Neuroscience and Neurobiology Commons^™

Special Muscles, Annamaria C. Scaccia

Capstones

Special Muscles is a documentary that explores living with Duchenne muscular dystrophy, a fatal degenerative disease that weakens the muscles at an aggressive rate. The film will give an uncensored look at how one family copes with inevitability of the disease and their journey chasing a promising experimental cure.

Special Muscles follows 7-year-old Pietro Scarso and his family as they face the challenges, complications and promise of treating Pietro’s progressive muscle disorder. The film travels from New York to Los Angeles to Philadelphia to document the Scarso family’s race against time as Pietro undergoes a 96-week clinical trial for Eteplirsen, …

Testing The Efficacy Of Lsn2463359, A Metabotropic Glutamate 5 Receptor Positive Allosteric Modulator, In Animal Models Of Schizophrenia, Dierdre M. Freamon

Seton Hall University Dissertations and Theses (ETDs)

For many years the dominant theory surrounding the cause of schizophrenia was focused on elevated dopamine levels found in critical areas of the brain. Recently a new theory has emerged pointing to elevated glutamate levels resulting from hypofunction of NMDA receptors and hypoactivity of GABAergic neurons which normally inhibit glutamatergic cells in a tonic manner. Therefore, while traditional antipsychotics directly block dopamine receptors, some of the newly generated compounds are designed to modulate glutamate to normal levels.

I propose testing the efficacy of the metabotropic glutamate 5 receptor modulator LSN2463359, previously shown to act as an indirect agonist of the …

Reliability And Validity Of Neurobehavioral Function On The Psychology Experimental Building Language Test Battery In Young Adults, Brian J. Piper, Shane Mueller, Alexander R. Geerken, Kyle L. Dixon, Gregory Kroliczak, Reid H. Olsen, Jeremy K. Miller

Michigan Tech Publications

Background. The Psychology Experiment Building Language (PEBL) software consists of over one-hundred computerized tests based on classic and novel cognitive neuropsychology and behavioral neurology measures. Although the PEBL tests are becoming more widely utilized, there is currently very limited information about the psychometric properties of these measures.

Methods. Study I examined inter-relationships among nine PEBL tests including indices of motor-function (Pursuit Rotor and Dexterity), attention (Test of Attentional Vigilance and Time-Wall), working memory (Digit Span Forward), and executive-function (PEBL Trail Making Test, Berg/Wisconsin Card Sorting Test, Iowa Gambling Test, and Mental Rotation) in a normative sample (N = 189, …

Rat Hind Limb Nociceptive Withdrawal Response Depends On Initial Paw Position But Not Stimulus Location, Kimberly Seamon

Senior Honors Projects, 2010-2019

There have been numerous studies in non-human animals on the effect of stimulus location on the NWR and at least a few studies that address the role of initial posture. However, all of these studies were conducted in anesthetized, decerebrated, or spinalized mammals. Since descending modulation and long loop reflexes may influence the NWR, the anesthetized spinalized/decerebrated animal may not be an adequate model of normal animals. Therefore, the primary aim of this study was to determine the effect of the stimulus location and initial paw position on the direction and magnitude of the nociceptive withdrawal response to heat stimulus …

Dbx1 Precursor Cells Are A Source Of Inspiratory Xii Premotoneurons., Ann L. Revill, Nicolas C. Vann, Victoria T. Akins, Andrew Kottick, Paul A. Gray, Christopher A. Del Negro, Gregory D. Funk

Arts & Sciences Articles

All behaviors require coordinated activation of motoneurons from central command and premotor networks. The genetic identities of premotoneurons providing behaviorally relevant excitation to any pool of respiratory motoneurons remain unknown. Recently, we established in vitro that Dbx1-derived pre-Bo¨ tzinger complex neurons are critical for rhythm generation and that a subpopulation serves a premotor function (Wang et al., 2014). Here, we further show that a subpopulation of Dbx1-derived intermediate reticular (IRt) neurons are rhythmically active during inspiration and project to the hypoglossal (XII) nucleus that contains motoneurons important for maintaining airway patency. Laser ablation of Dbx1 IRt neurons, 57% of which …

Compensatory Mechanisms And T Cell Migration In Mouse Models Of Dopaminergic Loss, Kristi M. Anderson

Theses & Dissertations

Parkinson’s disease (PD) is the most common neurodegenerative movement disorder and second most common neurodegenerative disorder. PD is characterized by the selective loss of dopaminergic neurons and dopamine neurotransmitter within the substantia nigra and termini in the striatum. Progressive loss of dopaminergic neurons occurs over many years in PD, and by the time movement disorder symptoms manifest, up to 50-70% of dopaminergic neurons have been lost. Several aspects of PD pathology have been described in detail, but a better understanding of PD progression is needed to develop more efficient treatments.

Motor symptoms associated with PD do not manifest until significant …

Development Of Manganese-Enhanced Magnetic Resonance Imaging (Memri) Methods To Study Pathophysiology Underlying Neurodegenerative Diseases In Murine Models, Aditya N. Bade

Theses & Dissertations

Manganese-enhanced magnetic resonance imaging (MEMRI) opens the great opportunity to study complex paradigms of central nervous system (CNS) in freely behaving animals and reveals new pathophysiological information that might be otherwise difficult to gain. Due to advantageous chemical and biological properties of manganese (Mn²⁺), MEMRI has been successfully applied in the studies of several neurological diseases using translational animal models to assess comprehensive information about neuronal activity, morphology, neuronal tracts, and rate of axonal transport. Although previous studies highlight the potential of MEMRI for brain imaging, the limitations concerning the use of Mn²⁺ in living animals and …

The Temporal Nature Of The Acute Stress Response And Its Impact On Explicit Learning, Steven B. Hutchinson

Electronic Theses and Dissertations

Acute stress is commonly experienced by many throughout their lives. Given the demanding lifestyle of many career paths, it's important to gauge the influence of these stressors upon cognitive performance. The present dissertation focus' upon explicit learning in attempts to explore one avenue of the stress-cognition relationship. The Trier Social Stress Test (TSST) was used as a lab stressor for Experiments 1 and 2, in which participants are asked to give a speech and complete a difficult math task in front of 2 evaluators trained to monitor non-verbal behavior. Experiment 1 investigates the dynamic stress response during the minutes following …

Serotonergic System And Gait: Dorsal Raphe Nucleus As A Control System For Gait, Nahal Farhani

Electronic Thesis and Dissertation Repository

In advanced stages of Parkinson Disease (PD), gait and postural abnormalities emerge. These symptoms are not prominent at early stages of PD despite significant dopaminergic neuronal loss. Gait abnormalities are largely not responsive to levodopa. Therefore, other types of neurons might be responsible for gait abnormalities of the PD.

Since the reticulospinal tract (RET) is mainly implicated in the control of axial muscles, the degeneration of this pathway or populations of neurons controlling this pathway might be responsible for axial symptoms. However, there is limited data about the neurons controlling the RET. Our aim in this study is to delineate …

Animal Cryptochromes Mediate Magnetoreception By An Unconventional Photochemical Mechanism, Robert Gegear, Lauren Foley, Amy Casselman, Steven Reppert

Robert J. Gegear

Understanding the biophysical basis of animal magnetoreception has been one of the greatest challenges in sensory biology. Recently it was discovered that the light-dependent magnetic sense of Drosophila melanogaster is mediated by the ultraviolet (UV)-A/blue light photoreceptor cryptochrome (Cry). Here we show, using a transgenic approach, that the photoreceptive, Drosophila-like type 1 Cry and the transcriptionally repressive, vertebrate-like type 2 Cry of the monarch butterfly (Danaus plexippus) can both function in the magnetoreception system of Drosophila and require UV-A/blue light (wavelength below 420 nm) to do so. The lack of magnetic responses for both Cry types at wavelengths above 420 …

Genetic And Acute Cpeb1 Depletion Ameliorate Fragile X Pathophysiology, Tsuyoshi Udagawa, Natalie Farny, Mira Jakovcevski, Hanoch Kaphzan, Juan Alarcon, Shobha Anilkumar, Maria Ivshina, Jessica Hurt, Kentaro Nagaoka, Vijayalaxmi Nalavadi, Lori Lorenz, Gary Bassell, Schahram Akbarian, Sumantra Chattarji, Eric Klann, Joel Richter

Natalie G. Farny

Fragile X syndrome (FXS), the most common cause of inherited mental retardation and autism, is caused by transcriptional silencing of FMR1, which encodes the translational repressor fragile X mental retardation protein (FMRP). FMRP and cytoplasmic polyadenylation element-binding protein (CPEB), an activator of translation, are present in neuronal dendrites, are predicted to bind many of the same mRNAs and may mediate a translational homeostasis that, when imbalanced, results in FXS. Consistent with this possibility, Fmr1(-/y); Cpeb1(-/-) double-knockout mice displayed amelioration of biochemical, morphological, electrophysiological and behavioral phenotypes associated with FXS. Acute depletion of CPEB1 in the hippocampus of adult Fmr1(-/y) mice …

Navigational Mechanisms Of Migrating Monarch Butterflies, Steven Reppert, Robert Gegear, Christine Merlin

Robert J. Gegear

Recent studies of the iconic fall migration of monarch butterflies have illuminated the mechanisms behind their southward navigation while using a time-compensated sun compass. Skylight cues, such as the sun itself and polarized light, are processed through both eyes and are probably integrated in the brain's central complex, the presumed site of the sun compass. Time compensation is provided by circadian clocks that have a distinctive molecular mechanism and that reside in the antennae. Monarchs might also use a magnetic compass because they possess two cryptochromes that have the molecular capability for light-dependent magnetoreception. Multiple genomic approaches are now being …

Discordant Timing Between Antennae Disrupts Sun Compass Orientation In Migratory Monarch Butterflies, Patrick Guerra, Christine Merlin, Robert Gegear, Steven Reppert

Robert J. Gegear

To navigate during their long-distance migration, monarch butterflies (Danaus plexippus) use a time-compensated sun compass. The sun compass timing elements reside in light-entrained circadian clocks in the antennae. Here we show that either antenna is sufficient for proper time compensation. However, migrants with either antenna painted black (to block light entrainment) and the other painted clear (to permit light entrainment) display disoriented group flight. Remarkably, when the black-painted antenna is removed, re-flown migrants with a single, clear-painted antenna exhibit proper orientation behaviour. Molecular correlates of clock function reveal that period and timeless expression is highly rhythmic in brains and clear-painted …

Antennal Circadian Clocks Coordinate Sun Compass Orientation In Migratory Monarch Butterflies, Christine Merlin, Robert Gegear, Steven Reppert

Robert J. Gegear

During their fall migration, Eastern North American monarch butterflies (Danaus plexippus) use a time-compensated Sun compass to aid navigation to their overwintering grounds in central Mexico. It has been assumed that the circadian clock that provides time compensation resides in the brain, although this assumption has never been examined directly. Here, we show that the antennae are necessary for proper time-compensated Sun compass orientation in migratory monarch butterflies, that antennal clocks exist in monarchs, and that they likely provide the primary timing mechanism for Sun compass orientation. These unexpected findings pose a novel function for the antennae and open a …

Human Cryptochrome Exhibits Light-Dependent Magnetosensitivity, Lauren Foley, Robert Gegear, Steven Reppert

Robert J. Gegear

Humans are not believed to have a magnetic sense, even though many animals use the Earth's magnetic field for orientation and navigation. One model of magnetosensing in animals proposes that geomagnetic fields are perceived by light-sensitive chemical reactions involving the flavoprotein cryptochrome (CRY). Here we show using a transgenic approach that human CRY2, which is heavily expressed in the retina, can function as a magnetosensor in the magnetoreception system of Drosophila and that it does so in a light-dependent manner. The results show that human CRY2 has the molecular capability to function as a light-sensitive magnetosensor and reopen an area …

Defining Behavioral And Molecular Differences Between Summer And Migratory Monarch Butterflies, Haisun Zhu, Robert Gegear, Amy Casselman, Sriramana Kanginakudru, Steven Reppert

Robert J. Gegear

BACKGROUND: In the fall, Eastern North American monarch butterflies (Danaus plexippus) undergo a magnificent long-range migration. In contrast to spring and summer butterflies, fall migrants are juvenile hormone deficient, which leads to reproductive arrest and increased longevity. Migrants also use a time-compensated sun compass to help them navigate in the south/southwesterly direction en route for Mexico. Central issues in this area are defining the relationship between juvenile hormone status and oriented flight, critical features that differentiate summer monarchs from fall migrants, and identifying molecular correlates of behavioral state. RESULTS: Here we show that increasing juvenile hormone activity to induce summer-like …

Genes And Gene Networks Related To Age-Associated Learning Impairments, Raihan Uddin

Electronic Thesis and Dissertation Repository

The incidence of cognitive impairments, including age-associated spatial learning impairment (ASLI), has risen dramatically in past decades due to increasing human longevity. To better understand the genes and gene networks involved in ASLI, data from a number of past gene expression microarray studies in rats are integrated and used to perform a meta- and network analysis. Results from the data selection and preprocessing steps show that for effective downstream analysis to take place both batch effects and outlier samples must be properly removed. The meta-analysis undertaken in this research has identified significant differentially expressed genes across both age and ASLI …

Exploring And Training Spatial Reasoning Via Eye Movements: Implications On Performance, Victoria A. Roach

Electronic Thesis and Dissertation Repository

This dissertation sought to determine if eye movements could serve as an indicator of success in spatial reasoning, and if eye movements associated with successful completion could be applied to strategically improve spatial reasoning.

Using the line images of Shepard and Metzler, an electronic test of mental rotations ability (EMRT) was designed. Two versions of the test were created, allowing for both a timed (6 seconds per question) and untimed testing environment. Four experiments were designed and completed to relate mental rotation ability (MRA) scores from the EMRT, to patterns in chrononumeric and visual salience data. In each experiment, participants …

Chronic Systemic Immune Dysfunction In African-Americans With Small Vessel-Type Ischemic Stroke, Candice M. Brown, Cheryl D. Bushnell, Gregory P. Samsa, Larry B. Goldstein, Carol A. Colton

Neurology Faculty Publications

The incidence of small vessel-type (lacunar) ischemic strokes is greater in African-Americans compared to whites. The chronic inflammatory changes that result from lacunar stroke are poorly understood. To elucidate these changes, we measured serum inflammatory and thrombotic biomarkers in African-Americans at least 6 weeks post-stroke compared to control individuals. Cases were African-Americans with lacunar stroke (n = 30), and controls were age-matched African-Americans with no history of stroke or other major neurologic disease (n = 37). Blood was obtained > 6 weeks post-stroke and was analyzed for inflammatory biomarkers. Freshly isolated peripheral blood mononuclear cells were stimulated with lipopolysaccharide …

Functionally Distinct Pools Of Calcineurin Contribute To Depotentiation-Like Synaptic Changes In The Lateral Amygdala During Auditory Fear Extinction, Elena Kay Rotondo

Theses and Dissertations

Until recently, auditory fear extinction was not thought to modify substrates involved in the storage of the original auditory fear memory. Evidence now suggests that extinction results in the reversal of the fear conditioning-induced potentiation of thalamic inputs to the lateral amygdala. However, little is known about the molecular mechanisms that support this depotentiation of synaptic strength. Here we present behavioral and molecular evidence in support of the contribution of two distinct pools of the protein phosphatase calcineurin to depotentiation-like changes in lateral amygdala AMPA receptor trafficking during auditory fear extinction. Calcineurin protein that exists prior to the onset of …

Disentangling Embodied Cognition: An Examination Of The State, Problems, And Possibilities Of Embodied Cognition, Cody Cash

Graduate Theses and Dissertations

Embodied cognition has received a fair amount of attention in philosophical, neuroscientific, and robotic research during the past several decades, yet the precise nature of its goals, methods, and claims are unclear. This dissertation will ascertain and examine the primary themes in the field of embodied cognition as well as why, and if, they offer significant challenges to traditional cognitive science models. Though many theories believe they are providing accounts that should replace traditional models, to do so they will have to overcome the very difficult challenge of arguing that mental content and capabilities derived from sensorimotor activity can continue …

Neural Mechanisms Supporting Differential Auditory Fear Conditioning, Nicole Christine Ferrara

Theses and Dissertations

Pavlovian fear conditioning provides an ideal way to study memory formation, retention, and updating. Plasticity in the auditory thalamus is required during the acquisition and consolidation of a fear memory when a tone signals a foot shock. The medial geniculate nucleus (MgN) of the auditory thalamus sends projections to the amygdala and auditory cortex and is functionally divided into two different regions, the medial division (MGm) and the ventral division (MGv). Traditionally, these divisions are thought to relay auditory information to the amygdala during fear-related associative learning. However, recent research has suggested a more complex role for the MgN when …

Effects Of Global Dna Methylation Changes On Neurobehavior In Zebrafish, Matthew Christopher Pickens

Theses and Dissertations

A number of environmental neurotoxicants modulate DNA methylation, but its influence on neurobehavior remains unclear. The laboratory has established that low-level developmental methylmercury exposure induces neurobehavioral deficits; the current results demonstrate that it also induces global DNA hypomethylation. DNA methyltransferase 1-mutant zebrafish (exhibit ~70% reduction in enzymatic activity) were used to assess the role of DNA hypomethylation on behavior. Several neurobehavioral assays including the C-start escape, circadian rhythm, basic locomotion and visual-motor response (VMR) were also performed. There was a significant difference in VMR between the wild type and mutant animals. Other behavior assays revealed no significant difference, primarily due …

Analysis Of Neuronal Sequences Using Pairwise Biases, Zachary Roth

Department of Mathematics: Dissertations, Theses, and Student Research

Sequences of neuronal activation have long been implicated in a variety of brain functions. In particular, these sequences have been tied to memory formation and spatial navigation in the hippocampus, a region of mammalian brains. Traditionally, neuronal sequences have been interpreted as noisy manifestations of neuronal templates (i.e., orderings), ignoring much richer structure contained in the sequences. This paper introduces a new tool for understanding neuronal sequences: the bias matrix. The bias matrix captures the probabilistic tendency of each neuron to fire before or after each other neuron. Despite considering only pairs of neurons, the bias matrix captures the best …

Neuregulin 1 Promotes Glutathione-Dependent Neuronal Cobalamin Metabolism By Stimulating Cysteine Uptake, Yiting Zhang

Yiting Zhang

No abstract provided.

Dopaminergic Modulation Of Medial Prefrontal Cortex Deactivation In Parkinson Depression, Anders H. Andersen, Charles D. Smith, John T. Slevin, Richard J. Kryscio, Catherine A. Martin, Frederick A. Schmitt, Lee X. Blonder

Neuroscience Faculty Publications

Parkinson's disease (PD) is associated with emotional abnormalities. Dopaminergic medications ameliorate Parkinsonian motor symptoms, but less is known regarding the impact of dopaminergic agents on affective processing, particularly in depressed PD (dPD) patients. The aim of this study was to examine the effects of dopaminergic pharmacotherapy on brain activation to emotional stimuli in depressed versus nondepressed Parkinson disease (ndPD) patients. Participants included 18 ndPD patients (11 men, 7 women) and 10 dPD patients (7 men, 3 women). Patients viewed photographs of emotional faces during functional MRI. Scans were performed while the patient was taking anti-Parkinson medication and the day after …

The Human Intruder Test: An Anxiety Assessment In Rhesus Macaques (Macaca Mulatta), Emily J. Peterson

Masters Theses

The human intruder test (HIT) is a noninvasive tool widely used for assessing anxiety in rhesus macaques (Macaca mulatta). This thesis explores the HIT procedure and applies it to a population of monkeys with a self-injurious behavioral pathology. Individual variation on this test can be used to assess anxiety and temperament. The first experiment of this thesis applied two different procedures of the HIT to 17 monkeys at UMass. Monkeys displayed little response to the intruder, and no significant differences were detected for the two procedures. To determine whether these responses were unique to the UMass monkeys, their …

Regulation Of Jak1 And Jak2 Synthesis Through Non-Classical Progestin Receptors, Hillary Adams

Masters Theses

The anteroventral periventricular (AVPV) nucleus of the hypothalamus integrates estradiol (E₂) and progesterone (P₄) feedback signals from the ovaries to stimulate gonadotropin releasing hormone (GnRH) neurons and trigger an ovulatory surge in luteinizing hormone (LH). E₂ maintains the daily cyclic LH surge and P₄ quickly amplifies the surge and limits it to one day. P₄ amplification of the surge and rapid signaling in the AVPV may occur through its non-classical progestin receptors. Previous in vitro studies using a microarray analysis with N42 mouse embryonic hypothalamic neurons suggest that progesterone membrane component 1 (Pgrmc1) …

Seasonality Of The Stress Response In House Sparrows (Passer Domesticus)., Michael R. Hasstedt

Electronic Thesis and Dissertation Repository

Seasonal changes in plasma corticosterone (CORT) levels indicate that birds modify their stress response through the year. Although this has been well documented, the method by which birds achieve this seasonality is not well understood. In this study I used house sparrows to determine if changes in glucocorticoid receptor (GR) immunoreactivity in several stress-related brain nuclei showed seasonal variation. The house sparrowsshowed seasonal variation in their stress response with baseline CORT levels being highest during the breeding season and lowest during winter. There was also significant change in plasma CORT post-dexamethasone during breeding, but not during other times of the …

Investigating The Influences Of Language Delay And/Or Familial Risk For Dyslexia On Brain Structure In 5-Year-Olds, Nora Maria Raschle, Bryce Larkin Chessell Becker, Sara Smith, Lynn Valérie Fehlbaum, Yingying Wang, Nadine Gaab

Center for Brain, Biology, and Behavior: Faculty and Staff Publications

Early language delay has often been associated with atypical language/literacy development. Neuroimaging studies further indicate functional disruptions during language and print processing in school-age children with a retrospective report of early language delay. Behavioral data of 114 5-year-olds with a retrospective report of early language delay in infancy (N = 34) and those without (N = 80) and with a familial risk for dyslexia and those without are presented. Behaviorally, children with a retrospective report of early language delay exhibited reduced performance in language/reading-related measures. A voxel-based morphometry analysis in a subset (N = 46) demonstrated an association between reduced …