Neuroscience and Neurobiology Commons^™

Reef Society And The Tyranny Of Data, Robert Wintner

Animal Sentience

Modern science now approaches divergent processes in many areas, including health assessments of marine eco-systems and social aspects of marine species. Scientific data have long enjoyed a reputation for objectivity but incidents of science-for-hire, data spinning/skewing and political jading are more frequent than ever. In the field of reef creature sensitivity, technical treatises can “logically” explain away what a person of average education can clearly observe on any given reef. Western medicine discounted anecdotal evidence of any cure outside the 4% margin of error until those cures demanded attention and in some cases application. Modern science must now enter an …

Still Wondering How Flesh Can Feel, Gwen J. Broude

Animal Sentience

Reber believes he has simplified Chalmers’s “hard problem” of consciousness by arguing that subjectivity is an inherent feature of biological forms. His argument rests on the related notions of continuity of mind and gradual accretion of capacities across evolutionary time. These notions need to be defended, not just asserted. Because Reber minimizes the differences in mental faculties among species across evolutionary time, it becomes easier to assert, and perhaps believe, that sentience is already present in early biological forms. The more explicit we are about the differences among these mental faculties and the differences across species, the less persuasive is …

Protein Kinase M Zeta-Mediated Ltp Maintenance In The Non-Human Primate Hippocampus: A Role For Stress And Serotonergic Signaling In Affective Processing, Sasha L. Fulton

Theses and Dissertations

Early-Life Stress (ELS) is associated with vulnerability to mood disorder, but it’s not well understood how ELS contributes to deficits in cognitive function. Atypical PKMzeta is critical for LTP maintenance and memory. The current study aims to characterize the ELS phenotype with respect to this key marker of hippocampal LTP.

Pdz Protein Regulation Of Β-Arrestin Recruitment And Gpcr Trafficking, Sarah Gupta

Electronic Thesis and Dissertation Repository

β-arrestins are versatile adaptor proteins that play a vital role in regulation of G protein coupled receptor (GPCR) trafficking and signalling properties. PDZ proteins have previously been shown to modulate β-arrestin2 recruitment and receptor internalization for many GPCRs including Corticotropin-Releasing Factor Receptor 1 (CRFR1), a receptor whose antagonists have been shown to demonstrate both anxiolytic- and antidepressant-like effects. Further characterization of the interplay between β-arrestins and PDZ proteins may aid in determining a potential mechanism for PDZ protein regulation of GPCR trafficking. Our findings suggest that PDZ proteins PSD-95, MAGI1, and PDZK1 complex with β-arrestin2 by interacting via the PDZ …

Riding The Mind Lightning, William A. Fortuna

Capstones

Neuromodulation is the practice of applying external stimulation, either electric or magnetic, to the human in order to affect positive change. TDCS or transcranial direct current stimulation is a neuromodulatory technique using a 9-volt battery. Because of the simplicity of the device, and it's relatively low potential for harm, the technique is popular with both researchers and at-home enthusiasts. To find out whether this technique works the way some people say it does, I built my own.

Target Validation And Pharmacological Characterization Of Novel Nmdar Modulators, Kiran Sapkota

Theses & Dissertations

The N-methyl-D aspartate receptors (NMDARs) are ligand-gated ion channels, which play important roles in learning and memory. Excessive activity of NMDARs is implicated in damage due to stroke and neurodegenerative diseases, whereas hypoactivity of NMDARs contributes to schizophrenia. The initial goal of my dissertation is to evaluate the potential role of the GluN2D-containing NMDARs in neuropathological, behavioral and cognitive alterations associated with schizophrenia and characterize the pharmacology and mechanisms of action of NMDAR modulators which could potentially be used to modulate these receptors in schizophrenia.

A subanesthetic dose of the NMDAR antagonist ketamine elicits symptoms of schizophrenia. This property led …

Global Gene Expression Profiling Of Healthy Human Brain And Its Application In Studying Neurological Disorders, Simarjeet K. Negi

Theses & Dissertations

The human brain is the most complex structure known to mankind and one of the greatest challenges in modern biology is to understand how it is built and organized. The power of the brain arises from its variety of cells and structures, and ultimately where and when different genes are switched on and off throughout the brain tissue. In other words, brain function depends on the precise regulation of gene expression in its sub-anatomical structures. But, our understanding of the complexity and dynamics of the transcriptome of the human brain is still incomplete. To fill in the need, we designed …

Mitogen And Morphogen Signaling Dysregulation: Pathophysiological Influence In Pancreatic Cancer And Alzheimer’S Disease, Eric Cruz

Theses & Dissertations

Although the etiology of a particular disease will vary, there are genetic and epigenetic bottlenecks that frequently converge resulting in dysregulation of mitogenic and morphogenetic signaling. This propensity is acutely experienced in malignancy and neurodegenerative disease.

Here, we have first investigated the role of dysregulated signaling in the context of pancreatic cancer (PC). Morphogenetic signaling has been regarded as a pleiotropic pathway with the potential to promote and inhibit metastatic features. Our investigation of bone morphogenetic protein 2 (BMP-2), an archetypical member of the BMP superfamily, has revealed the presence of extracellular, intracellular, and long non-coding RNA products. Our findings …

Motor Control In Individuals With Multiple Sclerosis, David Arpin

Theses & Dissertations

This dissertation explored motor control in individuals with multiple sclerosis (MS) by quantifying the behavioral and neurophysiological deficits present in these individuals. We behaviorally quantified the precision of the ankle plantarflexor musculature of individuals with MS. Our results indicated that the individuals with MS had a greater amount of variability in the precision of the isometric ankle torques, and that this greater variability was related to decreased walking performance. To further explore whether these motor control deficits were due to aberrant cortical activity associated with planning motor actions, we used magnetoencephalography to assess the motor planning and execution stages of …

Selective Suppression Of The Α Isoform Of P38 Mapk Rescues Late-Stage Tau Pathology, Nicole Maphis, Shanya Jiang, Guixiang Xu, Olga N. Kokiko-Cochran, Saktimayee M. Roy, Linda J. Van Eldik, D. Martin Watterson, Bruce T. Lamb, Kiran Bhaskar

Sanders-Brown Center on Aging Faculty Publications

Background: Hyperphosphorylation and aggregation of tau protein are the pathological hallmarks of Alzheimer’s disease and related tauopathies. We previously demonstrated that the microglial activation induces tau hyperphosphorylation and cognitive impairment via activation of p38 mitogen-activated protein kinase (p38 MAPK) in the hTau mouse model of tauopathy that was deficient for microglial fractalkine receptor CX3CR1.

Method: We report an isoform-selective, brain-permeable, and orally bioavailable small molecule inhibitor of p38α MAPK (MW181) and its effects on tau phosphorylation in vitro and in hTau mice.

Results: First, pretreatment of mouse primary cortical neurons with MW181 completely blocked inflammation-induced p38α MAPK activation and AT8 …

Animals Aren’T Persons, But Is It Time For A Neologism?, Helen Steward

Animal Sentience

Mark Rowlands argues that at least some animals are persons, based on the idea that (i) many animals have a property he calls “pre-reflective awareness,” (ii) the capacity for pre-reflective awareness is sufficient to satisfy the traditional Lockean definition of personhood, and (iii) satisfaction of the traditional Lockean definition of personhood is sufficient for being a person. I agree with (i) and can see that there is a persuasive case for (ii), but I think the case against (iii) blocks the conclusion that animals are persons. I suggest that we may need instead to coin a neologism in order to …

Reber’S Caterpillar Offers No Help, Carl Safina

Animal Sentience

Reber’s target article “Caterpillars, consciousness and the origins of mind” seems only to shift but not to address the question of where the mind is and how minds occur.

Striatal Dopaminergic Innervation Regulates Subthalamic Beta-Oscillations And Cortical-Subcortical Coupling During Movements: Preliminary Evidence In Subjects With Parkinson’S Disease, Andrea Canessa, Nicolo G. Pozzi, Gabriele Arnulfo, Joachim Brumberg, Martin M. Reich, Gianni Pezzoli, Maria F. Ghilardi, Cordula Matthies, Frank Steigerwald, Jens Volkman, Ioannis U. Isais

Publications and Research

Activation of the basal ganglia has been shown during the preparation and execution of movement. However, the functional interaction of cortical and subcortical brain areas during movement and the relative contribution of dopaminergic striatal innervation remains unclear. We recorded local field potential (LFP) activity from the subthalamic nucleus (STN) and high-density electroencephalography (EEG) signals in four patients with Parkinson’s disease (PD) off dopaminergic medication during a multi-joint motor task performed with their dominant and non-dominant hand. Recordings were performed by means of a fully-implantable deep brain stimulation (DBS) device at 4 months after surgery. Three patients also performed a single-photon …

Very Rapid Onset Cannabis Dependence Risk In Relation To Co-Occurring Use Of Other Psychoactive Drugs, Olga A. Vsevolozhskaya, Fernando A. Wagner, James C. Anthony

Biostatistics Presentations

Background: Epidemiological estimates for lifetime cumulative incidence indicate that for every 9-11 who start using cannabis, one becomes a case of the cannabis dependence syndrome (CDS) – i.e., roughly 9%-11%. More recent estimates clarify that CDS risk might be much lower among ’cannabis only’ users, due in part to the fact that many ’cannabis only’ users try the drug a few times and never again. We turned to Hill functional analysis in order to study CDS probability soon after 1st cannabis use, estimated across strata defined by the number of recent days of cannabis use, with an acknowledgment that a …

Ros Regulation Of Axonal Mitochondrial Transport, Pin-Chao Liao

Open Access Dissertations

Mitochondria perform critical functions including aerobic ATP production and calcium (Ca2+) homeostasis, but are also a major source of reactive oxygen species (ROS) production. To maintain cellular function and survival in neurons, mitochondria are transported along axons, and accumulate in regions with high demand for their functions. Oxidative stress and abnormal mitochondrial axonal transport are associated with neurodegenerative disorders. However, we know little about the connection between these two. Using primaryDrosophila neuronal cell culture and the third instar larval nervous system as in vitro and in vivo models, respectively, we studied mitochondrial transport under oxidative stress conditions. In vitro …

Characterizing The Effects Of Repetitive Head Trauma In Female Soccer Athletes For Prevention Of Mild Traumatic Brain Injury, Diana Otero Svaldi

Open Access Dissertations

As participation in women’s soccer continues to grow and the longevity of female athletes’ careers continues to increase, prevention of mTBI in women’s soccer has become a major concern for female athletes as the long-term risks associated with a history of mTBI are well documented. Among women’s sports, soccer exhibits the highest concussion rates, on par with those of men’s football at the collegiate level. Head impact monitoring technology has revealed that “concussive hits” occurring directly before symptomatic injury are not predictive of mTBI, suggesting that the cumulative effect of repetitive head impacts experienced by collision sport athletes should be …

Dopamine D1 Receptor Activity In The Basolateral Amygdala Is Important For Mediating Fear, Reward And Safety Discrimination Learning, Ka Ho Ng

Open Access Theses

Post traumatic stress disorder (PTSD) patients frequently show impairment in safety learning (Jovanovic, Kazama, Bachevalier, & Davis, 2012). Since the amygdala is known to be critical for emotional processing(Wassum & Izquierdo, 2015) and dopamine signaling in the amygdala is important for mediating both fear and reward learning, current experiments examined the role of dopamine signaling in the BLA in mediating both safety learning and reward seeking. We manipulated dopamine D1 receptor activity with a D1 receptor agonist (SKF 38393) or D1 receptor antagonist (SCH23390) either systemically or infused directly into the BLA 20 minutes prior to training rats in a …

Characterization Of Vesicular Monoamine Transporter 2 And Its Role In Parkinson's Disease Pathogenesis Using Drosophila, Antonio Joel Tito Jr., Sheng Zhang

Dissertations & Theses (Open Access)

Parkinson’s disease (PD) is a progressive neurodegenerative disorder caused by the selective loss of the dopaminergic neurons in the Substantia nigra pars compacta region of the brain. PD is also the most common neurodegenerative disorder and the second most common movement disorder. PD patients exhibit the cardinal symptoms, including tremor of the extremities, rigidity, slowness of movement, and postural instability, after 70-80% of DA neurons degenerate. It is, therefore, imperative to elucidate the underlying mechanisms involved in the selective degeneration of DA neurons. Although increasing numbers of PD genes have been identified, why these largely widely expressed genes induce …

Apoaequorin Differentially Modulates Fear Conditioning In Adult And Aged Rats, Vanessa Ehlers

Theses and Dissertations

Normal aging is associated with a number of changes in behavioral and cellular function, and is often linked to increased susceptibility to cognitive impairment. The hippocampus has been widely implicated in learning and memory, and many forms of learning that are hippocampus-dependent (e.g. trace fear conditioning) are impaired in aged animals. A proposed contributor to aging-related cognitive impairment is aging-related calcium (Ca2+) dysregulation. This dysregulation is thought to result from changes in specific Ca2+-regulatory mechanisms, including abnormal Ca2+ ion channel activity or expression, as well as reduced Ca2+-binding protein (CaBP) expression, which is associated with cognitive and synaptic impairment. Previous …

The Effects Of Exercise Pattern And Intensity On The Expression Of Flk-1 And Flt-1 Receptors In The Hippocampus And Cerebellum, Morgan E. Stevenson

Theses and Dissertations

Aerobic exercise benefits the body and brain. In the brain, these benefits include neuroprotection and improved cognition. These exercise-induced changes are attributed in part to angiogenesis: the growth of new capillaries from preexisting vessels. One critical factor involved in the regulation of angiogenesis is VEGF and its receptors Flk-1 and Flt-1. Although exercise is generally found to be beneficial, there are wide variations in the exercise regimens used across experiments. This study standardized some of these variations. In this study, rats were either assigned to a voluntary wheel running or a forced wheel running exercise condition. Within each condition, animals …

Cellular And Genetic Bases Of Cold Nociception And Nociceptive Sensitization In Drosophila Larvae, Heather N. Turner

Dissertations & Theses (Open Access)

Organisms from flies to mammals utilize thermoreceptors to detect and respond to noxious thermal stimuli. Although much is understood about noxious heat avoidance, our understanding of the basic biology of noxious cold perception is gravely minimal. Numerous clinical conditions disrupt the sensory machinery, such as in patients suffering from tissue damage (from wound or sunburn), or injury to the peripheral nerves, as in patients with diabetes or undergoing chemotherapy. Our goal is to determine the genetic basis for noxious cold perception and injury-induced nociceptive sensitization using the genetically tractable Drosophila model. Using a novel "cold probe" tool and assay we …

Consensus Paper: Cerebellar Development., K Leto, M Arancillo, Ebe Becker, A Chiang, Et Al.

Faculty Publications

The development of the mammalian cerebellum is orchestrated by both cell-autonomous programs and inductive environmental influences. Here, we describe the main processes of cerebellar ontogenesis, highlighting the neurogenic strategies used by developing progenitors, the genetic programs involved in cell fate specification, the progressive changes of structural organization, and some of the better-known abnormalities associated with developmental disorders of the cerebellum.

Maguk Scaffolds Organize A Key Synaptic Complex In Horizontal Cell Processes Contacting Photoreceptors, Alejandro Vila, Ph.D.

Dissertations & Theses (Open Access)

Synaptic processes and plasticity of synapses are mediated by large suites of proteins. In most cases, many of these proteins are tethered together by synaptic scaffold proteins. Scaffold proteins have a large number and typically a variety of protein interaction domains that allow many different proteins to be assembled into functional complexes. As each scaffold protein has a different set of protein interaction domains and a unique set of interacting partners, the presence of synaptic scaffolds can provide insight into the molecular mechanisms that regulate synaptic processes. In studies of rabbit retina, we found SAP102 and Chapsyn110 selectively localized in …

Transient Receptor Potential Cation Channel, Subfamilies V, Member 1 (Trpv1) And M, Member 1 (Trpm1) Contribute To Neural Signaling In Mouse Retina., Jennifer Noel

Electronic Theses and Dissertations

The retina processes light information through parallel pathways in order to extract and encode the visual scene. Light information is transmitted to the brain through approximately 30 ganglion cells (GCs), the retinal output neurons. Trp channels modulate the responses of retinal neurons within specific pathways. The study of the expression and function of the majority of Trp channels in the retina is largely in its infancy. My dissertation first investigated the expression and function of the transient receptor potential vanilloid-1 (TRPV1) receptor/channel in the retina. TRPV1, the first cloned and most highly studied Trp channel in the peripheral nervous system, …

Effects Of Repeated Aripiprazole Treatment On The Camp And Akt Pathways In The Dorsal Striatum Of Preadolescent And Adult Rats, Megan Leigh Becker

Electronic Theses, Projects, and Dissertations

The positive symptoms of schizophrenia primarily result from an excess of high affinity D2-like receptors (i.e. D2^High receptors). First-generation antipsychotics, such as haloperidol, are D2-like antagonists that can cause severe extrapyramidal effects. Aripiprazole, a dopamine and serotonin partial agonist, has fewer side effects, making it tolerable for adults and children. Extrapyramidal effects (e.g. Parkinsonism, dystonia, and akathisia) are among the most problematic side effects produced by antipsychotic compounds, which likely result from an excess of D2-like receptors in the dorsal striatum. In order to examine the effects of repeated antipsychotic treatment on dopamine system functioning, this thesis compared the …

Exploring The Production Of Extracellular Matrix By Astrocytes In Response To Mimetic Traumatic Brain Injury, Addison Walker

Graduate Theses and Dissertations

Following injury to the central nervous system, extracellular modulations are apparent at

the site of injury, often resulting in a glial scar. Astrocytes are mechanosensitive cells, which can create a neuroinhibitory extracellular environment in response to injury. The aim for this research was to gain a fundamental understanding of the affects a diffuse traumatic brain injury has on the astrocyte extracellular environment after injury. To accomplish this, a bioreactor culturing astrocytes in 3D constructs delivered 150G decelerations with 20% biaxial strain to mimic a traumatic brain injury. Experiments were designed to compare the potential effects of media type, number of …

Rna Sequencing Analysis Of The Developing Chicken Retina, Christophe Langouet-Astrie*, Annamarie Meinsen*, Emily R. Grunwald*, Stephen Turner, Raymond A. Enke

Ray Enke Ph.D.

Insect Consciousness: Commitments, Conflicts And Consequences, Colin Klein, Andrew B. Barron

Animal Sentience

Our target article, “Insects have the capacity for subjective experience,” has provoked a diverse range of commentaries. In this response we have collated what we see as the major themes of the discussion. It is clear that we differ from some commentators in our commitments to what subjective experience is and what the midbrain is capable of. Here we clarify where we stand on those points and how our view differs from some other influential perspectives. The commentaries have highlighted the most lively areas of disagreement. We revisit here the debates surrounding whether the cortex is essential for any form …

Consciousness And Evolutionary Biology, Yew-Kwang Ng

Animal Sentience

Reber’s axiom: “Any organism with flexible cell walls, a sensitivity to its surrounds and the capacity for locomotion will possess the biological foundations of mind and consciousness” does not seem to be supported by things we know and the logic of evolutionary biology. The latter leads to the conclusion that conscious species are flexible in their behavior (rather than in their cell walls), as argued in Ng (1995, 2016). Locomotion may be completely hard-wired and need not involve consciousness. It is hard enough to explain how consciousness could emerge in a sophisticated brain: Isn’t it a harder problem to show …

Dopamine Effects Of Stimulant And Non-Stimulant Drugs Used In The Treatment Of Attention Deficit Hyperactivity Disorder, Preeti Chalwadi

Theses and Dissertations

Attention deficit hyperactivity disorder (ADHD) is thought to be associated with dysfunction of ascending catecholamine neuronal systems, particularly dopamine (DA) and norepinephrine (NE). Dysfunction of these catecholamine neurons innervating the prefrontal cortex is hypothesized to underlie impaired executive functions. Dysfunction of the DA neurons innervating the striatum is additionally hypothesized to underlie deficits in motivation and reinforcement learning. However, mechanisms of action of therapeutic drugs used for treating ADHD have mainly focused on catecholamines in the prefrontal cortex and have not adequately addressed the role played by DA signaling in the striatum. Stimulants such as Adderall® and Ritalin® are chemically …