Behavioral Neurobiology Commons^™

Effect Of Ambient Temperature On Recovery Of Surgically Instrumented Sprague-Dawley Rats, Gianna Mangone

Senior Honors Projects, 2020-current

Based on current guidelines for housing rodents after surgical instrumentation, rodents may be housed at temperatures that hinder surgical recovery and cause thermal stress– room temperature (21°C) being one of them. Rodents are often housed at room temperature since this temperature is easy for humans to be caring for them. However, if recovering rodents are thermally stressed, experimental results will be confounded. To address this issue, Sprague-Dawley rats were surgically instrumented with radiotelemtry thermoprobes (Data Sciences, #TA-10F40) to monitor their core temperatures, then housed at one of five temperatures to assess the effect ambient temperature had on multiple aspects of …

The Role Of Dopamine In Decision Making Processes In Drosophila Melanogaster, Michelle C. Bowers

Undergraduate Honors Theses

Understanding the neural processes that mediate decision making is a relatively new field of investigation in the scientific community. With the ultimate goal of understanding how humans decide between one path and another, simpler models such as Drosophila Melanogaster, the common fruit fly, are often utilized as a way of determining the neural circuits involved in these decision-making processes. One of the most important decisions flies make is the decision of where to lay their eggs (oviposit). Choosing the proper substrate upon which to lay eggs is a crucial decision that can ultimately impact their fecundity. This paper investigates the …

The Role Of Inter-Enlargement Propriospinal Neurons In Locomotion Following Spinal Cord Injury., Courtney Therese Shepard

Electronic Theses and Dissertations

The focus of this dissertation is to explore the functional role of two anatomically-defined pathways in the adult rat spinal cord before and after spinal cord injury (SCI). To do this, a Tet^On dual virus system was used to selectively and reversibly silence neurons with cell bodies at spinal segment L2 and projections to spinal segment C6 (long ascending propriospinal neurons, LAPNs) and neurons that originate in the C6 spinal segment and terminate at L2 spinal segment (long descending propriospinal neurons, LDPNs). This dissertation is divided into five chapters. Chapter One provides background information regarding spinal cord injury, locomotion, …

Hypothalamic Circuits Mediating Consumption And Anxiety, Ryan Cassidy

Dissertations and Theses (Open Access)

From 1960-2016, U.S. obesity prevalence increased 13-40% and diabetes increased from 3-15%. There is an epidemic of metabesity, the aggregate metabolic disorders produced by chronic overeating. Drugs for metabesity were developed in the 1930s with limited effectiveness; agents today rely on the same principles and are similarly ineffective. Particularly surprising has been the failure of satiety enhancers; this indicates it may not be that physiologic hunger drives chronic overeating. Although hunger and satiety affect traditional reward circuitry (Cassidy & Tong 2017), evidence for the primacy of this effect is mixed. Being hungry reduces anxiety-like behavior in mice; whether the …

Activation Of The Sonic Hedgehog Effector Smoothened Counteracts L-Dopa Induced Dyskinesia By Restoring Cholinergic Interneuron Function, Lauren Malave

Dissertations, Theses, and Capstone Projects

Many types of neurons act as multimodal signaling centers. Yet, we have only limited insight into the regulation and functional consequences of neuronal co-transmission. For example, dopamine (DA) neurons, whose degeneration causes motor deficits characteristic of Parkinson’s Diseases (PD), communicate with all their targets by DA but only a selective subset of their targets using GABA, Glutamate, and the secreted cell signaling protein Sonic Hedgehog (Shh). It is unknown whether Levo-dopamine (L-Dopa) induced dyskinesia (LIDs), a severely debilitating side effect of DA supplementation in PD, might appear because DA neuron targets are exposed to high DA- but low Shh- signaling …

Assessing A Two-Hit Model Of Schizophrenia: Prenatal Choline Deficiency And Induced Hypofunction Of Nmda Receptors In Male And Female Long Evans Rats, Samuel Gray, Samuel W. Gray

Honors Theses

Choline is an essential dietary nutrient essential to the development and function of the central nervous system. Prenatal choline deficiency alters hippocampal development as well as acetylcholine metabolism, leading to cognitive impairments and attentional and sensory processing deficits into adulthood. MK-801 is an NMDA receptor antagonist frequently used in rodent models of neuropsychiatric conditions, particularly schizophrenia. Acutely and sub- chronically, it causes hyperlocomotion and social withdrawal. One primary goal of the present study were to investigate prenatal choline deficiency induces a biological vulnerability to the motor deficits, anhedonia, and social impairment precipitated by low-dose sub-chronic MK-801 administration in adulthood. Another …

Characterization Of Sensory And Shelter Enrichment In The Rodent Research Habitat, Amber M. Paul, Yasaman Shirazi-Fard, America Reyes, Moniece Lowe, Margareth Cheng-Campbell, Sungshin Choi, Eduardo Almeida, April Ronca, Ruth K. Globus

Publications

The ISS provides a platform for conducting Rodent Research (RR) in microgravity and 9 missions have been successfully conducted. The results from these experiments have begun to provide new insights into the effects of spaceflight on mammalian physiological systems. After RR-1-4, the Flight IACUC required inclusion of additional cage enrichment into the Rodent Habitats (RH) to “enhance animal well-being by providing animals with sensory and motor stimulation, through structures and resources that facilitate the expression of species typical behaviors”. A Hut, in the form of a rigid, mesh igloo-like shelter was implemented beginning with RR-5. The potential influence of the …

Influence Of Social Isolation During Prolonged Simulated Weightlessness By Hindlimb Unloading, Candice G.T. Tahimic, Amber M. Paul, Ann-Sofie Schreurs, Samantha M. Torres, Linda Rubinstein, Sonette Steczina

Publications

The hindlimb unloading (HU) model has been used extensively to simulate the cephalad fluid shift and musculoskeletal disuse observed in spaceflight with its application expanding to study immune, cardiovascular and central nervous system responses, among others. Most HU studies are performed with singly housed animals, although social isolation also can substantially impact behavior and physiology, and therefore may confound HU experimental results. Other HU variants that allow for paired housing have been developed although no systematic assessment has been made to understand the effects of social isolation on HU outcomes. Hence, we aimed to determine the contribution of social isolation …

Emotion Processing Deficits In Psychopathy: Does Cueing To Relevant Facial Features Increase Cognitive And Emotional Empathy?, Shawn E. Fagan

Dissertations, Theses, and Capstone Projects

Psychopathy is a multifaceted disorder characterized by a lack of cognitive and emotional empathy. The traditional model of psychopathy divides the disorder into two factors: Factor 1 consists of the interpersonal and affective traits of psychopathy while Factor 2 measures antisocial behaviors and lifestyle choices. The attention-to-the-eyes hypothesis argues that psychopathic individuals have impaired emotion recognition (specifically for fear) due to deficits in orienting attention to salient facial features like the eyes. Psychopathic individuals also display blunted autonomic responding to emotional stimuli, though whether this is due to attention-orienting deficits remains to be clarified. The present project investigated whether empathy-related …

Spirituality And The Infant Brain: Implications For Attachment Theory And Therapeutic Process Across The Life Span, Caitlin Eliasson

Consensus

No abstract provided.

Feedforward And Feedback Signals In The Olfactory System, Srimoy Chakraborty

Graduate Theses and Dissertations

The conglomeration of myriad activities in neural systems often results in prominent oscillations. The primary goal of the research presented in this thesis was to study effects of sensory stimulus on the olfactory system of rats, focusing on the olfactory bulb (OB) and the anterior piriform cortex (aPC). Extracellular electrophysiological measurements revealed distinct frequency bands of oscillations in OB and aPC. However, how these oscillatory fluctuations help the animal to process sensory input is not clearly understood. Here we show high frequency oscillations in olfactory bulb carry feedforward signals to anterior piriform cortex whereas feedback from the aPC is predominantly …

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 Effects Of Two Novel Anti-Inflammatory Compounds On Prepulse Inhibition And Neural Microglia Cell Activation In A Rodent Model Of Schizophrenia, Heath W. Shelton

Electronic Theses and Dissertations

Recent studies have shown elevated neuroinflammation in a large subset of individuals diagnosed with schizophrenia. A pro-inflammatory cytokine, tumor necrosis factor-alpha (TNFα), has been directly linked to this neuroinflammation. This study examined the effects of two TNFα modulators (PD2024 and PD340) produced by our collaborators at P2D Bioscience, Inc., to alleviate auditory sensorimotor gating deficits and reduce microglial cell activation present in the polyinosinic:polycytidylic (Poly I:C) rodent model of schizophrenia. Auditory sensorimotor gating was assessed using prepulse inhibition and microglial activation was examined and quantified using immunohistochemistry and confocal microscopy, respectively. Both PD2024 and PD340 alleviated auditory sensorimotor gating deficits …

Redefining Burnout: Exploring Common Conceptualizations And The Neurophysiology Of Chronic Stress To Establish An Integrated Allostatic Model, Danny A. Guzzi

Dissertations

Burnout is a widely researched stress-related phenomenon associated with numerous adverse outcomes for employees and organizations. Unfortunately, burnout is not well understood and research to this point has been flawed due to a lack of consensus on the definition, dimensionality, and context of the construct. Prevalent conceptualizations of burnout have been criticized for being arbitrarily developed without solid theoretical foundation and for failing to clearly distinguish burnout from depression or other work-related conditions such as compassion fatigue, secondary traumatization, and vicarious traumatization. The current project first examines relevant literature to identify commonalities among prevalent burnout conceptualizations. Then relevant stress research …

Forgotten Children & Bonds That Heal: The Critical Nature Of Attachment, August Ashbaker

Lesley University Community of Scholars Day

Human attachment is one of the most critical factors in proper neurological and physiological development. Attachment is built through the mutuality of emotional impact, as well as the regular reception of physical touch. Infants and children who have been deprived of these vital necessities through the lacking initiatives of their caregivers—through neglect—display visible signs of its physiological, cognitive, emotional, and behavioral impact. Research has found neglect to be the highest risk factor for permanent damage to brain development in comparison to other forms of complex trauma (i.e. chronic caregiver interpersonal trauma in childhood); it is also the most prevalent …

Effects Of Altered Gravity On The Central Nervous System Of Drosophila Melanogaster, Amber M. Paul, Siddhita Mhatre, Janani Iyer, Jhony A. Zavaleta, Ravikumar Hosamani

Publications

A comprehensive understanding of the effects of spaceflight and altered gravity on human physiology is necessary for continued human space exploration and long-term space habitation. Spaceflight includes multiple factors such as microgravity, hyper gravity, ionizing radiation, physiological stress, and disrupted circadian rhythms and these have been shown to contribute to pathophysiological responses that target immunity, bone and muscle integrity, cardiovascular and nervous systems. In terrestrial conditions, some of these factors can lead to cancer and neuroimmunological disorders. In this study, we used a well-established spaceflight model organism, Drosophila melanogaster, to assess spaceflight-associated changes in the nervous system. We hypothesize that …

The Effects Of Ocular Dominance On Visual Processing In College Students, William Alexander Holland

James Madison Undergraduate Research Journal (JMURJ)

The role of ocular dominance in processing visual memory and analytic tasks is unknown. Research has variably showed both significant effects and no effect of ocular dominance on visual perception, motor control, and sports performance. The goal of this study was to determine if there is a relationship between ocular dominance and visual processing under a variety of computer gaming tasks. This was accomplished by first determining subjects’ ocular dominance through the Miles test, and then examining the subjects’ visual performance on four different Lumosity games under three conditions: left eye, right eye, and both eyes. Results suggest a relationship …

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 …

Design, Synthesis And Pharmacological Characterization Of Potential Mu Opioid Receptor Selective Ligands, Abhishek S. Kulkarni

Theses and Dissertations

Selective Mu Opioid Receptor (MOR) antagonists possess immense potential in the treatment of opioid abuse/addiction. Utilizing the “message-address” concept, our laboratory reported a novel, reversible, non-peptide MOR selective antagonist 17-cyclopropylmethyl-3,14β-dihydroxy-4,5α-epoxy-6β-[(4՛-pyridyl)carboxamido]morphinan (NAP). Molecular modeling studies revealed that the selectivity of NAP for the MOR is because of a π-π stacking interaction of its pyridine ring with the Trp318residue in theMOR. Pharmacological characterization showed that NAP is a P-glycoprotein substrate, thereby limiting its use in the treatment of opioid abuse/addiction. Thus, to modify NAP, we replaced the pyridine ring with its isosteric counterpart thiophene. Isosteric replacement …

Relations Among Maternal And Paternal Behavior And Children's Stress Biology, S.K. Jiaming Lin, Stacey N. Doan, John Milton

Scripps Senior Theses

Parenting behavior has been shown to have a wide range of effects, influencing children’s psychological and biological stress outcomes. Most research focuses on maternal parenting behaviors, with few studies observing the effects of paternal behaviors or the influence of both parents on their children. In this study, the relationship between maternal and paternal parenting behaviors was examined in its association to predict children’s cortisol levels. Cultural differences in parenting styles was also observed. American (N=86) and Chinese (N=97) families participated in the study, with parents reporting their behaviors. Children’s cortisol was collected during a stressor task and correlational analysis was …

Differential Expression Of Genes Related To Innate Immune Responses In Ex Vivo Spinal Cord And Cerebellar Slice Cultures Infected With West Nile Virus, Amber M. Paul, Parminder J.S. Vig, Deyin Lu, Ram Kuwar, Maria Lopez, Dobrivoje S. Stokic, A. Arturo Leis, Michael R. Garrett, Fengwei Bai

Publications

West Nile virus (WNV) infection results in a spectrum of neurological symptoms, ranging from a benign fever to severe WNV neuroinvasive disease with high mortality. Many who recover from WNV neuroinvasive infection present with long-term deficits, including weakness, fatigue, and cognitive problems. While neurons are a main target of WNV, other cell types, especially astrocytes, play an important role in promoting WNV-mediated central nervous system (CNS) damage. Conversely, it has been shown that cultured primary astrocytes secrete high levels of interferons (IFNs) immediately after WNV exposure to protect neighboring astrocytes, as well as neurons. However, how intrinsic responses to WNV …

Characterization Of G-Protein Coupled Receptors In Pain, Depression And Anxiety, Neil Lax

Electronic Theses and Dissertations

Chronic pain and major depressive disorder are widespread conditions in the world. Interestingly, these conditions often occur comorbidly, with each individual disease amplifying the symptoms of the other. A significant amount of preclinical research in pain and depression focuses on G-protein coupled receptors (GPCRs), implying that GPCRs may be useful in treating this comorbidity. Our efforts have sought to characterize several poorly understood GPCRs, including the serotonin receptor subtypes 2C and 7 (5-HT2CR and 5-HT7R) and metabotropic glutamate receptor 5 (mGluR5), along with more well-known GPCRs such as the mu opioid receptor (MOR), and the role that they play in …

Hypothalamic Circuits In The Control Of Feeding And Emotional Behaviors, Leandra Mangieri

Dissertations and Theses (Open Access)

Feeding results from the integration of both nutritional and affective states, and is guided by complex neural circuitry in the brain. The hypothalamus is a critical center controlling feeding and motivated behaviors. We found that targeted photostimulation of projections from the lateral hypothalamus (LH) to the paraventricular hypothalamus (PVH) in mice elicited voracious feeding and repetitive self-grooming behavior. GABA neurotransmission in the LH->PVH circuit mediated the evoked feeding behavior, and elicited behavioral approach, whereas glutamate release promoted repetitive self-grooming, which was stress-related in nature. Optogenetic inhibition of LH^GABA ->PVH circuit reduced feeding after fasting, whereas photostimulation abruptly …

Behavioral Insights Into Nociceptor Function: A Systematic Approach To Understanding Postsurgical And Neuropathic Pain Mechanisms In Rats, Max Odem

Dissertations and Theses (Open Access)

Postsurgical and neuropathic pain are each clinically common, and often associated with ongoing pain. Ongoing pain has been linked to ongoing activity (OA) in human C-fiber nociceptors. Preclinical studies using rodent neuropathic models have concentrated on allodynia driven by OA generated in non-nociceptive Aβ fibers, but little attention has been paid to postsurgical pain in sham controls or to C-fiber nociceptor OA promoting ongoing pain.

Operant assays that reveal negative motivational and cognitive aspects of voluntary pain-related behavior may be particularly sensitive to pain-related alterations. In the mechanical conflict (MC) test, rodents can freely choose to escape from a brightly …

Neutrophil To Lymphocyte Ratio: A Prognostic Indicator For Astronaut Health, Amber M. Paul, Siddhita D. Mhatre, Egle Cekanaviciute, Ann-Sofie Schreurs, Candice G.T. Tahimic, Ruth K. Globus, Brian Crucian, Sharmila Bhattacharya

Publications

Short-term and long-term spaceflight missions can cause immune system dysfunction in astronauts. Recent studies indicate elevated white blood cells (WBC) and polymorphonuclear neutrophils (PMN) in astronaut blood, along with unchanged or reduced lymphocyte counts, and reduced T cell function, during short-(days) and long-(months) term spaceflight. A high PMN to lymphocyte ratio (NLR) can acts as a strong predictor of poor prognosis in cancer, and as a biomarker for subclinical inflammation in humans and chronic stress in mouse models, however, the NLR has not yet been identified as a predictor of astronaut health during spaceflight. For this, complete blood cell count …

Stress-Induced Heat Shock Protein 40 And Immune Function In Altered Gravity, Amber M. Paul, Brooke D. Shepard, Sharmila Bhattacharya

Publications

In space, astronauts are more susceptible to pathogens, viral reactivation and immunosuppression, which poses limits to their health and the mission. Interestingly, during space flight, stress-inducible heat shock proteins (HSP) are robustly induced, and the overexpression of HSPs have been implicated in immune dysregulation, therefore HSPs may be critically involved in regulating immune homeostasis. HSP40/DNAJ1 plays a major role in proper protein translation and folding. Its loss of function has been implicated in susceptibility to microbial infection, while its overexpression has been implicated in autoimmunity, collectively suggesting its complicated, but necessary, role in maintaining immunological function. To determine the role …

Curcumin Inhibits The Ikk:Nf-Kappa B Pathway In Neural Fear Circuits, Miguel A. Briones

Dissertations, Theses, and Capstone Projects

The study of how the brain acquires fearful memories has attracted considerable experimental attention, due in part to the promise of discovering novel therapeutic approaches for psychiatric disorders that are characterized by unusually strong and persistent traumatic memories. In recent years, extensive research has focused on studying the neural and molecular mechanisms by which fear memories are acquired, stored, and retrieved in the brain. Once acquired, fear memories may be attenuated using one of 2 procedures: 1) fear extinction, which involves repeated presentation of the fear-arousing stimulus in the absence of an aversive consequence, or 2) interference with the reconsolidation …

Congenital Zika Virus Infection In Immunocompetent Mice Causes Postnatal Growth Impediment And Neurobehavioral Deficits, Amber M. Paul, Dhiraj Acharya, Biswas Neupane, E. Ashley Thompson, Gabriel Gonzalez-Fernandez, Katherine M. Copeland

Publications

A small percentage of babies born to Zika virus (ZIKV)-infected mothers' manifest severe defects at birth, including microcephaly. Among those who appeared healthy at birth, there are increasing reports of postnatal growth or developmental defects. However, the impact of congenital ZIKV infection in postnatal development is poorly understood. Here, we report that a mild congenital ZIKV-infection in pups born to immunocompetent pregnant mice did not display apparent defects at birth, but manifested postnatal growth impediments and neurobehavioral deficits, which include reduced locomotor and cognitive deficits that persisted into adulthood. We found that the brains of these pups were smaller, had …

Modeling And Mapping Addiction In The Zebrafish, Danio Rerio, Bradley Serpa

Master of Science in Integrative Biology Theses

Driven by the communication of dopamine, the vertebrate reward system has been evolutionarily conserved to maintain survival and optimize fitness. The neural circuits governing this system integrate sensory stimuli to produce appropriate, self-preserving responses that underlie experience-based learning. In the most primitive vertebrates, dopamine release in neuronal circuits drives homeostatic behaviors, such as seeking nutrients, finding a mate, or avoiding danger. From agnathans to mammals, dopaminergic synthesis and signaling genes and molecules, along with neuronal pathways and reward system-based behaviors, remain highly conserved. Dopamine signaling proteins include two classes of metabotropic G-Protein Receptor Coupled Dopamine Receptors, D1-like (DRD1) and D2-like …

Defining The Radioresponse Of Mossy Cells, Devon Ivy

Electronic Theses, Projects, and Dissertations

Clinical radiotherapy is used to treat a variety of brain tumors within the central nervous system. While effective, it can result in progressive and debilitating cognitive impairment that can diminish quality of life. These impairments have been linked to hippocampal dysfunction and corresponding deficits in spatial learning and memory. Mossy cells are a major population of excitatory neurons located within the dentate hilus and highly involved in hippocampal circuitry. They play critical roles in spatial navigation, neurogenesis, memory, and are particularly vulnerable to a variety of neurotoxic insults. However, their sensitivity to ionizing radiation has yet to be investigated in …