Neuroscience and Neurobiology Commons^™

Meyer Navigator: User Scanimage Functions To Show X/Y Positions Of The Stage/Objective In A Coordinate System, Stephan Meyer Zum Alten Borgloh

Gilbert Laboratory

These Matlab functions extend Janelia Farms' ScanImage microscope control software. The functions allow the user to view, mark and track positions of the motor stage/objective in x, y, and z, which get displayed in a separate window. This helps to keep track of the stage movements, regions of interest and makes it easy to document areas imaged and map out the specimen being investigated. For detailed information about the functionality as well as installation, view the included manual file.

The Expanding Genomic Landscape Of Autism: Discovering The 'Forest' Beyond The 'Trees', Valerie Wailin Hu

Biochemistry and Molecular Medicine Faculty Publications

Autism spectrum disorders (ASDs) are neurodevelopmental disorders characterized by significant deficits in reciprocal social interactions, impaired communication, and restricted, repetitive behaviors. Because ASDs are among the most heritable of neuropsychiatric disorders, much of autism research has focused on the search for genetic variants in protein-coding genes (i.e., the "trees"). However, no single gene can account for more than 1% of the cases of ASD. Yet, genome-wide association studies have often identified statistically significant associations of genetic variations in regions of DNA that do not code for proteins (i.e., intergenic regions). There is increasing evidence that such noncoding regions are actively …

Microglial Activation Decreases Retention Of The Protease Inhibitor Saquinavir: Implications For Hiv Treatment, Shannon Dallas, Michelle L. Block, Deborah M. Thompson, Marcelo G. Bonini, Patrick T. Ronaldson, Reina Bendayan, David S. Miller

Anatomy and Neurobiology Publications

Background

Active HIV infection within the central nervous system (CNS) is confined primarily to microglia. The glial cell compartment acts as a viral reservoir behind the blood-brain barrier. It provides an additional roadblock to effective pharmacological treatment via expression of multiple drug efflux transporters, including P-glycoprotein. HIV/AIDS patients frequently suffer bacterial and viral co-infections, leading to deregulation of glial cell function and release of pro-inflammatory mediators including cytokines, chemokines, and nitric oxide.

Methods

To better define the role of inflammation in decreased HIV drug accumulation into CNS targets, accumulation of the antiretroviral saquinavir was examined in purified cultures of rodent …

Seeded Propagation Of Tau Fibrils, Paul David Dinkel

Electronic Theses and Dissertations

In various neurodegenerative diseases, including Alzheimer's disease, progressive supranuclear palsy, Pick's disease, and corticobasal degeneration, the deposition of fibrils composed of misfolded tau protein is observed. Recent evidence suggests that tau fibrils transfer between cells and spread throughout the brain, underscoring the significance of fibril propagation.

Six tau isoforms exist in the adult human brain that can be grouped into 4-repeat (4R) tau and 3-repeat (3R) tau based on the presence or absence of the second of four microtubule binding repeats. We demonstrate in vitro that seeded fibril growth, a prerequisite for the spreading of the tau pathology, is crucially …

Nocturnal Diaphoresis Secondary To Mild Obstructive Sleep Apnea In A Patient With A History Of Two Malignancies, Robert Daniel Vorona, Mariana Szklo-Coxe, Mark Fleming, J. Catesby Ware

Community & Environmental Health Faculty Publications

Numerous medical disorders, including obstructive sleep apnea, may cause nocturnal diaphoresis. Previous work has associated severe obstructive sleep apnea with nocturnal diaphoresis. This case report is of import as our patient with severe nocturnal diaphoresis manifested only mild sleep apnea, and, for years, his nocturnal diaphoresis was ascribed to other causes, i.e., first prostate cancer and then follicular B-cell lymphoma. Additionally, it was the nocturnal diaphoresis and not more common symptoms of obstructive sleep apnea, such as snoring, that led to the definitive diagnosis of his sleep apnea and then to treatment with a gratifying resolution of his onerous symptom.

Isoform-Specific Effects Of Apoe On Neurite Outgrowth In Olfactory Epithelium Culture, Aseem Hussain, Minh Luong, Apryl Pooley, Britto P. Nathan

Faculty Research & Creative Activity

The apolipoprotein E4 (apoE4) genotype is a major risk factor for developing late-onset Alzheimer’s disease (AD). Inheritance of apoE4 is also associated with impairments in olfactory function in early stages of AD. In this project we examined the effects of the three common isoforms of human apoE (apoE2, apoE3, and apoE4) on neuronal differentiation and neurite outgrowth in explant cultures of mouse olfactory epithelium (OE).

Isoform-Specific Effects Of Apoe On Neurite Outgrowth In Olfactory Epithelium Culture, Aseem Hussain, Minh Luong, Apryl Pooley, Britto Nathan

Faculty Research & Creative Activity

The apolipoprotein E4 (apoE4) genotype is a major risk factor for developing late-onset Alzheimer’s disease (AD). Inheritance of apoE4 is also associated with impairments in olfactory function in early stages of AD. In this project we examined the effects of the three common isoforms of human apoE (apoE2, apoE3, and apoE4) on neuronal differentiation and neurite outgrowth in explant cultures of mouse olfactory epithelium (OE).

A One-Hour Sleep Restriction Impacts Brain Processing In Young Children Across Tasks: Evidence From Event-Related Potentials, Dennis Molfese, Anna Ivanenko, Alexandra P.F. Key, Adrienne Roman, Victoria J. Molfese, Louise M. O'Brien, David Gozal, Srinivas Kota, Caitlin M. Hudac

Center for Brain, Biology, and Behavior: Faculty Publications

The effect of mild sleep restriction on cognitive functioning in young children is unclear, yet sleep loss may impact children's abilities to attend to tasks with high processing demands. In a preliminary investigation, six children (6.6 - 8.3 years of age) with normal sleep patterns performed three tasks: attention (“Oddball”), speech perception (conconant-vowel syllables) and executive function (Directional Stroop). Event-related potentials (ERP) responses were recorded before (Control) and following one-week of 1-hour per day of sleep restriction. Brain activity across all tasks following Sleep Restriction differed from activity during Control Sleep, indicating that minor sleep restriction impacts children's neurocognitive functioning.

Normative Topographic Erp Analyses Of Speed Of Speech Processing And Grammar Before And After Grammatical Treatment, Paul J. Yoder, Dennis Molfese, Micah M. Murray, Alexandra P.F. Key

Center for Brain, Biology, and Behavior: Faculty Publications

Typically developing (TD) preschoolers and age-matched preschoolers with specific language impairment (SLI) received event-related potentials (ERPs) to four monosyllabic speech sounds prior to treatment and, in the SLI group, after 6 months of grammatical treatment. Before treatment, the TD group processed speech sounds faster than the SLI group. The SLI group increased the speed of their speech processing after treatment. Post-treatment speed of speech processing predicted later impairment in comprehending phrase elaboration in the SLI group. During the treatment phase, change in speed of speech processing predicted growth rate of grammar in the SLI group.

Loss Of Dendritic Inhibition In The Hippocampus After Repeated Early-Life Hyperthermic Seizures In Rats., Richard Boyce, L Stan Leung

Physiology and Pharmacology Publications

Seizures are relatively common in children and are a risk factor for subsequent temporal lobe epilepsy. To investigate whether early-life seizures themselves are detrimental to the proper function of the adult brain, we studied whether dendritic excitation and inhibition in the hippocampus of adult rats were altered after hyperthermia-induced seizures in immature rats. In particular, we hypothesized that apical dendritic inhibition in hippocampal CA1 pyramidal cells would be disrupted following hyperthermia-induced seizures in early life. Seizure rats were given three hyperthermia-induced seizures per day for three days from postnatal day (PND) 13 to 15; control rats were handled similarly but …

The Control Of Crawling Movement By Interneuron Circuits Of The Drosophila Larva, Mary Sweet

Honors Theses, 1963-2015

The organization of the human brain is extremely complex. Therefore, scientists have relied upon model organisms like the fruit fly Drosophila melanogaster for nervous system studies, because these organisms are less complex and can be experimentally manipulated with genetic tools. In this study, we focus on fruit fly larval crawling behavior and how it can be altered by the manipulation of subsets of neurons that may be involved in generating crawling behavior. Eight subsets were tested and all of them were found to limit normal larval crawling behavior to some degree. The elucidation of these subsets will help us to …

The Effect Of Visual Wulst Lesions And Trigeminal Nerve Sectioning On The Discrimination Of Magnetic Inclination In The Homing Pigeon (Columba Livia), Merissa Acerbi

Honors Projects

The ability of homing pigeons to return to their loft from unknown places has fascinated scientists for centuries. It is well established that homing pigeons, like migratory birds, posses an innate magnetic inclination compass to determine direction by measuring the angle between the magnetic field vector and the Earth's surface. Recent work has indicated that the avian magnetic compass is light mediated and appears to mediate magnetic information to the brain. This occurs via a visual pathway with processing in the visual Wulst area of the forebrain. There is, however, also evidence from other avian species that magnetic direction may …

The Effects Of Acute Nicotine Administration On Memory Formation And Neural Activity In The Hippocampus, Perirhinal Cortex, And Medial Septum: Implications For Neurodegenerative Disorders, Matthew Wishnoff

Behavioral Neuroscience Honors Papers

Within the general public, nicotine is commonly thought of as a harmful molecule due to its role in tobacco addiction. However, nicotinic stimulation of the cholinergic system has also been shown to enhance cognitive functioning. This enhancement is thought to be caused by an increase in the release of the neurotransmitter, acetylcholine (ACh), which is responsible for mediating a variety of cognitive processes, such as REM sleep and memory formation. Recent research by Melichercik and colleagues shows that systemic nicotine administration enhances memory acquisition for both object location and object recognition memory in rats, as assessed by a modified version …

Combined Effects Of Rearing Environment And Lead (Pb2+) Exposure On Visuospatial Learning And Memory In Rats, Nicholas Tolman

Behavioral Neuroscience Honors Papers

Critical periods of neural development occur during early postnatal life that correspond with increases in synaptic plasticity and the formation of neural circuits needed for learning and memory. This development can be profoundly influenced by experience and negatively affected by environmental toxins. Environmental enrichment and lead exposure inversely affect mediators of synaptic plasticity, which suggests that enrichment may have an attenuating effect on lead induced cognitive deficits. A wealth of evidence has indicated that exposure to excessive amounts of inorganic Pb2+ during early development can produce long lasting cognitive deficits in humans. Evidence also suggests that children raised in an …

Impairment Of Trkb-Psd-95 Signaling In Angelman Syndrome, Cong Cao, Mengia S. Rioult-Pedotti, Paolo Migani, Crystal J. Yu, Rakesh Tiwari, Keykavous Parang, Mark R. Spaller, Dennis J. Goebel, John Marshall

Pharmacy Faculty Articles and Research

Angelman syndrome (AS) is a neurodevelopment disorder characterized by severe cognitive impairment and a high rate of autism. AS is caused by disrupted neuronal expression of the maternally inherited Ube3A ubiquitin protein ligase, required for the proteasomal degradation of proteins implicated in synaptic plasticity, such as the activity-regulated cytoskeletal-associated protein (Arc/Arg3.1). Mice deficient in maternal Ube3A express elevated levels of Arc in response to synaptic activity, which coincides with severely impaired long-term potentiation (LTP) in the hippocampus and deficits in learning behaviors. In this study, we sought to test whether elevated levels of Arc interfere with brain-derived neurotrophic factor (BDNF) …

Paved With Good Intentions: Sentencing Alternatives From Neuroscience And The Policy Of Problem-Solving Courts, Emily R. Murphy

Faculty Scholarship

No abstract provided.

Regulation Of The Glycine Transporter 1 (Glyt1) By Pkca-Dependent Ubiquitination, Susana Barrera

Open Access Theses & Dissertations

Glycine is one of the major inhibitory neurotransmitters in the central nervous system. It is implicated in the regulation of motor-sensory function such as; pain perception, reflex responses, and is essential for early development of the CNS. In addition to its inhibitory actions, it acts as an obligatory co-agonist for the activation of glutamatergic NMDARs, which are of pivotal importance in the process of learning and memory, its dysfunction leads to several neurodegenerative diseases. Two high affinity Na+/Cl- dependent transporters GlyT1 and GlyT2 tightly regulate the availability of glycine present at the synapse for the activation of NMDARs and GlyRs. …

Aβ Alters The Dna Methylation Status Of Cell-Fate Genes In An Alzheimer’S Disease Model, Gary D. Isaacs, Noor Taher, Courtney Mckenzie, Rebecca Garrett, Matthew Baker, Nena Fox

Faculty Publications and Presentations

Alzheimer’s disease (AD) is characterized by neurofibrillary tangles and extracellular amyloid-β plaques (Aβ). Despite ongoing research, some ambiguity remains surrounding the role of Aβ in the pathogenesis of this neurodegenerative disease. While several studies have focused on the mutations associated with AD, our understanding of the epigenetic contributions to the disease remains less clear. To that end, we determined the changes in DNA methylation in differentiated human neurons with and without Aβ treatment. We isolated the DNA from neurons treated with Aβ or vehicle, and digested the two samples with either a methylation-sensitive (HpaII) or a methylation-insensitive (MspI) restriction endonuclease. …

Structure-Activity Relationship Of 2,3-Benzodiazepin-4-Ones As Noncompetitive Ampa Receptor Antagonists, Mohammad Shaban Qneibi

Legacy Theses & Dissertations (2009 - 2024)

2,3-Benzodiazepin-4-one (BDZ-11) derivatives are a special group of 2,3-benzodiazepine compounds. These compounds have been previously synthesized as AMPA receptor inhibitors, and they are also potential drugs for the treatment of various neurological diseases involving excessive AMPA receptor activity. AMPA receptors are a subtype of glutamate ion channel proteins and are responsible for the majority of excitatory neurotransmission in the mammalian central nervous system. Specifically, they are critically involved in neuronal development and brain activities, including learning and memory. Overstimulation of AMPA receptors is associated with some neurological diseases such as ALS, stroke and Alzheimer's disease. Despite the fact that hundreds …

Post-Translational Modification Regulates Heterogeneous Nuclear Ribonucleoprotein K Function During Axon Outgrowth In Xenopus Laevis, Erica J. Hutchins

Legacy Theses & Dissertations (2009 - 2024)

The RNA-binding protein, heterogeneous nuclear ribonucleoprotein K (hnRNP K), is required for axon outgrowth. Its suppression in Xenopus embryos causes defects in the translation of mRNAs of multiple cytoskeletal genes. Studies in cell lines have established that hnRNP K shuttles between the nucleus and the cytoplasm to bind and regulate the fates of its target RNAs, from splicing to export and translation. At each step, hnRNP K is regulated through post-translational modifications that alter its nucleic acid and protein interactions, and subcellular localization. Precisely how this happens in developing neurons to coordinate cytoskeletal gene expression with the extracellular signals directing …

Btbr-Fvb Chromosome 4 Congenic Displays Rescue Of Behavior And Neuro-Anatomical Phenotypes, Jessica F. Gracias

Legacy Theses & Dissertations (2009 - 2024)

Autism is commonly called the most genetic of neuropsychiatric disorders. Currently, the only diagnostic test is a behavioral evaluation performed by trained physicians and psychologists. There is an urgent need for biomarkers to diagnose autism instead of just relying on behavior and there is also a need to understand the basis of this disorder. One of the theories is that malformation of the corpus callosum is one of the factors that lead to the behavior deficits seen in autism. This theory is based on the fact that human MRI studies have shown that the corpus callosum is absent or malformed …

Functional Roles Of The Insulin-Regulated Glucose Transporter-4 In The Hippocampus, Jiah Pearson-Leary

Legacy Theses & Dissertations (2009 - 2024)

Although a great deal of research has elucidated both localization and function of many glucose transporters (GluTs) throughout the brain, the function of brain insulin-responsive glucose transporter-4 (GluT4) remains unclear (McEwen & Reagan, 2004). Because type 2 diabetes mellitus (T2DM; insulin resistance, i.e., impaired insulin signaling) is a risk factor for Alzheimer's disease (AD), and because the signaling mechanisms insulin uses to mediate hippocampal processes and memory are unclear, a major purpose of this dissertation was to determine whether hippocampal GluT4, which is responsible for insulin's glucoregulatory and canonical effects in the periphery, is necessary for insulin's effects in the …

The Role Of Progesterone Receptor In The Development Of The Mesocortical Dopaminergic Pathway, Jari Willing

Legacy Theses & Dissertations (2009 - 2024)

The mesocortical dopaminergic pathway, comprised of projections from the ventral tegmental area (VTA) to the prefrontal cortex (PFC), mediates many of the most complex forms of cognitive behaviors and has been associated with clinical disorders such as ADHD and schizophrenia. While this circuit continues to develop throughout much of the lifespan, there is a rapid period of maturation, early in development, in which this circuit is highly sensitive to disruption. Steroid hormone receptors are powerful transcription factors, capable of affecting a variety of neurodevelopmental processes and are expressed in many regions throughout the developing brain. Specifically, the nuclear progesterone receptor …

Peripheral Nerve Injury Is Associated With Chronic, Reversible Changes In Global Dna Methylation In The Mouse Prefrontal Cortex, Maral Tajerian, Sebastian Alvarado, Magali Millecamps, Pascal Vachon, Cecilia Crosby, M. Catherine Bushnell, Moshe Szyf, Laura S. Stone

Publications and Research

Changes in brain structure and cortical function are associated with many chronic pain conditions including low back pain and fibromyalgia. The magnitude of these changes correlates with the duration and/or the intensity of chronic pain. Most studies report changes in common areas involved in pain modulation, including the prefrontal cortex (PFC), and pain-related pathological changes in the PFC can be reversed with effective treatment. While the mechanisms underlying these changes are unknown, they must be dynamically regulated. Epigenetic modulation of gene expression in response to experience and environment is reversible and dynamic. Epigenetic modulation by DNA methylation is associated with …

Effects Of Intranasally Administered Dnsp-11 On The Central Dopamine System Of Normal And Parkinsonian Fischer 344 Rats, James H. Sonne

Theses and Dissertations--Neuroscience

Due to the blood-brain barrier, delivery of many drugs to the brain has required intracranial surgery which is prone to complication. Here we show that Dopamine Neuron Stimulating Peptide 11 (DNSP-11), following non-invasive intranasal administration, protects dopaminergic neurons from a lesion model of Parkinson’s disease in the rat. A significant and dose-dependent increase in an index of dopamine turnover (the ratio of DOPAC to dopamine) was observed in the striatum of normal young adult Fischer 344 rats by whole-tissue neurochemistry compared to vehicle administered controls.

Among animals challenged with a moderate, unilateral 6-hydroxy-dopamine (6-OHDA) lesion of the substantia nigra, those …

Post-Traumatic Sleep Following Diffuse Traumatic Brain Injury, Rachel K. Rowe

Theses and Dissertations--Neuroscience

Traumatic brain injury (TBI) is a major cause of death and disability throughout the world with few pharmacological treatments available for individuals who suffer from neurological morbidities associated with TBI. Cellular and molecular pathological processes initiated at the time of injury develop into neurological impairments, with chronic sleep disorders (insomnia, hypersomnolence) being among the somatic, cognitive and emotional neurological impairments. Immediately post-injury, TBI patients report excessive daytime sleepiness, however, discordant opinions suggest that individuals should not be allowed to sleep or should be frequently awoken following brain injury. To provide adequate medical care, it is imperative to understand the role …

Changes In Sleep Architecture And Cognition With Age And Psychosocial Stress: A Study In Fischer 344 Rats, Heather M. Buechel

Theses and Dissertations--Pharmacology and Nutritional Sciences

Changes in both sleep architecture and cognition are common with age. Typically these changes have a negative connotation: sleep fragmentation, insomnia, and deep sleep loss as well as forgetfulness, lack of focus, and even dementia and Alzheimer’s disease. Research has shown that psychosocial stressors, such as isolation from family and friends or loss of a loved one can also have significant negative effects on sleep architecture and cognitive capabilities. This leaves the elderly in a particularly vulnerable situation: suffering from cognitive decline and sleep dysregulation already, and more likely to respond negatively to psychosocial stressors. Taking all of these factors …

Nmda Receptors In The Dorsal Vagal Complex Of Normal And Diabetic Mice, Eva C. Bach

Theses and Dissertations--Physiology

The dorsal vagal complex (DVC), containing the nucleus of the solitary tract (NTS) and the dorsal motor nucleus of the vagus nerve (DMV), plays a pivotal role in autonomic regulation. Afferent fibers from peripheral organs and higher brain centers synapse in the NTS, which integrates these synaptic connections as well as information from systemically circulating hormones and metabolites. The integrated information is relayed to the dorsal motor nucleus of the vagus nerve (DMV), which in turn, projects motor fibers to elicit parasympathetic control of digestive and other viscera. Physiological functions mediated by the DVC are disrupted in diabetic patients and …

Diet-Induced Obesity: Dopaminergic And Behavioral Mechanisms As Outcomes And Predictors, Vidya Narayanaswami

Theses and Dissertations--Pharmacy

Obesity and drug abuse share common neural circuitries including the mesocoticolimbic and striatal dopamine reward system. In the current study, a rat model of diet-induced obesity (DIO) was used to determine striatal dopamine function, impulsivity and motivation as neurobehavioral outcomes and predictors of obesity. For the outcome study, rats were randomly assigned a high-fat (HF) or a low-fat (LF) diet for 8 wk. Following the 8-wk HF-diet exposure, rats were segregated into obesity-prone and obesity-resistant groups based on maximum and minimum body weight gain, respectively, and neurobehavioral outcomes were evaluated. For the predictor study, neurobehavioral antecedents were evaluated prior to …

Injury Establishes Constitutive Μ-Opioid Receptor Activity Leading To Lasting Endogenous Analgesia And Dependence, Gregory F. Corder

Theses and Dissertations--Physiology

Injury causes increased pain sensation in humans and animals but the mechanisms underlying the emergence of persistent pathological pain states, which arise in the absence of on-going physical damage, are unclear. Therefore, elucidating the physiological regulation of such intractable pain is of exceptional biomedical importance. It is well known that endogenous activation of µ-opioid receptors (MORs) provides relief from acute pain but the consequences of prolonged endogenous opioidergic signaling have not been considered. Here we test the hypothesis that the intrinsic mechanisms of MOR signaling promote pathological sensitization of pain circuits in the spinal cord. We found that tissue inflammation …