Neuroscience and Neurobiology Commons^™

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 …

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

Dissertations and 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 …

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

Dissertations and 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 …

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

Dissertations and 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 …

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 …

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 …

Methylphenidate And Memory And Attention Adaptation Training For Persistent Cognitive Symptoms After Traumatic Brain Injury: A Randomized, Placebo-Controlled Trial, Brenna C. Mcdonald, Laura A. Flashman, David B. Arciniegas, Robert J. Ferguson, Li Xing, Jaroslaw Harezlak, Gwen C. Sprehn, Flora M. Hammond, Arthur C. Maerlender, Carrie L. Kruck, Karen L. Gillock, Kim Frey, Rachel N. Wall, Andrew J. Saykin, Thomas W. Mcallister

Center for Brain, Biology, and Behavior: Faculty Publications

The purpose of this multicenter, prospective, randomized, placebo-controlled study was to evaluate and compare the efficacy of two cognitive rehabilitation interventions (Memory and Attention Adaptation Training (MAAT) and Attention Builders Training (ABT)), with and without pharmacologic enhancement (i.e., with methylphenidate (MPH) or placebo), for treating persistent cognitive problems after traumatic brain injury (TBI). Adults with a history of TBI at least four months prior to study enrollment with either objective cognitive deficits or subjective cognitive complaints were randomized to receive MPH or placebo and MAAT or ABT, yielding four treatment combinations: MAAT/MPH (N=17), ABT/MPH (N=19), MAAT/placebo (N=17), and ABT/placebo (N=18). …

The Difference Between Conscious And Unconscious Brain Circuits, Ezequiel Morsella, Zaviera Reyes

Animal Sentience

Theoretical frameworks in which consciousness is an inherent property of the neuron must account for the contrast between conscious and unconscious processes in the brain and address how neural events can ever be unconscious if consciousness is a property of all neurons. Other approaches have sought answers regarding consciousness by contrasting conscious and unconscious processes and through investigating the complex interactions between the two kinds of processes, as occurs most notably in human voluntary action. In voluntary action, consciousness is associated most, not with motor control or low-level perceptual processing, but with the stage of processing known as action selection.

Resolving The Hard Problem And Calling For A Small Miracle, Arthur S. Reber

Animal Sentience

With the exception of the commentary by Key, the commentaries on Reber have a common feature: the commenters feel, with varying levels of enthusiasm, that there is at least some virtue in the core assumption of the Cellular Basis of Consciousness (CBC) theory that consciousness (or subjectivity or sentience) accompanies the earliest forms of life. The model has two important entailments: (a) it resolves the (in)famous Hard Problem by redirecting the search for the biochemical foundations of sentience away from human consciousness; and (b) it reduces the need for an emergentist miracle to a far simpler scale than is currently …

No Help On The Hard Problem, Derek Ball

Animal Sentience

The hard problem of consciousness is to explain why certain physical states are conscious: why do they feel the way they do, rather than some other way or no way at all? Arthur Reber (2016) claims to solve the hard problem. But he does not: even if we grant that amoebae are conscious, we can ask why such organisms feel the way they do, and Reber’s theory provides no answer. Still, Reber’s theory may be methodologically useful: we do not yet have a satisfactory theory of consciousness, but perhaps the study of simple minds is a way to go about …

Unconscious Higher-Order Thoughts (Hots) As Pre-Reflective Self-Awareness?, Rocco J. Gennaro

Animal Sentience

Rowlands argues that many nonhuman animals are “persons,” contrary to the prevailing orthodoxy which rests on a mistaken conception of the kind of self-awareness relevant to personhood. He argues that self-awareness bifurcates into two importantly different forms — reflective self-awareness and pre-reflective self-awareness — and that many animals can have the latter, which is sufficient for personhood. I agree that there is good reason to think that many animals can have pre-reflective self-awareness, but I think Rowlands is mistaken about its nature. His account runs the risk of leading to an infinite regress objection, and his notion of pre-reflective self-awareness …

Towards Deeper Understanding In Neuroimaging, Rex Devon Hjelm

Computer Science ETDs

Neuroimaging is a growing domain of research, with advances in machine learning having tremendous potential to expand understanding in neuroscience and improve public health. Deep neural networks have recently and rapidly achieved historic success in numerous domains, and as a consequence have completely redefined the landscape of automated learners, giving promise of significant advances in numerous domains of research. Despite recent advances and advantages over traditional machine learning methods, deep neural networks have yet to have permeated significantly into neuroscience studies, particularly as a tool for discovery. This dissertation presents well-established and novel tools for unsupervised learning which aid in …

Memorable Audiovisual Narratives Synchronize Sensory And Supramodal Neural Responses, Samantha S. Cohen, Lucas C. Parra

Publications and Research

Our brains integrate information across sensory modalities to generate perceptual experiences and form memories. However, it is difficult to determine the conditions under which multisensory stimulation will benefit or hinder the retrieval of everyday experiences. We hypothesized that the determining factor is the reliability of information processing during stimulus presentation, which can be measured through intersubject correlation of stimulus-evoked activity. We therefore presented biographical auditory narratives and visual animations to 72 human subjects visually, auditorily, or combined, while neural activity was recorded using electroencephalography. Memory for the narrated information, contained in the auditory stream, was tested 3 weeks later. While …

The Psychological Concept Of “Person”, Kristin Andrews

Animal Sentience

Reluctance to overextend personhood seems to drive many of the skeptical responses in the first round of commentaries on Rowlands's target article. Despite Rowlands’s straightforward Response that we already accept some nonhumans as persons, there is still hesitation to accept that other nonhuman animals are persons. Rowlands's argument is sound but the skeptics don’t accept the Lockean notion of person. The metaphysical sense of person is a psychological one, however, and psychological properties grant one moral status according to many ethical theories.

Design Of Novel Ion Channel Modulators, Vladimir Yarov-Yarovoy

Science Seminar Series

Function and modulation of neuronal sodium channels are critical for the neuromodulation of electrical excitability and synaptic transmission in neurons - the basis for many aspects of signal transduction, learning, memory and physiological regulation. Mutations in neuronal voltage-gated sodium channel genes are responsible for various human neurological disorders. Furthermore, human neuronal voltage-gated sodium channels are primary targets of therapeutic drugs used as local anesthetics and for treatment of neurological and cardiac disorders. Yarov-Yarovoy's lab is working on rational design of novel therapeutically useful blockers of voltage-gated sodium channels for treatment of pain and epilepsy. Serious, chronic pain affects at least …

Understanding The Differences Between Neuronal Calcium Sensor Proteins: A Comparison Of Neurocalcin Delta And Hippocalcin, Jeffrey M. Viviano

Graduate School of Biomedical Sciences Theses and Dissertations

Many neuronal functions, including learning and memory are driven by changes in intracellular Ca2+concentrations. The Neuronal Calcium Sensor (NCS) family of proteins is responsible for mediating the response to calcium. They are typically comprised of 4 EF hands; of which EF 2, 3, and 4 bind calcium.

Hypothesis: NCS proteins carry out unique, non-overlapping functions, and that specific characteristics of the family can be mapped to precise regions of the proteins.

Results: The effect on the following properties were investigated primarily on two highly similar NCS proteins, Neurocalcin Delta (NCALD) and Hippocalcin (HPCA): (1) Response to calcium was determined through …

Neurobehavioral Markers Of Resilience To Depression Amongst Adolescent Exposed To Child Abuse, Meg J. Dennison, Margaret A. Sheridan, Daniel S. Busso, Jessica L. Jenness, Matthew Peverill, Maya L. Rosen, Katie A. Mclaughlin

Neuroscience: Faculty Publications

Childhood maltreatment is strongly associated with depression, which is characterized by reduced reactivity to reward. Identifying factors that mitigate risk for depression in maltreated children is important for understanding etiological links between maltreatment and depression as well as improving early intervention and prevention. We examine whether high reward reactivity at behavioral and neurobiological levels is a marker of resilience to depressive symptomology in adolescence following childhood maltreatment. A sample of 59 adolescents (21 with a history of maltreatment; Mean Age = 16.95 years, SD = 1.44) completed an fMRI task involving passive viewing of emotional stimuli. BOLD signal changes to …

Molecular Mechanisms Of Stress-Induced Increases In Fear Memory Consolidation Within The Amygdala, Antonio V. Aubry, Peter A. Serrano, Nesha S. Burghardt

Publications and Research

Stress can significantly impact brain function and increase the risk for developing various psychiatric disorders. Many of the brain regions that are implicated in psychiatric disorders and are vulnerable to the effects of stress are also involved in mediating emotional learning. Emotional learning has been a subject of intense investigation for the past 30 years, with the vast majority of studies focusing on the amygdala and its role in associative fear learning. However, the mechanisms by which stress affects the amygdala and amygdala-dependent fear memories remain unclear. Here we review the literature on the enhancing effects of acute and chronic …