Developmental Neuroscience Commons^™

Sex Differences In Mood And Anxiety-Related Outcomes In Response To Adolescent Nicotine Exposure, Tsun Hay Jason Ng

Electronic Thesis and Dissertation Repository

Nicotine dependence is causally linked to increased risk of mood/anxiety disorders in later life. Females are reported to experience a higher prevalence of anxiety/depressive disorders and challenges in smoking cessation therapies, suggesting a potential sex-specific response to nicotine exposure and mood/anxiety disorder risk. However, pre-clinical evidence of sex-specific responses to adolescent nicotine exposure is unclear. Thus, to determine any sex differences in anxiety/depressive-related outcomes, adolescent male and female Sprague Dawley rats received nicotine (0.4 mg/kg; 3x daily) or saline injections for 10 consecutive days, followed by behavioural testing, in-vivo electrophysiology and Western Blot analyses. Our results revealed that adolescent nicotine …

Neural Mechanisms Of Language Development In Infancy, Scott Huberty, Christian O'Reilly, Virginia Carter Leno, Mandy Steiman, Sara J. Webb, Mayada Elsabbagh, The Basis Team

Publications

Understanding the neural processes underpinning individual differences in early language development is of increasing interest, as it is known to vary in typical development and to be quite heterogeneous in neurodevelopmental conditions. However, few studies to date have tested whether early brain measures are indicative of the developmental trajectory of language, as opposed to language outcomes at specific ages. We combined recordings from two longitudinal studies, including typically developing infants without a family history of autism, and infants with increased likelihood of developing autism (infant-siblings) (N = 191). Electroencephalograms (EEG) were recorded at 6 months, and behavioral assessments at …

Examining Development And Function Of Pretectal Visual Neural Circuits In Gs Homeobox 1 Mutant Zebrafish, Alexandra Rose Schmidt

Graduate Theses, Dissertations, and Problem Reports

Brain development requires a coordinated genetic code to regulate initial cell identity determination, migration, and connectivity, to establish function of neural circuits. Independent neural circuits underlie our ability to produce both complex and innate behavioral responses to sensory stimuli that are often conserved across vertebrate organisms. Sensory processing disruptions are associated with several neurodevelopmental disorders (NDDs). Therefore, gene mutations altering neurodevelopment can lead to changes influencing structure and function of individual neural circuits, causing behavioral deviations in sensory responsiveness. Crucial gene networks that define functional properties of sensory domains are often explored using non-mammalian vertebrate models, such as the zebrafish. …

The Effects Of D2 Receptor Modulation On Locomotor Development In Danio Rerio, Isaiah Thomas Mcroberts

Senior Projects Spring 2022

This study utilized a novel design to investigate the sensitivity of D2 dopamine receptors to modulating compounds through multiple exposures over early development of zebrafish larvae. Zebrafish were dosed for 30 minutes from 5-8 days post fertilization (dpf) with 16µ/mol of either a D2 antagonist, haloperidol, or a D2 agonist, quinpirole hydrochloride. Two other groups were then dosed with these compounds from 9-12dpf. The effects of D2 receptor modulation were measured by analyzing motor activity on measures of movement distance, frequency, and velocity. Results indicated that larvae dosed with haloperidol on 5dpf had increased activity after the first dosage, but …

Estrogen Disruption Of Hypothalamic Neural Activity, Princess Dickson

Cal Poly Humboldt theses and projects

The brain is highly dependent on the endocrine system for proper neurodevelopment, as it plays a key role in many biological processes. Bisphenol A is a chemical found in plastics that has the potential to mimic the effects of Estrogen in the body, at least weakly. People interact with plastic that contains BPA regularly, and people are at risk for exposure even before being born. The abundance of BPA, along with other exogenous estrogens, makes examining the relationship between early exposure and changes in brain activity imperative. The current study aims to establish a relationship between disrupted estrogen function and …

The Role Of Vps54 In Drosophila Melanogaster Neuronal Development And Age Progressive Neurodegeneration, Emily Wilkinson

Electronic Theses and Dissertations

Vps54 is a subunit of the Golgi-associated retrograde protein (GARP) complex, which is involved in tethering endosome-derived vesicles to the trans-Golgi network (TGN). The “wobbler” mouse is the phenotypic result of a destabilizing point mutation in Vps54. This mutation causes neurodegeneration and is subsequently used as a model for human motor neuron disease. Presently, it is unclear how disruption of GARP complex function leads to motor neuron degeneration. To better understand the role of Vps54 in motor neuron development, function, and age-related neurodegeneration, we disrupted expression of the Vps54 ortholog in Drosophila and examined the impact on larval neuromuscular junction …

Using Zebrafish To Elucidate The Expression And Gene Regulatory Network Of The Genomic Screen Homeobox Transcription Factors And Bring Innovative Science Learning Experiences To West Virginia, Rebecca Ann Coltogirone

Graduate Theses, Dissertations, and Problem Reports

Central nervous system (CNS) development requires a code of regionally expressed transcription factors that impart initial neuronal cell identity, connectivity, and function. The absence of a transcription factor code would eliminate the neurodevelopmental logic producing diverse cell types in the CNS. Furthermore, early disruptions in transcription factor expression can affect later connectivity and function of neuronal circuits mediating sensory processing, defects in which are often observed as comorbid with various neurodevelopmental disorders (NDDs). Characterizing transcription factor expression and function is therefore an essential step in discerning the molecular mechanisms underlying human NDDs. genomic screen homeobox 1 and 2 (gsx1 …

The Subplate And Its Role In The Gaba System In The Prefrontal Cortex, Gaeul Kyla Lee

Electronic Thesis and Dissertation Repository

During early brain development, the subplate relays thalamocortical afferents. Lesions to the subplate have been implicated in developmental abnormalities of cortical GABAergic circuits. This thesis examined the effects of subplate lesions in the prefrontal cortex of rats on the expression of GABA markers (parvalbumin and GAD67) and GABA synapse maturation [potassium-chloride cotransporter (KCC2) and sodium-potassium- chloride cotransporter (NKCC1)] with relevance to the characterization of a rat model for schizophrenia. Lesions were made on postnatal day 1 (P1). Lesioned and control rats were sacrificed between P5 and P90 and immunolabelled for parvalbumin, GAD67, KCC2, and NKCC1. We found decreased parvalbumin expression …

Notch Inhibitors And The Bet Inhibitor Jq-1 Decrease The Growth Of Primary Tumor Cells Derived From A Novel Mouse Model Of C11orf95-Rela Induced Brain Tumor, Ericka Randazzo, Jesse Dunnack, Justin Fang, Joseph Loturco Phd

University Scholar Projects

Brain tumors are the most common childhood solid malignancy, and because of remarkable advances in treating many cancers outside of the brain, they have become the leading cause of cancer mortality in children. Ependymomas are a class of brain tumors which can be further subdivided into three groups based upon their location and genetic features. Of the three classes, supratentorial ependymomas are the only subgroup known to be marked by an oncogenic driver gene, which consists of a fusion mutation between the C11orf95 and RELA genes. C11orf95-RELA positive tumors are the most aggressive and lethal of …

The 5-Ht1a-R Knockout Mouse As A Model Of Later Life Anxiety Disorders: Implications For Sex Differences, Tatyana Budylin

Dissertations, Theses, and Capstone Projects

Anxiety affects nearly twice as many women as it affects men across all cultures and economic groups. Importantly, girls have a higher chance of inheriting anxiety disorders than boys, and many anxiety disorders appear at a very young age. However, little is known about sex differences in brain and behavioral development and how they relate to anxiety in adulthood. Serotonin 1A receptor (5-HT_1A-R) mediated signaling has been implicated in depression and anxiety, however most studies that focus on the involvement of the 5-HT_1A-R have been conducted in adults. Little is known about how the 5-HT_{1A …}

Arid1b And Macf1 In Murine Brain Development And Behavior, Jeffrey Jay Moffat

Theses & Dissertations

Intellectual disability (ID) and autism spectrum disorder (ASD) affect between one and three percent of the global population. These disorders represent a significant emotional and financial burden for affected individuals and their families. Treatment for these conditions remains limited because many of the key molecular factors and associated pathogenic mechanisms are still poorly understood.

In this report we examine two genes related to ASD and ID, AT-rich interactive domain-containing protein 1B (ARID1B) and Microtubule-actin crosslinking factor 1 (MACF1). ARID1B is a subunit of the mammalian BRG1/BRM associated factor (BAF) chromatin-remodeling complex, which broadly regulates gene expression. ARID1B also …

Mechanisms And Targeting Of Neurodevelopmental Regulator Rest In Medulloblastoma Dissemination, Keri Callegari

Dissertations & Theses (Open Access)

Molecular subgrouping of medulloblastoma (MB) has produced four subgroups: wingless (WNT), sonic hedgehog (SHH), group 3, and group 4. While patients with WNT tumors have the best prognosis, patients with SHH tumors have a more variable prognosis concurrent with metastatic disease. This subset of SHH patients have elevated levels of the neurogenic regulator, RE1 Silencing Transcription factor (REST). To understand the role of REST in MB, we utilized a novel transgenic mouse model wherein REST expression can be conditionally elevated during postnatal development in the cells of origin of SHH MB, cerebellar granule neural progenitors (GNPs). While these mice did …

Maturation In Auditory Event-Related Potentials Explains Variation In Language Ability In Children., Elaine Yuen Ling Kwok, Marc F Joanisse, Lisa Archibald, Margot E. Stothers, Heather M Brown, Janis Oram Cardy

Health and Rehabilitation Sciences Publications

Processing of auditory information in the cortex continues to develop into later childhood and adolescence. Recent research has indicated that intraclass correlation (ICC) is the best method for capturing maturation in auditory event-related potentials (AEPs) of school-age children. However, the sensitivity of the ICC approach in discerning AEP changes in children has not been consistently demonstrated and positive results have not been replicated. We attempted this replication and further explored whether AEP maturation estimated using the ICC approach predicts cognitive and linguistic abilities in addition to chronological age. We measured AEPs in response to simple tones in groups of 7-, …

Neurostructural Organization And Neocortical Projecting Neuron Distribution In A Mouse Model Of Timothy Syndrome-Mediated Autism Spectrum Disorder, Aiden L. Ford

Honors Scholar Theses

Aims: This study investigates the nuanced effect of the CACNA1C mutation on neurocognition and neurodevelopment via an extended study of the Timothy Syndrome (TS) mediated Autism Spectrum Disorder (ASD) mouse model – TS2-neo. It includes: (1) an expanded assessment of the TS2-neo behavioral phenotype, and (2) a comprehensive histological analysis of cortical structural and laminar features.

Methods: 24 age-matched male mice – 12 TS2-neo (B6.Cg-Cacna1c^tm2Itl, knock-in G406R mutation), 12 WT (C57BL/6J) – were tested on paradigms examining motor, socio-communicative and cognitive abilities. Neural tissue was processed for either volumetric analysis through Nissl stain (8 TS2-neo, 8 WT) or …

Functional Connectivity In The Motor Network Largely Matures Before Motor Function, Jordynne L V Ropat

Electronic Thesis and Dissertation Repository

The brain changes in many ways in the first year. It is not known which of these changes are most critical for the development of cognitive functions. According to the Interactive Specialization Theory, developments in behaviour result from changes in brain connectivity. We tested this using functional connectivity magnetic resonance imaging (fcMRI) of the motor system. fcMRI was acquired at three and nine months – two time-points between which motor behaviour develops enormously. Infants were additionally compared with adults. Subjects were scanned with a 3T MRI scanner, yielding BOLD signal time-courses that were correlated with one another. Our results do …

Early Neurodevelopment: Notch Signaling, Axial Differentiation, Brain Patterning, And Neurogenesis, Adrian M. Bebenek '17

Independent Study

The vastly complex, delicate nature of the nervous system calls for a highly effective development system. The development of the nervous system begins early in embryogenesis and is one of the last systems to be completed after birth. Deemed to be one of the most important steps in the evolutionary progression towards sophisticated life, the pathways regulating neurodevelopment are highly specialized and conserved. Embryonic neurodevelopment is an important starting point for the understanding of brain anatomy, function, and its neurobiology. The past few decades have brought about numerous technological advancements allowing for the study of the earliest stages of embryonic …

Characterizing And Treating The Neuropathology Of Tuberous Sclerosis Complex In The Mouse, Sharon W. Way

Dissertations & Theses (Open Access)

Tuberous sclerosis complex (TSC) is a multisystem, autosomal dominant disorder affecting approximately 1 in 6000 births. Developmental brain abnormalities cause substantial morbidity and mortality and often lead to neurological disease including epilepsy, cognitive disabilities, and autism. TSC is caused by inactivating mutations in either TSC1 or TSC2, whose protein products are known inhibitors of mTORC1, an important kinase regulating translation and cell growth. Nonetheless, neither the pathophysiology of the neurological manifestations of TSC nor the extent of mTORC1 involvement in the development of these lesions is known. Murine models would greatly advance the study of this debilitating disorder. This thesis …