Neuroscience and Neurobiology Commons^™

The Abl And Arg Non-Receptor Tyrosine Kinases Regulate Different Zones Of Stress Fiber, Focal Adhesion, And Contractile Network Localization In Spreading Fibroblasts, Justin G. Peacock, Brian A. Couch, Anthony J. Koleske

School of Biological Sciences: Faculty Publications

Directed cell migration requires precise spatial control of F-actin-based leading edge protrusion, focal adhesion (FA) dynamics, and actomyosin contractility. In spreading fibroblasts, the Abl family kinases, Abl and Arg, primarily localize to the nucleus and cell periphery, respectively. Here we provide evidence that Abl and Arg exert different spatial regulation on cellular contractile and adhesive structures. Loss of Abl function reduces FA, F-actin, and phosphorylated myosin light chain (pMLC) staining at the cell periphery, shifting the distribution of these elements more to the center of the cell than in wild-type (WT) and arg^—/— cells. Conversely, loss of Arg function …

Synaptic Clustering Of Psd-95 Is Regulated By C-Abl Through Tyrosine Phosphorylation, Karen Perez De Arce, Lorena Varela-Nallar, Olivia Farias, Alejandra Cifuentes, Paulina Bull, Brian A. Couch, Anthony J. Koleske, Nibaldo C. Inestrosa, Alejandra R. Alvarez

School of Biological Sciences: Faculty Publications

The c-Abl tyrosine kinase is present in mouse brain synapses, but its precise synaptic function is unknown. We found that c-Abl levels in the rat hippocampus increase postnatally, with expression peaking at the first postnatal week. In 14 d in vitro hippocampal neuron cultures, c-Abl localizes primarily to the postsynaptic compartment, in which it colocalizes with the postsynaptic scaffold protein postsynaptic density protein-95 (PSD-95) in apposition to presynaptic markers. c-Abl associates with PSD-95, and chemical or genetic inhibition of c-Abl kinase activity reduces PSD-95 tyrosine phosphorylation, leading to reduced PSD-95 clustering and reduced synapses in treated neurons. c-Abl can phosphorylate …

Mental Reversal Of Imagined Melodies: A Role For The Posterior Parietal Cortex, Robert J. Zatorre, Andrea R. Halpern, Marc Bouffard

Faculty Journal Articles

Two fMRI experiments explored the neural substrates of a musical imagery task that required manipulation of the imagined sounds: temporal reversal of a melody. Musicians were presented with the first few notes of a familiar tune (Experiment 1) or its title (Experiment 2), followed by a string of notes that was either an exact or an inexact reversal. The task was to judge whether the second string was correct or not by mentally reversing all its notes, thus requiring both maintenance and manipulation of the represented string. Both experiments showed considerable activation of the superior parietal lobe (intraparietal sulcus) during …

Perception Of Emotion In Sounded And Imagined Music, Brian L. Lucas, Emery Schubert, Andrea R. Halpern

Faculty Journal Articles

WE STUDIED THE EMOTIONAL RESPONSES BY MUSICIANS to familiar classical music excerpts both when the music was sounded, and when it was imagined.We used continuous response methodology to record response profiles for the dimensions of valence and arousal simultaneously and then on the single dimension of emotionality. The response profiles were compared using cross-correlation analysis, and an analysis of responses to musical feature turning points, which isolate instances of change in musical features thought to influence valence and arousal responses. We found strong similarity between the use of an emotionality arousal scale across the stimuli, regardless of condition (imagined …

Robust Dynamic Balance Of Ap-1 Transcription Factors In A Neuronal Gene Regulatory Network., Gregory M Miller, Babatunde A Ogunnaike, James S Schwaber, Rajanikanth Vadigepalli

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

BACKGROUND: The octapeptide Angiotensin II is a key hormone that acts via its receptor AT1R in the brainstem to modulate the blood pressure control circuits and thus plays a central role in the cardiac and respiratory homeostasis. This modulation occurs via activation of a complex network of signaling proteins and transcription factors, leading to changes in levels of key genes and proteins. AT1R initiated activity in the nucleus tractus solitarius (NTS), which regulates blood pressure, has been the subject of extensive molecular analysis. But the adaptive network interactions in the NTS response to AT1R, plausibly related to the development of …

Involvement Of The Nmda Receptor In Moderate Ethanol Preconditioning-Dependent Neuroprotection From Amyloid-Beta In Vitro, Robert Matthew Mitchell

Dissertations

Alzheimer's disease (AD) is a progressive, mentally crippling, and eventually fatal form of dementia with growing prevalence in aging populations. In 2009 it was estimated that 5.3 million Americans have AD, with 5.1 million older than age 65 and 200,000 under 65. That accounts for 1 in 8 adults over 65. Furthermore, AD costs Americans 148 billion dollars in direct expenses, and is the leading cause of dementia and the 6th leading cause of death. Since improved medical care in general is increasing average life span and age is the primary risk factor for AD, there is need for basic …

Hindbrain Serotonin Neurons Activate 5-Ht1a Receptors In The Nucleus Tractus Solitarius (Nts) To Modulate Sympathetic And Ventilatory Recovery Following Hypotensive Hemorrhage, Ling-Hsuan Kung

Dissertations

Trauma is the leading cause of death of young people in the United States. Most such deaths result either from the initial blood loss or from secondary reperfusion injury following resuscitation.

Currently, the standard treatments for hypovolemic shock include volume resuscitation and using of vasoconstrictors to raise pressure. However, these treatments can exacerbate reperfusion injury, and require technical care when apply to patients. Therefore, novel therapies that can safely restore perfusion pressure are needed.

Our lab has found that 5-HT1A-receptor agonist, 8-OH-DPAT, increases perfusion pressure and improves acid-base balance in hypovolemic rats by stimulation of sympathetic-mediated increases in venous tone. …

Mechanisms Of Ipsapirone-Mediated Neuroprotection Of Ethanol-Treated Fetal Rhombencephalic Neurons: Role Of Endogenous Antioxidants, Jongho Lee

Dissertations

Prenatal exposure to ethanol can cause serious damage to the developing central nervous system. Both in vivo and in vitro studies demonstrate the vulnerability of the developing serotonergic system to the damaging effects of ethanol. However, treatment with a serotonin-1A (5-HT1A) agonist prevents the ethanol-associated apoptosis in developing 5-HT neurons. One mechanism by which 5-HT1A agonists exert their neuroprotective effects appears to involve activation of the phosphatidylinositol 3'kinase (PI-3K) pro-survival pathway and activation of NF-κB dependent anti-apoptotic genes. Additional NF-κB dependent genes might also be involved with the neuroprotective effects of ipsapirone.

There is also considerable evidence that ethanol augments …

Dopamine D1 Receptor-Mediated Enhancement Of Nmda Receptor Trafficking Requires Rapid Pkc-Dependent Synaptic Insertion In The Prefrontal Neurons, Yan-Chun Li, Gang Liu, Jian-Li Hu, Wen-Jun Gao, Yueqiao Huang

PCOM Scholarly Works

Understanding the interaction between dopamine and glutamate, particularly the interaction of dopamine and NMDA receptors, may enable a more rational approach to the treatment of schizophrenia, drug addiction, and other psychiatric disorders. We show that, in prefrontal cortical neurons, dopamine D1-induced enhancement of NMDA receptor function depends on rapid insertion of new NMDA receptor 2B subunits on the synaptic surface. Protein kinase A (PKA) inhibitor, but not protein kinase C (PKC) inhibitor, completely blocked dopamine D1 agonist SKF-81297-induced increase of the total expression of NMDA receptors. Furthermore, SKF-81297 failed to alter the surface expression and synaptic insertion of NMDA receptors …

Phase-Linking And The Perceived Motion During Off-Vertical Axis Rotation, Jan Holly, Scott Wood, Gin Mccollum

Mathematics and Statistics Faculty Publications and Presentations

Human off-vertical axis rotation (OVAR) in the dark typically produces perceived motion about a cone, the amplitude of which changes as a function of frequency. This perception is commonly attributed to the fact that both the OVAR and the conical motion have a gravity vector that rotates about the subject. Little-known, however, is that this rotating-gravity explanation for perceived conical motion is inconsistent with basic observations about self-motion perception: (a) that the perceived vertical moves toward alignment with the gravito-inertial acceleration (GIA) and (b) that perceived translation arises from perceived linear acceleration, as derived from the portion of the GIA …

The Principled Control Of False Positives In Neuroimaging, Craig M. Bennett, George L. Wolford, Michael B. Miller

Dartmouth Scholarship

An incredible amount of data is generated in the course of a functional neuroimaging experiment. The quantity of data gives us improved temporal and spatial resolution with which to evaluate our results. It also creates a staggering multiple testing problem. A number of methods have been created that address the multiple testing problem in neuroimaging in a principled fashion. These methods place limits on either the familywise error rate (FWER) or the false discovery rate (FDR) of the results. These principled approaches are well established in the literature and are known to properly limit the amount of false positives across …

Dopamine D2 Receptor Priming Enhances Dopaminergic Response To Amphetamine In The Nucleus Accumbens: Role Of The D1 And D2 Receptors., Kimberly Norris Huggins

Electronic Theses and Dissertations

In past work, we have shown neonatal quinpirole (dopamine D₂/D₃ agonist) treatment produces a significant increase in dopamine D₂ receptor sensitivity, a phenomenon known as D₂ receptor priming. Dopamine D₂ receptor priming is common in psychosis. Male and female rats were administered quinpirole (1mg/kg) or saline from postnatal days 1-11 and raised to adulthood (P60). As adults, rats were administered d-amphetamine sulfate (1mg/kg) or saline every other day for 14 days. Approximately 10 min before each amphetamine or saline injection, animals were administered the D1 antagonist SCH 23390 (0.1 mg/kg), the D2 antagonist eticlopride …

Cocaine And Mefloquine-Induced Acute Effects In Ventral Tegmental Area Dopamine And Gaba Neurons, David Wilbanks Allison

Theses and Dissertations

The aim of the two studies presented here was to evaluate the effects of cocaine and mefloquine (MFQ) on γ-aminobutyric acid (GABA) and dopamine (DA) neurons in the ventral tegmental area (VTA). Cocaine: In vivo, lower doses of intravenous cocaine (0.25-0.5 mg/kg), or methamphetamine (METH), enhanced VTA GABA neuron firing rate via D2/D5 receptor activation. Higher cocaine doses (1.0-2.0 mg/kg) inhibited their firing rate. Cocaine and lidocaine inhibited the firing rate and spike discharges induced by stimulation of the internal capsule (ICPSDs) at dose levels 0.25-2 mg/kg (IC50 1.2 mg/kg), but neither DA nor METH reduced ICPSDs. In VTA …

Damage To Association Fiber Tracts Impairs Recognition Of The Facial Expression Of Emotion, Carissa Philippi, Shruti Mehta, Thomas Grabowski, Ralph Adolphs, David Rudrauf

Psychology Faculty Works

No abstract provided.

Lmproving Education Through Brain Research, Lisa J. Ihnen

Master of Education Program Theses

Educational practices are improved because of brain research. Cognitive and behavior sciences have provided important concepts for educational practice. Within recent decades, neuroscience has also contributed to the field of brain research, thus enhancing our understanding oflearning. Three main concepts from neuroscience are explored: synaptogenesis, critical periods, and enriched environments. When the entire body of knowledge from all disciplines of brain research is viewed together, then fmdings can be applied to educational practices.

A Functional Role For The Ventrolateral Prefrontal Cortex In Non-Spatial Auditory Cognition, Y. E. Cohen, B. E. Russ, S. J. Davis, A. E. Baker, A. L. Ackelson, R. Niteck

Dartmouth Scholarship

Spatial and non-spatial sensory information is hypothesized to be evaluated in parallel pathways. In this study, we tested the spatial and non-spatial sensitivity of auditory neurons in the ventrolateral prefrontal cortex (vPFC), a cortical area in the non-spatial pathway. Activity was tested while non-human primates reported changes in an auditory stimulus' spatial or non-spatial features. We found that vPFC neurons were reliably modulated during a non-spatial auditory task but were not modulated during a spatial auditory task. The degree of modulation during the non-spatial task correlated positively with the monkeys' behavioral performance. These results are consistent with the hypotheses that …

Aging Influences The Neural Correlates Of Lexical Decision But Not Automatic Semantic Priming, Brian T. Gold, Anders H. Andersen, Greg A. Jicha, Charles D. Smith

Neuroscience Faculty Publications

Human behavioral data indicate that older adults are slower to perform lexical decisions (LDs) than young adults but show similar reaction time gains when these decisions are primed semantically. The present study explored the functional neuroanatomic bases of these frequently observed behavioral findings. Young and older groups completed unprimed and primed LD tasks while functional magnetic resonance imaging (fMRI) was recorded, using a fully randomized trial design paralleling those used in behavioral research. Results from the unprimed task found that age-related slowing of LD was associated with decreased activation in perceptual extrastriate regions and increased activation in regions associated with …

Manipulating Neuronal Circuits With Endogenous And Recombinant Cell-Surface Tethered Modulators, Mande Holford, Sebastian Auer, Martin Laqua, Ines Ibanez-Tallon

Publications and Research

Neuronal circuits depend on the precise regulation of cell-surface receptors and ion channels. An ongoing challenge in neuroscience research is deciphering the functional contribution of specifi c receptors and ion channels using engineered modulators. A novel strategy, termed “tethered toxins”, was recently developed to characterize neuronal circuits using the evolutionary derived selectivity of venom peptide toxins and endogenous peptide ligands, such as lynx1 prototoxins. Herein, the discovery and engineering of cell-surface tethered peptides is reviewed, with particular attention given to their cell-autonomy, modular composition, and genetic targeting in different model organisms. The relative ease with which tethered peptides can be …

The Brain In Its Body: Motor Control And Sensing In A Biomechanical Context, Hillel J. Chiel

Faculty Scholarship

Although it is widely recognized that adaptive behavior emerges from the ongoing interactions among the nervous system, the body, and the environment, it has only become possible in recent years to experimentally study and to simulate these interacting systems. We briefly review work on molluscan feeding, maintenance of postural control in cats and humans, simulations of locomotion in lamprey, insect, cat and salamander, and active vibrissal sensing in rats to illustrate the insights that can be derived from studies of neural control and sensing within a biomechanical context. These studies illustrate that control may be shared between the nervous system …

Higher Education And The Society For Neuroscience: A Website Proposal That Helped Catalyze A Change In Policy, Richard F. Olivo

Neuroscience: Faculty Publications

In the spring of 2007, the Society for Neuroscience (SfN) did not include support for higher education as a priority in its strategic plan. By the spring of 2009, its priorities had changed. One catalyst for that change was a proposal for a website that would list, review, and rate resources for teaching neuroscience at the graduate and undergraduate level. The proposal was sent to and accepted by SfN Council in August 2008; by spring 2009, SfN had taken initial steps to implement it. Two documents are presented here that mark the change in policy: the website proposal, and SfN …

A Smart-Phone Application For Improving Communication Skills In Children With Autism, Lakshmi Padmaja Battagiri

Electrical & Computer Engineering Theses & Dissertations

The prevalence of autism, a complex neurobiological disorder, has grown at a staggering rate in the recent past. Today, one out of 150 American children is diagnosed with autism. Generally, the disorder appears during an individual's first three years of life of and persists through his/her entire life span. The individual faces various social interaction, communication and behavioral problems. Developmental disabilities, extreme withdrawal, lack of social behaviour, severe language and attention deficits, repetitive behaviours and limited interests are the characteristics of this disorder. There is no verified cure yet, but several therapies and intervention systems especially focused on the early …

Impairments In Attention In Occasionally Snoring Children: An Event-Related Potential Study., Maria E. Barnes, Elizabeth A. Huss, Krista N. Garrod, Eric Van Ray, Ehab Dayyat, David Gozal, Dennis L. Molfese

Faculty and Staff Scholarship

Objective: To determine whether minimal snoring is benign in children. Procedure: 22 rarely snoring children (mean age = 6.9 years, 11 females) and age- and sex-matched controls participated in an auditory oddball task wearing 128-electrode nets. Parents completed the Conners Parent Rating Scales–Revised Long (CPRS–R:L). Results: Snorers scored significantly higher on four CPRS-R:L subscales. Stepwise regression indicated that two ERP variables from a region of the ERP that peaked at 844 msec post-stimulus onset predicted CPRS-R:L Attention Deficit Hyperactivity Disorder (ADHD) Index scores. Conclusions: Occasional snorers, according to parental report, do exhibit ADHD-like behaviors. Basic sensory processing is longer than …

Sleep-Disordered Breathing Affects Auditory Processing In 5–7 Year-Old Children: Evidence From Brain Recordings, Alexandra P.F. Key, Dennis L. Molfese, Louise O’Brien, David Gozal

Center for Brain, Biology, and Behavior: Faculty Publications

Poor sleep in children is associated with lower neurocognitive functioning and increased maladaptive behaviors. The current study examined the impact of snoring (the most common manifestation of sleep-disordered breathing) on cognitive and brain functioning in a sample of 35 asymptomatic children ages 5–7 years identified in the community as having habitual snoring (SDB). All participants completed polysomnographic, neurocognitive (NEPSY) and psychophysiological (ERPs to speech sounds) assessments. The results indicated that sub-clinical levels of SDB may not necessarily lead to reduced performance on standardized behavioral measures of attention and memory. However, brain indices of speech perception and discrimination (N1/P2) are sensitive …

P2x Antagonists Inhibit Styryl Dye Entry Into Hair Cells, M. A. Crumling, M. Tong, K. L. Aschenbach, L. Liu

University Faculty Publications and Creative Works

The styryl pyridinium dyes, FM1-43 and AM1-43, are fluorescent molecules that can permeate the mechanotransduction channels of hair cells, the sensory receptors of the inner ear. When these dyes are applied to hair cells, they enter the cytoplasm rapidly, resulting in a readily detectable intracellular fluorescence that is often used as a molecular indication of mechanotransduction channel activity. However, such dyes can also permeate the ATP receptor, P2X2. Therefore, we explored the contribution of P2X receptors to the loading of hair cells with AM1-43. The chick inner ear was found to express P2X receptors and to release ATP, similar to …

P2x Antagonists Inhibit Styryl Dye Entry Into Hair Cells, M. A. Crumling, M. Tong, K. L. Aschenbach, L. Liu

University Faculty Publications and Creative Works

The styryl pyridinium dyes, FM1-43 and AM1-43, are fluorescent molecules that can permeate the mechanotransduction channels of hair cells, the sensory receptors of the inner ear. When these dyes are applied to hair cells, they enter the cytoplasm rapidly, resulting in a readily detectable intracellular fluorescence that is often used as a molecular indication of mechanotransduction channel activity. However, such dyes can also permeate the ATP receptor, P2X2. Therefore, we explored the contribution of P2X receptors to the loading of hair cells with AM1-43. The chick inner ear was found to express P2X receptors and to release ATP, similar to …

Developmental Emergence Of Power-Law Wake Behavior Depends Upon The Functional Integrity Of The Locus Coeruleus, Andrew J. Gall, Badal Joshi, Janet Best, Virginia R. Florang, Jonathan A. Doorn, Mark S. Blumberg

Faculty Publications

STUDY OBJECTIVES:

Daily amounts of sleep and wakefulness are accumulated in discrete bouts that exhibit distinct statistical properties. In adult mammals, sleep bout durations follow an exponential distribution whereas wake bout durations follow a power-law distribution. In infant Norway rats, however, wake bouts initially follow an exponential distribution and only transition to a power-law distribution beginning around postnatal day 15 (P15). Here we test the hypothesis that the locus coeruleus (LC), one of several wake-active nuclei in the brainstem, contributes to this developmental transition.

DESIGN:

At P7, rats were injected subcutaneously with saline or DSP-4, a neurotoxin that targets noradrenergic …

Effects Of Estrogen On Muscle Damage In Response To An Acute Resistance Exercise Protocol, Megan R. Wolf

Honors Scholar Theses

Creatine Kinase (CK) is used as a measure of exercise-induced muscle membrane damage. During acute eccentric (muscle lengthening) exercise, muscle sarcolemma, sarcoplasmic reticulum, and Z-lines are damaged, thus causing muscle proteins and enzymes to leak into the interstitial fluid.

Strenuous eccentric exercise produces an elevation of oxygen free radicals, which further increases muscle damage. Muscle soreness and fatigue can be attributed to this membrane damage. Estradiol, however, may preserve membrane stability post-exercise (Brancaccio, Maffulli, & Limongelli, 2007; Carter, Dobridge, & Hackney, 2001; Tiidus, 2001). Because estradiol has a similar structure to Vitamin E, which is known to have antioxidant properties, …

Intrinsic Ph-Sensitivity Of Cells In The Retrotrapezoid Nucleus: Possible Role Of Glia In Respiratory Drive, Nicole Edwards

Honors Scholar Theses

An increase in carbon dioxide (CO2) and protons (H+) are the primary signals for breathing. Cells that sense changes in CO2/H+ levels and increase breathing accordingly are located in a region of the caudal medulla oblongata called the retrotrapezoid nucleus (RTN). Specifically, select RTN neurons are intrinsically pH sensitive and send excitatory projections to the respiratory rhythm generator to drive breathing. Glial cells in the RTN are thought to contribute to this respiratory drive, possibly by releasing ATP in response to increases in CO2/H+ levels.

However, pH sensitivity of RTN glial cells has yet to be determined.

Therefore, the goal …

Head And Neck Embryology: An Overview Of Development, Growth And Defect In The Human Fetus, Allison Baylis

Honors Scholar Theses

The purpose of this research is to explore the growth and formation of the head and neck from embryological development through puberty in order to understand how this knowledge is necessary for the development of dental and medical treatments and procedures. This is a necessary aspect of the medical and dental school curriculum at the University of Connecticut Health Center Schools of Medicine and Dental Medicine that needs to be incorporated into the current study of embryology for first-year students. Working with Dr. Christine Niekrash, D.M.D, this paper will cover the embryology and growth of the head, face and oral …

The Role Of Epha4 In Glial Scar Formation Following Injury, Krysti Todd

Honors Scholar Theses

Although many areas of the brain lose their regenerative capacity with age, stem cell niches have been identified in both the subventricular zone (SVZ) along the lateral walls of the lateral ventricles and the subgranular zone (SGZ) of the dentate gyrus (Gage, 2000; Alvarez-Buylla et al., 2001; Alvarez-Buylla and Lim, 2004). The SVZ niche utilizes many mechanisms to determine the migration patterns of neuroblasts along the RMS into the olfactory bulb, one being Eph/ephrin signaling (Conover et al., 2000; Holmberg et al., 2005). EphA4-mediated signaling is necessary for axon guidance during development, and its continued expression in the SVZ niche …