Physiology Commons^™

Identifying The Cell Composition And Clonal Diversity Of Supratentorial Ependymoma Using Single Cell Rna-Sequencing, James He

Honors Scholar Theses

Ependymoma is a primary solid tumor of the central nervous system. Supratentorial ependymoma (ST-EPN), a subtype of ependymomas, is driven by an oncogenic fusion between the ZFTA and RELA genes in 70% of cases. We introduced this fusion into neural progenitor cells of mice embryos via in utero electroporation of a non-viral binary piggyBac transposon system containing ZFTA-RELA. From preliminary data in the LoTurco lab, inducing the expression of ZFTA-RELA into different neural progenitor cells produces tumors of varying lethality and cellular composition. To define the cellular composition and subclonal diversity of ST-EPN tumors, we used single cell RNA-sequencing …

Microglia-Neuron Interactions In A Mouse Model Of Low Grade Neuroepithelial Tumors, Veolette Hanna

Honors Scholar Theses

Microglia are the macrophages of the brain and spinal cord, playing an important role in the immune response to disease states of the nervous system. This study conducts an investigation on the activity of microglia in response to low grade neuroepithelial tumors. Using mouse models and microglial markers, a qualitative and quantitative analysis of microglia activation, migration, and invasion within the brain cortex during early stages of tumor development was conducted. It was found that the presence of a low grade neuroepithelial tumor in the cortex of one hemisphere of the brain causes significant microglia activation in comparison to the …

Amygdala And Neocortical Structural Volume Analysis In The Shank3b Mutant Mouse Model Of Autism Spectrum Disorder, Preet Sawhney

Honors Scholar Theses

Autism Spectrum Disorder (ASD) is a neurodevelopmental disorder that is characterized by abnormal social behavior, deficits in communication, and motor stereotypy. The SHANK3 gene, responsible for the generation of a scaffolding protein that is integral for the development of synapses, has been identified as one of the primary candidate genes implicated in the disorder. Shank3B is the rodent homolog for this gene. Research has shown that when this gene is disrupted in rodent models (e.g., via knock-out (KO)), ASD-like behaviors result. These include deficits in social interaction, increased anxiety, and repetitive self-grooming. The current study aimed to identify a physiological …

Assessing The Morphology Of Vesicles In Inhibitory Symmetric Synapses In Safety And Fear Conditions In The Rat Lateral Amygdala, Valerie Kress

Honors Scholar Theses

There is a significant lack of research on vesicle morphology in inhibitory synapses in the rat lateral amygdala. Published research focuses heavily on excitatory synapses in different parts of the rat brain and even this research rarely focuses on the different vesicle types in axons. It is reported that in these axons, synaptic vesicles traditionally contain neurotransmitters while small dense core vesicles contain active zone proteins and large dense core vesicles contain neuropeptides. This study aims to find correlations between vesicle morphology, location, contents, and potential function of each of the different types of vesicle in inhibitory axons.

After reviewing …

Reconstitution Of Gabaergic Postsynapses In Host Cells, Karthik Kanamalla

Honors Scholar Theses

Type A GABA receptors (GABAARs) can be found embedded in postsynaptic membranes or in a variety of extrasynaptic locations. Receptors with synaptic function are recruited to the postsynapse by submembranous scaffolds composed of gephyrin and collybistin (CB). This study was aimed at assessing whether the ability to interact with the scaffold differentiates synaptic from non-synaptic receptors. Using HEK293 cells as an expression system, and indirect immunofluorescence (IF), co-localization of extrasynaptic receptors α1β3δ and α4β3δ with the CB-gephyrin scaffold was assessed and compared with that of the synaptic receptor α1β3γ2. Results indicated that both extrasynaptic receptors were able to colocalize with …

Development Of Vip-Sst Interneuron Associations In Mouse Neocortex And Entorhinal Cortex, Aayushi A. Mehta

Honors Scholar Theses

Cortical networks depend upon inhibition through the neurotransmitter GABA to control and coordinate specific spatiotemporal circuit patterns, underlying the exquisite complexity of neural signaling. Disinhibition, a form of inhibition where inhibitory neurons inhibit other inhibitory cells, further aids in amplifying local neural processing in a selective, organized manner. A subset of GABAergic interneurons, vasoactive intestinal peptide-expressing (VIP) cells, preferentially inhibit somatostatin interneurons, which provide inhibitory input onto pyramidal cells, thus creating an archetypal circuit illustrating disinhibition in the cortex. The aim of this anatomical study was to investigate variations in GABAergic VIP synapses onto somatostatin-expressing inhibitory interneurons in mice at …

Pathological Effects Of Repeated Concussive Tbi In Mouse Models: Periventricular Damage And Ventriculomegaly, Richard H. Wolferz Jr.

Honors Scholar Theses

Repeated concussive traumatic brain injury (rcTBI) is the most prominent form of head injury affecting the brain, with an estimated 1.7 million Americans affected each year (Kuhn 2012). Neurologists have been concerned about the danger of repeated head impacts since the 1920’s, but researchers have only begun to understand the long-term effects of rcTBI (McKee 2009). Although symptoms can be as mild as dizziness, current research suggests that multiple concussions can lead to a progressive degenerative brain disease known as chronic traumatic encephalopathy (CTE) (Luo 2008, McKee 2009, Kane 2013). Research on the brain is just beginning to scratch the …

Direct Reprogramming Of Mouse Embryonic Fibroblasts Into Gabaergic Neurons, Nicholas J. Wasko

Honors Scholar Theses

Recent studies in which mouse and human fibroblasts were directly reprogrammed into functional neurons have demonstrated that lineage-specific transcription factors can override differentiation processes previously thought to be irreversible. Notably, three factors have been shown to be required for the induction of neural cell fate. Subsequent experiments have identified additional factors capable of generating specific neuronal subtypes, including motor neurons and dopaminergic neurons, but the factors necessary for inducing GABAergic neuronal fate have yet to be elucidated. Here, factors linked to GABAergic fate were transfected into mouse fibroblasts in order to identify candidate factors for inhibitory interneuron direct reprogramming. Results …

Evidence For Pit-Type (Slc20) And Napi-Ii-Type (Slc34) Transporters In The Rat Choroid Plexus, Hien M. Le

Honors Scholar Theses

: A major function of the brain choroid plexus (CP) is to regulate the exchange of solutes between the blood plasma and the cerebrospinal fluid (CSF) using selective transporters. CSF inorganic phosphate (P_i) concentration is maintained at about one-half that of plasma and is potentially important because of its regulatory, structural, and biochemical functions. Phosphate is critical for ATP and DNA formation, the linked regulation between phosphate and calcium, and as an intracellular buffer. The human body has two major P_i transporter gene families known as SLC34 (NaPi-II) and SLC20 (PiT), which have wide tissue distribution. Although …

The Effects Of Rectal Temperature And Hydration Status On Perceptual Ratings In Dehydrating Males, Ethan A. Talbot

Honors Scholar Theses

Athletes push the limits of what the human body can handle every day. When they exercise in the heat, they can attain dangerous levels of internal temperature and dehydration. Since athletes are sometimes not aware when they are experiencing severe hyperthermia or hypohydration, it is of interest to anyone who exercises in the heat to study whether athletes are consciously aware that they are approaching dangerous physiological limits. This study compares the perceptual values of athletes exercising in the heat to the changes in their internal temperature and hydration status, to see if athletes can reliably predict their heat and …

Changes In The Proliferation Of The Subventricular Zone Neural Stem Cell Pool Throughout Aging In The Murine Brain, Olayinka Edwards

Honors Scholar Theses

Previous studies regarding subventricular zone (SVZ) neural stem cells (NSCs) have either observed global changes in the SVZ niche containing NSCs or an impure NSC population. By imaging wholemount preparations of mouse brains and staining with molecular markers specific for proliferating NSC nuclei, the study was able to give a more accurate depiction of the SVZ NSC population than its predecessors. This study will quantify the percentage of proliferating NSCs at various ages of adult murine brain development in order to elucidate a possible correlation between NSC division kinetics and the declining neurogenic output witnessed with aging.

Investigating The Diversity Of Radial Glia Fates In The Rat Neocortex, Abraham William Aron

Honors Scholar Theses

Radial Glia (RG) are a mitotically active population of cells which reside within the ventricular zone at the lateral ventricle and give rise to the pyramidal neurons and astrocytes of the neocortex. Through cellular divisions, RG produce two daughter cells, one which resides in the ventricular zone and becomes another RG while the other is an immature progenitor which migrates away from the ventricle and populates the growing cortex. RG have been found to be a heterogeneous population of cells which express different surface antigens and genetic promoters which may influence the cellular fate of their progeny. In this study …

Oxygen Supplementing, Biocompatible Outer Membranes For Enhanced Performance Of Implantable Glucose Sensors, Hardeep Singh

Honors Scholar Theses

Lack of linearity and sensitivity, oxygen dependence, biofouling and tissue inflammation hinder the development of implantable biosensors for continuous monitoring of glucose. Herein, we report the development of stacked outer membranes based on LBL/PVA hydrogels that improve sensor sensitivity, linearity, oxygen independence and counter biofouling and inflammation. While the inner LBL membrane affords tunable diffusivity, the outer PVA is capable of releasing anti-inflammatory drugs/tissue response modifying agents to counter acute and chronic inflammation, and to induce neo-angiogenesis at the implant site. Sensors were fabricated by immobilizing GOx enzyme on top of 50 μm platinum wires, followed by deposition of stacked …

Head And Neck Embryology: An Overview Of Development, Growth And Defect In The Human Fetus, Allison Baylis

Honors Scholar Theses

The purpose of this research is to explore the growth and formation of the head and neck from embryological development through puberty in order to understand how this knowledge is necessary for the development of dental and medical treatments and procedures. This is a necessary aspect of the medical and dental school curriculum at the University of Connecticut Health Center Schools of Medicine and Dental Medicine that needs to be incorporated into the current study of embryology for first-year students. Working with Dr. Christine Niekrash, D.M.D, this paper will cover the embryology and growth of the head, face and oral …

Effects Of Estrogen On Muscle Damage In Response To An Acute Resistance Exercise Protocol, Megan R. Wolf

Honors Scholar Theses

Creatine Kinase (CK) is used as a measure of exercise-induced muscle membrane damage. During acute eccentric (muscle lengthening) exercise, muscle sarcolemma, sarcoplasmic reticulum, and Z-lines are damaged, thus causing muscle proteins and enzymes to leak into the interstitial fluid.

Strenuous eccentric exercise produces an elevation of oxygen free radicals, which further increases muscle damage. Muscle soreness and fatigue can be attributed to this membrane damage. Estradiol, however, may preserve membrane stability post-exercise (Brancaccio, Maffulli, & Limongelli, 2007; Carter, Dobridge, & Hackney, 2001; Tiidus, 2001). Because estradiol has a similar structure to Vitamin E, which is known to have antioxidant properties, …

Salivary Cortisol, Psychological Stress And Depressive Symptoms Among Patients Undergoing Colon Cancer Screenings, Allyson Reid

Honors Scholar Theses

As the second leading cause of cancer-related deaths in the United States, colon cancer has a high cure rate if detected early by a colonoscopy (U.S.

Cancer Statistics Working Group, 2007). However, more than 41 million at-risk Americans are not properly receiving colonoscopy screenings according to the recommendations of the Center for Disease Control. This study provides insight into the physiological and psychological benefits of the colonoscopy procedure over and above cancer detection and prevention. Thirty-six patients receiving colonoscopic screening at the University of Connecticut Health Center participated in this study. A questionnaire battery that assessed perceived stress, depressive symptoms, …

Differentiation Of Human Embryonic Stem Cell (Hesc) Derived Pyramidal Neurons, Eagan Jacqueline

Honors Scholar Theses

The mammalian cerebral neocortex is a complex six-layered structure containing multiple types of neurons. Pyramidal neurons of the neocortex are formed during development in an inside-out manner, by which deep layer (DL) neurons are generated first, and upper layer (UL) neurons are generated last. Neurons within the six-layered neocortex express unique markers for their position, showing whether they are subplate, deep layer, upper layer, or Cajal-Retzius neurons. The sequential generation of cortical layers, which exists in vivo, has been partially recapitulated in vitro by differentiation of mouse embryonic stem cells (Gaspard et al., 2008) and human embryonic stem cells (hESC) …

Intrinsic Ph-Sensitivity Of Cells In The Retrotrapezoid Nucleus: Possible Role Of Glia In Respiratory Drive, Nicole Edwards

Honors Scholar Theses

An increase in carbon dioxide (CO2) and protons (H+) are the primary signals for breathing. Cells that sense changes in CO2/H+ levels and increase breathing accordingly are located in a region of the caudal medulla oblongata called the retrotrapezoid nucleus (RTN). Specifically, select RTN neurons are intrinsically pH sensitive and send excitatory projections to the respiratory rhythm generator to drive breathing. Glial cells in the RTN are thought to contribute to this respiratory drive, possibly by releasing ATP in response to increases in CO2/H+ levels.

However, pH sensitivity of RTN glial cells has yet to be determined.

Therefore, the goal …

Colocalization And Distribution Of Hcn4 Channels And A Maguk Protein In Mammalian Sinoatrial Myocytes, Padmastuti Akella

Honors Scholar Theses

The sinoatrial node is known as the pacemaker of the heart. It controls the rate at which action potentials are generated and propagate through the sinoatrial myocytes. This thesis is an attempt to identify the colocalization of a specific ion channel (HCN4 channel) with a class of scaffolding protein (MAGUK proteins) within the sinoatrial myocyte. The colocalization of these two variables was performed using immunocytochemistry on murine sinoatrial myocytes and experimental results revealed the existence of a strong colocalization between the two variables. Images collected from the confocal microscope and analyzed using ImageJ software revealed a strong dependent correlation between …