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2012

Neuroscience and Neurobiology

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Full-Text Articles in Life Sciences

The Posterior Hypothalamus Exerts Opposing Effects On Nociception Via The A7 Catecholamine Cell Group In Rats, Y. Jeong, J. R. Moes, M. Wagner, J. E. Holden Dec 2012

The Posterior Hypothalamus Exerts Opposing Effects On Nociception Via The A7 Catecholamine Cell Group In Rats, Y. Jeong, J. R. Moes, M. Wagner, J. E. Holden

University Faculty Publications and Creative Works

Stimulation of the posterior hypothalamic area (PH) produces antinociception in rats and humans, but the precise mechanisms are unknown. The PH forms anatomical connections with the parabrachial area, which contains the pontine A7 catecholamine cell group, a group of spinally projecting noradrenergic neurons known to produce antinociception in the dorsal horn. The aim of the present study was to determine whether PH-induced antinociception is mediated in part through connections with the A7 cell group in female Sprague-Dawley rats, as measured by the tail flick and foot withdrawal latency. Stimulation of the PH with the cholinergic agonist carbachol (125nmol) produced antinociception …


The Posterior Hypothalamus Exerts Opposing Effects On Nociception Via The A7 Catecholamine Cell Group In Rats, Y. Jeong, J. R. Moes, M. Wagner, J. E. Holden Dec 2012

The Posterior Hypothalamus Exerts Opposing Effects On Nociception Via The A7 Catecholamine Cell Group In Rats, Y. Jeong, J. R. Moes, M. Wagner, J. E. Holden

University Faculty Publications and Creative Works

Stimulation of the posterior hypothalamic area (PH) produces antinociception in rats and humans, but the precise mechanisms are unknown. The PH forms anatomical connections with the parabrachial area, which contains the pontine A7 catecholamine cell group, a group of spinally projecting noradrenergic neurons known to produce antinociception in the dorsal horn. The aim of the present study was to determine whether PH-induced antinociception is mediated in part through connections with the A7 cell group in female Sprague-Dawley rats, as measured by the tail flick and foot withdrawal latency. Stimulation of the PH with the cholinergic agonist carbachol (125nmol) produced antinociception …


Chronic Stress Elevates Telomerase Activity In Rats, Annaliese K. Beery, Jue Lin, Joshua S. Biddle, Darlene D. Francis, Elizabeth H. Blackburn, Elissa S. Epel Dec 2012

Chronic Stress Elevates Telomerase Activity In Rats, Annaliese K. Beery, Jue Lin, Joshua S. Biddle, Darlene D. Francis, Elizabeth H. Blackburn, Elissa S. Epel

Neuroscience: Faculty Publications

The enzyme telomerase lengthens telomeres—protective structures containing repetitive DNA sequences at chromosome ends. Telomere shortening is associated with diseases of ageing in mammals. Chronic stress has been related to shorter immune-cell telomeres, but telomerase activity under stress may be low, permitting telomere loss, or high, partially attenuating it. We developed an experimental model to examine the impacts of extended unpredictable stress on telomerase activity in male rats. Telomerase activity was 54 per cent higher in stressed rats than in controls, and associated with stress-related physiological and behavioural outcomes. This significant increase suggests a potential mechanism for resilience to stress-related replicative …


Adenosine Deaminase Enhances The Immunogenicity Of Human Dendritic Cells From Healthy And Hiv-Infected Individuals, Víctor Casanova, Isaac Isaac Naval-Macabuhay, Marta Massanella, Marta Rodríguez-García Dec 2012

Adenosine Deaminase Enhances The Immunogenicity Of Human Dendritic Cells From Healthy And Hiv-Infected Individuals, Víctor Casanova, Isaac Isaac Naval-Macabuhay, Marta Massanella, Marta Rodríguez-García

Dartmouth Scholarship

ADA is an enzyme implicated in purine metabolism, and is critical to ensure normal immune function. Its congenital deficit leads to severe combined immunodeficiency (SCID). ADA binding to adenosine receptors on dendritic cell surface enables T-cell costimulation through CD26 crosslinking, which enhances T-cell activation and proliferation. Despite a large body of work on the actions of the ecto-enzyme ADA on T-cell activation, questions arise on whether ADA can also modulate dendritic cell maturation. To this end we investigated the effects of ADA on human monocyte derived dendritic cell biology. Our results show that both the enzymatic and non-enzymatic activities of …


Process And Domain Specificity In Regions Engaged For Face Processing: An Fmri Study Of Perceptual Differentiation, Heather R. Collins, Xun Zhu, Ramesh S. Bhatt, Jonathan D. Clark, Jane E. Joseph Dec 2012

Process And Domain Specificity In Regions Engaged For Face Processing: An Fmri Study Of Perceptual Differentiation, Heather R. Collins, Xun Zhu, Ramesh S. Bhatt, Jonathan D. Clark, Jane E. Joseph

Psychology Faculty Publications

The degree to which face-specific brain regions are specialized for different kinds of perceptual processing is debated. This study parametrically varied demands on featural, first-order configural, or second-order configural processing of faces and houses in a perceptual matching task to determine the extent to which the process of perceptual differentiation was selective for faces regardless of processing type (domain-specific account), specialized for specific types of perceptual processing regardless of category (process-specific account), engaged in category-optimized processing (i.e., configural face processing or featural house processing), or reflected generalized perceptual differentiation (i.e., differentiation that crosses category and processing type boundaries). ROIs were …


Spectrum Of Acute Clinical Characteristics Of Diagnosed Concussions In College Athletes Wearing Instrumented Helmets, Ann-Christine Duhaime,, Jonathan G. Beckwith, Arthur C. Maerlender, Thomas W. Mcallister, Joseph J. Crisco, Stefan M. Duma, P. Gunnar Brolinson, Steven Rowson, Laura A. Flashman, Jeffrey J. Chu, Richard M. Greenwald Dec 2012

Spectrum Of Acute Clinical Characteristics Of Diagnosed Concussions In College Athletes Wearing Instrumented Helmets, Ann-Christine Duhaime,, Jonathan G. Beckwith, Arthur C. Maerlender, Thomas W. Mcallister, Joseph J. Crisco, Stefan M. Duma, P. Gunnar Brolinson, Steven Rowson, Laura A. Flashman, Jeffrey J. Chu, Richard M. Greenwald

Department of Psychology: Faculty Publications

Object. Concussive head injuries have received much attention in the medical and public arenas, as concerns have been raised about the potential shortand long-term consequences of injuries sustained in sports and other activities. While many student athletes have required evaluation after concussion, the exact definition of concussion has varied among disciplines and over time. The authors used data gathered as part of a multiinstitutional longitudinal study of the biomechanics of head impacts in helmeted collegiate athletes to characterize what signs, symptoms, and clinical histories were used to designate players as having sustained concussions.

Methods. Players on 3 college …


Septohippocampal Gabaergic Neurons Mediate The Altered Behaviors Induced By N-Methyl-D-Aspartate Receptor Antagonists., Jingyi Ma, Siew Kian Tai, L Stan Leung Dec 2012

Septohippocampal Gabaergic Neurons Mediate The Altered Behaviors Induced By N-Methyl-D-Aspartate Receptor Antagonists., Jingyi Ma, Siew Kian Tai, L Stan Leung

Physiology and Pharmacology Publications

We hypothesize that selective lesion of the septohippocampal GABAergic neurons suppresses the altered behaviors induced by an N-methyl-D-aspartate (NMDA) receptor antagonist, ketamine or MK-801. In addition, we hypothesize that septohippocampal GABAergic neurons generate an atropine-resistant theta rhythm that coexists with an atropine-sensitive theta rhythm in the hippocampus. Infusion of orexin-saporin (ore-SAP) into the medial septal area decreased parvalbumin-immunoreactive (GABAergic) neurons by ~80%, without significantly affecting choline-acetyltransferase-immunoreactive (cholinergic) neurons. The theta rhythm during walking, or the immobility-associated theta induced by pilocarpine, was not different between ore-SAP and sham-lesion rats. Walking theta was, however, more disrupted by atropine sulfate in ore-SAP than …


Targeting Astrocytes Ameliorates Neurologic Changes In A Mouse Model Of Alzheimer's Disease, Jennifer L. Furman, Diana M. Sama, John C. Gant, Tina L. Beckett, M. Paul Murphy, Adam D. Bachstetter, Linda J. Van Eldik, Christopher M. Norris Nov 2012

Targeting Astrocytes Ameliorates Neurologic Changes In A Mouse Model Of Alzheimer's Disease, Jennifer L. Furman, Diana M. Sama, John C. Gant, Tina L. Beckett, M. Paul Murphy, Adam D. Bachstetter, Linda J. Van Eldik, Christopher M. Norris

Pharmacology and Nutritional Sciences Faculty Publications

Astrocytes are the most abundant cell type in the brain and play a critical role in maintaining healthy nervous tissue. In Alzheimer's disease (AD) and most other neurodegenerative disorders, many astrocytes convert to a chronically "activated" phenotype characterized by morphologic and biochemical changes that appear to compromise protective properties and/or promote harmful neuroinflammatory processes. Activated astrocytes emerge early in the course of AD and become increasingly prominent as clinical and pathological symptoms progress, but few studies have tested the potential of astrocyte-targeted therapeutics in an intact animal model of AD. Here, we used adeno-associated virus (AAV) vectors containing the astrocyte-specific …


Brief Embryonic Strychnine Exposure In Zebrafish Causes Long-Term Adult Behavioral Impairment With Indications Of Embyronic Synaptic Changes, Nicole M. Roy, Brianna Arpie, Joseph Lugo, Elwood Linney, Edward D. Levin, Daniel Cerutti Nov 2012

Brief Embryonic Strychnine Exposure In Zebrafish Causes Long-Term Adult Behavioral Impairment With Indications Of Embyronic Synaptic Changes, Nicole M. Roy, Brianna Arpie, Joseph Lugo, Elwood Linney, Edward D. Levin, Daniel Cerutti

Biology Faculty Publications

Zebrafish provide a powerful model of the impacts of embryonic toxicant exposure on neural development that may result in long-term behavioral dysfunction. In this study, zebrafish embryos were treated with 1.5mM strychnine for short embryonic time windows to induce transient changes in inhibitory neural signaling, and were subsequently raised in untreated water until adulthood. PCR analysis showed indications that strychnine exposure altered expression of some genes related to glycinergic, GABAergic and glutamatergic neuronal synapses during embryonic development. In adulthood, treated fish showed significant changes in swimming speed and tank diving behavior compared to controls. Taken together, these data show that …


Cocaine-Induced Reinstatement Of A Conditioned Place Preference In Developing Rats: Involvement Of The D2 Receptor, Kimberly A. Badanich, Cheryl L. Kirstein Oct 2012

Cocaine-Induced Reinstatement Of A Conditioned Place Preference In Developing Rats: Involvement Of The D2 Receptor, Kimberly A. Badanich, Cheryl L. Kirstein

Psychology Faculty Publications

Reinstatement of conditioned place preferences have been used to investigate physiological mechanisms mediating drug-seeking behavior in adolescent and adult rodents; however, it is still unclear how psychostimulant exposure during adolescence affects neuron communication and whether these changes would elicit enhanced drug-seeking behavior later in adulthood. The present study determined whether the effects of intra-ventral tegmental area (VTA) or intra-nucleus accumbens septi (NAcc) dopamine (DA) D2 receptor antagonist infusions would block (or potentiate) cocaine-induced reinstatement of conditioned place preferences. Adolescent rats (postnatal day (PND 28–39)) were trained to express a cocaine place preference. The involvement of D2 receptors on cocaine-induced reinstatement …


Rod Microglia: Elongation, Alignment, And Coupling To Form Trains Across The Somatosensory Cortex After Experimental Diffuse Brain Injury, Jenna M. Ziebell, Samuel E. Taylor, Tuoxin Cao, Jordan L. Harrison, Jonathan Lifshitz Oct 2012

Rod Microglia: Elongation, Alignment, And Coupling To Form Trains Across The Somatosensory Cortex After Experimental Diffuse Brain Injury, Jenna M. Ziebell, Samuel E. Taylor, Tuoxin Cao, Jordan L. Harrison, Jonathan Lifshitz

Neuroscience Faculty Publications

BACKGROUND: Since their discovery, the morphology of microglia has been interpreted to mirror their function, with ramified microglia constantly surveying the micro-environment and rapidly activating when changes occur. In 1899, Franz Nissl discovered what we now recognize as a distinct microglial activation state, microglial rod cells (Stäbchenzellen), which he observed adjacent to neurons. These rod-shaped microglia are typically found in human autopsy cases of paralysis of the insane, a disease of the pre-penicillin era, and best known today from HIV-1-infected brains. Microglial rod cells have been implicated in cortical 'synaptic stripping' but their exact role has remained unclear. This is …


Computational Model Of Neuron-Astrocyte Interputational Model Of Neuron-Astrocyte Interactions During Focal Seizure Generationactions During Focal Seizure Generation, Davide Reato, Mario Cammarota, Lucas C. Parra, Giorgio Carmignoto Oct 2012

Computational Model Of Neuron-Astrocyte Interputational Model Of Neuron-Astrocyte Interactions During Focal Seizure Generationactions During Focal Seizure Generation, Davide Reato, Mario Cammarota, Lucas C. Parra, Giorgio Carmignoto

Publications and Research

Empirical research in the last decade revealed that astrocytes can respond to neurotransmitters with Ca2+ elevations and generate feedback signals to neurons which modulate synaptic transmission and neuronal excitability. This discovery changed our basic understanding of brain function and provided new perspectives for how astrocytes can participate not only to information processing, but also to the genesis of brain disorders, such as epilepsy. Epilepsy is a neurological disorder characterized by recurrent seizures that can arise focally at restricted areas and propagate throughout the brain. Studies in brain slice models suggest that astrocytes contribute to epileptiform activity by increasing neuronal excitability …


Distinct Retinohypothalamic Innervation Patterns Predict The Developmental Emergence Of Species-Typical Circadian Phase Preference In Nocturnal Norway Rats And Diurnal Nile Grass Rats, William D. Todd, Andrew J. Gall, Joshua A. Weiner, Mark S. Blumberg Oct 2012

Distinct Retinohypothalamic Innervation Patterns Predict The Developmental Emergence Of Species-Typical Circadian Phase Preference In Nocturnal Norway Rats And Diurnal Nile Grass Rats, William D. Todd, Andrew J. Gall, Joshua A. Weiner, Mark S. Blumberg

Faculty Publications

How does the brain develop differently to support nocturnality in some mammals, but diurnality in others? To answer this question, one might look to the suprachiasmatic nucleus (SCN), which is entrained by light via the retinohypothalamic tract (RHT). However, because the SCN is more active during the day in all mammals studied thus far, it alone cannot determine circadian phase preference. In adult Norway rats (Rattus norvegicus), which are nocturnal, the RHT also projects to the ventral subparaventricular zone (vSPVZ), an adjacent region that expresses an in-phase pattern of SCN-vSPVZ neuronal activity. In contrast, in adult Nile grass rats (Arvicanthis …


Collaborative Online Writing Assignments To Foster Active Learning, Richard F. Olivo Oct 2012

Collaborative Online Writing Assignments To Foster Active Learning, Richard F. Olivo

Neuroscience: Faculty Publications

To help students master the content of a neurophysiology course, they were asked to participate in collaborative writing projects. In the first two years, students contributed to a class wiki by summarizing one lecture and editing summaries of several others. In the second two years, students worked in teams of three or four to write a series of illustrated chapters spanning the entire semester. The second assignment kept students more engaged than the wiki project, and although they found it a significant amount of work, they also believed that it helped them learn the subject matter. Working in teams, however, …


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 Oct 2012

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 …


The Human Brain Intracerebral Microvascular System: Development And Structure, Miguel Marín-Padilla Sep 2012

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 …


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 Sep 2012

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 …


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 Sep 2012

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 …


Long-Term Effects Of Estradiol Replacement In The Olfactory System, Britto P. Nathan, Michael Tonsor, Robert G. Struble Sep 2012

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 Sep 2012

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 Aug 2012

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 …


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 Aug 2012

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.


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 Aug 2012

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 and Staff 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, …


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 Jul 2012

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 …


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 Jul 2012

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 …


Autism Spectrum Disorders In Hispanics And Non-Hispanics, Virginia Chaidez, Robin L. Hansen, Irva Hertz-Picciotto Jul 2012

Autism Spectrum Disorders In Hispanics And Non-Hispanics, Virginia Chaidez, Robin L. Hansen, Irva Hertz-Picciotto

Department of Nutrition and Health Sciences: Faculty Publications

Objectives: To compare differences in autism between Hispanics and non-Hispanics. We also examined the relationship between multiple language exposure and language function and scores of children. Methods: The Childhood Autism Risks from Genetics and the Environment (CHARGE) study is an ongoing population-based case-control study with children sampled (n = 1061) from three strata: those with autism (AU) or autism spectrum disorder (ASD); developmental delay (DD); or the general population (GP). Results: Non-Hispanic cases demonstrated higher cognitive composite scores for the Mullen Scales of Early Learning (MSEL). There were significant associations between multiple language exposure and MSEL subscales for receptive …


Coordination Between Proteasome Impairment And Caspase Activation Leading To Tau Pathology: Neuroprotection By Camp, M. J. Metcalfe, Q. Huang, Maria E. Figueiredo-Pereira Jun 2012

Coordination Between Proteasome Impairment And Caspase Activation Leading To Tau Pathology: Neuroprotection By Camp, M. J. Metcalfe, Q. Huang, Maria E. Figueiredo-Pereira

Publications and Research

Neurofibrillary tangles (NFTs) are hallmarks of Alzheimer’s disease (AD). The main component of NFTs is TAU, a highly soluble microtubule-associated protein. However, when TAU is cleaved at Asp421 by caspases it becomes prone to aggregation leading to NFTs. What triggers caspase activation resulting in TAU cleavage remains unclear. We investigated in rat cortical neurons a potential coordination between proteasome impairment and caspase activation. We demonstrate that upon proteasome inhibition, the early accumulation of detergent-soluble ubiquitinated (SUb) proteins paves the way to caspase activation and TAU pathology. This occurs with two drugs that inhibit the proteasome by different means: the product …


Evidence Accumulator Or Decision Threshold - Which Cortical Mechanism Are We Observing?, Patrick Simen Jun 2012

Evidence Accumulator Or Decision Threshold - Which Cortical Mechanism Are We Observing?, Patrick Simen

Faculty & Staff Scholarship

Most psychological models of perceptual decision making are of the accumulation-to- threshold variety. The neural basis of accumulation in parietal and prefrontal cortex is therefore a topic of great interest in neuroscience. In contrast, threshold mechanisms have received less attention, and their neural basis has usually been sought in subcortical structures. Here I analyze a model of a decision threshold that can be implemented in the same cortical areas as evidence accumulators, and whose behavior bears on two open questions in decision neuroscience: (1) When ramping activity is observed in a brain region during decision making, does it reflect evidence …


Focal Adhesion Kinase Modulates Cdc42 Activity Downstream Of Positive And Negative Axon Guidance Cues, Jonathan P. Myers, Estuardo Robles, Allison Ducharme-Smith, Timothy M. Gomez Jun 2012

Focal Adhesion Kinase Modulates Cdc42 Activity Downstream Of Positive And Negative Axon Guidance Cues, Jonathan P. Myers, Estuardo Robles, Allison Ducharme-Smith, Timothy M. Gomez

Neuroscience: Faculty Publications

There is biochemical, imaging and functional evidence that Rho GTPase signaling is a crucial regulator of actin-based structures such as lamellipodia and filopodia. However, although Rho GTPases are believed to serve similar functions in growth cones, the spatiotemporal dynamics of Rho GTPase signaling has not been examined in living growth cones in response to known axon guidance cues. Here we provide the first measurements of Cdc42 activity in living growth cones acutely stimulated with both growth-promoting and growthinhibiting axon-guidance cues. Interestingly, we find that both permissive and repulsive factors can work by modulating Cdc42 activity, but in opposite directions. We …


Endogenous Dynorphin Protects Against Neurotoxin-Elicited Nigrostriatal Dopaminergic Neuron Damage And Motor Deficits In Mice, Qingshan Wang, Eun-Joo Shin, Xuan-Khanh Thi Nguyen, Quan Li, Jae-Hyung Bach, Guoying Bing, Won-Ki Kim, Hyoung-Chun Kim, Jau-Shyong Hong Jun 2012

Endogenous Dynorphin Protects Against Neurotoxin-Elicited Nigrostriatal Dopaminergic Neuron Damage And Motor Deficits In Mice, Qingshan Wang, Eun-Joo Shin, Xuan-Khanh Thi Nguyen, Quan Li, Jae-Hyung Bach, Guoying Bing, Won-Ki Kim, Hyoung-Chun Kim, Jau-Shyong Hong

Neuroscience Faculty Publications

BACKGROUND: The striato-nigral projecting pathway contains the highest concentrations of dynorphin in the brain. The functional role of this opioid peptide in the regulation of mesencephalic dopaminergic (DAergic) neurons is not clear. We reported previously that exogenous dynorphin exerts potent neuroprotective effects against inflammation-induced dopaminergic neurodegeneration in vitro. The present study was performed to investigate whether endogenous dynorphin has neuroprotective roles in vivo.

METHODS: 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) and methamphetamine (MA), two commonly used neurotoxins in rodent models of Parkinson's disease, were administered to wild-type (Dyn⁺/⁺) and prodynorphin-deficient mice (Dyn⁻/⁻). We examined dopaminergic neurotoxicity by using an automated video tracking system, HPLC, …