Neuroscience and Neurobiology Commons^™

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 …

Mechanisms Of Astrocyte Contribution To Bortezomib-Induced Peripheral Neuropathy, Caleb R. Robinson

Dissertations and Theses (Open Access)

Bortezomib is a proteasome inhibitor used in the treatment of multiple myeloma and other non-solid malignancies, alone or in combination with other chemotherapy drugs. Like other chemotherapeutic agents, bortezomib treatment is frequently accompanied by chemotherapy-induced peripheral neuropathy (CIPN) that may be dose-limiting, adversely affecting quality of life and prognosis. The mechanisms behind bortezomib-induced peripheral neuropathy (BIPN) and CIPN overall are largely unknown. Recent findings in other pain models have indicated substantial involvement of glial cells in chronic pain. Although injury models have shown activation of both astrocytes and microglia following insult, research in other CIPN models has shown astrocytic activation …

Discovery And Elucidation Of The Fgfr3-Tacc3 Recurrent Fusion In Glioblastoma, Brittany C. Parker Kerrigan

Dissertations and Theses (Open Access)

Fusion genes occur due to chromosomal instability where two previously separate genes rearrange and fuse together, forming a hybrid gene. The first fusions were reported in leukemias; however, with the advent of more powerful sequencing technologies, fusions have recently been reported in several solid tumors. Using next-generation deep sequencing approaches, we discovered a fusion gene connecting the fibroblast growth factor receptor 3 (FGFR3) gene to the transforming coiled-coil containing protein 3 (TACC3) gene in glioblastoma multiforme. The fusion occurred in 8.3% of patient samples, but not in low grade or normal samples. FGFR3-TACC3 produced an in-frame …

The Effect Of Acute Lps-Induced Immune Activation And Brain Insulin Signaling Disruption In A Diabetic Model Of Alzheimer's Disease, Andrew Scott Murtishaw

UNLV Theses, Dissertations, Professional Papers, and Capstones

Alzheimer's disease (AD) is a neurodegenerative disorder marked by progressive cognitive impairments and pathological hallmarks that include amyloid plaques, neurofibrillary tangles, and neuronal loss. Several well-known mutations exist that lead to early-onset familial AD (fAD). However, these cases only account for a small percentage of total AD cases. The vast majority of AD cases are sporadic in origin (sAD) and are less clearly influenced by a single mutation but rather some combination of genetic and environmental risk.

The etiology of sAD remains unclear but numerous risk factors have been identified that increase the chance of developing AD. Among these risk …

Alternating Current And Infrared Produce An Onset-Free Reversible Nerve Block, Emilie H. Lothet, Kevin L. Kilgore, Niloy Bhadra, Narendra Bhadra, Tina Vrabec, Yves T. Wang, Michael W. Jenkins, Hillel J. Chiel

Faculty Scholarship

Nerve block can eliminate spasms and chronic pain. Kilohertz frequency alternating current (KHFAC) produces a safe and reversible nerve block. However, KHFAC-induced nerve block is associated with an undesirable onset response. Optical inhibition using infrared (IR) laser light can produce nerve block without an onset response, but heats nerves. Combining KHFAC with IR inhibition [alternating current and infrared (ACIR)] produces a rapidly reversible nerve block without an onset response. ACIR can be used to rapidly and reversibly provide onset-free nerve block in the unmyelinated nerves of the marine mollusk Aplysia californica and may have significant advantages over either modality alone. …

Neuroinflammation And Neurodegeneration In Adult Rat Brain From Binge Ethanol Exposure: Abrogation By Docosahexaenoic Acid, Nuzhath Tajuddin, Kwan-Hoon Moon, Simon Alex Marshall, Kimberly Nixon, Edward J. Neafsey, Hee-Yong Kim, Michael A. Collins

Pharmaceutical Sciences Faculty Publications

Evidence that brain edema and aquaporin-4 (AQP4) water channels have roles in experimental binge ethanol-induced neurodegeneration has stimulated interest in swelling/edema-linked neuroinflammatory pathways leading to oxidative stress. We report here that neurotoxic binge ethanol exposure produces comparable significant effects in vivo and in vitro on adult rat brain levels of AQP4 as well as neuroinflammation-linked enzymes: key phospholipase A2 (PLA2) family members and poly (ADP-ribose) polymerase-1 (PARP-1). In adult male rats, repetitive ethanol intoxication (3 gavages/d for 4 d, ∼ 9 g/kg/d, achieving blood ethanol levels ∼ 375 mg/dl; "Majchrowicz" model) significantly increased AQP4, Ca+2-dependent PLA2 GIVA (cPLA2), phospho-cPLA2 GIVA …

Inter- And Intralimb Adaptations To A Sensory Perturbation During Activation Of The Serotonin System After A Low Spinal Cord Transection In Neonatal Rats, Misty M. Strain, Sierra D. Kauer, Tina Kao, Michele R. Brumley

Publications and Research

Activation of the serotonin system has been shown to induce locomotor activity following a spinal cord transection. This study examines how the isolated spinal cord adapts to a sensory perturbation during activation of the serotonergic system. Real-time and persistent effects of a perturbation were examined in intact and spinal transected newborn rats. Rats received a spinal surgery (sham or low thoracic transection) on postnatal day 1 and were tested 9 days later. At test, subjects were treated with the serotonergic receptor agonist quipazine (3.0 mg/kg) to induce stepping behavior. Half of the subjects experienced range of motion (ROM) restriction during …

Increasing Maternal Or Post-Weaning Folic Acid Alters Gene Expression And Moderately Changes Behavior In The Offspring, Subit Barua, Kathryn K. Chadman, Salomon Kuizon, Diego Buenaventura, Nathan W. Stapley, Felicia Ruocco, Umme Begum, Sara R. Guariglia, W. Ted Brown, Mohamad Junaid

Publications and Research

Background: Studies have indicated that altered maternal micronutrients and vitamins influence the development of newborns and altered nutrient exposure throughout the lifetime may have potential health effects and increased susceptibility to chronic diseases. In recent years, folic acid (FA) exposure has significantly increased as a result of mandatory FA fortification and supplementation during pregnancy. Since FA modulates DNA methylation and affects gene expression, we investigated whether the amount of FA ingested during gestation alters gene expression in the newborn cerebral hemisphere, and if the increased exposure to FA during gestation and throughout the lifetime alters behavior in C57BL/6J mice.

Methods …

The Effects Of Cognitively Engaging Physical Activity On The Executive Function Of Sixth Graders, Alyssa Michele Humphreys

Theses and Dissertations

This purpose of this study was to examine the effects of cognitively engaging exercise, aerobic exercise, and resting conditions on the executive function of 6th graders. Four conditions were tested: cognitively engaging exercise, repetitive aerobic exercise, cognitively engaging rest, and rest. Executive function was measured by pre and post Stroop tests, which is a test of reaction time and inhibition. Results showed no significant differences between conditions in the choice reaction time test, however the cognitively engaging exercise was significantly different from all other conditions on the Stroop test.

Functional Correlates Of Optic Flow Motion Processing In Parkinson's Disease, Deepti Putcha, Robert S. Ross, Maya L. Rosen, Daniel J. Norton, Alice Cronin-Golomb, David C. Somers, Chantal E. Stern

Neuroscience: Faculty Publications

The visual input created by the relative motion between an individual and the environment, also called optic flow, influences the sense of self-motion, postural orientation, veering of gait, and visuospatial cognition. An optic flow network comprising visual motion areas V6, V3A, and MT+, as well as visuo-vestibular areas including posterior insula vestibular cortex (PIVC) and cingulate sulcus visual area (CSv), has been described as uniquely selective for parsing egomotion depth cues in humans. Individuals with Parkinson's disease (PD) have known behavioral deficits in optic flow perception and visuospatial cognition compared to age- and education-matched control adults (MC). The present study …

Behavioral And Neuroanatomical Abnormalities In Pleiotrophin Knockout Mice, Jason W. Krellman, Henry H. Ruiz, Veronica A. Marciano, Bracha Mondrow, Susan D. Croll

Publications and Research

Pleiotrophin (PTN) is an extracellular matrix-associated protein with neurotrophic and neuroprotective effects that is involved in a variety of neurodevelopmental processes. Data regarding the cognitive-behavioral and neuroanatomical phenotype of pleiotrophin knockout (KO) mice is limited. The purpose of this study was to more fully characterize this phenotype, with emphasis on the domains of learning and memory, cognitive-behavioral flexibility, exploratory behavior and anxiety, social behavior, and the neuronal and vascular microstructure of the lateral entorhinal cortex (EC). PTN KOs exhibited cognitive rigidity, heightened anxiety, behavioral reticence in novel contexts and novel social interactions suggestive of neophobia, and lamina-specific decreases in neuronal …

Particle Swarm Optimization Using Multiple Neighborhood Connectivity And Winner Take All Activation Applied To Biophysical Models Of Inferior Colliculus Neurons, Brandon S. Coventry

Open Access Theses

Age-related hearing loss is a prevalent neurological disorder, affecting as many as 63% of adults over the age of 70. The inability to hear and understand speech is a cause of much distress in aged individuals and is becoming a major public health concern as age-related hearing loss has also been correlated with other neurological disorders such as Alzheimer's dementia. The Inferior Colliculus (IC) is a major integrative auditory center, receiving excitatory and inhibitory inputs from several brainstem nuclei. This complex balance of excitation and inhibition gives rise to complex neural responses, which are measured in terms of firing rate …

Proliferation, Migration, And Survival Of Cells In The Telencephalon Of The Ball Python, Python Regius, Thomas B. Bales

Master's Theses

Reptiles exhibit neurogenesis throughout the brain during adulthood. However, very few studies have quantified telencephalon-wide neurogenesis in adulthood, and no studies have performed these investigations in snakes. Quantifying neurogenesis in the adult snake is essential to understanding class-wide adult neurogenesis and providing insight into the evolution of this trait. The thymidine analog 5-bromo-2’-deoxyuridine (BrdU) was used to quantify cell proliferation, migration, and survival in the ball python (Python regius). First, to determine the proper dose of BrdU for injection we subcutaneously injected 50mg/kg, 100mg/kg, and 250mg/kg into 15 adult male P. regius. We found the 250mg/kg dose …

Effects Of Dfo-Induced Hypoxia On Key Signaling Mediators, Jennifer Candelora

Seton Hall University Dissertations and Theses (ETDs)

While diseases such as cancer and diabetes, or surgery and traumatic injury can cause hypoxia through a decrease in blood circulation to bodily regions or decrease cardiac output they can also associate with hypoxia-induced pain. Clinically, opioids, such as morphine, are used to modulate pain. The mu-opioid receptors (MORs) are one of three main types of opioid receptors and are key mediators in morphine-induced analgesia. Therefore, in this study, the effect of hypoxia on MOR gene expression was examined using human neuronal cells treated with DFO to create a hypoxic-mimic condition. We found that MOR expression was shown to decrease …

Fty720 (Fingolimod) Provides Insight Into The Molecular Mechanisms Of Multiple Sclerosis, Madelyn Elizabeth Crawford

Pursuit - The Journal of Undergraduate Research at The University of Tennessee

Multiple sclerosis (MS) is a neurodegenerative disorder caused by a prolonged immune- mediated inflammatory response that targets myelin. Nearly all of the drugs approved for the treatment of MS are general immunosuppressants or only function in symptom management. The oral medication fingolimod, however, is reported to have direct therapeutic effects on cells of the central nervous system in addition to immunomodulatory functions. Fingolimod is known to interact with sphingosine-1-phosphate (S1P) receptors, and the most widely- accepted theory for its mechanism of action is functional antagonism of the receptor. This review examines significant neuromodulatory effects achieved by functional antagonism of the …

Motor Cortex Electrical Stimulation Augments Sprouting Of The Corticospinal Tract And Promotes Recovery Of Motor Function, Jason B. Carmel, John H. Martin

Publications and Research

The corticospinal system—with its direct spinal pathway, the corticospinal tract (CST) – is the primary system for controlling voluntary movement. Our approach to CST repair after injury in mature animals was informed by our finding that activity drives establishment of connections with spinal cord circuits during postnatal development. After incomplete injury in maturity, spared CST circuits sprout, and partially restore lost function. Our approach harnesses activity to augment this injury-dependent CST sprouting and to promote function. Lesion of the medullary pyramid unilaterally eliminates all CST axons from one hemisphere and allows examination of CST sprouting from the unaffected hemisphere. We …

Unconscious Neural Processing Differs With Method Used To Render Stimuli Invisible, Sergey V. Fogelson, Peter J. Kohler, Kevin J. Miller, Richard Granger, Peter U. Tse

Dartmouth Scholarship

Visual stimuli can be kept from awareness using various methods. The extent of processing that a given stimulus receives in the absence of awareness is typically used to make claims about the role of consciousness more generally. The neural processing elicited by a stimulus, however, may also depend on the method used to keep it from awareness, and not only on whether the stimulus reaches awareness. Here we report that the method used to render an image invisible has a dramatic effect on how category information about the unseen stimulus is encoded across the human brain. We collected fMRI data …

Roles Of Dopamine D1 And D2, Opioid And Glutamate Nmda Receptor Signaling In The Acquisition And Expression Of Fat- And Glucose-Conditioned Flavor Preferences In Rats And C-Fos Analysis Of The Dopamine Mesotelencephalic And Nigrostriatal Pathways Following Intake Of Sugars And Fats In Rats, Julie Dela Cruz

Dissertations, Theses, and Capstone Projects

Systemic administration of the non-competitive NMDA antagonist, MK-801, demonstrated that acquisition, but not expression, were found to affect the orosensory-mediated (flavor/flavor: f/f) fructose-conditioned flavor preference (CFP). The present studies demonstrated a similar outcome when f/f and f/n processes were combined. Fat-CFP and glucose-CFP studies indicated that systemic injections of the NMDA antagonist, MK-801, were able to significantly reduce acquisition, but not expression, of Corn-Oil (CO)-CFP and glucose-CFP. Both studies appear to have mitigated effects on acquisition as compared to the separate orosensory and postingestive CFP studies.

Previous studies found that systemic administration of dopamine (DA) D1 (SCH23390) and D2 (raclopride) …