Neuroscience and Neurobiology Commons^™

Pten Regulation Of Local And Long-Range Connections In Mouse Auditory Cortex, Qiaojie Xiong, Hysell V. Oviedo, Lloyd C. Trotman, Anthony M. Zador

Publications and Research

Autism spectrum disorders (ASDs) are highly heritable developmental disorders caused by a heterogeneous collection of genetic lesions. Here we use a mouse model to study the effect on cortical connectivity of disrupting the ASD candidate gene PTEN (phosphatase and tensin homolog deleted on chromosome 10). Through Cre-mediated recombination, we conditionally knocked out PTEN expression in a subset of auditory cortical neurons. Analysis of long-range connectivity using channelrhodopsin-2 revealed that the strength of synaptic inputs from both the contralateral auditory cortex and from the thalamus onto PTEN-cko neurons was enhanced compared with nearby neurons with normal PTEN expression. Laser-scanning photostimulation showed …

Brainstorm: What Testosterone Has In Common With Schrodinger’S Cat, John J. Medina Ph.D.

Brainstorm

People are often startled by the extent to which environment plays a part in mediating the biological processes behind their behaviors.

Spartin Protein Associates With Phospholipids Via Its Plant-Related Senescence Domain And Functions As A Lipid Transfer Protein, Maureen Ashlee Shaw

Theses (1 year embargo)

Troyer syndrome is a hereditary spastic paraplegia caused by a mutation that leads to a complete loss of expression of spartin protein. The plant-related senescence domain in spartin is highly conserved and present in over 150 proteins, but its function is unknown. Our results indicate that spartin associates with phospholipids via its senescence domain.

Phospholipids are important components of intracellular membranes and play roles in many cellular processes. Knock-down of spartin results in impaired cell division. The phospholipid phosphatidylinositol 3-phosphate (PI3P) is present at midbodies, where it recruits proteins for cytokinesis. Our findings demonstrate that spartin colocalizes with PI3P at …

Serotonin 1a Receptor-Mediated Signaling Through Erk And Pkcα Is Essential For Normal Synaptogenesis In Neonatal Mouse Hippocampus, A. Mogha, Sara R. Guariglia, Priya Ranjan Debata, Guang Y. Wen, Probal Banerjee

Publications and Research

Aberrant expression of the presynaptic serotonin 1A receptor (5-HT_1A-R) because of a polymorphism in the 5-HT_1A-R gene is associated with severe depression in human, whereas its absence up to postnatal day 21 (P21) in the forebrain of mice results in heightened anxiety in adulthood. These observations collectively indicate that the 5-HT1A-R has a crucial role in brain development. To understand the mechanistic underpinnings of this phenomenon, we used organotypic slice cultures of hippocampi from C57BL6 mice (C57) at P15, which coincides with the peak of neonatal synaptogenesis. Stimulation of the hippocampal 5-HT1A-R caused a dramatic increase …

Derivation Of A Novel Efficient Supervised Learning Algorithm From Cortical-Subcortical Loops, Ashok Chandrashekar, Richard Granger

Dartmouth Scholarship

Although brain circuits presumably carry out powerful perceptual algorithms, few instances of derived biological methods have been found to compete favorably against algorithms that have been engineered for specific applications. We forward a novel analysis of a subset of functions of cortical-subcortical loops, which constitute more than 80% of the human brain, thus likely underlying a broad range of cognitive functions. We describe a family of operations performed by the derived method, including a non-standard method for supervised classification, which may underlie some forms of cortically dependent associative learning. The novel supervised classifier is compared against widely used algorithms for …

Hiv-1 Tat Triggers Nuclear Localization Of Zo-1 Via Rho Signaling And Camp Response Element-Binding Protein Activation, Yu Zhong, Bei Zhang, Sung Yong Eum, Michal Toborek

Neurosurgery Faculty Publications

The human immunodeficiency virus (HIV)-specific protein trans-activator of transcription (Tat) can contribute to the dysfunction of brain endothelial cells and HIV trafficking into the brain by disrupting tight junction (TJ) integrity at the blood–brain barrier (BBB) level. Specific TJ proteins, such as zonula occludens (ZO) proteins, localize not only at the cell–cell borders but are also present in the nuclei. The objective of the present study was to evaluate the mechanisms and significance of Tat-induced nuclear localization of ZO-1. Treatment of a brain endothelial cell line (hCMEC/D3 cells) with Tat resulted in a decrease in total levels of ZO-1 but …

Brainstorm: A Tale Of Two Video Clips, John J. Medina Ph.D.

Brainstorm

I have spent a lifetime trying to understand the distance between a gene and a behavior. Using the lens of psychiatric disorders, I’ve spent most of my professional life as a private research consultant, primarily to the pharmaceutical and biotech industries, on issues related to mental health. Despite great strides made in the field by literally thousands of colleagues, I am here to report that the rocky terrain between behaviors and genes lies mostly unmapped. For that I blame two video clips, both featuring legendary golfer and famously troubled ex­husband, Tiger Woods.

Domain Architecture Of A Calcium-Permeable Ampa Receptor In A Ligand-Free Conformation, Charles R. Midgett, Avinash Gill, Dean R. Madden

Dartmouth Scholarship

Ligand-gated ion channels couple the free energy of agonist binding to the gating of selective transmembrane ion pores, permitting cells to regulate ion flux in response to external chemical stimuli. However, the stereochemical mechanisms responsible for this coupling remain obscure. In the case of the ionotropic glutamate receptors (iGluRs), the modular nature of receptor subunits has facilitated structural analysis of the N-terminal domain (NTD), and of multiple conformations of the ligand-binding domain (LBD). Recently, the crystallographic structure of an antagonist-bound form of the receptor was determined. However, disulfide trapping of this conformation blocks channel opening, suggesting that channel activation involves …

Shared Resistance To Aging And Als In Neuromuscular Junctions Of Specific Muscles, Gregorio Valdez, Juan C. Tapia, Jeff W. Lichtman, Michael A. Fox, Joshua R. Sanes

Anatomy and Neurobiology Publications

Normal aging and neurodegenerative diseases both lead to structural and functional alterations in synapses. Comparison of synapses that are generally similar but respond differently to insults could provide the basis for discovering mechanisms that underlie susceptibility or resistance to damage. Here, we analyzed skeletal neuromuscular junctions (NMJs) in 16 mouse muscles to seek such differences. We find that muscles respond in one of three ways to aging. In some, including most limb and trunk muscles, age-related alterations to NMJs are progressive and extensive during the second postnatal year. NMJs in other muscles, such as extraocular muscles, are strikingly resistant to …

Brainstorm: John J. Medina Biography, John J. Medina Ph.D.

Brainstorm

John J. Medina, Ph.D., is director of the Brain Center for Applied Learning Research at Seattle Pacific University. He is a developmental molecular biologist whose research interests are focused on the genes involved in human brain development and the genetics of psychiatric disorders.

The Impact Of Sleep Quality On Cognitive Functioning In Parkinson's Disease, Karina Stavitsky, Sandra Neargarder, Yelena Bogdanova, Patrick Mcnamara, Alice Cronin-Golomb

Psychology Faculty Publications

In healthy individuals and those with insomnia, poor sleep quality is associated with decrements in performance on tests of cognition, especially executive function. Sleep disturbances and cognitive deficits are both prevalent in Parkinson's disease (PD). Sleep problems occur in over 75% of patients, with sleep fragmentation and decreased sleep efficiency being the most common sleep complaints, but their relation to cognition is unknown. We examined the association between sleep quality and cognition in PD. In 35 non-demented individuals with PD and 18 normal control adults (NC), sleep was measured using 24-hr wrist actigraphy over 7 days. Cognitive domains tested included …

Su People, Yuhan Xu, Paula Meseroll, Kathleen Haley, Jay Cox, Jim Reilly, Carol L. Boll

Syracuse University Magazine

No abstract provided.

Optogenetic Stimulation Of The Corticothalamic Pathway Affects Relay Cells And Gabaergic Neurons Differently In The Mouse Visual Thalamus, Chris W. D. Jurgens, Karen A. Bell, A. Rory Mcquiston, William Guido

Anatomy and Neurobiology Publications

The dorsal lateral geniculate nucleus (dLGN) serves as the primary conduit of retinal information to visual cortex. In addition to retinal input, dLGN receives a large feedback projection from layer VI of visual cortex. Such input modulates thalamic signal transmission in different ways that range from gain control to synchronizing network activity in a stimulus-specific manner. However, the mechanisms underlying such modulation have been difficult to study, in part because of the complex circuitry and diverse cell types this pathway innervates. To address this and overcome some of the technical limitations inherent in studying the corticothalamic (CT) pathway, we adopted …

Pain As Fact And Heuristic: How Pain Neuroimaging Illuminates Moral Dimensions Of Law, Amanda C. Pustilnik

Faculty Scholarship

Legal statuses, prohibitions, and protections often turn on the presence and degree of physical pain. In legal domains ranging from tort to torture, pain and its degree do important definitional work by delimiting boundaries of lawfulness and of entitlements. The omnipresence of pain in law suggests that the law embodies an intuition about the ontological primacy of pain. Yet, for all the work done by pain as a term in legal texts and practice, it has had a confounding lack of external verifiability. As with other subjective states, we have been able to impute pain’s presence but have not been …

Neurotechnology And Psychiatric Biomarkers, William Bosl

Nursing and Health Professions Faculty Research and Publications

No abstract provided.

Novel Report Of Expression And Function Of Cd97 In Malignant Gliomas: Correlation With Wilms Tumor 1 Expression And Glioma Cell Invasiveness Laboratory Investigation, Archana Chidambaram, Helen L. Fillmore, Timothy E. Van Meter, Catherine I. Dumur, William C. Broaddus

Division of Research and Economic Development Faculty & Staff Publications

Object. The Wilms tumor 1 (WT1) protein—a developmentally regulated transcription factor—is aberrantly expressed in gliomas and promotes their malignant phenotype. However, little is known about the molecular allies that help it mediate its oncogenic functions in glioma cells.

Methods. The authors used short interfering RNA (siRNA) to suppress WT1 expression in glioblastoma (GBM) cells and evaluated the effect of this on GBM cell invasiveness. Gene expression analysis was then used to identify the candidate genes that were altered as a result of WT1 silencing. One candidate target, CD97, was then selected for further investigation into its role by suppressing …

Cognitive Effects Of One Season Of Head Impacts In A Cohort Of Collegiate Contact Sport Athletes, Thomas W. Mcallister,, Laura A. Flashman, Arthur C. Maerlender, Richard M. Greenwald, Jonathan G. Beckwith, Tor D. Tosteson, Joe Crisco, Per Gunner Brolinson, Stefan Duma, Ann-Christine Duhaime, M. R. Grove, John H. Turco

Center for Brain, Biology, and Behavior: Faculty Publications

Objective: To determine whether exposure to repetitive head impacts over a single season negatively affects cognitive performance in collegiate contact sport athletes.

Methods: This is a prospective cohort study at 3 Division I National Collegiate Athletic Association athletic programs. Participants were 214 Division I college varsity football and ice hockey players who wore instrumented helmets that recorded the acceleration-time history of the head following impact, and 45 noncontact sport athletes. All athletes were assessed prior to and shortly after the season with a cognitive screening battery (ImPACT) and a subgroup of athletes also were assessed with 7 measures from a …

Nutraceutical Antioxidants And Their Therapeutic Potential In Neurodegeneration, Erika Kristine Ross

Electronic Theses and Dissertations

Amyotrophic lateral sclerosis (ALS) is a fatal neuromuscular disease that affects motor neurons of the brain and spinal cord. Many studies indicate that mitochondrial oxidative stress (MOS) is a principal mechanism underlying the pathophysiology of this and other devastating neurodegenerative diseases. Here, we investigated a unique whey protein supplement (Immunocal®) to determine its neuroprotective efficacy in several in vitro models of MOS and in an in vivo mouse model of ALS. This non-denatured whey supplement contains cystine which is an oxidized form of cysteine, an essential precursor for synthesis of the endogenous antioxidant, glutathione (GSH). In primary cultured rat cerebellar …

Taste Neophobia And C-Fos Expression In The Rat Brain, Jian-You Lin, Christopher T. Roman, Joe Arthurs, Steve Reilly

Scholarship and Professional Work – COPHS

Taste neophobia refers to a reduction in consumption of a novel taste relative to when it is familiar. To gain more understanding of the neural basis of this phenomenon, the current study examined whether a novel taste (0.5% saccharin) supports a different pattern of c-Fos expression than the same taste when it is familiar. Results revealed that the taste of the novel saccharin solution evoked more Fos immunoreactivity than the familiar taste of saccharin in the basolateral region of the amygdala, central nucleus of the amygdala, gustatory portion of the thalamus, and the gustatory insular cortex. No such differential expression …

Conditioned Response Evoked By Nicotine Conditioned Stimulus Preferentially Induces C-Fos Expression In Medial Regions Of Caudate-Putamen, Sergios Charntikov, Matthew E. Tracy, Changjiu Zhao, Ming Li, Rick A. Bevins

Department of Psychology: Faculty Publications

Nicotine has both unconditioned and conditioned stimulus properties. Conditioned stimulus properties of nicotine may contribute to the tenacity of nicotine addiction. The purpose of this experiment was to use neurohistochemical analysis of rapidly developing c-Fos protein to elucidate neurobiological loci involved in the processing of nicotine as an interoceptive conditioned stimulus (CS). Rats were injected (SC) in an intermixed fashion with saline or nicotine (16 sessions of each) and placed in conditioning chambers where they were given one of the three conditions depending on group assignment: (a) nicotine paired 100% of the time with intermittent access to sucrose (nicotine-CS condition), …

Structure-Function Analysis Of Nel, A Thrombospondin-1-Like Glycoprotein Involved In Neural Development And Functions, Masaru Nakamoto

Biology Faculty Publications

Nel (neural epidermal growth factor (EGF)-like molecule) is a multimeric, multimodular extracellular glycoprotein with heparin-binding activity and structural similarities to thrombospondin-1. Nel is predominantly expressed in the nervous system and has been implicated in neuronal proliferation and differentiation, retinal axon guidance, synaptic functions, and spatial learning. The Nel protein contains an N-terminal thrombospondin-1 (TSP-N) domain, five cysteine-rich domains, and six EGF-like domains. However, little is known about the functions of specific domains of the Nel protein. In this study, we have performed structure-function analysis of Nel, by using a series of expression constructs for different regions of the Nel protein. …

Expression Of Suppressor Of Cytokine Signaling 2 (Socs2) During Optic Nerve Regeneration In Xenopus Laevis, Rupa Priscilla Choudhary

Legacy Theses & Dissertations (2009 - 2024)

The optic nerve and other central nervous system (CNS) axons tend to lose their capacity to regenerate following an injury in adult amniotes, but these axons are able to regenerate throughout life in anamniotes. The long-term goal of my study is to identify molecular mechanisms responsible for the retention of this regenerative capacity. Specifically, I will examine the role of the gene Suppressor of Cytokine Signaling 2 (SOCS2) in the successful regeneration of retinal ganglion cell (RGC) axons of the South African claw-toed frog, Xenopus laevis, after injury.

Spatial Working Memory And Adult Hippocampal Neurogenesis In Male Rats With Hight Fat Diet-Induced Obesity, Andrew Karl Recknagel

Legacy Theses & Dissertations (2009 - 2024)

Granule cells are continually produced in the dentate gyrus of the hippocampus throughout life. These new neurons integrate into the local circuitry and contribute to hippocampal function. Insulin directly affects hippocampal function and may also influence the process of adult neurogenesis. Some of the cognitive deficits that occur in Type 2 Diabetes Mellitus (T2DM) and Alzheimer's disease (AD) may be caused by hyperinsulinemia and systemic insulin resistance. Sedentary lifestyles combined with over-consumption of energy rich foods are responsible for the rising incidence of metabolic syndrome and chronic obesity, both of which represent major risk factors for T2DM and AD. Therefore, …

Identification Of Trophic And Transcriptional Requirements For Human Embryonic Stem Cell Culture And Guided Neural Differentiation, Nicolas Edward Tokas

Legacy Theses & Dissertations (2009 - 2024)

Translational biomedical research holds potential for the development of novel therapeutics for the treatment of injury, illness or disability. To better understand intrinsic cellular and molecular biology, human embryonic stem cells (hESCs) can be used as a tool. hESCs are pluripotent with the abilities to be held in a self-renewal state or become induced to a desired germ layer then to be later directed through differentiation.

Mechanism Of Inhibition Of The Glua2 Receptors By N-3 Derivatives Of 2,3-Benzodiazepines With C-4 Methyl Group, Congzhou Wang

Legacy Theses & Dissertations (2009 - 2024)

α-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors are one of the three subtypes of ionotropic glutamate receptors. AMPA receptors mediate fast synaptic neurotransmission in the central nervous system (CNS). Over-activation of calcium permeable AMPA receptors causes intracellular calcium overload, which leads to neurodegeneration and cell death. As such, AMPA receptors have been implicated in a number of neurological disorders and diseases, such as epilepsy, amyotrophic lateral sclerosis (ALS), and Parkinson's disease. 2,3-Benzodiazepine derivatives (or GYKI compounds) are a group of structurally similar compounds synthesized as inhibitors of AMPA receptors, and they have been used as potential drug candidates for the treatment of various …

The Role Of An Rna Binding Protein Hnrnp K During Axon Development And Regeneration In Xenopus Laevis, Yuanyuan Liu

Legacy Theses & Dissertations (2009 - 2024)

Coordinated synthesis and assembly of the cytoskeletal network contribute significantly to morphological changes during axon outgrowth. Previous studies demonstrated that heterogeneous ribonucleoprotein K (hnRNP K), an RNA binding protein, binds to the 3'-untranslated regions of all neurofilament triplet subunits, the most abundant components of the axonal cytoskeleton. These findings raised the hypothesis that hnRNP K post-transcriptionally mediates the coordinated expression of axonal cytoskeletal components. In my thesis, I test this hypothesis during both axonal development and regeneration.

Characterization Of Postsynaptic Calcium(Ii) Signals And Their Role In Synaptic Regulation At The Drosophila Larval Neuromuscular Junction, Sunil Ashok Desai

Legacy Theses & Dissertations (2009 - 2024)

Postsynaptic [Ca2+]i has been proposed to play an important role in both synaptic plasticity and synaptic homeostasis. Postsynaptic Ca2+ signals appear to regulate synaptic transmission at the Drosophila larval NMJ; however, they have not been characterized at a NMJ. We were interested in examining the postsynaptic Ca2+ signals in this system and determining its influence on synaptic strength. The muscle Ca2+ transients were recorded by injecting the muscle fibers with Ca2+ indicators; discrete postsynaptic Ca2+ transients were observed along the NMJ during evoked and spontaneous transmitter release. The magnitude of the Ca2+ signals was correlated with synaptic efficacy, terminals producing …

Characterization Of The Behavioral, Biochemical And Molecular Indices Of Stress Produced By Nicotine Exposure And Withdrawal In Male And Female Rats, Oscar Valentin Torres

Open Access Theses & Dissertations

Introduction: Tobacco use is a major economic and health problem. Particularly concerning is that women consume more tobacco products, have a more difficult time quitting, and are less likely to benefit from cessation therapies than men. As a result, women are at higher risk of developing tobacco-related diseases. Women are generally more susceptible to stress and are more likely to cope with stress by smoking as compared to men. During abstinence, women also experience intense anxiety as compared to men and report that the anxiety-reducing effects of smoking are the main reason for continued use and relapse. Thus, stress produced …

Explore, Educate, Expand: The Exploratorium’S Education Abroad Youth Program, Nina Rubin

Capstone Collection

This capstone describes the design of an outbound, education abroad program that will take place in Dharamsala, India over a five-week period. It will bring together young adults from the U.S. and Tibet for an intercultural learning experience. The program will provide hands-on opportunities for participants to be engaged in academic, philosophical and personal growth. The educational workshops and activities will be centered on neuroscience, meditation, and Buddhist conceptions of science and the natural world. At the same time, themes of intercultural communication and competence will be explored in-depth.

As a foundation, the program will build from an existing partnership …

Investigating The Role Of Prion Protein Polymorphisms On Prion Pathogenesis, Eri Saijo

Theses and Dissertations--Microbiology, Immunology, and Molecular Genetics

Transmissible spongiform encephalopathies (TSEs), also known as prion diseases, are lethal and infectious neurodegenerative diseases of humans and animals. The misfolding of the normal, or cellular isoform of the prion protein (PrP^C) into the abnormal disease-associated isoform of PrP (PrP^Sc) could change the properties of PrP, consequently, PrP^Sc has lethal infectivity to transmit diseases. The proteinaceous infectious particle consisting mainly of PrP^Sc is called prion. Transmissibility of prions is strongly influenced by multiple factors including PrP polymorphisms, species barriers (PrP sequence specificity) and prion strains (conformational specificity) by unknown mechanisms. Even though the ability …