Molecular and Cellular Neuroscience Commons^™

Development And Sensory Experience Dependent Regulation Of Microglia In Barrel Cortex, Joshua C. Brumberg, John Kalambogias, Chia-Chien Chen, Safraz Khan, Titus Son, Carolyn Headlam, Cindy Lin

Publications and Research

The barrel cortex is within the primary somatosensory cortex of the rodent, and processes signals from the vibrissae. Much focus has been devoted to the function of neurons, more recently, the role of glial cells in the processing of sensory input has gained increasing interest. Microglia are the principal immune cells of the nervous system that survey and regulate the cellular constituents of the dynamic nervous system. We investigated the normal and disrupted development of microglia in barrel cortex by chronically depriving sensory signals via whisker trimming for the animals’ first postnatal month. Using immunohistochemistry to label microglia, we performed …

Hyaluronan At The Brain-Environment Interface, Donald M. Thevalingam

Dissertations, Theses, and Capstone Projects

Hyaluronan (HA; Hyaluronic Acid), a primary scaffolding component of the brain extracellular matrix, serves as an integral structural component to the brain extracellular space (ECS). The fossorial African naked mole-rat (Heterocephalus glaber; NM-R), a mammal which lives in a low-oxygen environment and is capable of tolerating hypoxia and hypercapnia, has been shown to synthesize and sustain a unique high-molecular-mass variant of hyaluronan macromolecule (HMM-HA). This body of work highlights HA’s role in mediating the interplay between brain ECM composition, ECS structure, and cell viability.

Here we employ the NM-R as a unique animal model to observe the role of the …

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 …}

Interhemispheric Communication And Lateralization In The Mouse Hippocampus, Jake Jordan

Dissertations, Theses, and Capstone Projects

The hippocampus is essential for memory and spatial navigation. Many theories have been proposed to explain how the hippocampus contributes to cognition; however, none has fully explained relevant neurophysiological and behavioral data. Hemispheric lateralization of hippocampal function has been reported in humans and in rodents, and lateralization of hippocampal neural circuitry has been reported in rodents. Most theories of hippocampal function fail to consider the hippocampus as a bilateral structure with hemispheric differences. Further, proposed theories of hippocampal lateralization have their own limitations in explaining empirical data concerning left/right function. Little is known about communication between the hippocampi across hemispheres. …

Modeling Changes In Cellular Micro-Environment In Mild To Moderate Head Trauma, Xiangfu Zhang, Subhendra N. Sarkar Phd, Rt

Publications and Research

Our work aims to connect and model multiple small, inter-related tissue injuries as a consequence of mild traumatic brain injuries (mTBI). It has been shown that frontal and temporal lobes are vulnerable regions for brain traumatic injury. A brain injury from a blow or high-speed impact can cause undersurface of the frontal and temporal lobes to deform against the anterior and cranial fossae. This deformation can often trigger damage to the cerebral vasculature, which is ill-understood and can result in chronic damage to larger vessels over time. These physiological injuries can be manifested psychologically; such as patients’ sleep-wake disturbances. The …

A Novel Kinesin Adapter Directly Mediates Dendritic Mrna Localization During Synapse Development, Hao Wu

Dissertations, Theses, and Capstone Projects

Cytoskeleton based active transport with motor proteins is essential for mRNA localization and local protein translation in animal cells, yet how mRNA granules interact with motor proteins remains poorly understood. Using an unbiased screen for interaction between mRNA binding proteins (RBP) and motor proteins, we identified protein interacting with APP tail 1 (PAT1) as a potential direct adapter between the β-actin mRNA Zipcode-binding protein 1 (ZBP1) and Kinesin-1 motor complex.

Mouse PAT1 is similar to the Kinesin Light Chain (KLC) in amino acid sequence and binds directly to KLC. High-resolution images from structured illumination microscopy (SIM) indicates that synaptic stimulation …

Ck2 Negatively Regulates 5-Ht4 Receptor Signaling In The Prefrontal Cortex And Mediates Depression-Like Behaviors, Julia Castello Saval

Dissertations, Theses, and Capstone Projects

The serotonergic system has been the major candidate in the pathophysiology of mood related disorders such as anxiety and major depressive disorder (MDD). Unfortunately, current antidepressant drugs are ineffective in 50% of the population and require chronic administration for a period of 3-6 weeks before the onset of therapeutic response. 5-HT4 receptor (5-HT₄R) agonists have emerged as potential candidates for fast antidepressant action, since an antidepressant response can be achieved after 3 days of pharmacological administration in rodents.

This dissertation aims to investigate the role of casein kinase 2 (CK2) as a regulator of 5-HT₄R expression …

The Master Synaptic Regulator: Activity Regulated Cytoskeleton Associated Protein, Arc, In Normal Aging And Diseases With Cognitive Impairment, Amber Khan

Dissertations, Theses, and Capstone Projects

Alzheimer’s disease (AD) is a progressive neurodegenerative disease with complex underlying pathogenic mechanisms. Epidemiological studies have forecasted that in the next 3 decades, the number of AD cases will rise to epidemic proportions with enormous medical, emotional and financial burdens impacting individuals affected and society. Among many risk factors for AD, advancing age is clearly essential and necessary. Revelation of molecular changes in synaptic activities leading to the prodromal, mild cognitive impairment (MCI) stage may help illuminate the course of pathogenic progression and its cause-effect relationship with various targets thereby enabling target-driven disease-modifying therapeutic agents for AD.

Activity-regulated cytoskeleton-associated (Arc) …

Post-Synaptic Mechanisms Of Early And Late Prepulse Inhibition In The Goldfish, Daniel Bronson

Dissertations, Theses, and Capstone Projects

Sensorimotor gating, or prepulse inhibition (PPI), attenuates the startle response during sensory processing by limiting sensory input to the startle circuit. In the goldfish startle circuit, a single action potential in the Mauthner-cell (M-cell) triggers the startle response. PPI in the M-cell is mediated by multiple post-synaptic mechanisms, including the activation of a tonic, shunting inhibition as well as a voltage-sensitive conductance, both of which briefly reduce M-cell excitability. However, the specific channels and pathways that modulate PPI are not fully known. This work further characterizes the post-synaptic conductances that mediate PPI by blocking voltage-gated and inward-rectifying potassium channels, antagonizing …

The Integration Of Multiple Sources Of Sonic Hedgehog In The Spinal Cord Contribute To The Production Of First-Born Oligodendrocyte Precursor Cells Which Become Critical For Synapse Remodeling In Response To Adult Motor Neuron Injury, Lev Starikov

Dissertations, Theses, and Capstone Projects

Oligodendrocyte precursor cells (OPCs) arise sequentially first from a ventral and then from a dorsal precursor domain during spinal cord development. Whether the sequential production of OPCs is of physiological significance has not been examined. Here I show that interrupting Sonic hedgehog (Shh) signaling originating from nascent ventricular zone derivatives (VZD), motor neurons and the lateral floor plate, almost completely blocks ventral but not dorsal oligodendrogenesis without noticeably affecting early tissue patterning and embryonic development. In the absence of ventral OPCs, dorsal OPCs increase proliferation and populate the entire spinal cord with increased density. In these mutant mice, dOPCs take …

Molecular Analysis Of Cone Photoreceptor Genesis From A Specific Retinal Progenitor Population, Diego F. Buenaventura

Dissertations, Theses, and Capstone Projects

There are two types of photosensitive cells of the retina that contribute to image formation: Cone photoreceptors that mediate color discrimination and rods that provide photosensitivity in low-light conditions. Given the importance of cones in high acuity and color vision, deficiencies in this cell type that result from ailments such as retinitis pigmentosa and macular degeneration can lead to a debilitating loss of vision. Currently, one of the most pressing goals in the field of retinal development is the elucidation of the gene regulatory networks (GRN) involved in inducing an undifferentiated cell into becoming a functional cone photoreceptor.

Recently, an …

Mechanisms Of Microglia Mediated Apolipoprotien E Neurotoxicity, Pardeep Singh

Dissertations and Theses

No abstract provided.