Neuroscience and Neurobiology Commons^™

Acrolein As A Novel Therapeutic Target For Spinal Cord Injury Induced Neuropathic Pain, Jonghyuck Park

Open Access Dissertations

Despite years of research, post-spinal cord injury (SCI) chronic neuropathic pain remains refractory to treatment and drastically impairs quality of life for SCI victims beyond paralysis. Although inflammation and free radicals contribute to neuropathic pain in SCI, the mechanism is not completely clear. We have recently demonstrated that acrolein, a product and catalyst of lipid peroxidation, induces a vicious cycle of oxidative stress, amplifying its effects and perpetuating oxidative stress and inflammation. In the current study, we have confirmed that acrolein is elevated significantly at least two weeks post-SCI which coincides with the emergence of hyperalgesia (mechanical, cold and thermal). …

Morphometric Characterization Of Individual Sympathetic Postganglionic Axons Innervating The Muscle Layers Of The Gastrointestinal Tract Of The Rat: A Complex Effector Model, Gary C. Walter

Open Access Dissertations

A full description of the terminal morphology of sympathetic postganglionic axons innervating the musculature of the gastrointestinal (GI) tract has not been available. Furthermore, common assumptions about the morphology and distribution of catecholaminergic terminal fields have been strongly shaped by the limitations of the techniques employed to distinguish the fibers and complicated by inconsistent findings generated with various methodologies. Thus, the present experiment used modern neural tracer techniques to provide high-resolution labeling of sympathetic fibers projecting to the smooth muscle wall of the GI tract. Fischer 344 rats (N = 50) received injections of dextran biotin into the left …

Nano-Engineered Polymers In Drug Delivery: Potential Approaches For Attenuation Of Secondary Injury After Spinal Cord Trauma, Wen Gao

Open Access Dissertations

Secondary injury elicits a complex series of pathophysiological events after the primary spinal cord trauma and even after its implantation treatment for neural functional recovery. These secondary injuries include an up-regulation of glial cells associated reactive oxygen species, nitrogen species, and reactive astrogliosis, and they can result in various levels of cellular and tissue damage. The inhibition of them has been proved to lead to functional recovery of the spinal cord. In this study, we concentrated on developing polymers and nano-techniques based drug delivery strategies to eliminate these secondary injuries. ^ To maintain and improve the performance of the implants …

The Effects Of Environmental Enrichment On Abstinence And Relapse Using An Animal Conflict Model, Joshua Alan Peck

Dissertations, Theses, and Capstone Projects

Heroin addiction is a significant health and societal problem for which there is no effective and well-accepted long-term behavioral or pharmacological treatment. Therefore, strategies that prolong heroin abstinence should be the primary focus of heroin treatment research. There is promising evidence that environmental enrichment may indeed support drug abstinence in animals using the reinstatement model of abstinence and relapse. The current studies used an animal conflict model that captures the aversive consequences of drug seeking (as are typical in humans, e.g., arrest, incarceration, job loss, and strained social relationships) to test the effects of environmental enrichment on heroin abstinence, prolonged …

Attention Shapes Our Expectations And Perceptions: The Neural Mechanisms Of Top-Down Attention During Adulthood And Development, Snigdha Banerjee

Dissertations, Theses, and Capstone Projects

Top-down attention is the focusing of attention at one's will through knowledge regarding a current task. There is evidence that top-down attention involves the modulation of sensory cortices by higher order regions. However, the mechanisms of top-down attention across sensory modalities, its influence on early sensory inputs, as well as interactions with motivational systems remain unclear. We performed the following set of electrophysiological experiments in typically developed adults and adolescents to examine these areas. 1) The supramodal attentional theory holds that parietally-based attentional mechanisms are shared across sensory modalities. We tested the supramodal theory by examining if lateralized parieto-occipital alpha-band …

Executive Dysfunction And Reward Dysregulation: Interactions In Drug Addiction, Kristen Paula Morie

Dissertations, Theses, and Capstone Projects

Cocaine addiction is a serious public health hazard, and contributes to disastrous outcomes for individuals who suffer from it. Addiction is accompanied by an inability to control one's own behavior, and a preoccupation with cocaine at the expense of other rewarding pursuits. Previous research has suggested that difficulties with executive function and reward processing may underlie these problems, but the extent to which each contributes to addiction severity, or how these two factors may interact, remains to be elucidated. By using event related potential (ERP) measures in combination with information about self-reported anhedonia over three experiments, we set out to …

Psychic Collapse And Traumatic Defense: How The Mind Mediates Trauma Living In The Body, Patricia Kim Yoon

Dissertations, Theses, and Capstone Projects

The aim of this exploratory study was to link psychoanalytic theories of trauma and its impact on the mind with psychobiological research of how trauma lives in the body. The study has expanded on prior research (Cramer, 2003) to evidence that defense mechanisms do in fact moderate the relationship between stress and physiological response, and that there are likely individual differences in physiological response to traumatic stress. This study goes further to identify the psychological concomitants of these individual differences within an adult population exposed to potentially traumatic events (PTEs), and their proclivity for using different defense mechanisms. Defense use …

A Behavioral And Biopsychological Investigation Of The Role Of The Illusion Of Control And Perseverative Chasing Between Problem And Non-Problem Gamblers, Brett Evan Bauchner

Dissertations, Theses, and Capstone Projects

The illusion of control is associated with problem gambling. The perception that one is in control of a random event, when in reality there is no control, can facilitate problem gambling behaviors. The degree or extent of control may activate physiological mechanism of increased excitation and reward that reinforce gambling. In the studies presented here, performance on simulated gambling tasks that provided varying levels gambling participation were compared to physiological measures of behavioral activation in problem gambler and nongamblers. Participants watched video clips of three horseraces scenarios that permitted different degrees of participation and control over wagering. Concurrently saliva samples …

Mental Representations, Social Exclusion, And Neurobiological Processes In Borderline Personality Disorder: A Multi-Level Study, Jeffrey K. Erbe

Dissertations, Theses, and Capstone Projects

Borderline Personality Disorder (BPD) is an ongoing public health crisis. Poor developmental quality of differentiation-relatedness of object representations and attachment insecurity have been clinically and empirically demonstrated as core patterns of intrapsychic and interpersonal dysfunction in this particular form of personality pathology. Differentiation-relatedness (D-R), which involves a complementary relationship between intrapsychic autonomy and interpersonal relatedness, has been shown to be a significant aspect of internal psychic experience that relates directly to external relationship patterns, including characteristic response to interpersonal interactions and has been a specific target for treatment of BPD. Specifically, individuals with BPD have shown lower developmental quality of …

The Function Of The Phospholipid Flippase Atp8a1 In Neurotransmission, Brain Development And Autistic Behavior, Daniel Joseph Kerr

Dissertations, Theses, and Capstone Projects

The function of the phospholipid flippase Atp8a1 in neurotransmission, brain development, and autistic behavior

By

Daniel J. Kerr

The plasma membrane consists of lipids and proteins. Among the integral membrane proteins are P-type ATPases, widely expressed in both prokaryotes and eukaryotes, which use ATP to translocate ions across a plasma membrane. Type IV enzymes are putative aminophospholipid translocases (APLTs) and catalyze phosphatidylserine (PS) transfer into the cytosolic leaflet of a lipid bilayer. Previously, our group showed pronounced PS externalization in Atp8a1 (-/-) mice but not wild type (WT). Subsequent behavioral testing demonstrated that these Atp8a1 (-/-) mice display significant deficiency …

Large-Scale Identification Of Chemically Induced Mutations In Drosophila Melanogaster, Nele A Haelterman, Lichun Jiang, Yumei Li, Vafa Bayat, Hector Sandoval, Berrak Ugur, Kai Li Tan, Ke Zhang, Danqing Bei, Bo Xiong, Wu-Lin Charng, Theodore Busby, Adeel Jawaid, Gabriela David, Manish Jaiswal, Koen J T Venken, Shinya Yamamoto, Rui Chen, Hugo J Bellen

Faculty, Staff and Students Publications

Forward genetic screens using chemical mutagens have been successful in defining the function of thousands of genes in eukaryotic model organisms. The main drawback of this strategy is the time-consuming identification of the molecular lesions causative of the phenotypes of interest. With whole-genome sequencing (WGS), it is now possible to sequence hundreds of strains, but determining which mutations are causative among thousands of polymorphisms remains challenging. We have sequenced 394 mutant strains, generated in a chemical mutagenesis screen, for essential genes on the Drosophila X chromosome and describe strategies to reduce the number of candidate mutations from an average of …

The Role Of The Striatal Neuropeptide Neurotensin In The Methamphetamine-Induced Neural Injury In Mice, Qingkun Liu

Dissertations, Theses, and Capstone Projects

Methamphetamine (METH) is a widely abused psychostimulant that induces neurotoxicity to several brain regions, including the striatum. Similar to dopamine (DA) in chemical structure, METH can be transported into DA pre-synaptic terminals, evoking the neurodegeneration in DA terminals and post-synaptic striatal neurons. Despite the critical role of DA in METH-induced neurodegeneration, no pharmaceutical therapeutics has been approved for these conditions. It is therefore essential to investigate the endogenous factors regulating the dopaminergic system. The neuropeptide neurotensin has emerged as a potential modulator of METH-induced striatal neurodegeneration mainly due to its intimate interactions with dopamine in the striatum.

In this study, …

Biological Motion Processing In Typical Development And In The Autism Spectrum, Aaron Krakowski

Dissertations, Theses, and Capstone Projects

Biological motion (BM) analysis and interpretation is a fundamental process of human neurocognition that has been only minimally explored neurophysiologically. In addition to its importance in understanding the underlying roots and development of social cognition, BM processing is a prime candidate domain for exploring the underlying etiology of social cognitive disorders such as the autism spectrum.

In an initial experiment, typical adults observed BM point-light displays of a human actor (UM) as well as their spatially scrambled counterparts (SM), in both an unattended distractor task as well as an explicit attention task. Results showed a neurophysiological response manifested as three …

What Your Body Knows About God: How We Are Designed To Connect, Serve And Thrive, Rob Moll

Alumni Book Gallery

Have you ever had an experience where you felt particularly aware of God? If God is real, and we are created in God's image, then it makes sense that our minds and bodies would be designed with the perceptive ability to sense and experience God. Scientists are now discovering ways that our bodies are designed to connect with God. Brain research shows that our brain systems are wired to enable us to have spiritual experiences. The spiritual circuits that are used in prayer or worship are also involved in developing compassion for others. Our bodies have actually been created to …

Sticking Your Neck Out And Burying The Hatchet: What Idioms Reveal About Embodied Simulation, Natalie A. Kacinik

Publications and Research

Idioms are used in conventional language twice as frequently as metaphors, but most research, particularly recent work on embodiment has focused on the latter. However, idioms have the potential to significantly deepen our understanding of embodiment because their meanings cannot be derived from their component words. To determine whether sensorimotor states could activate idiomatic meaning, participants were instructed to engage in postures/actions reflecting various idioms (e.g.,sticking your neck out) relative to non-idiomatic control postures/actions while reading and responding to statements designed to assess idiomatic meaning. The results showed that statements were generally more strongly endorsed after idiom embodiment than control …

Hemispheric Asymmetry In New Neurons In Adulthood Is Associated With Vocal Learning And Auditory Memory, Shuk C. Tsoi, Utsav V. Aiya, Kobi D. Wasner, Mimi L. Phan, Carolyn L. Pytte, David S. Vicario

Publications and Research

Many brain regions exhibit lateral differences in structure and function, and also incorporate new neurons in adulthood, thought to function in learning and in the formation of new memories. However, the contribution of new neurons to hemispheric differences in processing is unknown. The present study combines cellular, behavioral, and physiological methods to address whether 1) new neuron incorporation differs between the brain hemispheres, and 2) the degree to which hemispheric lateralization of new neurons correlates with behavioral and physiological measures of learning and memory. The songbird provides a model system for assessing the contribution of new neurons to hemispheric specialization …

Asenapine Sensitization From Adolescence To Adulthood And Its Potential Molecular Basis, Qing Shu, Rongyin Qin, Yingzhu Chen, Gang Hu, Ming Li

Department of Psychology: Faculty Publications

Asenapine is a new antipsychotic drug that induces a long-lasting behavioral sensitization in adult rats. The present study investigated the developmental impacts of adolescent asenapine treatment on drug sensitivity and on 3 proteins implicated in the action of antipsychotic drugs (i.e. Brainderived neurotrophic factor (BDNF), dopamine D₂ receptor, and ΔFosB) in adulthood. Male adolescent Sprague-Dawley rats (postnatal days, P 43-48) were first treated with asenapine (0.05, 0.10 or 0.20 mg/kg, sc) and tested in the conditioned avoidance or PCP (2.0 mg/kg, sc)-induced hyperlocomotion tasks for 5 days. After they became adults (∼P 76), asenapine sensitization was assessed in a …

Integrating Cognitive Science With Innovative Teaching In Stem Disciplines, Mark A. Mcdaniel, Regina F. Frey, Susan M. Fitzpatrick, Henry L. Roediger Iii

Books and Monographs

This volume collects the ideas and insights discussed at a novel conference, the Integrating Cognitive Science with Innovative Teaching in STEM Disciplines Conference, which was held September 27-28, 2012 at Washington University in St. Louis. With funding from the James S. McDonnell Foundation, the conference was hosted by Washington University’s Center for Integrative Research on Cognition, Learning, and Education (CIRCLE), a center established in 2011. Available for download as a PDF. Titles of individual chapters can be found at http://openscholarship.wustl.edu/circle_book/.

Intergeniculate Leaflet Lesions Result In Differential Activation Of Brain Regions Following The Presentation Of Photic Stimuli In Nile Grass Rats, Andrew J. Gall, Lily Yan, Laura Smale, Antonio A. Nunez

Faculty Publications

The intergeniculate leaflet (IGL) plays an important role in the entrainment of circadian rhythms and the mediation of acute behavioral responses to light (i.e., masking). Recently, we reported that IGL lesions in diurnal grass rats result in a reversal in masking responses to light as compared to controls. Here, we used Fos as a marker of neural activation to examine the mechanisms by which the IGL may influence this masking effect of light in grass rats. Specifically, we examined the patterns of Fos activation in retinorecipient areas and in brain regions that receive IGL inputs following 1-h light pulses given …

The Significance Of Dynamical Architecture For Adaptive Responses To Mechanical Loads During Rhythmic Behavior, Kendrick M. M. Shaw, David N. Lyttle, Jeffrey P. Gill, Miranda J. Cullins, Jeffrey M. Mcmanus, Hui Lu, Peter J. Thomas, Hillel J. Chiel

Faculty Scholarship

Many behaviors require reliably generating sequences of motor activity while adapting the activity to incoming sensory information. This process has often been conceptually explained as either fully dependent on sensory input (a chain reflex) or fully independent of sensory input (an idealized central pattern generator, or CPG), although the consensus of the field is that most neural pattern generators lie somewhere between these two extremes. Many mathematical models of neural pattern generators use limit cycles to generate the sequence of behaviors, but other models, such as a heteroclinic channel (an attracting chain of saddle points), have been suggested. To explore …

Dba/2j Mice Are Susceptible To Diabetic Nephropathy And Diabetic Exacerbation Of Iop Elevation, Ileana Soto Reyes, Gareth R. Howell, Cai W. John, Joseph L. Kief, Richard T. Libby, Simon W.M. John

College of Science & Mathematics Departmental Research

Some pathological manifestations of diabetes in the eye include retinopathy, cataracts and elevated intraocular pressure (IOP). Loss of retinal ganglion cells (RGCs) in non-proliferative stages of diabetic retinopathy and small increases in IOP in diabetic patients has raised the possibility that diabetes affects the development and progression of ocular hypertension and glaucoma. The Ins2Akita mutation is known to cause diabetes and retinopathy on a C57BL/6J (B6) background by as early as 3 months of age. Here, the impact of the Akita mutation on glaucoma was assessed using DBA/2J (D2) mice, a widely used mouse model of ocular hypertension induced glaucoma. …

Long-Term Cre-Mediated Retrograde Tagging Of Neurons Using A Novel Recombinant Pseudorabies Virus, Hysell V. Oviedo, Hassasna K. Oyibo, Petr Znamenskiy, Lynn W. Enquist, Anthony M. Zador

Publications and Research

Brain regions contain diverse populations of neurons that project to different long-range targets. The study of these subpopulations in circuit function and behavior requires a toolkit to characterize and manipulate their activity in vivo. We have developed a novel set of reagents based on Pseudorabies Virus (PRV) for efficient and long-term genetic tagging of neurons based on their projection targets. By deleting IE180, the master transcriptional regulator in the PRV genome, we have produced a mutant virus capable of infection and transgene expression in neurons but unable to replicate in or spread from those neurons. IE180-null mutants showed no cytotoxicity, …

Lights And Larvae: Using Optogenetics To Teach Recombinant Dna And Neurobiology, John Titlow, Heidi Anderson, Robin L. Cooper

Biology Faculty Publications

Switching genes between organisms and controlling an animal’s brain using lasers may seem like science fiction, but with advancements in a technique called optogenetics, such experiments are now common in neuroscience research. Optogenetics combines recombinant DNA technology with a controlled light source to help researchers address biomedical questions in the life sciences. The technique has gained the most traction in neurobiology—the biology of the nervous system—where specific wavelengths of light are used to control or measure the activity of neurons in transgenic organisms (i.e., those with artificially inserted genes).

These optical recording and stimulation techniques are used in nervous system …

Modeling Of The Dorsal Gradient Across Species Reveals Interaction Between Embryo Morphology And Toll Signaling Pathway During Evolution, Priscilla Ambrosi, Juan Sebastian Chahda, Hannah R. Koslen, Hillel J. Chiel, Claudia Mieko Mizutani

Faculty Scholarship

Morphogenetic gradients are essential to allocate cell fates in embryos of varying sizes within and across closely related species. We previously showed that the maternal NF-κB/Dorsal (Dl) gradient has acquired different shapes in Drosophila species, which result in unequally scaled germ layers along the dorso-ventral axis and the repositioning of the neuroectodermal borders. Here we combined experimentation and mathematical modeling to investigate which factors might have contributed to the fast evolutionary changes of this gradient. To this end, we modified a previously developed model that employs differential equations of the main biochemical interactions of the Toll (Tl) signaling pathway, which …

Estrogens Stimulate Serotonin Neurons To Inhibit Binge-Like Eating In Mice, Xuehong Cao, Pingwen Xu, Mario G. Oyola, Yan Xia, Xiaofeng Yan, Kenji Saito, Fang Zou, Chunmei Wang, Yongjie Yang, Antentor Hinton Jr., Chunling Yan, Hongfang Ding, Liangru Zhu, Likai Yu, Bin Yang, Benjamin Feng, Deborah J. Clegg, Sohaib Khan, Richard Dimarchi, Shaila K. Mani, Qingchun Tong, Yong Xu

Peer Reviewed Articles

Binge eating afflicts approximately 5% of US adults, though effective treatments are limited. Here, we showed that estrogen replacement substantially suppresses binge-like eating behavior in ovariectomized female mice. Estrogen-dependent inhibition of binge-like eating was blocked in female mice specifically lacking estrogen receptor-α (ERα) in serotonin (5-HT) neurons in the dorsal raphe nuclei (DRN). Administration of a recently developed glucagon-like peptide-1–estrogen (GLP-1–estrogen) conjugate designed to deliver estrogen to GLP1 receptor–enhanced regions effectively targeted bioactive estrogens to the DRN and substantially suppressed binge-like eating in ovariectomized female mice. Administration of GLP-1 alone reduced binge-like eating, but not to the same extent as …

Activity-Dependent Serotonergic Excitation Of Callosal Projection Neurons In The Mouse Prefrontal Cortex, Emily K. Stephens, Daniel Avesar, Allan T. Gulledge

Dartmouth Scholarship

Layer 5 pyramidal neurons (L5PNs) in the mouse prefrontal cortex respond to serotonin (5-HT) according to their long-distance axonal projections; 5-HT_1A (1A) receptors mediate inhibitory responses in corticopontine (CPn) L5PNs, while 5-HT_2A (2A) receptors can enhance action potential (AP) output in callosal/commissural (COM) L5PNs, either directly (in “COM-excited” neurons), or following brief 1A-mediated inhibition (in “COM-biphasic” neurons). Here we compare the impact of 5-HT on the excitability of CPn and COM L5PNs experiencing variable excitatory drive produced by current injection (DC current or simulated synaptic current) or with exogenous glutamate. 5-HT delivered at resting membrane potentials, or paired …

What Can Individual Differences Reveal About Face Processing?, Galit Yovel, Jeremy B. Wilmer, Brad Duchaine

Dartmouth Scholarship

Faces are probably the most widely studied visual stimulus. Most research on face processing has used a group-mean approach that averages behavioral or neural responses to faces across individuals and treats variance between individuals as noise. However, individual differences in face processing can provide valuable information that complements and extends findings from group-mean studies. Here we demonstrate that studies employing an individual differences approach—examining associations and dissociations across individuals—can answer fundamental questions about the way face processing operates. In particular these studies allow us to associate and dissociate the mechanisms involved in face processing, tie behavioral face processing mechanisms to …

Rejection Positivity Predicts Trial-To-Trial Reaction Times In An Auditory Selective Attention Task: A Computational Analysis Of Inhibitory Control, Sufen Chen, Robert D. Melara

Publications and Research

A series of computer simulations using variants of a formal model of attention (Melara and Algom, 2003) probed the role of rejection positivity (RP), a slow-wave electroencephalographic (EEG) component, in the inhibitory control of distraction. Behavioral and EEG data were recorded as participants performed auditory selective attention tasks. Simulations that modulated processes of distractor inhibition accounted well for reaction-time (RT) performance, whereas those that modulated target excitation did not. A model that incorporated RP from actual EEG recordings in estimating distractor inhibition was superior in predicting changes in RT as a function of distractor salience across conditions. A …

Effect Of Environmental Cues On Behavioral Efficacy Of Haloperidol, Olanzapine And Clozapine In Rats, Tao Sun, Xinfeng Liu, Ming Li

Department of Psychology: Faculty Publications

Previous studies have reported that context can powerfully modulate the inhibitory effect of an antipsychotic drug on phencyclidine (PCP)-induced hyperlocomotion (a behavioral test used to evaluate putative antipsychotic drugs). The present study investigated the experimental conditions under which environmental stimuli exert their influence through associative conditioning processes. Experiment 1 examined the extent to which prior antipsychotic treatment in the home cages affected a drug’s ability to inhibit PCP-induced hyperlocomotion in a novel motor activity test apparatus. Five days of repeated haloperidol (0.05 mg/kg, sc) and olanzapine (2.0 mg/kg, sc) treatment in the home cages still potentiated their inhibition of PCP-induced …

Antidepressant Effects Of The Nts1 Agonist Pd149163 In The Forced Swim Test, Lawrence Carey Iv

All NMU Master's Theses

Neurotensin is a neuropeptide that influences monoaminergic neurotransmission in areas of the brain involved in the pathophysiology of depression. The forced swim test is a commonly used screening model for putative antidepressant medications. Drugs that have antidepressant effects in humans reliably decrease the time animals spend in an immobile posture in the forced swim test without increasing general locomotor activity as measured in an open field test. The present study sought to examine the effects of the neurotensin NTS₁ receptor agonist PD149163 and the tricyclic antidepressant drug imipramine on immobility in the forced swim test and on locomotor activity …