Molecular and Cellular Neuroscience Commons^™

Isolation Of Aged Mouse Primary Microglia As A Model System For Alzheimer’S Disease Research, Michael Landis

Biology Honors Papers

Microglia and their role as the immune cells of the central nervous system are an emerging area of interest within Alzheimer’s research, particularly as they have shown in a benevolent and malevolent cellular context. Models of Alzheimer’s disease are very light in studying microglia, so in this study a model of microglia isolated from aged mice is established in order to study the phagocytic activity and protein expression of microglia in response to Amyloid Beta. The cells were isolated from aged mice and cultured before being used to confirm cellular identity, as well as to measure phagocytic activity. This study …

Biophysical Model Of Retraction Motor Neurons And Their Modification By Operant Conditioning, Maria Rasheed

Dissertations & Theses (Open Access)

Operant conditioning (OC) is a form of associative learning in which an animal modifies its behavior based on the consequences that follow that behavior. Despite its ubiquity, the underlying mechanisms of OC are poorly understood. Insights into the mechanisms of OC can be obtained by studying Aplysia feeding behavior as it can be modified by OC. This behavior is mediated by a central pattern generator (CPG) network in the buccal ganglia that contains a relatively small number of neurons. This CPG generates rhythmic motor patterns (BMPs) that move food into the gut by closing a tongue-like structure (i.e., radula) during …

Dissecting The Tissue-Specific Contributions To Seizures, Cardiorespiratory Dysfunction, And Sudden Death In The Kv1.1 Mouse Model Of Epilepsy Using Conditional Knockout Approaches, Kelsey Paulhus

Biological Sciences Theses and Dissertations

Sudden unexpected death in epilepsy (SUDEP), the primary cause of mortality in epilepsy, remains poorly understood. Studies suggest seizures may trigger dangerous signals affecting the heart and lungs leading to collapse and death. The Kv1.1 deficiency mouse model mirrors clinical SUDEP cases, showing spontaneous seizures, cardiorespiratory issues, and premature death. However, this model lacks regional specificity in Kv1.1 deletion, hindering insights into SUDEP’s mechanisms and anatomical substrates.

This dissertation employs three distinct conditional knockout (cKO) techniques to investigate the individual roles for the forebrain, brainstem, and heart in SUDEP related phenotypes. The findings reveal that the forebrain alone can trigger …

Synaptic Properties Of Parabigeminal Circuits., Kyle Whyland

Electronic Theses and Dissertations

Subcortical structures of the visual system have been the subject of intense study in recent years, but there remain some important unanswered questions regarding the synaptic relationships linking the nuclei that comprise this important sensory network within the brain. In these studies, we use several modern and traditional approaches, including viral tract tracing, in vitro slice physiology, immunohistochemistry, optogenetics, and electron microscopy to characterize the circuits linking the superior colliculus (SC), parabigeminal nucleus (PBG), and lateral geniculate nucleus (LGN), with particular focus on GABAergic and cholinergic cell types. We found that the SC, an important visuomotor structure with connections to …

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 …

Role Of Nucleus Accumbens Dopamine Receptor Signaling In The Suppression Of Punished Reward Seeking, Grace M. Joyner, Anna Caroline Toburen

Senior Theses

Previous studies have shown that within the nucleus accumbens (NAc), a brain region associated with motivation and reinforcement learning, activity of neurons expressing the dopamine D2 receptor (D2R neurons) act as a “break” on risky behavior associated with negative outcomes. Moreover, when these neurons are stimulated, rats were found to become more risk averse. However, the impact of dopamine signaling through NAc D2R neurons in risk avoidance is still unclear. To further explore the role of NAc dopamine signaling in punished reward-seeking, we tested rats in a novel punished food-seeking paradigm in which subjects are trained to choose between a …

Characterizing The Roles Of The Variable Linker And Hub Domains In Camkii Activation, Noelle Dziedzic

Doctoral Dissertations

Learning and memory formation at the cellular level involves decoding complex electrochemical signals between nerve cells, or neurons. Understanding these processes at the molecular level requires a comprehensive study of calcium-sensitive proteins that serve as signal mediators within cells. More specifically, the protein calcium/calmodulin-dependent protein kinase II (CaMKII) is a key regulator of downstream cellular signaling events in the brain, playing an important role in long term memory formation. CaMKII is encoded in humans on four different genes: alpha, beta, gamma and delta. For added complexity, each of these gene products can be alternatively spliced and translated into multiple protein …

Age- And Sex-Dependent Alterations In Primary Somatosensory Neuronal Calcium Network Dynamics During Locomotion, Sami L. Case

Theses and Dissertations--Pharmacology and Nutritional Sciences

Over the past 30 years, the calcium (Ca2+) hypothesis of brain aging has provided clear evidence that hippocampal neuronal Ca2+ dysregulation is a key biomarker of aging. Indeed, age-dependent Ca2+-mediated changes in intrinsic excitability, synaptic plasticity, and activity have helped identify some of the mechanisms engaged in memory and cognitive decline. However, much of this work has been done at the single-cell level, mostly in slice preparations, and in restricted structures of the brain. Recently, our lab identified age- and Ca2+-related neuronal network dysregulation in the cortex of the anesthetized animal. Still, investigations in the awake animal are needed to …

Novel Strategies For Glutamate Clearance In The Glia-Deprived Synaptic Hub Of C. Elegans, Joyce Chan

Dissertations, Theses, and Capstone Projects

As the major excitatory neurotransmitter in the mammalian brain, Glutamate (Glu) is critical for normal neuronal physiology. Disruption in Glu clearance results in hyper-stimulation of glutamatergic circuits, potentially leading to excitotoxic neurodegeneration. The canonical model of brain connectivity describes glutamatergic synapses as well insulated and enveloped by glia. These glia express Glu Transporters (GluTs) which work to clear Glu following synaptic activity. However, critical areas of the brain such as the mammalian hippocampus display poor synaptic isolation, which may result in Glu spillover between adjacent synapses and subsequent loss of circuit specificity. How accurate signal transmission is achieved in these …

Muscarinic Excitation Of Dopamine Neurons In The Ventral Tegmental Area Via Activation Of A Trpc-Like Cation Conductance, Yu Tzu Chen

Theses and Dissertations

Dopaminergic (DA) neurons in the ventral tegmental area (VTA) play a crucial role in reward and motivational behaviors, including the development of drug addictions. VTA DA neurons receive excitatory cholinergic inputs from the mesopontine tegmentum. Blockage of the M5 muscarinic receptor in DA neurons has been shown to attenuate drug-induced DA release and abuse-related behaviors, but the molecular mechanism is unknown. In this study, experiments were designed to identify the electrophysiological effects of muscarinic agonism in the modulation of action potential kinetics and firing patterns in VTA DA neurons of mice. Pharmacology of the muscarinic receptor-evoked current was also characterized. …

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 …

Rela/P65 Blocks Histone Deacetylase-3 Neurotoxicity And Protects Neurons Against Neuronal Death Induced By Polyq-Expanded Huntingtin And Ataxin-1 In A P65 Phospho S276 Dependent Manner, Yiyu Zhang

Biological Sciences Theses and Dissertations

Neurodegenerative diseases have a large negative impact to human society. Symptoms of neurodegenerative diseases includes memory loss, impaired recognition, motor dysfunction due to dysregulated neuronal loss in different brain regions. However, the neurobiological basis of these brain diseases is not fully understood and there are no cures or effective treatments. Polyglutamine (Poly-Q) disorders is a class of neurodegenerative diseases that are caused by polyglutamine expansion within the protein coding regions of specific genes. Huntington’s disease (HD), Spinal Cerebellar Ataxia Type 1 (SCA1) and Spinal Cerebellar Ataxia Type 3 (SCA3) are three common diseases among Poly-Q disorders. To better understand the …

The Effects Of A New Mutation In Lis1 And Its Potential Role In Autism Spectrum Disorder, John A. Slovensky

Senior Theses

LIS1 is a protein, particularly concentrated in the brain, that is important in regulating the movement and transport capabilities of dynein. Dynein is protein that can move along pathways in the cell, carrying various cellular components and also helping brain cells migrate. These two proteins are crucial during the development of the nervous system, and mutations in them can lead to lissencephaly, a disorder in which the brain does not form properly. This disease causes patients to develop cognitive-motor defects and seizures that can lead to early death. While all previously identified mutations in LIS1 are known to cause lissencephaly, …

Optimization And Validation Of The Neurolux Wireless Optoelectronics System For Optogenetics, Karis Courey, Su Hyun Lee Ph.D., Adam Smith Ph.D., Nicholas Cilz Ph.D., Sarah K. Williams Avram Ph.D., Adi Cymerblit-Sabba Ph.D., June Song, Nicholas Leipzig Ph.D., W. Scott Young M.D., Ph.D.

Williams Honors College, Honors Research Projects

Utilizing light and genetic engineering, optogenetics permits the manipulation of events within cells via light using the light-sensitive properties of single-component microbial opsins. Microbial opsins are activated by a light source, such as lasers, light-emitting diodes, and incandescent sources that deliver light to the region of interest either directly or indirectly, such as through fiberoptics. In classical in vivo optogenetics, the wiring of optic fibers necessitates tethering of animals by the optic fiber to the light source. The novel NeuroLux wireless optoelectronic system for optogenetics circumvents issues pertaining to classical optogenetics by utilizing near-field power transfer via magnetic coil antennae …

Assessing Morphology Of Iprgcs After Traumatic Brain Injury, Brian Foresi, Matt Smith

Williams Honors College, Honors Research Projects

ipRGCs are retinal ganglion cells that project to visual processing centers of the brain for nonimage forming visual functions. The relation of ipRGCs to tramatic brain injury (TBI) is emerging as data has been published describing ipRGC functional changes in TBI affected military veterans. Major symptomologies of concussions, a mild form of TBI, also overlap with the function governed by sites in the brain with major ipRGC projection percentages. Assesing if a morphological change is occuring in the ipRGCs after a TBI could support the idea of a pathological mechanism of the injury. This study could also indicate further relevance …

Neuroanatomy Of The Blackspotted Rockskipper, Entomacrodus Striatus, Pooja Dayal

Williams Honors College, Honors Research Projects

Here I characterized the central neuroanatomy of the Blackspotted Rockskipper, Entomacrodus striatus, native to French Polynesia. The neuroanatomy of E. striatus has not been studied prior to this paper. I used several histology and antibody staining techniques to accomplish this, including Crystal Violet, immunohistochemistry, immunofluorescence, and Bielschowsky’s Silver Nitrate staining. This paper describes the most successful techniques used, identifies major structures in the species’ neuroanatomy, and also explains why studying E. striatus is important in the future of vertebrate research.

Investigation Of Even-Skipped, A Developmentally-Regulated Gene Controlling Neural Segmentation In Dragonflies, Kathryn Bangser

Honors Theses

A comprehensive understanding of the genetic mechanisms underlying pattern formation and neurogenesis is necessary in order to trace the evolutionary history of insect embryogenesis.

One of the most important processes of embryogenesis is the organized pattern formation that allows for proper body segmentation and neural development. Proper segmentation, which relies on a series of specific gene expressions, is necessary for the development of an operational nervous system. Even-skipped (eve), one such regulatory gene, has been studied extensively in certain model organisms, and theories regarding the evolution of its functional role could be further elucidated by visualizing its expression …

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 …}

The Role Of Ash1l During Human Neurodevelopment, Anna Bagnell

Senior Theses

Autism spectrum disorders (ASD) are associated with defects in neuronal connectivity and are highly heritable. A significant proportion of ASD cases are of complex genetic etiology; complexity which might reflect the impact of gene-environment interactions. However, there is a gap in our understanding of the mechanisms that underlie the gene-environment interaction in autism complex etiology. Genome wide association studies in large ASD cohorts identified high risk variants associated with autism in genes that regulate histone modifications and remodel chromatin. These findings highlight the relevance of chromatin regulatory mechanisms in the pathology of ASD. Changes in Histone H3 methylation have been …

Mechanisms Of Microglia Mediated Apolipoprotien E Neurotoxicity, Pardeep Singh

Dissertations and Theses

No abstract provided.

A Composite Review Of The Proposed Molecular Mechanisms And Genetic Components Underlying Parkinson’S Disease, Paige Brodrick

Scripps Senior Theses

Parkinson’s disease (PD) is a progressive neurodegenerative disorder characterized by the progressive death of dopaminergic neurons present in the substantia nigra. The clinical presentation of PD includes tremors, slowed movement (bradykinesia), muscle and limb rigidity, and difficulty with walking and balancing. While many environmental factors can affect the onset and progression of the disease, genetic mutations have a large influence. Of the identified PD-linked genetic mutations, mutations in the leucine-rich repeat kinase 2 (LRRK2) are one of the most common genetic causes of PD. Located in endosomes, LRRK2 has been shown to play a role in the sorting and endocytosis …

The Progression Of Aβ Proteins In The Retrosplenial Cortex Using An App/Ps1 Alzheimer’S Disease Transgenic Rodent Model, Maha H. Rashid

Senior Independent Study Theses

Alzheimer’s disease is the most common form of dementia in the world with a new case of dementia diagnosed every 3.2 seconds. For over 25 years the amyloid cascade hypothesis has existed as a mechanism of understanding and diagnosing Alzheimer’s Disease. The amyloid cascade hypothesis suggests that Alzheimer’s Disease is sequential in protein progression and proliferative from the medial temporal lobe to the rest of the brain. Hypometabolism of brain regions has also been correlated to plaque deposition and hypometabolism is observed in brain regions that make up the default mode network, specifically the retrosplenial cortex, which is not accounted …

Non-Canonical Activation Of Creb/Crh-1 Mediates Neuroprotection In A Caenorhabditis Elegans Model Of Excitotoxic Necrosis, K. Genevieve Feldmann

Dissertations, Theses, and Capstone Projects

Excitotoxicity, which is a major cause of neurodegeneration in brain ischemia, can also activate neuroprotective pathways. A frequently suggested neuroprotective cascade involves the activation of the transcription factor CREB by its phosphorylation, but on its own this mode of CREB activation is promiscuous. We aim to elucidate the specific mechanism of CREB activation in excitotoxicity-induced neuroprotection, focusing on three suggested models: CREB phosphorylation by calcium-activated kinases in the cytoplasm or nucleus, and the activation of CREB by CRTC (an important cofactor). Using a C. elegans model of excitotoxicity, we demonstrate that CREB’s neuroprotective effect is mainly seen in neurons exposed …

An Analysis Of Neurogenesis In A Mouse Model Of Chemotherapy Related Cognitive Impairment, Maxwell A. Hennings

Electronic Theses and Dissertations

Cancer patients treated with adjuvant chemotherapy often experience cognitive decline following treatment. This phenomenon, often dubbed “chemo brain” or “chemo fog” is usually temporary, but for a subset of survivors, these cognitive impairments can be long-lasting (>10 years) and negatively affect patients’ quality of life, career performance, and social fulfillment. While it is unclear what neurobiological mechanisms underlie chemotherapy related cognitive impairment, the majority of the animal literature has focused on adult neurogenesis. One process important for neurogenesis is the proliferation of new neurons within the dentate gyrus of the hippocampus. It is evident that many chemotherapy agents can …

Characterization Of Vesicular Monoamine Transporter 2 And Its Role In Parkinson's Disease Pathogenesis Using Drosophila, Antonio Joel Tito Jr., Sheng Zhang

Dissertations & Theses (Open Access)

Parkinson’s disease (PD) is a progressive neurodegenerative disorder caused by the selective loss of the dopaminergic neurons in the Substantia nigra pars compacta region of the brain. PD is also the most common neurodegenerative disorder and the second most common movement disorder. PD patients exhibit the cardinal symptoms, including tremor of the extremities, rigidity, slowness of movement, and postural instability, after 70-80% of DA neurons degenerate. It is, therefore, imperative to elucidate the underlying mechanisms involved in the selective degeneration of DA neurons. Although increasing numbers of PD genes have been identified, why these largely widely expressed genes induce …

Cellular And Genetic Bases Of Cold Nociception And Nociceptive Sensitization In Drosophila Larvae, Heather N. Turner

Dissertations & Theses (Open Access)

Organisms from flies to mammals utilize thermoreceptors to detect and respond to noxious thermal stimuli. Although much is understood about noxious heat avoidance, our understanding of the basic biology of noxious cold perception is gravely minimal. Numerous clinical conditions disrupt the sensory machinery, such as in patients suffering from tissue damage (from wound or sunburn), or injury to the peripheral nerves, as in patients with diabetes or undergoing chemotherapy. Our goal is to determine the genetic basis for noxious cold perception and injury-induced nociceptive sensitization using the genetically tractable Drosophila model. Using a novel "cold probe" tool and assay we …

Modulation Of Synaptic Transmission By Adenosine In Layer 2/3 Of The Rat Visual Cortex In Vitro, Nicholas M. Bannon

Master's Theses

No abstract provided.