Neuroscience and Neurobiology Commons^™

Kcnq2 Localization In The Brainstem, Christina Valera

Honors Scholar Theses

KCNQ2 channels are potassium channels that serve to control neuronal excitability. Loss of function mutations in these channels are known to cause various forms of epilepsy. Recently, KCNQ2 R201C and R201H gain of function mutations have been shown to exhibit an exaggerated startle response and other unique phenotypes uncharacteristic of epilepsy. These phenotypes resemble hyperekplexia, a condition in which glycine neurotransmission in the spinal cord and brainstem is affected. While KCNQ2 has widespread localization throughout the brain, its presence in the brainstem remains unknown. We used immunostaining to determine the localization of KCNQ2 in the vagus nerve and hypoglossal nerve …

Using Machine Learning To Conduct A Detailed Behavioral Analysis In An Appetitive Social Learning Task, Thomas Shao

Honors Scholar Theses

Learning by watching others, or observational learning, is important for social development and survival. However, not much is known about the brain mechanisms underlying this type of learning. Since the 1960s, observational learning has been widely studied in humans, but developing and analyzing experiments for animals has been challenging. Here, I explore observational learning using a novel paradigm while performing an analysis that involves tracking the rats using an active learning paradigm called DeepLabCut. In this novel paradigm, customized operant conditioning chambers are used for the rats to observe and learn from another animal repeatedly on multiple trials each day. …

Remapping Of Place Cells In The Dorsal And Ventral Hippocampus In Response To Environmental Change, Aditi Anam

Honors Scholar Theses

The hippocampus is an important brain structure involved in memory and navigation of both rats and humans. Neurons in the hippocampus can be “spatially” tuned, meaning they fire in specific physical locations. These spatially tuned cells are referred to as place cells. Collectively, they are thought to provide a map-like representation of the environment around us. If the environment is changed, some place cells can adjust by “remapping”, or altering their firing patterns. There are multiple sub-regions within the hippocampus. During experiments, cells were recorded simultaneously from the dorsal and ventral hippocampus of rats running on a track for food …

Detection Of Tinnitus In Cba/Caj Mice Using The Active Avoidance Shuttle Box Test, Grace Nichols

University Scholar Projects

Tinnitus is a neurological condition that involves the perception of a sound that is not actually there. Individuals affected with tinnitus describe the condition as a ringing, buzzing, or whooshing sound in their ears. One-third of the population is estimated to have tinnitus, and for many individuals, the condition negatively impacts quality of life. Difficulty falling asleep, trouble with hearing and concentrating, and in some cases, depression, have all been observed to occur with tinnitus.

Tinnitus has been extensively studied in animals, and behavioral tests are the primary method of evaluating the presence of tinnitus in animals. This study evaluates …

Reorganization Of The Human Ventricular-Subventricular Zone Neural Stem Cell Niche In Fetal-Onset Hydrocephalus, Saurabh Kumar

University Scholar Projects

Fetal-onset hydrocephalus is a relatively common birth defect occurring in 1-2 cases per thousand births and is characterized by abnormally expanded brain ventricles. Current diagnosis for this complex pathology often involves relatively simple metrics and heavy reliance on clinician experience over objective measures. Those affected often suffer chronic headaches and cognitive deficits and may present with a bulging skill. Shunting is considered the standard treatment for communicating hydrocephalus (i.e. cerebrospinal fluid flow is physically unobstructed in the ventricular system). Shunting remains a highly invasive procedure often performed during the critical period of infancy and has a high failure rate of …

Detection Of Tinnitus In Cba/Caj Mice Using The Active Avoidance Shuttle Box Test, Grace Nichols

Honors Scholar Theses

Tinnitus is a neurological condition that involves the perception of a sound that is not actually there. Individuals affected with tinnitus describe the condition as a ringing, buzzing, or whooshing sound in their ears. One-third of the population is estimated to have tinnitus, and for many individuals, the condition negatively impacts quality of life. Difficulty falling asleep, trouble with hearing and concentrating, and in some cases, depression, have all been observed to occur with tinnitus.

Tinnitus has been extensively studied in animals, and behavioral tests are the primary method of evaluating the presence of tinnitus in animals. This study evaluates …

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 …

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 …

Optical Clearing Reveals Tnbs-Induced Morphological Changes Of Vglut2-Positive Nerve Endings In The Colorectum, Shivam Patel

Honors Scholar Theses

Sensitization of colorectal afferents and colorectal hypersensitivity have been observed in a mouse model of post-infectious irritable bowel syndrome via intracolonic treatment of 2,4,6-trinitrobenzenesulfonic acid (TNBS). In this study, we investigated the distribution and morphology of microscopic colorectal afferent endings before and after intracolonic treatment of TNBS. We genetically labeled predominantly extrinsic colorectal afferents using the vesicular glutamate transporter type 2 (VGLUT2) promoter. Then, we used an optical tissue clearing method of whole-mount colorectum to image labeled VGLUT2-nerve endings that are otherwise obscured in untreated samples. We used vector path tracing to quantify the density and degree of curliness of …

The Effects Of The Atypical Dopamine Uptake Inhibitor Ce-158 On Extracellular Dopamine In The Nucleus Accumbens, Julia Neri

Honors Scholar Theses

Major Depressive Disorder (MDD) is characterized by symptoms such as cognitive dysfunctions, inflammatory changes, and motivational symptoms such as amotivation, fatigue, and anergia. While depressed people are commonly treated by traditional antidepressants such as serotonin reuptake inhibitors (SSRIs), previous studies have reported that SSRI medications do not treat fatigue and anergia symptoms well, and in some cases, can even worsen those symptoms. Subjects treated with dopamine (DA) uptake inhibitors, on the other hand, have been less likely to report symptoms of anergia and fatigue compared to those treated with SSRIs. Common DA uptake inhibitors such as methylphenidate and amphetamines, however, …

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 …

Investigating The Neurobiology Of Motivational Deficiencies In Major Depressive Disorder: 5-Ht1b Receptor Involvement In Behavioral Effects Of Fluoxetine (Prozac), Sarah Ferrigno

University Scholar Projects

Selective serotonin reuptake inhibitors (SSRIs) such as fluoxetine (Prozac) are the most commonly prescribed treatments for depression. Although efficacious for symptoms such as a depressed mood, SSRIs do not alleviate symptoms of amotivation, anergia, and fatigue. Furthermore, in clinical and preclinical studies, SSRIs have been shown to exacerbate motivational impairments and general fatigue. It is likely that fluoxetine-induced dysfunctions are due to overstimulation of one or more 5-HT receptors, with one possible candidate being the 5-HT_1B receptor. Therefore, the aim of the study was to evaluate the role of 5-HT_1BRs in fluoxetine-induced amotivation using a rodent behavioral …

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 …

Quantifying Expression Of Interneuron Subtype Markers For Dlx-2 Transfected Ng2 Cells, Timothy Nolan

Honors Scholar Theses

Neurons are a post-mitotic cell population, and therefore, they are not able to regenerate in vivo after a traumatic injury. Because inhibitory GABAergic interneurons and oligodendrocyte precursor cells (OPCs) are derived from the same precursor, recent studies have focused on transforming these OPCs into GABAergic neurons. However, there are different types of GABAergic interneurons that have different electrophysiological responses, which can lead to functional differences. The Nishiyama laboratory had already used a key gene in GABAergic interneuron and OPC differentiation, Distal-less homeobox 2 (Dlx-2), to transfect OPCs; early electrophysiology tests showed most of these transfected cells behaved like immature neurons, …

The Ush2a Gene: An Analysis Of Ultrasonic Vocalizations In A Mouse Model Of Usher Syndrome Type 2, Kiana R. Akhundzadeh

Honors Scholar Theses

Usher syndrome type 2 is a complex autosomal recessive genetic disorder that is characterized by moderate to severe congenital sensorineural hearing loss, the onset of retinitis pigmentosa in the second decade of life, and in some cases, vestibular dysfunction. Mutations in the USH2A gene account for 85% of cases of type 2. The USH2A gene is responsible for encoding the protein usherin, which has an important role in the development and function of inner ear hair cells and retinal photoreceptors. Until recently, it has been believed that carriers of the USH2A mutation were phenotype free. However, recent data has suggested …

Is Concussion-Related Sleep Disturbance Present After Return To Play In College Athletes?, Alexander Gallaer

Honors Scholar Theses

As one of the most commonly experienced symptoms, the ramifications of sleep disruption as a result of concussion are potentially great, yet widely unexplored. Particularly troublesome is murky data regarding the length of sleep disruption following a concussion. By analyzing self-reported sleep data via the Pittsburgh Sleep Quality Index, this study seeks to investigate potential differences in sleep quality between injured college athletes 40 days after they have been cleared to play and matched controls. Data was analyzed using ANOVA analysis as well as Pearson correlation. No significant differences were found in sleep quality between groups, nor was there a …

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 …

Neuroscience Underlying Temporal Cue Discrimination In The Auditory Cortex, Samantha D. Rosicke

Honors Scholar Theses

Animals, including rats and humans, use the auditory cortex to discriminate auditory cues for communication and survival. It has been shown that individual neurons in the A1, ventral auditory field (VAF), and suprarhinal auditory field (SRAF) of the rat auditory cortex respond to different noise burst lengths to help the rat comprehend an auditory stimulus. In this experiment, we demonstrate the behavioral ability of male Long Evans rats to discriminate between noise bursts of different temporal lengths: 12 ms and 66 ms, in a Two-Alternative Forced Choice task. The study of temporal cue discrimination in the auditory cortex can be …

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 …

Exploring The Effect Of Novel Small Molecules On Oligodendrocyte Precursor Proliferation, Sagune Sakya

University Scholar Projects

Gliomas, a type of brain tumor, can be difficult to treat and have a poor survival rate. One pathway that leads to glioma formation is excessive signaling by platelet derived growth factors (PDGF) through PDGF receptor α (PDGFRα). Through this research, I found that novel compounds that downregulate PDGFRα decrease proliferation of Oli-neu cells, an oligodendrocyte precursor cell model, and identified signaling pathways through which these compounds may exert their effect. Further investigation may identify targets for development of glioma treatments.

Histological Verification Of Electrode Placement In Single Unit Recorded Rats, Dana Lew

Honors Scholar Theses

The hippocampus is a region of the brain which plays a major role in encoding spatial and episodic memory. The hippocampus is divided in to two main subregions, dorsal and ventral. These subregions are connected, but their functional organization remains widely unknown. Place cells are cells of the hippocampus which fire in a specific spatial area and help create a mental map of our surroundings. Place cells have been seen to remain constant during slight fluctuations in surroundings, but completely remap in response to large fluctuations in the environment. There is little known about the relatively few place cells in …

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 …

Intensive Sound Production Treatment For Apraxia Of Speech: An Analysis Of Error Consistency, Victoria M. Abolafia

Honors Scholar Theses

In the past, clinicians have diagnosed acquired apraxia of speech based upon the presentation of an inconsistent error pattern. However, recent research studies have begun to suggest quite the contrary, pointing towards a consistent pattern of errors in the speech of those with apraxia. The present study utilized an intensive Sound Production Treatment (SPT) for a 51-year-old male with severe acquired apraxia of speech and moderate-severe aphasia. Treatment was administered over a period of five days per week, three hours a day, for two consecutive weeks. During this treatment, probes were gathered daily to evaluate the efficacy of the intensive …

Behavioral And Neuroanatomical Outcomes Of Early And Late Preterm Hypoxic-Ischemic Injury And The Neuroprotective Effects Of Whole-Body Hypothermia: An Animal Model, Haley C. Garbus

University Scholar Projects

The overarching aims of this research were: first, to characterize the anatomical and behavioral effects of preterm hypoxic-ischemic (HI) injury in rodent models; and second, to explore the method of passively induced whole-body hypothermia as a neuroprotective intervention following HI. Clinical research of preterm injured infants has shown a large range of behavioral deficits, including delays in language learning, spatial and non-spatial memory, visual attention, and motor coordination. The current studies focused on these behavioral abnormalities, using HI rodent models. Specifically, we explored a model for early preterm HI (HI induced on postnatal day (P) 3 in rats), and compared …

Spike Field Coherence (Sfc) For Ripples In Rat Hippocampus, Pranav Singla

Honors Scholar Theses

The aim of this project was to determine coherence between two types of neural recordings which can be obtained from the rat hippocampus: spikes and local field potentials. Extracellular recording makes it possible to determine spiking activity from individual neurons in the vicinity of the recording electrode. Local field potential recording gives a combined activity of many neurons (thousands) at once to determine an overall picture of the coordination of the cells in real time. Here we examine the relationship between these two signals, focusing on place cells which spike at their maximal rate only at certain positions in physical …

Design, Programming, And User-Experience, Kaila G. Manca

Honors Scholar Theses

This thesis is a culmination of my individualized major in Human-Computer Interaction. As such, it showcases my knowledge of design, computer engineering, user-experience research, and puts into practice my background in psychology, com- munications, and neuroscience.

I provided full-service design and development for a web application to be used by the Digital Media and Design Department and their students.This process involved several iterations of user-experience research, testing, concepting, branding and strategy, ideation, and design. It lead to two products.

The first product is full-scale development and optimization of the web appli- cation.The web application adheres to best practices. It was …

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 …

Oscillatory Activity In The Subthalamic Nucleus And Motor Cortex In A Pharmacological Model Of Parkinsonian Tremor, Aileen F. Haque

Honors Scholar Theses

Parkinson’s Disease (PD) is a motor disorder with symptoms including resting tremor, akinesia, bradykinesia, and rigidity. A major neuropathological feature of PD is degeneration of nigrostriatal dopamine (DA) neurons. The resulting DA depletions lead to the production of severe motor deficits. Pharmacological agents that reduce DA transmission can also induce these motor abnormalities. In addition to the involvement of DA, drugs acting on acetylcholine, namely cholinomimetics, can induce or exacerbate Parkinsonian symptoms. In humans, one of the main motor symptoms associated with PD is resting tremor, occurring at a frequency of 3-7 Hz. This can be modeled in rodents using …

Electrophysiological Changes Of N100 Latency And Amplitude In Healthy Participants Performing The Jitter Orientated Visual Integration Task: A Multi-Block Design Study, Fariya Naz

University Scholar Projects

The present study investigated the differences in processing during visual integration in healthy adults. The visual N100 indexes early visual discrimination and in this case, was hypothesized to show differences in both latency and amplitude depending on the level of difficulty which corresponds to orientational jitter in a visual integration task. Four blocks with pseudo-random levels of jitter were presented to participants in the Jitter Oriented Visual Integration (JOVI) task. Results looking at the Oz channel showed significant reduction in amplitude in the visual N100 during the more difficult levels condition of the task. The multi-block design, originally expected to …

Astroglial Boundary Formation And Epha4 Signaling In Neuroblast Migration, Nicholas B. Gallo

University Scholar Projects

Adult neurogenesis, the process of generating new neurons from neural precursors, is a highly complex process that is limited to two specific areas of the brain, the dentate gyrus of the hippocampus and the subventricular zone (SVZ). Despite continued research investigating neurogenesis in these two regions, we still lack a fundamental understanding of the molecular mechanisms of neural cell division, migration, differentiation, and integration in the postnatal brain. In particular, the rostral migratory stream (RMS), which is a cellular migratory route for newly generated neuronal precursors that travel from the SVZ to the olfactory bulb, will provide a useful model …