Life Sciences Commons^™

Novel Therapeutic Strategies For Alzheimer’S Disease: Prostaglandin D2 Signaling And Its Human Polymorphisms As Well As A Polypharmacological Approach, Charles H. Wallace

Dissertations, Theses, and Capstone Projects

Alzheimer’s disease (AD) is an age related neurodegenerative disease with pathology that includes amyloid plaques, neurofibrillary tangles and non-resolving neuroinflammation. Non-resolving neuroinflammation lasts the entire course of the disease and has deleterious effects and is often thought to accelerate AD pathology. Non-Steroidal Anti-inflammatory Drugs (NSAIDs) have commonly been used as therapeutics to treat pain, inflammation and vascular. NSAIDs work by altering the cyclooxygenase (COX) mediated biosynthesis of prostaglandins which are lipid mediators that have many physiological functions, for example nociception, inflammation and vasodilation. Epidemiological studies support the notion that NSAIDs could be used to treat AD. Yet, clinical trials using …

Unexpected Arousal Suppresses Memory And Metamemory Predictions During Associative Face-Name Recognition Task, Sameer Sabharwal-Siddiqi

Dissertations, Theses, and Capstone Projects

Successful recognition often depends on probabilistic estimation of memory-signal. Arousal has been shown to offset the influence of heuristic evidence on memory prediction. We conducted three experiments that tested whether arousal also suppresses predictions relevant to memory confidence. Experiments employed associative face-name memory tasks that included retrospective (Experiments 1 and 2) or concurrent (Experiment 3) judgements of confidence. During test, subjects were presented with a masked-affective face on a subset of trials. By timing the masked-affective face to precede a recognition judgement (Experiment 1), we replicated the finding that unexpected arousal offsets the influence of heuristic evidence on expectations of …

Competitive And Facilitative Interactions Between Pavlovian Cues In Human Associative Learning: A Behavioral And Neural Analysis, Fahd Alhazmi

Dissertations, Theses, and Capstone Projects

Learning to anticipate significant events accurately is a crucial element of survival for all species. The process by which animals acquire this knowledge has been a central question of psychological research. A fundamental assumption of many learning theories is that the predictive value assigned to cues is not simply determined by their probability of reinforcement but rather by their ability to compete with other cues present during learning. The assumption of cue competition has significantly contributed to the development of behavioral and neuroscience research for decades, as it has opened the door to new empirical and theoretical advances on the …

Clustered Protocadherins Ubiquitination And Phosphorylation Regulates Surface Expression, Albert Ptashnik

Dissertations, Theses, and Capstone Projects

Clustered protocadherins (Pcdhs) are a family of 60 adhesion-like molecules forming a neural barcode. In vertebrate neurons, 60 Pcdhs are coded by a large gene cluster. Numerous axons in the cluster are coding for the different extracellular, transmembrane, variable portion of the cytoplasmic and constant cytoplasmic domains where their expression is controlled epigenetically. These proteins mediate interactions between axons, dendrites, and glial cells during neural development. Yet, Pcdhs are not strictly adhesion molecules. In the amacrine cells of the retina, Pcdhs promote avoidance of the same cell dendrites, where in the cortex Pcdhs promote interactions between dendrites and astrocytes. In …

Development And Characterization Of A Novel, Genetically- Encoded Sensor To Image Sonic Hedgehog Signaling In Functional Circuits, Sonia Bernal

Dissertations, Theses, and Capstone Projects

Dynamic neurotransmitter and neuromodulator signaling in functional circuits is the neural substrate of animal behavior and cognition. The study of said circuits requires tools with sufficient spatiotemporal dynamics that can probe complex signaling patterns and decode their functional relevance by coupling the signal to behavioral output, ideally in awake, behaving animals. Much is known about the role of classical neurotransmitters such as dopamine in behavior, but a wide variety of peptides and small molecules also regulate neuronal transmission. One of these is Shh, whose presence has been observed in a variety of brain regions known to modulate movement, perception, and …

The Impact Of Focused Attention And Opening Monitoring Meditation Styles On Attention, Jennifer Wheary

Dissertations, Theses, and Capstone Projects

Mindfulness meditation – often broken down into two distinct types, focused attention (FA) and open monitoring (OM) – has been associated with a range of affective and attentional benefits. Using an attentional blink (AB) paradigm that demonstrated improved attention for novice FA meditators, we explored whether novices who engaged in a single, brief bout of meditation exhibited any differences in alpha or theta power during meditation, and whether these differences were apparent by meditation type. In the AB paradigm, participants are asked to identify two targets, T1 and T2, which are separated by 200-500 ms. Our results showed no significant …

Investigating Steady State Visually Evoked Potentials As A Novel Biosignature For Anxiety-Related Attention Bias, Elizabeth R. Davis

Dissertations, Theses, and Capstone Projects

Anxiety-related attention bias (AB), a type of cognitive bias underlying the development and maintenance of anxiety disorders, is typically defined as exaggerated attention towards threat; however, some individuals also demonstrate AB away from threat and in some instances, no detectable AB at all. Debate about the reliability and validity of AB behavioral measures has prompted examination of additional assessment methods. Neurophysiological methods, such electroencephalography (EEG), have yielded encouraging early findings. The steady-state visually evoked potential (SSVEP), a measure of selective visual attention derived from EEG, holds promise as a biosignature for AB. Research documents heightened SSVEP power to emotionally salient …

Testing An Overtraining Protocol For Fear Learning In Humans, Gordon M. Haskell

Dissertations, Theses, and Capstone Projects

Successful regulation of fear memories is a fundamental tenet to the exposure-based therapies often employed by mental health professionals for individuals with PTSD, phobias, and other anxiety disorders. Consequently, the efficacy of these treatment methodologies is largely dependent on the strength of the fear memory, as stronger memories are often characterized by an increased resistance to extinction and heightened fear recovery. However, there is little consensus within the scientific community regarding how to effectively maximize fear memory strength in human studies, and the literature exploring the impact of variability in acquisition parameters on memory strength is sparse. Here, we tested …

Genetic Circadian Mosaics And The Clock Network’S Contributions To Sleep, Lukasz Widziszewski

Dissertations, Theses, and Capstone Projects

Circadian rhythms are physiological and behavioral changes which follow a 24-hour cycle. Drosophila Melanogaster’s circadian clock neuronal network (CCNN) has been identified and several subpopulations have been characterized based on previous studies; the classifications of subpopulations of neurons within the CCNN are based on a return of anticipatory locomotor activity preceding the two daily light transitions (Lights on = dawn/Lights off = dusk). The neurons responsible for the return of anticipatory morning locomotor activity have been referred to as the M-cells, the group of neurons known to rescue evening anticipatory locomotor activity have been termed the E-cells. In this …

The Effects Of Near-Threshold Color Manipulation On Perceptual Decision-Making And Confidence Report, Trevor Caruso

Dissertations, Theses, and Capstone Projects

Confidence measures are sometimes used to index awareness below a participant’s criterion for what counts as being subjectively aware of a stimulus or stimulus property. If confidence ratings index awareness below subjective thresholds, then one might be tempted to use confidence ratings in place of subjective reports of whether a stimulus/stimulus property was “seen” or “unseen”. As such, a dissociation of confidence from performance may be construed as a dissociation of subjective awareness from objective task performance. This methodology has been used as supporting evidence for blindsight in typical observers (Balsdon and Azzopardi 2015; Peters and Lau 2015; Peters et …

Withdrawal From Voluntary Oral Methamphetamine Reveals Female Specific Susceptibilities To Behavioral Deficits And Neurochemical Perpetuators Of Neurotoxicity And Drug Seeking Behavior, Nicoletta K. Memos

Dissertations, Theses, and Capstone Projects

MA is a potent, highly addictive psychomotor stimulant known to produce neurotoxic effects on the brain leading to neurological impairments^1-6 characterized by neurodegeneration of dopaminergic fibers, cell bodies and pathways, as well as brain regions such as the hippocampus, frontal cortex, and midbrain^1,5.

In MA addiction, women are more vulnerable to the behavioral and cognitive effects of MA compared to men. Adult human literature reveals gender differences in usage patterns and women demonstrate increased vulnerability to the neurotoxic effects and health effects of MA use. Women begin drug use at an earlier age, escalate drug use quicker, …