehensive data for the three common forms of methylation in brain is challenging for methylome-wide association studies (MWAS). To address this we optimized a panel of enrichment methods for screening the brain methylome. Results show that these enrichment techniques approach the coverage and fidelity of the current gold standard bisulfite based techniques. Our MBD-based method can also be used with low amounts of genomic material from limited human biomaterials. Psychiatric disorders have high prevalence and are often chronic …

The Effects Of The Hiv-1 Tat Protein And Morphine On The Structure And Function Of The Hippocampal Ca1 Subfield, William D. Marks

Theses and Dissertations

HIV is capable of causing a set of neurological diseases collectively termed the HIV Associated Neurocognitive Disorders (HAND). Worsening pathology is observed in HIV+ individuals who use opioid drugs. Memory problems are often observed in HAND, implicating HIV pathology in the hippocampus, and are also known to be exacerbated by morphine use. HIV-1 Tat was demonstrated to reduce spatial memory performance in multiple tasks, and individual subsets of CA1 interneurons were found to be selectively vulnerable to the effects of Tat, notably nNOS+/NPY- interneurons of the pyramidal layer and stratum radiatum, PV+ neurons of the pyramidal layer, and SST+ neurons …

Integrating Genetics And Neuroimaging To Study Subtypes Of Binge Drinkers, Megan E. Cooke

Theses and Dissertations

Risky alcohol use is a major health concern among college students, with 40.1% reporting binge drinking (5 or more drinks in one occasion) and 14.4% reporting heavy drinking (binge drinking on 5 or more occasions) in the past month. Risky alcohol use is thought to be the result of a complex interplay between genes, biological processes, and other phenotypic characteristics. Understanding this complex relationship is further complicated by known phenotypic heterogeneity in the development of alcohol use. Developmental studies have suggested two pathways to risky alcohol use, characterized by externalizing and internalizing characteristics, respectively. However, the underlying biological processes that …