Nervous System Commons^™

Cpla2alpha-/- Sympathetic Neurons Exhibit Increased Membrane Excitability And Loss Of N-Type Ca2+ Current Inhibition By M1 Muscarinic Receptor Signaling, Liwang Liu, Joseph V. Bonventre, Ann R. Rittenhouse

Open Access Articles

Group IVa cytosolic phospholipase A2 (cPLA2alpha) mediates GPCR-stimulated arachidonic acid (AA) release from phosphatidylinositol 4,5-bisphosphate (PIP2) located in plasma membranes. We previously found in superior cervical ganglion (SCG) neurons that PLA2 activity is required for voltage-independent N-type Ca2+ (N-) current inhibition by M1 muscarinic receptors (M1Rs). These findings are at odds with an alternative model, previously observed for M-current inhibition, where PIP2 dissociation from channels and subsequent metabolism by phospholipase C suffices for current inhibition. To resolve cPLA2alpha's importance, we have investigated its role in mediating voltage-independent N-current inhibition (~40%) that follows application of the muscarinic agonist oxotremorine-M ...

The Use Of Current Steering During Subthalamic Deep Brain Stimulation To Alleviate Upper Limb Symptoms Of Parkinson's Disease, Shabna Iftikar Mohideen

Electronic Thesis and Dissertation Repository

Subthalamic (STN) deep brain stimulation (DBS) is an established treatment to alleviate the appendicular motor symptoms of Parkinson's Disease (PD). Current steering during DBS allows the unequal fractionation of current between two electrodes on the lead, resulting in a non-spherical electrical field. It is hypothesized that the way the electrical field is shaped will affect a patient’s upper limb symptom alleviation. Seven PD patients who underwent bilateral STN-DBS were tested over four weeks post-operation. 16 current fractionation settings were tested each week at an amplitude that increased weekly. Optimal setting was defined as the setting that provided the ...

Drosophila Ror Is A Nervous System-Specific Co-Receptor For Wnt Ligands, Caroline Ripp, Julia Loth, Iveta Petrova, Karen Linnemannstons, Monique Ulepic, Lee G. Fradkin, Jasprien Noordermeer, Andreas Wodarz

Open Access Articles

Wnt ligands are secreted glycoproteins that control many developmental processes and are crucial for homeostasis of numerous tissues in the adult organism. Signal transduction of Wnts involves the binding of Wnts to receptor complexes at the surface of target cells. These receptor complexes are commonly formed between a member of the Frizzled family of seven-pass transmembrane proteins and a co-receptor, which is usually a single-pass transmembrane protein. Among these co-receptors are several with structural homology to receptor tyrosine kinases, including Ror, PTK7, Ryk and MUSK. In vertebrates, Ror-2 and PTK7 are important regulators of planar cell polarity (PCP). By contrast ...

Cell Specific Control Of The Pallidostriatal Pathway: Poster Presentation, Shubha Verma '19

Student Publications & Research

Parkinson’s Disease is a neurodegenerative disorder of the basal ganglia. The main cause for Parkinson’s Disease is the depletion of dopamine, a neurotransmitter. The basal ganglia contains four major nuclei: the substantia nigra, the subthalamic nucleus, the external globus pallidus, and the striatum. These nuclei communicate with each other by the use of neurons.

Cell Specific Control Of The Pallidostriatal Pathway: Presentation, Shubhi Verma '19

Student Publications & Research

Parkinson’s Disease is a neurodegenerative disorder of the basal ganglia. The main cause for Parkinson’s Disease is the depletion of dopamine, a neurotransmitter. The basal ganglia contains four major nuclei: the substantia nigra, the subthalamic nucleus, the external globus pallidus, and the striatum. These nuclei communicate with each other by the use of neurons.

Reduced Gut Microbiome Protects From Alcohol-Induced Neuroinflammation And Alters Intestinal And Brain Inflammasome Expression, Patrick P. Lowe, Benedek Gyongyosi, Abhishek Satishchandran, Arvin Iracheta-Vellve, Yeonhee Cho, Aditya Ambade, Gyongyi Szabo

Open Access Articles

BACKGROUND: The end-organ effects of alcohol span throughout the entire body, from the gastrointestinal tract to the central nervous system (CNS). In the intestine, alcohol use changes the microbiome composition and increases gut permeability allowing translocation of microbial components into the circulation. Gut-derived pathogen-associated signals initiate inflammatory responses in the liver and possibly elsewhere in the body. Because previous studies showed that the gut microbiome contributes to alcohol-induced liver disease, we hypothesized that antibiotic administration to reduce the gut microbiome would attenuate alcohol-induced inflammation in the brain and small intestine (SI).

METHODS: Six- to 8-week-old C57BL/6J female mice were ...

Disrupted Asymmetry Of Inter- And Intra-Hemispheric Functional Connectivity In Patients With Drug-Naive, First-Episode Schizophrenia And Their Unaffected Siblings, Furong Zhu, Feng Liu, Wenbin Guo, Jindong Chen, Qinji Su, Zhikun Zhang, Huabing Li, Xiaoduo Fan, Jingping Zhao

Open Access Articles

BACKGROUND: Lack of normal asymmetry in the brain has been reported in patients with schizophrenia. However, it remains unclear whether disrupted asymmetry originates from inter-hemispheric functional connectivity (FC) and/or intra-hemispheric FC in this patient population.

METHODS: Forty-four patients with drug-naive, first-episode schizophrenia, 42 unaffected siblings, and 44 healthy controls underwent resting-state functional magnetic resonance imaging (fMRI) scan. The parameter of asymmetry (PAS) and support vector machine (SVM) were used to analyze the data. Patients were treated with olanzapine for 8 weeks.

FINDINGS: Compared with healthy controls, patients showed lower PAS scores in the left middle temporal gyrus (MTG)/inferior ...

Defective Cortex Glia Plasma Membrane Structure Underlies Light-Induced Epilepsy In Cpes Mutants, Govind Kunduri, Daniel Turner-Evans, Yutaka Konya, Yoshihiro Izumi, Kunio Nagashima, Stephen Lockett, Joost Holthuis, Takeshi Bamba, Usha Acharya, Jairaj K. Acharya

Open Access Articles

Seizures induced by visual stimulation (photosensitive epilepsy; PSE) represent a common type of epilepsy in humans, but the molecular mechanisms and genetic drivers underlying PSE remain unknown, and no good genetic animal models have been identified as yet. Here, we show an animal model of PSE, in Drosophila, owing to defective cortex glia. The cortex glial membranes are severely compromised in ceramide phosphoethanolamine synthase (cpes)-null mutants and fail to encapsulate the neuronal cell bodies in the Drosophila neuronal cortex. Expression of human sphingomyelin synthase 1, which synthesizes the closely related ceramide phosphocholine (sphingomyelin), rescues the cortex glial abnormalities and ...

Targeting The Mitochondrial Permeability Transition Pore In Traumatic Central Nervous System Injury, Joe E. Springer, Pareshkumar Prajapati, Patrick G. Sullivan

Spinal Cord and Brain Injury Research Center Faculty Publications

The mitochondrion serves many functions in the central nervous system (CNS) and other organs beyond the well-recognized role of adenosine triphosphate (ATP) production. This includes calcium-dependent cell signaling, regulation of gene expression, synthesis and release of cytotoxic reactive oxygen species, and the release of cytochrome c and other apoptotic cell death factors. Traumatic injury to the CNS results in a rapid and, in some cases, sustained loss of mitochondrial function. One consequence of compromised mitochondrial function is induction of the mitochondrial permeability transition (mPT) state due to formation of the cyclosporine A sensitive permeability transition pore (mPTP). In this mini-review ...

Neurexin Directs Partner-Specific Synaptic Connectivity In C. Elegans, Alison Philbrook, Shankar Ramachandran, Christopher M. Lambert, Devyn Oliver, Jeremy Florman, Mark J. Alkema, Michele Lemons, Michael M. Francis

Open Access Articles

In neural circuits, individual neurons often make projections onto multiple postsynaptic partners. Here, we investigate molecular mechanisms by which these divergent connections are generated, using dyadic synapses in C. elegans as a model. We report that C. elegans nrx-1/neurexin directs divergent connectivity through differential actions at synapses with partnering neurons and muscles. We show that cholinergic outputs onto neurons are, unexpectedly, located at previously undefined spine-like protrusions from GABAergic dendrites. Both these spine-like features and cholinergic receptor clustering are strikingly disrupted in the absence of nrx-1. Excitatory transmission onto GABAergic neurons, but not neuromuscular transmission, is also disrupted. Our ...

Neuronal Modulation Of Brown Adipose Activity Through Perturbation Of White Adipocyte Lipogenesis, Adilson L. Guilherme, David J. Pedersen, Felipe Henriques, Alexander H. Bedard, Elizabeth Henchey, Mark Kelly, Donald A. Morgan, Kamal Rahmouni, Michael P. Czech

Open Access Articles

OBJECTIVE: Crosstalk between adipocytes and local neurons may be an important regulatory mechanism to control energy homeostasis. We previously reported that perturbation of adipocyte de novo lipogenesis (DNL) by deletion of fatty acid synthase (FASN) expands sympathetic neurons within white adipose tissue (WAT) and stimulates the appearance of "beige" adipocytes. Here we tested whether WAT DNL activity can also influence neuronal regulation and thermogenesis in brown adipose tissue (BAT).

METHODS AND RESULTS: Induced deletion of FASN in all adipocytes in mature mice (iAdFASNKO) enhanced sympathetic innervation and neuronal activity as well as UCP1 expression in both WAT and BAT. This ...

A Meta-Analysis: A Functional Neuroanatomical Comparison Of Self-Esteem-Related And Postpartum Depression-Related Processing, Meghana Damaraju

Honors Theses

Background: Postpartum depression (PPD) is a psychiatric mood disorder that effects 1 in 10 women in the United States. There are relatively few behavioral studies looking at the association between PPD and self-esteem. There are even fewer studies looking at neuroimaging comparisons between PPD and self-esteem.. The goal of this study was to look at the neuroanatomical overlap of activated brain regions involved in both self-esteem and PPD processing. We hypothesized that the right amygdala, PCC, and insula would be involved in both processes.

Methods: Maps were created using the MKDA program in MATLAB. These images were extent-based cluster-wise activation ...

Childhood Poverty And Its Effects On The Brain: Physiological And Functional Implications, Lauren Scandrett

Honors Theses AY 17/18

One out of every five American children lives below the federal poverty line. Considering that poverty is deemed one of the most influential risk factors for poor developmental outcomes, it is critical to understand what effect poverty has on the developing brain and how those brain changes affect a child’s life. Poverty is chiefly defined by having a low socioeconomic status (SES), but a low SES is often accompanied by other influencers, such as nutrition and mental stimulation, termed poverty co-factors. Other poverty co-factors include, but are not limited to, maternal stress and malnutrition, environmental toxins, parental nurturance, and ...

Spinal Cord Trauma: An Overview Of Normal Structure And Function, Primary And Secondary Mechanisms Of Injury, And Emerging Treatment Modalities, Daniel Morin

Senior Honors Theses

The structures of the spinal cord and vertebral column are designed to provide flexibility, while still providing ample protection for the spinal cord deep within. While it does offer remarkable protection against most routine trauma, the spinal cord is still vulnerable to high-force etiologies of trauma and may become damaged as a result. These events are referred to as primary injury. Following the initial injury, the body’s own physiological responses cause a cascade of deleterious effects, known as secondary injury. Secondary injury is a major therapeutic target in mitigating the effects of spinal cord injury (SCI), and much research ...

Thalamocortical Processing Of Temporal Cues In Sounds, Kasey Smith

Honors Scholar Theses

The ability of the brain to extract meaningful information from complex sounds is what allows mammals to understand species-specific communication as well as important environmental cues such as the sound of water or of potential predators or prey. The auditory cortex of humans and other mammals contains multiple cortical regions that unique sensitivities to both spectral and temporal sound cues. This discourse will explore three main factors proposed to determine these distinct processing capabilities in regard to temporal sound cues; the distribution of glutamate transporters in the thalamus, the architecture of afferent pathways between the thalamus and auditory cortex, and ...

Immunodeficient R2g2 Mouse Strain Yields Spleens With Unusual Cytoarchitecture And Sympathetic Innervation, Nicholas Mason Britt, Madeleine Kate Miller, Donald B. Hoover Ph.D., John B. Schweitzer M.D.

Appalachian Student Research Forum

The nervous system and immune system contact one another through two-way communication in order to establish and preserve homeostasis. The sympathetic neurotransmitter norepinephrine has an impact on how the immune system responds by affecting regional blood flow and activation of adrenergic receptors on leukocytes. Former studies showed that immune cells are capable of releasing nerve growth factor allowing for the establishment and continuation of sympathetic nerves in targeted tissues. From this gathered information, it was hypothesized that sympathetic nerves would prove to be less frequent in spleens from the immunodeficient R2G2 mouse strain (Envigo) when compared to 129P3/J (129 ...

Concussion Competencies: A Framework For School-Based Concussion Management (Flyer), Arthur C. Maerlender, Jonathan Lichtenstein, Jennifer Parent-Nichols

Center for Brain, Biology and Behavior: Papers & Publications

This volume grew out of many years of clinical practice, research, and program projects. It is the culmination of more than 50 years of work with kids, brains, and schools. While there is research behind the Competencies and the underlying content, the intent was to create a user-friendly manual that cut across levels of responsibility and care. Concussion Competencies was not intended to be a textbook in the traditional manner; however, the Competencies have been shown to be a useful approach to teaching this material.

This volume is organized around a set of Competencies that have been shown to be ...

Factor Structure And Gender Invariance Testing For The Sport Anxiety Scale-2 (Sas-2), Leilani Madrigal, Vincenzo Roma, Todd Caze, Arthur C. Maerlender, Debra Hope

Center for Brain, Biology and Behavior: Papers & Publications

This study aimed to provide further psychometric validation of the Sport Anxiety Scale-2 (SAS-2) by assessing the factor structure, invariance across gender, and convergent and divergent validity of the SAS-2 by correlating both related (i.e., anxiety sensitivity, brief fear of negative evaluation, intolerance of uncertainty, and negative affect) and unrelated constructs (i.e., positive affect, self-confidence). A total of 542 current and former competitive athletes completed a questionnaire through Amazon’s Mechanical Turk system. All data were collected via online survey. Participants were randomly assigned to an exploratory factor analysis (n = 271) and confirmatory factor analysis group (n = 271 ...

Mesotocin Influences Pinyon Jay Prosociality, J. F. Duque, W. Leichner, H. Ahmann, Jeffrey R. Stevens

Center for Brain, Biology and Behavior: Papers & Publications

Many species exhibit prosocial behavior , in which one individual’s actions benefit another individual, often without an immediate benefit to itself. The neuropeptide oxytocin is an important hormonal mechanism influencing prosociality in mammals, but it is unclear whether the avian homologue mesotocin plays a similar functional role in birds. Here, we experimentally tested prosociality in pinyon jays (Gymnorhinus cyanocephalus), a highly social corvid species that spontaneously shares food with others. First, we measured prosocial preferences in a prosocial choice task with two different pay-off distributions: Prosocial trials delivered food to both the subject and either an empty cage or a ...

Ccl11 As A Biomarker For The In Vivo Diagnosis Of Chronic Traumatic Encephalopathy, Robert Weissenfels

CMC Senior Theses

Chronic traumatic encephalopathy is the neurodegenerative disease that is ascribed to the long term development of cognitive, behavioral, emotional, and motor deficits as a result of the exposure to high amounts of sub concussive traumatic brain injuries. The disease has gained recent popularity in the media for its prevalence in American football as a response to recent research that has suggested the prominence of the disease in nearly every NFL player that is examined post mortem. This has produced a growing concern for the consequences of head impact and participation in contact sports. Despite media attention, little is currently known ...