Neuroscience and Neurobiology Commons^™

Understanding Melatonin Receptor Pharmacology: Latest Insights From Mouse Models, And Their Relevance To Human Disease, Gianluca Tosini, Sharon Owino, Jean Luc Guillaume, Ralf Jockers

Neuroscience: Faculty Publications

Melatonin, the neuro-hormone synthesized during the night, has recently seen an unexpected extension of its functional implications toward type 2 diabetes development, visual functions, sleep disturbances, and depression. Transgenic mouse models were instrumental for the establishment of the link between melatonin and these major human diseases. Most of the actions of melatonin are mediated by two types of G protein-coupled receptors, named MT1 and MT2, which are expressed in many different organs and tissues. Understanding the pharmacology and function of mouse MT1 and MT2 receptors, including MT1/MT2 heteromers, will be of crucial importance to evaluate the relevance of these mouse …

Gbetagamma-Microtubule Mediated Mechanism Of Neuronal Differentiation, Jorge Anibal Sierra Fonseca

Open Access Theses & Dissertations

Neurodegeneration, a progressive loss of nerve cells (neurons), occurs in many neurological disorders, including Alzheimer's and Parkinson's diseases, as well as in the aging brain. Disruption of microtubules in neurons and the aggregation of proteins associated with them is the hallmark of neurodegeneration. Nevertheless, the cause of this disorder is largely unknown, and no effective drugs are available to treat the disease processes. Therefore, there is a need to understand the molecular mechanisms that drive the assembly and disassembly of microtubules during neurite outgrowth and differentiation. Evidence suggests that nerve growth factor (NGF) induces neurite outgrowth from PC12 cells by …

Examining The Intersection Of The Cognitive Advantages And Disadvantages Of The Bilingual Brain, Irina Rabkina

Scripps Senior Theses

Two conflicting findings characterize cognitive processing accompanying bilingualism. The “bilingual advantage” refers to improved cognitive performance for bilingual compared to monolingual participants. Most bilingual advantages fall under the umbrella of cognitive control mechanisms, most frequently demonstrated using the Stroop task and the Simon task (e.g., Bialystok, 2008; Coderre, Van Heuven, & Conklin, 2013). The “bilingual disadvantage,” on the other hand, refers to bilinguals’ diminished performance on tasks that require word retrieval or switching between languages. This study examined the intersection of the bilingual advantage and the bilingual disadvantage to investigate whether they stem from a single cognitive control process. The …

Characterizing A Novel Monoclonal Ampa Receptor 1/2/3 Antibody In The Hippocampus And Prefrontal Cortex Of Rat, Monkey, And Human, Sebastian Aguiar

Pitzer Senior Theses

The excitatory, ionotropic glutamatergic AMPA receptor is the most common membrane-bound receptor in the central nervous system. AMPARs and the NMDA receptors are central to synaptic plasticity, memory, and mechanisms of neurodegeneration. The AMPAR is an obligate heterotetramer, composed of subunits GluA1-4. Subunit permutation determines ion conductance, trafficking and other functional characteristics. Few available antibodies are subunit-specific, disabling researchers from accurately visualizing differential AMPAR subunit distribution in the nervous system. This study sought to visualize a novel monoclonal GluA1/2/3 antibody with functional avidity for three of four receptor subunits and to characterize the ultrastructural localization of these receptors using confocal …

Calpain 5: A Non-Classical Calpain Highly Expressed In The Cns And Localized To Mitochondria And Nuclear Pml Bodies, Ranjana Singh

Theses and Dissertations--Neuroscience

Calpain 5 (CAPN5) is a non-classical member of the calpain family. It lacks the EF-hand motif characteristic of the classical calpains, calpain 1 and 2, but retains catalytic and Ca²⁺ binding non EF domains. Tra-3, an ortholog of CAPN5, is involved in necrotic cell death in C.elegans; although specific role of CAPN5 has not been investigated in the mammalian CNS. I compared relative mRNA levels of calpains in rat CNS, which revealed that CAPN5 is the second most highly expressed calpain. We examined relative levels of CAPN5 from late embryonic day 18 to postnatal day 90 and …

Immunotherapy In Combination With Behavioral Enrichment In A Canine Model Of Aging, Paulina R. Davis

Theses and Dissertations--Pharmacology and Nutritional Sciences

Alzheimer’s disease (AD) is characterized by cognitive decline and hallmark neuropathology, including β-amyloid (Aβ). Therapeutic strategies for AD are focusing on reducing Aβ. Canines develop Aβ neuropathology and cognitive decline with age similar to AD patients. In previous studies, immunization with Aβ1-42 (VAC) in aged canines decreased brain Aβ but did not improve cognition. Behavioral enrichment (ENR) improved cognition without reducing brain Aβ. We hypothesized that VAC combined with ENR would provide cognitive benefits and reduce Aβ neuropathology, as compared individual VAC and ENR treatments. Aged beagles were placed into groups: control, VAC with fibrillar Aβ1-42, ENR, and combination treatment …

Flavonoids With Novel Nicotinic Activity As Potential Pharmacotherapies To Treat Ethanol-Induced Neurotoxicity, Joseph A. Lutz

Theses and Dissertations--Pharmacy

Ethanol causes neurotoxicity via several mechanisms at different points in the cycle of dependence, including neuroinflammation and oxidative stress during ethanol exposure as well as excitotoxicity during ethanol withdrawal. The primary therapeutic implication is that ethanol-induced neurotoxicity requires multifunctional pharmacotherapies which reduce all mechanisms. Using an innovative pharmacological high throughput screening method on a large plant extract library we discovered flavonoids with alpha7 nicotinic acetylcholine receptor (nAChR) activity. In addition to their well-known anti-inflammatory and antioxidant properties, this novel activity means they can potentially reduce excitotoxicity and therefore makes them ideal for inhibition of ethanol-induced neurotoxicity. Rhamnetin, the candidate compound, …

An In Vivo Assay For Simultaneous Monitoring Of Neuronal Activity And Behavioral Output In The Stomatogastric Nervous System Of Decapod Crustaceans, Wolfgang Stein, Florian Diehl

Faculty Publications – Biological Sciences

Central pattern generators (CPGs) generate rhythmic output patterns and drive vital behaviors such as breathing, swallowing, locomotion and chewing ^1-10. While most insights into the rhythm generating mechanisms of CPGs have been derived from isolated nervous system preparations, the relationship between neural activity and corresponding behavioral expression is often unclear. The stomatogastric system of decapod crustaceans is one of the best characterized neural system for motor pattern generation ^9-12 and many mechanisms of motor pattern generation and selection have been discovered in this system. Since most studies are limited to the isolated nervous system, little is known about the …

Phosphodiesterase Inhibition And Adenosine A2b Receptor Signaling In Mitochondrial Function: Pharmacology And Toxicology Of 3-Isobutyl 1-Methylxanthine (Ibmx) In The 661w Retina-Derived Cell Line, Anthony Presley Leonard

MUSC Theses and Dissertations

3-isobutyl 1-methylxanthine (IBMX) is a commonly used inhibitor of cyclic nucleotide phosphodiesterases (PDE) and G protein coupled adenosine receptors. Administration of IBMX to retina photoreceptor-derived 661w cell line results in decreased mitochondrial respiration followed by cell death, mimicking phenomena observed in inherited retina neurodegeneration in humans and animals and thus suggesting their use as a cell-based model of retina degeneration. In this dissertation, the temporal relationship between pathways altered by IBMX and how these pathways affect mitochondrial physiology are evaluated. These studies utilize a novel high content microscopic method for simultaneously measuring mitochondrial morphology and membrane potential in living cultured …

Aiming Attention Using Selective Stimulation Of Locus Coeruleus And Its Medial Prefrontal Efferents, Zackary A. Cope

MUSC Theses and Dissertations

Appropriate modification of behavior in response to dynamic environmental conditions is essential for the adaptation and survival of most biological organisms. This adaptability allows for organisms to maximize the benefit of behavior related energy expenditure (utility) while minimizing cost. Modern theories of locus coeruleus (LC) function implicate a pivotal role for the noradrenergic (NA) nucleus in mediating switches between focused behavior during periods of high utility (exploit) versus disengagement of behavior and exploration of other, more rewarding opportunities. Two modes of activity in LC neurons have been well characterized. During periods of accurate and focused behavior, LC neurons exhibit suppressed …

Genetic Algorithm With Logistic Regression For Prediction Of Progression To Alzheimer's Disease, Piers Johnson, Luke Vandewater, William Wilson, Paul Maruff, Greg Savage, Petra Graham, Lance S. Macaulay, Kathryn A. Ellis, Cassandra Szoeke, Ralph N. Martins, Christopher Rowe, Colin L. Masters, David Ames, Ping Zhang

Research outputs 2014 to 2021

Assessment of risk and early diagnosis of Alzheimer's disease (AD) is a key to its prevention or slowing the progression of the disease. Previous research on risk factors for AD typically utilizes statistical comparison tests or stepwise selection with regression models. Outcomes of these methods tend to emphasize single risk factors rather than a combination of risk factors. However, a combination of factors, rather than any one alone, is likely to affect disease development. Genetic algorithms (GA) can be useful and efficient for searching a combination of variables for the best achievement (eg. accuracy of diagnosis), especially when the search …

The Benefits Of Breastfeeding, Avery Kordus

Senior Honors Theses

Breastfeeding research is plentiful, and the majority of the literature shows that breast milk is the superior form of infant nutrition except in the rare circumstances of infant metabolic disorders, maternal drug use, or positive HIV status. In comparison to formula, breast milk provides improved cognition, development, behavior, bonding, nutrition, digestion, immunity, and long-term health with fewer diseases and conditions in infants. Mothers are benefited by breastfeeding through bonding, faster weight loss, and reduction in certain cancers and conditions. Breast milk contains the proper amount of carbohydrates, fats, proteins, vitamins, and minerals, and is also specialized for each infant and …

Mechanisms To Mitigate Neurodegeneration By Maintaining Mitochondrial Health, Parijat Kabiraj

Open Access Theses & Dissertations

Cerebral accumulation of amyloidogenic protein aggregates is most frequently observed in the pathogenesis of neurodegenerative diseases. Recent studies showed prion like spreading of beta amyloid (A beta) in Alzheimer's disease (AD) and alpha synuclein protein in Parkinson's disease (PD) brain. Failure or compromise to the chaperone activity of protein disulfide isomerase (PDI) is also been reported as a major factor of aggregate formation. Nitrosative stress mediated S-nitrosylation (SNO) of protein disulfide isomerase (PDI), a housekeeping oxidoreductase, has been implicated in the pathogenesis of sporadic PD and AD. Mitochondrial dysfunction, leading to elevated levels of reactive oxygen species (ROS), is associated …

Leptin Resistance Induced Obesity And Diabetes Promote Neuropathological Changes In The Aging Brain, Thomas Platt

Theses and Dissertations--Molecular and Cellular Biochemistry

The aging brain is prone to the development of pathology and dementia. With a rapidly growing elderly population diagnoses of neurodegenerative diseases, such as Alzheimer’s disease (AD), frontotemporal dementia (FTD), and Parkinson’s disease are on the rise. Additionally, diabetes and obesity are linked to an increased risk of dementia. The convergence of this increasingly aged population with the obesity and diabetes epidemic give rise to new concerns regarding the future of prevention and treatment of neurodegenerative diseases. Our lab has previously shown that leptin, an adipokine involved in signaling satiety to the hypothalamus, can modulate the generation of the amyloid …

Investigating The Effects Of Applied Electric Fields On Microglial Cell Behaviour, Eman Bani

Theses and Dissertations

As surveyors of the central nervous system (CNS), microglial cells play an integral part in the inflammatory response following traumatic injuries. Thus, they have been implicated in the limited capability of neurons to regenerate in the CNS. Additionally, the roles of endogenous electric fields in the regenerative process of neurons in the mammalian peripheral nervous system (PNS) or amphibian CNS have long been studied. Further, previous studies in our lab have shown that physiological electric fields are capable of directing behaviours in astrocytes and schwann cells. Therefore in this study, a BV-2 microglia cell line was utilized to investigate whether …

The Camkkβ Inhibitor Sto-609 Causes Artefacts In Ca2+ Imaging And Selectively Inhibits Bkca In Mouse Carotid Body Type I Cells, Jennifer G. Jurcsisn

Browse all Theses and Dissertations

It has previously been reported that AMP-activated protein kinase (AMPK) may be critical for hypoxic chemotransduction in carotid body type I cells (Wyatt et al, 2007). This study sought to determine the importance of the regulatory upstream kinase of AMPK, CamKKβ, in the acute response to hypoxia in isolated mouse type I cells.

Initial studies indicated several previously unreported artefacts associated with using the CamKKβ inhibitor STO-609 and calcium imaging techniques. Strong STO-609 autofluorescence meant that Fura-2 could not be used and X-Rhod-1 imaging revealed that STO-609 quenched fluorescence even in the absence of intracellular Ca2+. The whole-cell configuration of …

Investigating Anatomical And Molecular Aspects Of Proprioceptive Sensory Neuron Diversity Using A Transgenic Mouse Model, Martha Jean Sonner

Browse all Theses and Dissertations

Muscle spindles (MS) and Golgi tendon organs (GTOs) are encapsulated, stretch-activated sensory receptors housed within skeletal muscles, yet their functional contributions to proprioceptive monitoring of limb movements are quite different. For example, MS are responsible for detecting stretch of muscle fibers, and GTOs provide feedback regarding muscle tension during contraction. Peripheral axons extending from proprioceptive sensory neurons (PSNs) in the dorsal root ganglia supply MS and GTOs. MS are innervated by Group Ia and II sensory fiber endings, while GTOs are innervated by a single Group Ib sensory fiber. The developmental processes guiding axons from PSNs to their targets and …

Effects Of Transcranial Direct Current Stimulation On Expression Of Immediate Early Genes (Ieg's), Jessica Wagner

Browse all Theses and Dissertations

Transcranial direct current stimulation (tDCS) has been utilized in human studies to modulate a multitude of psychological, cognitive, and psychiatric disorders. There have been positive behavioral results in human subjects but our knowledge of biological processes occurring during stimulation to elicit behavioral outcomes is limited. Our study utilizes a rodent tDCS (R-tDCS) model in which Sprague Dawley rats receive tDCS in order to examine whether tDCS affects neuronal activation. We examined two immediate early genes (IEG's), cFos and zif268, in order to discern if tDCS affects neuronal activation. Our findings indicate that tDCS does affect neuronal activation by means of …

Dopaminergic And Activity-Dependent Modulation Of Mechanosensory Responses In Drosophila Melanogaster Larvae, Josh S. Titlow

Theses and Dissertations--Biology

A central theme of this dissertation is nervous system plasticity. Activity-dependent plasticity and dopaminergic modulation are two processes by which neural circuits adapt their function to developmental and environmental changes. These processes are involved in basic cognitive functions and can contribute to neurological disorder. An important goal in modern neurobiology is understanding how genotypic variation influences plasticity, and leveraging the quantitative genetics resources in model organisms is a valuable component of this endeavor. To this end I investigated activity-dependent plasticity and dopaminergic modulation in Drosophila melanogaster larvae using neurobiological and genetic approaches.

Larval mechanosensory behavior is described in Chapter 2. …

Variance Predicts Salience In Central Sensory Processing, Ann M. Hermundstad, John J. Briguglio, Mary M. Conte, Jonathan D. Victor, Vijay Balasubramanian, Gašper Tkačik

Publications and Research

Information processing in the sensory periphery is shaped by natural stimulus statistics. In the periphery, a transmission bottleneck constrains performance; thus efficient coding implies that natural signal components with a predictably wider range should be compressed. In a different regime—when sampling limitations constrain performance—efficient coding implies that more resources should be allocated to informative features that are more variable. We propose that this regime is relevant for sensory cortex when it extracts complex features from limited numbers of sensory samples. To test this prediction, we use central visual processing as a model: we show that visual sensitivity for local multi-point …

The Effects Of Anxiety On Sensory Gating, Jonathon Meier

Honors Projects

Sensory gating is a proposed important physiological process of inhibiting neuronal responses of repetitious stimuli in the central nervous system to allocate more cognitive resources to additional salient information. Sensory gating is currently being studied to better understand psychiatric illnesses, especially those characterized by emotional changes and the inability to concentrate such as schizophrenia, ADHD, anxiety disorder, and Parkinson’s. Anxiety is a strong feeling of nervousness that occurs in all individuals at varying degrees and is associated with detrimental health effects as well as hindering concentration. Numerous brain regions are associated with anxiety levels such as the anterior limbic system, …

Neuroscientists In Court, Owen D. Jones, Anthony D. Wagner, David L. Faigman, Marcus E. Raichle

Vanderbilt Law School Faculty Publications

Neuroscientific evidence is increasingly being offered in court cases. Consequently, the legal system needs neuroscientists to act as expert witnesses who can explain the limitations and interpretations of neuroscientific findings so that judges and jurors can make informed and appropriate inferences. The growing role of neuroscientists in court means that neuroscientists should be aware of important differences between the scientific and legal fields, and, especially, how scientific facts can be easily misunderstood by non-scientists,including judges and jurors.

This article describes similarities, as well as key differences, of legal and scientific cultures. And it explains six key principles about neuroscience that …

Methods For Integrative Analysis Of Genomic Data, Paul Manser

Theses and Dissertations

In recent years, the development of new genomic technologies has allowed for the investigation of many regulatory epigenetic marks besides expression levels, on a genome-wide scale. As the price for these technologies continues to decrease, study sizes will not only increase, but several different assays are beginning to be used for the same samples. It is therefore desirable to develop statistical methods to integrate multiple data types that can handle the increased computational burden of incorporating large data sets. Furthermore, it is important to develop sound quality control and normalization methods as technical errors can compound when integrating multiple genomic …

Quantification Of Protoporphyrin Ix Accumulation In Glioblastoma Cells – A New Technique, John E Lawrence

Journal Articles

5-Aminolevulinic Acid (5-ALA) is a precursor of heme synthesis. A metabolite, protoporphyrin IX (PpIX), selectively accumulates in neoplastic tissue including glioblastoma. Presurgical administration of 5-ALA forms the basis of fluorescence-guided resection (FGR) of glioblastoma (GBM) tumors. However, not all gliomas accumulate sufficient quantities of PpIX to fluoresce, thus limiting the utility of FGR. We therefore developed an assay to determine cellular and pharmacological factors that impact PpIX fluorescence in GBM. This assay takes advantage of a GBM cell line engineered to express yellow fluorescent protein. Methods. The human GBM cell line U87MG was transfected with a YFP expression vector. After …

Testing A Structural Equation Model Of Language-Based Cognitive Fitness, Elizabeth Ann Moxley-Paquette

Walden Dissertations and Doctoral Studies

The normative development of language is often taken for granted, yet problems with language development can result in stress for the individual and family. A challenge with these language development problems lies within the contemporary education system, which assumes that children have appropriate skills when they begin school. The purpose of the study was to test a theoretical model of language readiness known as language-based cognitive fitness, which includes measures associated with structural concepts of language involving receptive language, expressive language, spontaneous narrative speech, and writing fluency. The sample included children from a private school who received an extensive battery …

Inhibition Of Phosphodiesterase10a Attenuates Morphine-Induced Conditioned Place Preference, Ying Mu, Zhaoxiang Ren, Jia Jia, Bo Gao, Longtai Zheng, Eitan Friedman

Publications and Research

Background: Phosphodiesterase (PDE) 10A is selectively expressed in medium spiny neurons of the striatum. Nucleus accumbens (NAc) is a key region that mediates drug reward and addiction-related behaviors. To investigate the potential role of PDE10A in the reinforcement properties of morphine, we tested the effect of MP-10, a selective inhibitor of PDE10A, on acquisition, expression, and extinction of morphine-induced conditioned place preference (CPP).

Results: The results show that 2.5 mg/kg MP-10, administered subcutaneously, significantly inhibited the acquisition of morphine-induced CPP. The same dose of MP-10 alone did not result in the CPP. Moreover, MP-10 did not alter the expression of …

The Molecular Components Of Estrogen Receptor Beta (Erβ) Signaling In Neuronal Sytems, Natasha Mott

Dissertations

With increasing life expectancy, women are now living upwards of 50 years without circulating estrogens, therefore, it is essential to investigate how the brain is changed by estrogen deprivation and also how aging influences these changes. The Women's Health Initiative (WHI) study spurred rigorous debate regarding estrogen therapy for postmenopausal women due to dichotomous effects of estrogens in menopausal and post-menopausal women. Meta-analyses of the WHI study revealed that after circulating estrogens are depleted for many years re-exposure may cause aberrant, negative health effects, indicating that there is an age-related `switch' in estrogen signaling around menopause. These age-related effects of …

A Systems Biology Approach To Detect Eqtls Associated With Mirna And Mrna Co-Expression Networks In The Nucleus Accumbens Of Chronic Alcoholic Patients, Mohammed Mamdani

Theses and Dissertations

Alcohol Dependence (AD) is a chronic substance use disorder with moderate heritability (60%). Linkage and genome-wide association studies (GWAS) have implicated a number of loci; however, the molecular mechanisms underlying AD are unclear. Advances in systems biology allow genome-wide expression data to be integrated with genetic data to detect expression quantitative trait loci (eQTL), polymorphisms that regulate gene expression levels, influence phenotypes and are significantly enriched among validated genetic signals for many commonly studied traits including AD.

We integrated genome-wide mRNA and miRNA expression data with genotypic data from the nucleus accumbens (NAc), a major addiction-related brain region, of 36 …

Psychotherapy And The Embodiment Of The Neuronal Identity: A Hermeneutic Study Of Louis Cozolino's (2010) The Neuroscience Of Psychotherapy: Healing The Social Brain , Ari Simon Natinsky

Antioch University Dissertations & Theses

In recent years, there have been several ways in which researchers have attempted to integrate psychotherapy and neuroscience research. Neuroscience has been proposed as a method of addressing lingering questions about how best to integrate psychotherapy theories and explain their efficacy. For example, some psychotherapy outcome studies have included neuroimaging of participants in order to propose neurobiological bases of effective psychological interventions (e.g., Paquette et al., 2003). Other theorists have used cognitive neuroscience research to suggest neurobiological correlates of various psychotherapy theories and concepts (e.g., Schore, 2012). These efforts seem to embody broader historical trends, including the hope that neuroscience …

Predictable And Predictive Emotions: Explaining Cheap Signals And Trust Re-Extension, Eric Schniter, Roman M. Sheremeta

ESI Publications

Despite normative predictions from economics and biology, unrelated strangers will often develop the trust necessary to reap gains from one-shot economic exchange opportunities. This appears to be especially true when declared intentions and emotions can be cheaply communicated. Perhaps even more puzzling to economists and biologists is the observation that anonymous and unrelated individuals, known to have breached trust, often make effective use of cheap signals, such as promises and apologies, to encourage trust re-extension. We used a pair of trust games with one-way communication and an emotion survey to investigate the role of emotions in regulating the propensity to …