Developmental Neuroscience Commons^™

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 …

Ethanol Exposure During Synaptogenesis In A Mouse Model Of Fetal Alcohol Spectrum Disorders: Acute And Long-Term Effects On Gene Expression And Behaviour, Morgan L. Kleiber

Electronic Thesis and Dissertation Repository

Alcohol is a neuroactive molecule that is able to exert variable and often detrimental effects on the developing brain, resulting in a broad range of physiological, behavioural, and cognitive phenotypes that characterize ‘fetal alcohol spectrum disorders’ (FASD). Factors affecting the manifestation of these phenotypes include alcohol dosage, timing of exposure, and pattern of maternal alcohol consumption; however, the biological processes that are vulnerable to ethanol at any given neurodevelopmental stage are unclear, as is how their disruption results in the emergence of specific pathological phenotypes later in life.

The research included in this thesis utilizes a C57BL/6J (B6) mouse model …

Behavioral And Neural Mechanisms Of Impulsive Choice, Jesse Mcclure

Doctoral Dissertations

Impulsive choice is defined as the preference for a small immediate reward over a larger delayed reward. Individual variablity in impulsive choice correlates with many socially relevant behaviors. Although forms of impulsive choice have been studied in both behavioral ecology and psychology, the exchange of knowledge between these fields is just beginning. Drawing from both of these fields will improve our research methods allowing for a more detailed understanding of this complex behavior. Existing tasks to measure impulsive choice conflate the delay and quantity of the reward. To address this, I have drawn from foraging research to establish a method …

Developmental Decline In Neuronal Regeneration By The Progressive Change Of Two Intrinsic Timers, Yan Zou, Hui Chiu, Anna Zinovyeva, Victor Ambros, Chiou-Fen Chuang, Chieh Chang

Victor R. Ambros

Like mammalian neurons, Caenorhabditis elegans neurons lose axon regeneration ability as they age, but it is not known why. Here, we report that let-7 contributes to a developmental decline in anterior ventral microtubule (AVM) axon regeneration. In older AVM axons, let-7 inhibits regeneration by down-regulating LIN-41, an important AVM axon regeneration-promoting factor. Whereas let-7 inhibits lin-41 expression in older neurons through the lin-41 3' untranslated region, lin-41 inhibits let-7 expression in younger neurons through Argonaute ALG-1. This reciprocal inhibition ensures that axon regeneration is inhibited only in older neurons. These findings show that a let-7-lin-41 regulatory circuit, which was previously …

Neural And Behavioural Responses To Rewards And Losses In Early Development: A Functional Magnetic Resonance Imaging Study, Niki Hosseini-Kamkar

Electronic Thesis and Dissertation Repository

Functional magnetic resonance imaging (fMRI) was used to investigate the neural and behavioural correlates of learning from rewards and losses in children. Greater blood-oxygen-level dependent (BOLD) responses in the ventral striatum (VS) and the ventromedial prefrontal cortex (VMPFC) were found when participants received rewards compared to when they missed out on an opportunity to receive rewards. In contrast, greater BOLD responses in the anterior insula (AI) and the anterior cingulate cortex (ACC) were found when participants received losses compared to when they avoided losing. The BOLD response to rewards in the VS and VMPFC correlated positively with the tendency to …

Estrogen-Sensitive Learning Is Not Affected By Combination Ethinyl Estradiol And Levonorgestrel Oral Contraceptive Use, Darlene F. Ficco

Doctoral Dissertations

Two studies were conducted to explore the cognitive effects of combination ethinyl estradiol and levonorgestrel contraceptive use during late adolescence and young adulthood. Three groups of females, naturally cycling, active pill phase, and hormone-free interval phase, were tested on a battery of estrogen-sensitive, i.e., place learning and word generation, and estrogen-insensitive, i.e., map drawing, mental rotation, digit span, story recall, and object recall, tasks. Study 2 was conducted as a means to replicate the findings observed in Study 1 and to manipulate task difficulty and sensitivity. Two measures of mood were administered, and salivary estradiol levels at time of testing …

Relationships Between Age And White Matter Integrity In Children With Phenylketonuria, Erika M. Wesonga

Arts & Sciences Electronic Theses and Dissertations

Objective: Phenylketonuria (PKU) is a hereditary metabolic disorder associated with cognitive compromise. Diffusion tensor imaging (DTI) has allowed detection of poorer microstructural white matter integrity in children with PKU, with decreased mean diffusivity (MD) in comparison with healthy children. However, very little research has been conducted to examine the trajectory of white matter development in this population. The present study investigated potential differences in the developmental trajectory of MD between children with early- and continuously-treated PKU and healthy children across a range of brain regions.

Methods: Children with PKU (n = 31, mean age = 12.2 years) were …

Structure And Composition Of Postsynaptic Densities, Madeline Farley

Dissertations & Theses (Open Access)

Communication between neurons within the brain occurs at chemical synapses and is fundamental for all brain functions. Modulation of the strength of communication is controlled by both presynaptic and postsynaptic mechanisms and is termed synaptic plasticity. One postsynaptic structure postulated to regulate synaptic strength is the postsynaptic density (PSD), a large electron dense protein complex located just below the synaptic membrane. The PSD, which is composed of signaling, scaffold and cytoskeletal proteins, supports and organizes neurotransmitter receptors within the synaptic membrane in addition to bridging signaling with the actin cytoskeletal network. The protein composition and structure of PSDs is known …

Concussion Awareness And Educational Outreach Through A Website And Mobile Application, Daniel J. Brogan

Neuroscience Summer Fellows

In recent years concussions have become a more apparent problem in youth and adolescent sports. 1 in 5 high school students will sustain a concussion during the season. Due to medical and scientific advances, the diagnosis of concussions is becoming much simpler with key markers that are signs for an injury. Returning to play too soon before an athlete is fully recovered increases the likelihood that serious and irreversible neurological deficits can occur. Symptoms for concussions are necessary to track in order for an athlete to properly report their recovery to a physician. Doctors primarily rely on a patient’s report …

Prenatal Predictors Of Infant Self-Regulation: The Contributions Of Placental Dna Methylation Of Nr3c1 And Neuroendocrine Activity, Elisabeth Conradt, Mary Fei, Linda Lagasse, Edward Tronick, Dylan Guerin, Daniel Gorman, Carmen J. Marsit, Barry M. Lester

Dartmouth Scholarship

We examined whether placental DNA methylation of the glucocorticoid receptor gene, NR3C1 was associated with self-regulation and neuroendocrine responses to a social stressor in infancy. Placenta samples were obtained at birth and mothers and their infants (n = 128) participated in the still-face paradigm when infants were 5 months old. Infant self-regulation following the still-face episode was coded and pre-stress cortisol and cortisol reactivity was assessed in response to the still-face paradigm. A factor analysis of NR3C1 CpG sites revealed two factors: one for CpG sites 1-4 and the other for sites 5-13. DNA methylation of the factor comprising NR3C1 …

The Short And Long-Term Effects Of Chronic Ketamine During Adolescence On Object Recognition Memory In Rats, William Hardin

Seton Hall University Dissertations and Theses (ETDs)

Prior research has demonstrated that ketamine causes deficits in object recognition and location memory following both acute and chronic administration (Pitsikas & Boultadakis, 2009; Venãncio et al., 2011). Although it is well established that abuse of many different kinds of drugs during the critical developmental period of adolescence can lead to impairments in cognition later in adulthood (Gilpin et al., 2012; Wagner et al., 2010), no research has investigated the effects of chronic ketamine administration during adolescence and its effects on behavior in adulthood. With recent research establishing that chronic ketamine during adolescence produces late-onset alterations in electrophysiology during adulthood …

Multimodal Inputs And Modularity Of The Inferior Colliculus Prior To Audition., Joseph A. Balsamo

Senior Honors Projects, 2010-2019

A fully functional nervous system requires assimilation of sensory modalities to adequately interpret stimuli and determine appropriate motor responses. Two such regions responsible for multimodal integration are found in the auditory system, the cochlear nucleus (CN) and the inferior colliculus (IC). The lateral cortex of the IC (LCIC) in particular receives a diverse multimodal input array to discrete modular/extramodular zones. Staining for certain neurochemicals, including GAD, a marker for GABAergic neurons, reveal this compartmentalized LCIC organization. The present study utilizes fluorescent anterograde tracttracing techniques to determine the development of a somatosensory brainstem projection from the spinal trigeminal nucleus (Sp5), to …

Sleep Deprivation And Voluntary Alcohol Consumption In Adolescent Rats, Sancho N. Sequeira

Masters Theses, 2010-2019

Alcohol is one of the most common psychoactive drugs, and has been used by humans for thousands of years. Research has focused on the effects of alcohol on sleep, however recent trends in the literature have taken a more bidirectional approach to the relationship between alcohol and sleep. This research investigates the effects of chronic, partial sleep deprivation on alcohol consumption. Twelve adolescent Sprague Dawley rats had free access to two bottles at all times, one containing water and one containing a 7% alcohol and water solution. Sleep deprivation was achieved by using a forced exercise wheel. All rats were …

Efficient In Vitro Development Of Photoreceptors From Human Pluripotent Stem Cells, Joseph C. Reynolds

Dissertations, Masters Theses, Capstones, and Culminating Projects

Degeneration of the rod and cone photoreceptors in the human retina is among the most common causes of blindness. Replacing these damaged photoreceptors may help to restore vision. Repairing the damaged retina relies on the insertion of new, healthy cells. Embryonic stem (ES) cells and induced pluripotent stem (iPS) cells are two possible sources of photoreceptors to restore vision. Previous data shows that human ES cells and iPS cells can be differentiated into photoreceptors and transplanted into the eye to restore some vision. However, this process is inefficient, and costly. Here, we show a new method for inducing photoreceptor production …

Abnormal Hippocampal Activation In Freely Behaving Mice Deficient For The Vesicular Acetylcholine Transporter, Shahin Moallem

Electronic Thesis and Dissertation Repository

Acetylcholine (Ach) has a fundamental role in cortical activation. The activation of the hippocampus, a cortex implicated in cognitive and sensorimotor functions, is characterized by an increase in power and frequency of oscillations in the theta (4-10 Hz) and gamma (30-100 Hz) frequency range. We studied hippocampal activation in two mutant mouse lines with deficiency in cholinergic functionality: VAChT KD^HET (HET), and VAChT^{Nkx2.1-Cre-flox/flox} (KO). We hypothesized that the mutant mice, relative to wild-type (WT) mice, will manifest abnormal theta and gamma oscillations during different behaviors, and in response to muscarinic cholinergic antagonist scopolamine hydrochloride and to the NMDA …

Reward Enhances Tic Suppression In Children Within Months Of Tic Disorder Onset, Deanna J. Greene, Jonathan M. Koller, Amy Robichaux-Viehoever, Emily C. Bihun, Bradley L. Schlaggar, Kevin J. Black

Kevin J. Black, MD

Tic disorders are childhood onset neuropsychiatric disorders characterized by motor and/or vocal tics. Research has demonstrated that children with chronic tics (including Tourette syndrome and Chronic Tic Disorder: TS/CTD) can suppress tics, particularly when an immediate, contingent reward is given for successful tic suppression. As a diagnosis of TS/CTD requires tics to be present for at least one year, children in these tic suppression studies had been living with tics for quite some time. Thus, it is unclear whether the ability to inhibit tics is learned over time or present at tic onset. Resolving that issue would inform theories of …

"And If Your Friends Jumped Off A Bridge, Would You Do It Too?": How Developmental Neuroscience Can Inform Legal Regimes Governing Adolescents, Michael N. Tennison, Amanda C. Pustilnik

Faculty Scholarship

Legal models of adolescent autonomy and responsibility in various domains of law span a spectrum from categorical prohibitions of certain behaviors to recognitions of total adolescent autonomy. The piecemeal approach to the limited decision-making capacity of adolescents lacks an empirical foundation in the differences between adolescent and adult decision-making, leading to counterintuitive and inconsistent legal outcomes. The law limits adolescent autonomy with respect to some decisions that adolescents are perfectly competent to make, and in other areas, the law attributes adult responsibility and imposes adult punishments on adolescents for making decisions that implicate their unique volitional vulnerabilities. As developmental neuroscientists …

Pcdh19 Expression In Normal And Regenerating Adult Zebrafish Retinas, Kristin N. Forkapa Ms.

Williams Honors College, Honors Research Projects

My Honors Research Project will test the function of the N-cadherin molecule on the zebrafish optic nerve regeneration. N-cadherin is a member of the cadherin superfamily. Cadherins are cell adhesion molecules important for animal development and maintenance of adult structures. Unlike mammals, fish and amphibians have the ability to regenerate their optic nerve after damages. Molecular mechanisms underlying the optic nerve regeneration are still under intense investigation. Studies in Dr. Liu’s laboratory showed that expression of several cadherins, including N-cadherin, was greatly increased during adult zebrafish optic nerve regeneration, suggesting that cadherins may be involved in the optic nerve regeneration …

A Structure/Function Analysis Of Nhsl1b In Facial Branchiomotor Neurons, John Ojumu

Theses and Dissertations

The goal of this study was to identify critical regions of a novel gene, Nance-Horan syndrome-like 1b (nhsl1b). It was previously discovered that C-terminal truncation of the Nhsl1b protein in nhsl1b mutants resulted in a loss of migration in the facial motor neurons of the hindbrain (Walsh et al. 2011). As nhsl1b expresses many isoforms, multiple targets were investigated in order to determine which transcript bears the largest impact on the motor neurons. Using confocal microscopy to observe immunostained embryos, we examined a mutation in an nhsl1b transcript that encodes a WHD, a domain that is known to …

Dual Functions For Insulinoma-Associated 1 In Retinal Development, Marie A. Forbes-Osborne

Theses and Dissertations--Biology

Proper visual system function requires tightly controlled proliferation of a pool of relatively homogeneous retinal progenitor cells, followed by the stepwise specification and differentiation of multiple distinct cell types. These retinal cells, both neuronal and glial, must be generated in the correct numbers, and the correct laminar location to permit the formation of synaptic connections between individual cell types. After synapses are made, constant signaling is required as part of normal retinal function, and to maintain cellular identity and connectivity. These processes rely on both extrinsic and intrinsic signaling, with regulation of gene expression by cascades of transcription factors having …

Role Of Sox11 During Vertebrate Ocular Morphogenesis And Retinal Neurogenesis, Lakshmi Shashidharan Pillai

Theses and Dissertations--Biology

Microphthalmia, anophthalmia, and coloboma (MAC) are distinct abnormalities demonstrating a continuum of developmental eye defects that contribute to 15-20% of blindness and severe vision deficiencies in children worldwide. The genetic etiology of MAC is large, complex and encompasses the whole developmental biology of the eye. Understanding how the eye develops will aid in identifying genes and developmental pathways involved in MAC. Although investigation of the genetic architecture of congenital anomalies is growing exponentially, much work remains to be accomplished to understand the complex, genetically heterogeneous congenital anomalies, which significantly impact childhood vision.

With an interest in elucidating the mechanisms that …