Molecular and Cellular Neuroscience Commons^™

Morphological Characterization Of Two Transgenic Strategies For Genetic Access To Semilunar Granule Neurons In The Mouse Dentate Gyrus, David T. Rexford

Masters Theses

Granule cells (GCs) of the dentate gyrus (DG) have been understood as a homogeneous class of neurons exhibiting a characteristic limited firing pattern. A subtype of GC called a semilunar granule cell (SGC) has been identified exhibiting variant morphology, electrophysiology, and positioning from normal GCs. SGCs represent an emerging novel subpopulation of GCs, however, there is presently no genetic tool to access SGCs separately from normal GCs. To provide access for future in vivo studies of this population, we examined two genetic strategies for putative SGC specificity in mouse brain slices. Morphological analysis was performed for quantitative identification of putative …

Chemosensory Receptors In Berghia Stephanieae: Bioinformatics And Localization, Kelsi L. Watkins

Masters Theses

Chemosensation is achieved through the binding of chemical signals to chemoreceptor proteins embedded in the membranes of sensory neurons. The molecular identity of these receptors, as well as the downstream processing of chemosensory signals, has been well studied in arthropods and vertebrates. However, very little is known about molluscan chemosensation. The identity of chemoreceptor proteins in the nudibranch mollusc Berghia stephanieae are unknown. Data from other protostome and molluscan studies suggest Berghia may use ionotropic receptors for some forms of chemoreception. This study used a bioinformatics approach to identify potential chemosensory ionotropic receptors in the transcriptome of Berghia. A …

Sensory Representation Of Social Stimuli In Aromatase Expressing Neurons In The Medial Amygdala, Charles J. Gualtieri

Masters Theses

The ability of animals to sense, interpret, and respond appropriately to social stimuli in their environment is essential for identifying and distinguishing between members of their own species. In mammals, social interactions both within and across species play a key role in determining if an animal will live to pass on its genes to the next generation or else be removed from the gene pool. The result of this selection pressure can be observed in specialized neural circuits that respond to social stimuli and orchestrate appropriate behavioral responses. This highly conserved network of brain structures is often referred to as …

Effects Of A Circadian Mutation On Adult Neurogenesis, Michael Bahiru

Masters Theses

Rotating shift work, irregular sleep patterns and jetlag disrupt circadian rhythms, induce or aggravate disease, and produce deficits in cognitive function. Internal misalignment, a state in which abnormal phase relationships prevail between and within organs, is widely proposed to account for these adverse effects of circadian disruption. This hypothesis has been difficult to test because phase shifts of the entraining environmental cycle lead to transient desynchrony. Thus, it remains possible that phase shifts, regardless of internal desynchrony, account for adverse effects of circadian disruption. I have used the duper mutant hamster, whose locomotor activity rhythms re-entrain 5-fold faster than wild …

Studies On High-Throughput Single-Neuron Rna Sequencing And Circadian Rhythms In The Nudibranch, Berghia Stephanieae, Thi Bui

Masters Theses

One of the goals of neuroscience is to classify all of the neurons in the brain. Neuronal types can be defined using a combination of morphology, electrophysiology, and gene expression profiles. Gene expression profiles allow differentiation between cells that share similar characteristics. Leveraging the advantage of Berghia stephanieae (Gastropoda; Nudibranchia), which has around 28,000 neurons, I constructed high-throughput single-neuron transcriptomes for its whole brain. I produced a single-cell dissociation protocol and a custom data analysis pipeline for data of this nature. Around 129,000 cells were collected from 18 rhinophore ganglia and 20 circumesophageal ring ganglia (brain), consisting of the cerebropleural, …

Transcriptome Analysis Of Neuro-2a Cells Treated With Asiatic And Madecassic Acid, Fatimah M. Alqam

Masters Theses

Traditional herbal medicine is ingrained as a source of therapeutic compounds to medicate various diseases. The family Araliaceae (Ginseng family) is rich in traditional medicine species, such as Centella asiatica (CA). For many centuries, CA has been used by the indigenous Indian and Chinese in Ayurvedic and traditional medicine, respectively, to improve intelligence, learning, memory, and cognitive performance. Previous studies on cell culture and animal models supported the beneficial effects of CA on the nervous system. However, the exact composition of CA extract and its molecular mechanism that leads to neuroprotection is still unclear. We examined the effect of asiatic …

Sex Specific Electrophysiology Of Aromatase Neurons In The Medial Amygdala, Marcelo Henrique Correia

Masters Theses

The medial amygdala (MeA) is a central node in the interwoven circuits that regulate social behavior based on pheromones. Aromatase-expressing (arom⁺) neurons in the MeA are key for the establishment and maintenance of sex differences. Here, we characterized the intrinsic electrophysiological properties of arom⁺ neurons and non-aromatase (arom^-) neurons in the MeA of male and female mice. Most electrophysiological properties were similar for arom⁺ neurons in the MeA between sexes, but the relative refractory period was twice as large in female mice. We also show that the firing pattern and firing frequency is markedly …

Mapping A Pup-Responsive Pathway From The Medial Preoptic Area To The Ventral Tegmental Area., Matias Andina

Masters Theses

Maternal behavior is the complex array of caregiving behaviors females display towards offspring. In rats, the transition to motherhood depends on the action of various hormones, especially estradiol near parturition, which primes the maternal circuitry to respond to pups upon first encounter at parturition with appropriate maternal behavior. Although virgin rats avoid pups, new mothers are highly motivated to interact with pups, and their maternal behavior depends on the functional interaction between the medial preoptic area (mPOA) and the ventral tegmental area (VTA). However, a precise mapping of the VTA-projecting mPOA neurons remains to be elucidated. To determine whether pup-responsive …

Effort-Related Motivational Dysfunctions: Behavioral And Neurochemical Studies Of The Wistar-Kyoto Rat Model Of Depression, Brendan Abbott

Masters Theses

Depression and related disorders are characterized by motivational dysfunctions, including deficits in behavioral activation and exertion of effort. Animal models of relevance to depression represent a critical starting point in elucidating the neurobiological mechanisms underlying motivational dysfunctions. The present study explored the use of the Wistar-Kyoto (WKY) animal model of depression to examine effort-related functions as measured by voluntary wheel running and performance on a mixed fixed ratio 5/progressive ratio (FR5/PR) operant task. Given the known link between activational aspects of motivation and the mesocorticolimbic dopamine (DA) system, the behavioral effects of d-amphetamine (0.5 and 1.0 mg/kg, IP), a psychostimulant …

Evaluating A Novel Photochemical Tool For Labeling And Tracking Live, Endogenous Calcium-Permeable Ampars, Rosamund Elizabeth Combs-Bachmann

Masters Theses

The purpose of this research is to advance development of a photochemical tool designed to probe the role of ionotropic glutamate receptor signaling in neurodegenerative processes, and to delve more deeply into the biological processes underlying the role of these receptors in signaling and memory formation. This ligand-targeted nanoprobe was designed and developed in our lab to label endogenous calcium-permeable AMPARs (CP-AMPARs) in live cells with minimal disruption to native receptor activity. Nanoprobe is designed to use naphthyl acetyl spermine (NASPM) as a photocleavable ligand to target and covalently label native CP-AMPARs with a non-perturbing, fluorescent marker that then allows …

Cellular And Molecular Mechanisms Underlying The Interaction Of Apoe And Estrogen In Olfactory Neuronal Growth-Potential Relevance To Alzheimer's Disease, Minh Luong

Masters Theses

In recent years, there have been many studies looking at estrogen therapy (ET) as a treatment for Alzheimer's disease. Literature review suggests a close relationship between estrogen and apolipoprotein E (apoE) in the central nervous system. The mechanism underlying the interaction of apoE genotype with estrogen in the nervous system is not yet known. Therefore, the objectives of this research are 1) to determine the effects of estradiol treatment on basal cell proliferation and neuronal differentiation and 2) to identify the estrogen receptor subtype (ERα and ERβ) that mediates the increase of apoE levels, neurite outgrowth and neuronal numbers.

Results …

Cell Biology Of Apoe In Cortical Cultured Neurons: Possible Roles In Alzheimer's Disease, Anna G. Barsukova

Masters Theses

The apolipoprotein E4 (apoE4) genotype is a major risk factor for Alzheimer's disease (AD). Previous studies have shown that apoE4 is less effective than apoE3 in supporting neurite outgrowth in adult mice cortical cultures. However the mechanism underlying this phenomenon is not known. To understand this mechanism and the broader role of apoE isoforms on neuronal biology I examined the rate of apoE isoforms internalization in neurons, effects of apoE isoforms on lipid uptake by neurons, effects of apoE isoforms on neuronal environment - microglia and on neuroregeneration, or neurogenesis.

I examined the binding and internalization of recombinant human apoE3 …

Effects Of E2 On Apoe Secretion And Neurite Outgrowth In Cultured Adult Mouse Cortical Neurons, Fei Shen

Masters Theses

Estrogen replacement therapy appears to delay the onset of Alzheimer's disease (AD). The mechanism whereby estrogen prevents the pathogenesis of AD is unknown. In the present study, I examined the effects of 17-β-estradiol (E2) on neurite outgrowth from adult mice cortical neurons (AMC) in culture. I found that E2 increases apoE secretion and neurite outgrowth in AMC neurons from wild type mice in a dose dependent fashion. The neurite outgrowth promoting effect of E2 was not observed in AMC neurons derived from age-, sex-, and stain-matched apoE deficient/apoE gene knockout (apoE KO) mice. Furthermore, E2 has isoform specific effects on …

Modulation Of Apolipoprotein E Expression And Glial Activation In Mouse Olfactory Bulb During Estrous Cycle: An Immunohistochemical Study, Matthew Kircher

Masters Theses

Estrogen (E2) plasma levels fluctuate as a function of estrous cycling in the mouse. Apolipoprotein E (apoE) mRNA has been shown to increase in both hippocampal astrocytes and microglia during proestrus when plasma estrogen levels are high. The current study was designed to evaluate apoE localization and glial activation in mouse olfactory bulb (OB) as a function of the estrous cycle. In the rat OB, estrogen receptor β (ERβ) is present in the glomerular and external plexiform layers, but not the internal plexiform and granule cell layers. Normal female mice 2-3 months old at the start of the study were …

Effects Of Apolipoprotein E On Olfactory Nerve Plasticity In Mice, Jody L. Short

Masters Theses

No abstract provided.

Regional Specific Brain Apoe Modulation By The Estrous Cycle And Exogenous Estrogen, Emily Rosario

Masters Theses

Previous studies have demonstrated that 17β-estradiol can modify apolipoprotein E (apoE) expression. I found that apoE protein varied as a function of the estrous cycle and 17β-estradiol (E2) in a region specific manner in the mouse brain. I also found that apoE concentration was lowest on estrus in the hippocampus, cingulate cortex and frontal cortex; apoE concentration was highest on estrus in the olfactory bulb and cerebellum. No changes in apoE were found in the striatum throughout the estrous cycle. Exogenous E2 significantly raised tissue levels in the olfactory bulb and cerebellum, but did not increase apoE in cortical samples …

Olfactory Behavior In Apoe Knockout Mice, John P. Yost

Masters Theses

Apolipoprotein E (apoE), a lipid transporting protein, has been shown to play a vital role in nerve repair and remodeling. Since the olfactory system is in a continuous state of remodeling, the present study tested the hypothesis that apoE is required for normal functioning of the olfactory system. Olfactory function of the wild type (WT) and apoE deficient (apoE KO) mice was assessed by using three standard olfactory tests: 1) the buried food pellet (BFP) test; 2) the odor choice (OC) test; and 3) the odor cued taste avoidance (OCTA) test. The visible food pellet test (VFP) was not used …

Relationship Between Protective Effects Of Estrogen, Apoe And Alzheimer's Disease, Sara M. Ludwig

Masters Theses

Alzheimer's disease (AD) is a neurodegerative disorder characterized by progressive memory loss and loss of cognitive function. The pathogenesis and progression of AD is poorly understood. Recently, several risk factors have been determined, however, how these risk factors function to induce AD onset has yet to be elucidated.

Apolipoprotein E genotype has been clearly demonstrated to be a risk factor for AD. The apoE2 and apoE3 isoforms appear to be protective against AD, whereas the apoE4 isoform has been implicated in the development of AD. The apoE4 allele works in a dosage-dependent fashion; that is, the greater the expression of …

Effects Of Apolipoprotein E On Neurite Outgrowth From Adult Mice Cortical Neurons, Yanwen Jiang

Masters Theses

Apolipoprotein (apo) E4, one of the three common isoforms of apoE, has been implicated in Alzheimer's disease (AD). The mechanism whereby apoE4 leads to the pathogenesis of AD is unknown. In the present study, I examined the effects of apoE on neurite outgrowth from adult mice cortical neurons (AMC) in culture. I found that neurite outgrowth from AMC neurons derived from apoE deficient/apoE gene knockout (apoE KO) mice is significantly shorter than that from age-, sex-, and strain-matched wild-type control mice. Furthermore, I present evidence for the differential effects of two isoforms of human apoE, apoE3 and apoE4, on neurite …

Effects Of Apolipoprotein E On Olfactory Neuron Plasticity In Mice, Rafia Nisar

Masters Theses

Previous studies have shown that apoE is upregulated in injured nerves, and that it may participate in nerve regeneration by recycling lipids from the degenerating myelin sheath to axonal growth cones. However, these studies fail to differentiate apoE function in degeneration and regeneration, because of temporal juxtaposition of degeneration and regeneration in these models. In this study, we characterized the apoE expression during olfactory nerve regeneration in mice, which occurs over an extended seven week period. Olfactory nerves were lesioned in 2-3-month-old mice by intransal irrigation of Triton X-100. Following lesioning the olfactory bulbs were collected at 0, 3, 7, …