Neuroscience and Neurobiology Commons^™

Myosin Isoforms And Regulation Of Tonic And Phasic Contraction In Smooth Muscle, Qian Huang

Dissertations (1934 -)

The contractile properties of smooth muscle (SM) are broadly classified as tonic and phasic. Among the hypothesized underlying regulatory mechanisms for this difference is the different actomyosin ATPase kinetic properties of SM SMA/SMB myosin heavy chain (MHC) isoforms and the preferential expression of SMA and SMB MHC isoforms in tonic and phasic SM respectively. Thus, we hypothesized that SM SMA/B MHC expression determines tonic and phasic contractile patterns in SM.

To test the this hypothesis, the role of SMA and SMB MHC isoforms in tonic and phasic contractions was studied in phasic (longitudinal ileum and stomach circular antrum) and tonic …

Regulation Of System Xc- And Its Contribution To Cell Death, Xiaoqian Liu

Dissertations (1934 -)

The main focus of the studies in this thesis involves examining the role of cystine/glutamate exchange (system xC-) in neuronal death in primary cortical cell culture, with an emphasis on how glial function affects neuronal cell death. System xC- is a sodium-independent transporter that mediates cystine uptake and glutamate release. It accounts for most of the cystine uptake in astrocytes in mature cultures, providing the rate limiting substrate for synthesis of the main endogenous antioxidant glutathione. The glutamate released by system xC- may lead to excessive extracellular glutamate and cause excitotoxicity.

β-N-methylamino-L-alanine (BMAA) is a non-protein amino acid that may …

Neurosteroid-Mediated Regulation Of Brain Innate Immunity In Hiv/Aids: Dhea-S Suppresses Neurovirulence, Amber Paul, Ferdinand G. Maingat, Maria J. Polyak, Pornpun Vivithanaporn, Farshid Noorbakhsh, Samir Ahboucha, Glen B. Baker, Keir Pearson, Christopher Power

Publications

Neurosteroids are cholesterol-derived molecules synthesized within the brain, which exert trophic and protective actions. Infection by human and feline immunodeficiency viruses (HIV and FIV, respectively) causes neuroinflammation and neurodegeneration, leading to neurological deficits. Secretion of neuroinflammatory host and viral factors by glia and infiltrating leukocytes mediates the principal neuropathogenic mechanisms during, although the effect of neurosteroids on these processes is unknown. We investigated the interactions between neurosteroid mediated effects and lentivirus infection outcomes. Analyses of HIV-infected uninfected human brains disclosed a reduction in neurosteroid synthesis enzyme expression. Human neurons exposed to supernatants from HIV macrophages exhibited suppressed enzyme expression without …

Development Of Scn Connectivity And The Circadian Control Of Arousal: A Diminishing Role For Humoral Factors?, Andrew J. Gall, William D. Todd, Mark S. Blumberg

Faculty Publications

The suprachiasmatic nucleus (SCN) is part of a wake-promoting circuit comprising the dorsomedial hypothalamus (DMH) and locus coeruleus (LC). Although widely considered a "master clock," the SCN of adult rats is also sensitive to feedback regarding an animal's behavioral state. Interestingly, in rats at postnatal day (P)2, repeated arousing stimulation does not increase neural activation in the SCN, despite doing so in the LC and DMH. Here we show that, by P8, the SCN is activated by arousing stimulation and that selective destruction of LC terminals with DSP-4 blocks this activational effect. We next show that bidirectional projections among the …

The Human Brain Intracerebral Microvascular System: Development And Structure, Miguel Marín-Padilla

Dartmouth Scholarship

The capillary from the meningeal inner pial lamella play a crucial role in the development and structural organization of the cerebral cortex extrinsic and intrinsic microvascular compartments. Only pial capillaries are capable of perforating through the cortex external glial limiting membrane (EGLM) to enter into the nervous tissue, although incapable of perforating the membrane to exit the brain. Circulatory dynamics and functional demands determine which capillaries become arterial and which capillaries become venous. The perforation of the cortex EGLM by pial capillaries is a complex process characterized by three fundamental stages: (1) pial capillary contact with the EGLM with fusion …

Time-Dependent Statistical And Correlation Properties Of Neural Signals During Handwriting, Valery I. Rupasov, Mikhail A. Lebedev, Joseph S. Erlichman, Stephen L. Lee, James C. Leiter, Michael Linderman

Dartmouth Scholarship

To elucidate the cortical control of handwriting, we examined time-dependent statistical and correlational properties of simultaneously recorded 64-channel electroencephalograms (EEGs) and electromyograms (EMGs) of intrinsic hand muscles. We introduced a statistical method, which offered advantages compared to conventional coherence methods. In contrast to coherence methods, which operate in the frequency domain, our method enabled us to study the functional association between different neural regions in the time domain. In our experiments, subjects performed about 400 stereotypical trials during which they wrote a single character. These trials provided time-dependent EMG and EEG data capturing different handwriting epochs. The set of trials …

Brainstorm: Head Injuries And The Nfl, Part 7: What Mops Have To Do With The Nfl, John J. Medina Ph.D.

Brainstorm

In the last few installments, we discussed some vulnerable regions of neurological real estate that suffer damage in afflicted athletes, and their association with changes in outwardly observable behavior. Unfortunately, this is only a partial list. Enough is now known that I could create three or four more installments of this blog and still not cover everything that is being researched.

Long-Term Effects Of Estradiol Replacement In The Olfactory System, Britto P. Nathan, Michael Tonsor, Robert G. Struble

Faculty Research & Creative Activity

Olfactory dysfunction often precedes other clinical symptoms in chronic neurodegenerative diseases like Alzheimer’s and Parkinson’s disease. Estrogen deficiency and apoE genotype are known risk factors in these diseases and these factors also affect olfaction. Therefore we examined the effects of estradiol replacement following ovariectomy on expression of apoE and markers of cell proliferation, neuronal maturation, synaptogenesis and reactive gliosis in the primary olfactory pathway of wild-type (WT) and apoE knockout (KO) mice. Estradiol replacement increased apoE staining in the olfactory nerve and glomerular layers. Estradiol increased astrocyte density and olfactory epithelium (OE) thickness regardless of the genotype. In addition estradiol …

Long-Term Effects Of Estradiol Replacement In The Olfactory System, Britto Nathan, Michael Tonsor, Robert Struble

Faculty Research & Creative Activity

Olfactory dysfunction often precedes other clinical symptoms in chronic neurodegenerative diseases like Alzheimer’s and Parkinson’s disease. Estrogen deficiency and apoE genotype are known risk factors in these diseases and these factors also affect olfaction. Therefore we examined the effects of estradiol replacement following ovariectomy on expression of apoE and markers of cell proliferation, neuronal maturation, synaptogenesis and reactive gliosis in the primary olfactory pathway of wild-type (WT) and apoE knockout (KO) mice. Estradiol replacement increased apoE staining in the olfactory nerve and glomerular layers. Estradiol increased astrocyte density and olfactory epithelium (OE) thickness regardless of the genotype. In addition estradiol …

Adrenal Steroids Uniquely Influence Sexual Motivation Behavior In Male Rats, George Taylor, Joshua Dearborn, Susan Maloney

Psychology Faculty Works

The androgenic adrenal steroids dehydroepiandrosterone (DHEA) and 4α-androstenedione (4-A) have significant biological activity, but it is unclear if the behavioral effects are unique or only reflections of the effects of testosterone (TS). Gonadally intact male Long-Evans rats were assigned to groups to receive supplements of DHEA, 4-A, TS, corticosteroid (CORT), all at 400 µg steroid/kg of body weight, or vehicle only for 5 weeks. All males were tested in a paradigm for sexual motivation that measures time and urinary marks near an inaccessible receptive female. It was found that DHEA and 4-A supplements failed to influence time near the estrous …

Brainstorm: Head Injuries And The Nfl, Part 6: Memory Loss, John J. Medina Ph.D.

Brainstorm

We are in the process of examining the relationship between neurological damage associated with repeated closed­-head injuries and the behaviors of CTE. We’ve been using the example of spearing, illustrating the effects of this banned football behavior on the biological integrity of the human brain. We discussed how damage to one such neurological circuit, the Papez Circuit, can lead to chronic changes in mood. Here we discuss changes in three cognitive gadgets: executive function, memory processing, and motor control.

Preserved Self-Awareness Following Extensive Bilateral Brain Damage To The Insula, Anterior Cingulate, And Medial Prefrontal Cortices, Carissa Philippi, Justin Feinstein, Sahib Khalsa, Antonio Damasio, Daniel Tranel, Gregory Landini, Kenneth Williford, David Rudrauf

Psychology Faculty Works

No abstract provided.

Brainstorm: Head Injuries And The Nfl, Part 5: On The Matter Of Damaging Neural Circuits, John J. Medina Ph.D.

Brainstorm

In the last installment, we examined the forces capable of causing brain injury, but left out the most important question: What happens to brain tissues unlucky enough to experience those forces? Now it is time to face the biological facts. In this installment, we will talk about neurological tissue and closed-­head injuries.

Sleep Hygiene And Problem Behaviors In Snoring And Non- Snoring School-Age Children, Lisa A. Witcher, David Gozal, Dennis L. Molfese, Scott M. Salathe, Karen Spruyt, Valerie Mclaughlin Crabtree

Center for Brain, Biology, and Behavior: Faculty Publications

Objectives—The effects of sleep-disordered breathing, sleep restriction, dyssomnias, and parasomnias on daytime behavior in children have been previously assessed. However, the potential relationship(s) between sleep hygiene and children’s daytime behavior remain to be explored. The primary goal of this study was to investigate the relationship between sleep hygiene and problematic behaviors in non-snoring and habitually snoring children.

Methods—Parents of 100 5- to 8-year-old children who were reported to snore “frequently” to “almost always,” and of 71 age-, gender-, and ethnicity-matched children who were reported to never snore participated in this study. As part of a larger, ongoing study, …

The Functional Organization Of Synaptic Vesicle Pools In A Retinal Bipolar Neuron, Proleta Datta

Dissertations and Theses (Open Access)

Ribbon synapses are found in sensory systems and are characterized by ‘ribbon-like’ organelles that tether synaptic vesicles. The synaptic ribbons co-localize with sites of calcium entry and vesicle fusion, forming ribbon-style active zones. The ability of ribbon synapses to maintain rapid and sustained neurotransmission is critical for vision, hearing and balance. At retinal ribbon synapses, three vesicle pools have been proposed. A rapid pool of vesicles that are docked at the plasma membrane, and whose fusion is limited only by calcium entry, a releasable pool of ATP-primed vesicles whose size also correlates with the number of ribbon-tethered vesicles, and a …

Effects Of Head Position And Head-Supported Mass On Nerve Function Of The Flexor Carpi Radialis Muscle In Healthy Individuals, Bethany Lauren Shivers

Graduate Theses and Dissertations

Long-term exposure to head-supported mass (HSM) has been linked with spinal degeneration including foraminal stenosis and disc deterioration. Anecdotally, HSM has also been linked to neck and arm pain and muscle atrophy, but nerve function has not been tested specifically. The combined effect of various head positions and HSM may be sufficient to compress the nerve root in aviators and Soldiers during job performance, potentially leading to short- and long-term neuromuscular effects. The Hoffmann (H) reflex, a well-established measure of nerve function, has shown to be sensitive to changes in nerve root space which occurs with different head positions. This …

Diffusion Barriers Of The Lateral Ventricular System, Anitha Saravanakumar

Master's Theses

Adult neurogenesis in mammalian brain has become a well-accepted phenomenon. The neural stem cells in the sub ventricular zone (SVZ) along the lateral wall of the lateral ventricle, the largest germinal center of adult neurogenesis, are maintained by the neural stem cell niche. One prominent feature of the niche is its close proximity to the cerebral spinal fluid (CSF). The role of micromolecules (such as ions, water and gases) present in the CSF and diffusing through the lateral ventricular wall and how the stem cell micro-environment is maintained is poorly understood. The cytoarchitecture of the lateral ventricular wall with a …

Early Stage Drug Treatment That Normalizes Proinflammatory Cytokine Production Attenuates Synaptic Dysfunction In A Mouse Model That Exhibits Age-Dependent Progression Of Alzheimer's Disease-Related Pathology, Adam D. Bachstetter, Christopher M. Norris, Pradoldej Sompol, Donna M. Wilcock, Danielle Goulding, Janna H. Neltner, Daret St. Clair, D. Martin Watterson, Linda J. Van Eldik

Sanders-Brown Center on Aging Faculty Publications

Overproduction of proinflammatory cytokines in the CNS has been implicated as a key contributor to pathophysiology progression in Alzheimer's disease (AD), and extensive studies with animal models have shown that selective suppression of excessive glial proinflammatory cytokines can improve neurologic outcomes. The prior art, therefore, raises the logical postulation that intervention with drugs targeting dysregulated glial proinflammatory cytokine production might be effective disease-modifying therapeutics if used in the appropriate biological time window. To test the hypothesis that early stage intervention with such drugs might be therapeutically beneficial, we examined the impact of intervention with MW01-2-151SRM (MW-151), an experimental therapeutic that …

Brainstorm: Head Injuries And The Nfl, Part 4: The Physics Of Head Trauma, John J. Medina Ph.D.

Brainstorm

One fine afternoon in the autumn of 2010, Minnesota Vikings defensive end Ray Edwards executed one of the most dangerous acts you can do in football: He speared another player.

Validation Of Interaction Between The Glyt2 And The Nsf, David Quispe Escudero, Hector Cuevas, Luciana Girotto Gentil, Manuel Miranda

COURI Symposium Abstracts, Summer 2012

The Glycine Transporter 2 (GlyT2) is a presynaptic membrane transporter in charge of re-uptake of glycine from the synaptic cleft back into the presynaptic neuron. GlyT2 is present only in vertebrate neurons and possesses a 200 amino- acid long N-terminal tail of unknown function. We hypothesize that such domain serve as a docking site for a network of presynaptic proteins, such as NSF that plays a pivotal role during vesicle transport. Therefore, our goal in this project is to analyze protein-protein interaction between GlyT2 and NSF. We have used co-immunoprecipitation experiments from rat brainstem with GlyT2 and NSF antibodies as …

Stress- And Sex-Related Differences In The Activation Of Neuronal Subtypes In The Basolateral Amygdala Of The Rat, Alejandra E. Lopez, Christina C. Ruiz, Juan M. Bolanos, Jameel N. Hamdan, Kristin Gosselink

COURI Symposium Abstracts, Summer 2012

Previous studies suggest that stress alters the activational profiles among phenotypically-distinct subpopulations of neurons within the basolateral amygdala (BLA) of the rat. Given the connectivity of this region of the brain to the hippocampus, and the implications of the role of the BLA in modulating long-term potentiation associated with memory and learning, inferences of stress having a negative impact on cognition and memory can be drawn. Observations regarding stress response disparities between males and females in our model prompted the investigation of the role gender plays in cognition under conditions of stress, as well as the responses to stress itself. …

Multivoxel Patterns In Face-Sensitive Temporal Regions Reveal An Encoding Schema Based On Detecting Life In A Face, Christine E. Looser, Jyothi S. Guntupalli, Thalia Wheatley

Dartmouth Scholarship

More than a decade of research has demonstrated that faces evoke prioritized processing in a ‘core face network’ of three brain regions. However, whether these regions prioritize the detection of global facial form (shared by humans and mannequins) or the detection of life in a face has remained unclear. Here, we dissociate form-based and animacy-based encoding of faces by using animate and inanimate faces with human form (humans, mannequins) and dog form (real dogs, toy dogs). We used multivariate pattern analysis of BOLD responses to uncover the representational similarity space for each area in the core face network. Here, we …

Resolving Disulfide Bond Patterns In Snap25b Cysteine-Rich Region Using Lc Mass Spectrometry, Nozomi Ogawa

Theses and Dissertations

A global analysis of the human proteome demonstrates that there are ~5500 tryptic fragments that contain four cysteines in close proximity. Elucidating whether they form disulfide bonds in vivo under different conditions is particularly important because cysteines are known to be a vital cellular redox sensor as well as a catalytic site for important biochemical reactions. However, currently there are no methods that can resolve disulfide patterns in closely-packed cysteine residues from a complex sample. In order to address this problem, we have developed a novel mass-spectrometry-based method to identify the different disulfide bonding patterns possible, using SNAP25B cysteine-rich region …

Rapid Activation Of Hindbrain Neurons Following Glycemic Challenge: Regions And Phenotypes, Sarah D. Chenausky, Teresia A. Carreon, Arshad M. Khan

COURI Symposium Abstracts, Summer 2012

Hindbrain neurons are critical for the coordination of feeding, autonomic, and metabolic responses to changes in circulating fuels, such as sugar and fatty acids. Using protein markers such as the Fos transcription factor, previous work has identified key regions of the hindbrain that may be involved in such coordination. However, in these studies, Fos protein staining of hindbrain neurons was performed hours after the hypo- or hyperglycemic challenge was delivered, making activation responses difficult to interpret in relation to the stimulus given. Moreover, these studies generally have employed immunoperoxidase methods to identify Fos-activated neurons without explicitly identifying the chemical phenotypes …

Inhibitors Of Polyisoprenylated Methylated Protein Methyl Esterase (Pmpmease) Cause Neurodegeneration By Altering Microtubules And Gβγ In Pc12 Cells, Jose A. Rivas Jr., Rebekah M. Bach, Jessica Martinez-Jurado, Jorge A. Siera-Fonseca, Sukla Roychowdhury

COURI Symposium Abstracts, Summer 2012

Neurodegeneration, a progressive loss of nerve cells (neurons), occurs in many neurological disorders including Alzheimer’s disease, Parkinson’s disease, Schizophrenia and drug addiction. Disruption of Microtubules (MTs), a major component of cytoskeleton and aggregation of proteins associated with them is the hallmark of neurodegeneration. Gβγ, an important component of G protein signaling has been shown to induce neurite outgrowth of PC12 cells by interacting with microtubules. The goal of the present study is to understand whether interfering with Gβγ-MT mediated pathway causes neurodegeneration. Because prenylation of γ subunits is important for the interaction of Gβγ with MTs, we used inhibitors (L-23 …

Gβγ-Microtubule Interaction And Neurodegeneration, Jane K. Martinez, Jorge Sierra, Sukla Roychowdhury Ph.D.

COURI Symposium Abstracts, Summer 2012

Aberrant organization of microtubules (MTs) is known to be a feature of neurodegeneration, which occurs in many neurological disorder including Alzheimer’s disease, Parkinson’s disease, neuropsychiatric illness such as schizophrenia, and drug addiction. Previously, Gβγ, an important component of G protein-coupled signaling pathways, has been shown to regulate neurite outgrowth by interacting with MTs. The aim of the present study is to understand the Gβγ regulation of MT assembly and its relation to neurodegeneration, using GRK-ct peptide (consists of the carboxy terminus of G protein-coupled-receptor kinase) which is known to inhibit Gβγ-dependent signaling by binding to and sequestering Gβγ. PC12 cells …

Calcium-Binding Proteins In The Lateral Hypothalamic Area: Spatial Relations To Hypocretin/Orexin And Melanin Concentrating Hormone, Briana E. Pinales, Paola Rojas, Claire E. Wells, Arshad M. Khan

COURI Symposium Abstracts, Summer 2012

Lateral hypothalamic area (LHA) neurons are critical for the coordination of feeding behavior and the autonomic control of peripheral hormone release. Although many studies have employed intracranial stimulation (chemical, electrical, optogenetic) in and around the LHA to stimulate food intake and/or control autonomic activity, the chemical phenotype(s) of the neurons responsible for these physiological functions are unknown. This is due, in part, to a lack of basic information regarding the various chemical phenotypes in the LHA and their spatial relations to one another.

We have extended our initial chemoarchitectural profiling efforts of the LHA to examine the LHA distribution of …

Characterization And Localization Of Glycinergic Neurons From The Mouse Brain Stem, Astrid M. Rodriguez, Alejandra C. Camacho, Manuel Miranda

COURI Symposium Abstracts, Summer 2012

The neurotransmitter glycine functions as the major inhibitory neurotransmitter in the brain stem, cerebellum and spinal cord, where is contained in synaptic vesicles within glycinergic neurons. However the location of cell bodies, neuronal projections and connections are undefined to date. While the presence of glycine, the glycine transporters GlyT1, GlyT2 and the vesicular glycine transporter VIAAT may define a glycinergic neuron, little efforts have been made to investigate these neurons. To better identify and characterize these glycinergic neurons, we prepared primary cultures from the brain stem and the retina, using a transgenic mouse that expresses the green fluorescent protein (GFP) …

The Regulation Of The Glycine Transporter 1 By Phosphorylation, Alejandro A. Acuna, Qi Zhang, Vicente Castrejon, Luciana Girotto Gentil, Manuel Miranda

COURI Symposium Abstracts, Summer 2012

The plasma membrane glycine transporters 1 (GlyT1) is the carrier molecule responsible for the fast removal of the inhibitory neurotransmitter glycine from the synaptic cleft back into the presynaptic terminals of glycinergic neurons by an electrogenic, Na⁺-Cl^- transport couple mechanism maintained by the Na⁺,K⁺-ATPase. GlyTs belong to SLC6 family that includes other neurotransmitter transporters, such as the dopamine, norepinephrine, serotonin, and GABA transporters. In order to determine the role of PKC-dependent phosphorylation on GlyT1, we have analyzed the effect of PKC activation by phorbol ester (PMA) on the activity, post-translational modifications and the …

Loss Of Circuits Promoting Appetite Are Associated With Increases In Circuits Promoting Satiety: Where Is The Plasticity Occurring?, Nicole Dominguez, Ellen M. Walker, Arshad M. Khan*

COURI Symposium Abstracts, Summer 2012

Hindbrain catecholamine (CA) neurons promote feeding, whereas arcuate hypothalamic alpha melanocyte-stimulating hormone (αMSH) neurons promote satiety. A key brain region receiving these CA feeding and αMSH satiety signals is the paraventricular hypothalamus (PVH). We have observed that the αMSH inputs unexpectedly increase if the feeding-promoting CA inputs are lesioned. Here, we asked whether the increased αMSH inputs reflect altered numbers of αMSH neurons in the arcuate hypothalamus after the lesion or represent only local changes at the level of the PVH. Immunofluorescently labeled ARH αMSH neurons from 28 control and lesioned rats were counted as follows: confocal images from left …