Neuroscience and Neurobiology Commons^™

Prenatal Cocaine Exposure Increases Synaptic Localization Of A Neuronal Rasgef, Grasp-1 Via Hyperphosphorylation Of Ampar Anchoring Protein, Grip, Kalindi Bakshi, Mary Kosciuk, Robert G. Nagele, Eitan Friedman, Hoau-Yan Wang

Publications and Research

Prenatal cocaine exposure causes sustained phosphorylation of the synaptic anchoring protein, glutamate receptor interacting protein (GRIP1/2), preventing synaptic targeting of the GluR2/3-containing alpha-amino-3-hydroxy-5-methyl-4- isoxazolepropionic acid-type glutamate receptors (AMPARs; J. Neurosci. 29: 6308–6319, 2009). Because overexpression of GRIP-associated neuronal rasGEF protein (GRASP-1) specifically reduces the synaptic targeting of AMPARs, we hypothesized that prenatal cocaine exposure enhances GRASP-1 synaptic membrane localization leading to hyper-activation of ras family proteins and heightened actin polymerization. Our results show a markedly increased GRIP1-associated GRASP-1 content with approximately 40% reduction in its rasGEF activity in frontal cortices (FCX) of 21-day-old (P21) prenatal cocaineexposed rats. This cocaine effect …

Serotonin 1a Receptor Signaling In The Hypothalamic Paraventricular Nucleus Of The Peripubertal Rat, Maureen Lynn Petrunich Rutherford

Dissertations (6 month embargo)

Serotonin (5-HT) is a ubiquitous neurotransmitter in the brain that is involved in various physiologic functions including the regulation of hypothalamic hormones and has been implicated in various mood disorders such as depression. Preclinical and clinical data from studies in adults have shown that antidepressant drugs produce time-dependent changes in serotonergic and other systems and can also normalize dysfunction associated with the hypothalamic-pituitary-adrenal (HPA) axis. To date, our understanding of the mechanisms of 5-HT receptor signaling and the actions of drugs on serotonergic function have been derived from extensive preclinical research carried out using cell lines in vitro or in …

Forced-Exercise Dependent Changes In Cellular Immunity: Effects On Experimental Autoimmune Neuritis, Michael W. Calik

Dissertations (6 month embargo)

Guillain-Barré Syndrome (GBS) is a debilitating inflammatory autoimmune disease of the peripheral nervous system that is characterized by rapid-onset paraparesis with areflexia progressing to neuromuscular paralysis. The most common form of GBS observed in North America and Europe is acute inflammatory demyelinating polyneuropathy (AIDP). Enhanced infiltration of pro-inflammatory type 1 helper T (Th1) cells into peripheral nerves of AIDP patients leads to demyelination.

Increasing evidence supports exercise as an effective rehabilitative intervention. Exercise attenuates the onset and progression of autoimmune diseases. Whether exercise alters the progression of GBS remains unclear.

In this study, we determined the effects of forced-exercise on …

A Model Of Intracellular Θ Phase Precession Dependent On Intrinsic Subthreshold Membrane Currents., L Stan Leung

Physiology and Pharmacology Publications

A hippocampal place cell fires at an increasingly earlier phase in relation to the extracellular theta rhythm as a rodent moves through the place field. The present report presents a compartment model of a CA1 pyramidal cell that explains the increase in amplitude and the phase precession of intracellular theta oscillations, with the assumption that the cell receives an asymmetric ramp depolarization (<10 >mV) in the place field and rhythmic inhibitory and/or excitatory synaptic driving. Intracellular subthreshold membrane potential oscillations (MPOs) increase in amplitude and frequency, and show phase precession within the place field. Theta phase precession and MPO power …

Insightful Problem Solving In An Asian Elephant, Preston Foerder, Marie Galloway, Tony Barthel, Donald E. Moore Iii, Diana Reiss

Publications and Research

The ‘‘aha’’ moment or the sudden arrival of the solution to a problem is a common human experience. Spontaneous problem solving without evident trial and error behavior in humans and other animals has been referred to as insight. Surprisingly, elephants, thought to be highly intelligent, have failed to exhibit insightful problem solving in previous cognitive studies. We tested whether three Asian elephants (Elephas maximus) would use sticks or other objects to obtain food items placed out-of-reach and overhead. Without prior trial and error behavior, a 7-year-old male Asian elephant showed spontaneous problem solving by moving a large plastic cube, on …

Targeted Over-Expression Of Glutamate Transporter 1 (Glt-1) Reduces Ischemic Brain Injury In A Rat Model Of Stroke, Brandon K. Harvey, Mikko Airavaara, Jason Michael Hinzman, Emily M. Wires, Matthew J. Chiocco, Douglas B. Howard, Hui Shen, Greg A. Gerhardt, Barry J. Hoffer, Yun Wang

Neuroscience Faculty Publications

Following the onset of an ischemic brain injury, the excitatory neurotransmitter glutamate is released. The excitotoxic effects of glutamate are a major contributor to the pathogenesis of a stroke. The aim of this study was to examine if overexpression of a glutamate transporter (GLT-1) reduces ischemic brain injury in a rat model of stroke. We generated an adeno-associated viral (AAV) vector expressing the rat GLT-1 cDNA (AAV-GLT1). Functional expression of AAV-GLT1 was confirmed by increased glutamate clearance rate in non-stroke rat brain as measured by in vivo amperometry. AAV-GLT1 was injected into future cortical region of infarction 3 weeks prior …

Interspecies Comparison Of Αii-Spectrin Abundance Between Chinook Salmon And Steelhead, Brielle D. Kemis, Ann L. Miracle, Katie A. Wagner, Christa M. Woodley

STAR Program Research Presentations

Salmonids, such as Chinook salmon (Oncorhynchus tshawytscha) and steelhead (O. mykiss), are a staple economic, recreational, tribal, and environmental resource, yet many populations are unsustainable. This study was part of a broad scale effort to monitor the impact of downstream migration obstacles on juvenile salmonid health and survival, which is an essential step towards increasing Smolt-to-Adult Return ratios (SARs). The objective of this study was to determine if juvenile Chinook salmon and steelhead exhibit differing quantities of alphaII-Spectrin Breakdown Products (SBDPs) over two consecutive spring migration periods, indicative of neurogenesis rate and/or biological response to head …

Transcranial Direct Current Stimulation’S Effect On Novice Versus Experienced Learning, L. M. Bullard, E. S. Browning, Vincent P. Clark, Brian A. Coffman, Christopher M. Garcia, R. E. Jung, A. J. Van Der Merwe, K. M. Paulson, A. A. Vakhtin, C. L. Wootton, Michael Patrick Weisend

Wright State Research Institute Publications

Transcranial direct current stimulation (TDCS) is a non-invasive form of brain stimulation applied via a weak electrical current passed between electrodes on the scalp. In recent studies, TDCS has been shown to improve learning when applied to the prefrontal cortex (e.g., Kincses et al. in Neuropsychologia 42:113–117, 2003; Clark et al. Neuroimage in 2010). The present study examined the effects of TDCS delivered at the beginning of training (novice) or after an hour of training (experienced) on participants’ ability to detect cues indicative of covert threats. Participants completed two 1-h training sessions. During the first 30 min of each training …

Initial Mlu Predicts The Relative Efficacy Of Two Grammatical Treatments In Preschoolers With Specific Language Impairments, Paul J. Yoder, Dennis L. Molfese, Elizabeth Gardner

Center for Brain, Biology, and Behavior: Faculty Publications

Purpose—We sought to confirm predictions based on past findings that pre-treatment mean length of utterance (MLU) would predict which of two grammatical treatments would best facilitate generalized and maintained grammatical development in preschoolers with specific language impairment (SLI).

Method—The participants were 57 preschoolers with specific language impairment (SLI). A randomized group experiment was used. The two grammatical treatments were Broad Target Recasts (BTR) and Milieu Language Teaching (MLT). MLU was assessed at Time 1 in two conversational language samples. Growth rate of productive grammar was quantified using growth curve modeling on the Index of Productive Syntax (IPSyn) from …

Regulation Of Endothelial Nitric Oxide Synthase In Pulmonary Myofibroblasts, Jonathan David Faughn

Masters Theses & Specialist Projects

Idiopathic pulmonary fibrosis (IPF) is an interstitial lung disease leading to decreased lung volume and eventual respiratory failure. At present, the median post-diagnosis lifespan is between three and six years. Myofibroblasts are collagen-secreting cells essential for wound healing, but also implicated in the fibroproliferation and extra cellular matrix deposition commonly seen in IPF. The nitric oxide (NO) signaling pathway is implicated in protomyofibroblast to myofibroblast transition and regulation. Previous work has shown that in pulmonary myofibroblasts, endothelial nitric oxide synthase (eNOS) is the primary NOS isoform expressed. The current study used cultured rat pulmonary myofibroblasts between passages two and five …

Analysis Of Chlamydia Pneumoniae And Ad-Like Pathology In The Brains Of Balb/C Mice Following Direct Intracranial Infection With Chlamydia Pneumoniae, Jessica Rachel Barton

PCOM Biomedical Studies Student Scholarship

Alzheimer’s disease (AD) is an age-related progressive neurodegenerative disorder and the most common form of dementia. The pathology in the central nervous system (CNS) impairs memory and cognition, hindering the capabilities and the quality of life of the individual. This project continues studying the role of infection and Alzheimer’s disease and contributes to the overall understanding of the possible causes of this disease. In this study, BALB/c mice were infected, via direct intracranial injection, with a respiratory isolate (AR-39) of Chlamydia pneumoniae. Their brains were analyzed at 7 and 14 days post-infection, using immunohistochemistry, for the presence of C. …

Bone Morphogenetic Protein Inhibition Promotes Neurological Recovery After Intraventricular Hemorrhage, Krishna Dummula, Govindaiah Vinukonda, Philip Chu, Yiping Xing, Furong Hu, Sabrina Mailk, Anna Csiszar, Caroline Chua, Peter Mouton, Robert J. Kayton, Joshua C. Brumberg, Rashmi Bansal, Praveen Ballabh

Publications and Research

Intraventricular hemorrhage (IVH) results in neural cell death and white matter injury in premature infants. No therapeutic strategy is currently available against this disorder. Bone morphogenetic protein (BMP) signaling suppresses oligodendrocyte development through basic-helix-loop-helix (bHLH) transcription factors and promotes astrocytosis. Therefore, we hypothesized that IVH in premature newborns initiates degeneration and maturation arrest of oligodendrocyte lineage and that BMP inhibition alleviates hypomyelination, gliosis, and motor impairment in the survivors of IVH. To test the hypotheses, a rabbit model of IVH was used in which premature rabbit pups (E29) are treated with intraperitoneal glycerol at 2 hours of age to induce …

The Role Of The Androgen Receptor Cofactor P44/Wdr77 In Astrocyte Activation, Bryce H. Vincent

Dissertations and Theses (Open Access)

Astrogliosis is induced by neuronal damage and is also a pathological feature of the major aging-related neurodegenerative disorders. The mechanisms that control the cascade of astrogliosis have not been well established. In a previous study, we identified a novel androgen receptor (AR)-interacting protein (p44/WDR77) and found that it plays a critical role in the control of proliferation and differentiation of prostate epithelial cells. In the present study, we found that deletion of the p44 gene in the mouse brain caused accelerated aging with dramatic astrogliosis. The p44/WDR77 is expressed in astrocytes and loss of p44/WDR77 expression in astrocytes leads to …

Upregulation Of Reactive Oxygen Species During The Retrovirus Life Cycle And Their Roles In A Mutant Of Moloney Murine Leukemia Virus, Ts1-Mediated Neurodegeneration, Soo Jin Kim

Dissertations and Theses (Open Access)

Viral invasion of the central nervous system (CNS) and development of neurological symptoms is a characteristic of many retroviruses. The mechanism by which retrovirus infection causes neurological dysfunction has yet to be fully elucidated. Given the complexity of the retrovirus-mediated neuropathogenesis, studies using small animal models are extremely valuable. Our laboratory has used a mutant moloney murine leukemia retrovirus, ts1-mediated neurodegneration. We hypothesize that astrocytes play an important role in ts1-induced neurodegeneration since they are retroviral reservoirs and supporting cells for neurons. It has been shown that ts1 is able to infect astrocytes in vivo and in …

Study Of Rest As A Negative Regulator Of P16ink4a, Monica B. Gireud

Dissertations and Theses (Open Access)

STUDY OF REST AS A NEGATIVE REGULATOR OF P16^INK4A

Monica Gireud, B.S.

Thesis Advisor: Vidya Gopalakrishnan, Ph.D.

The RE1 Silencing Transcription Factor (REST) is a negative regulator of neuronal differentiation. It is expressed ubiquitously in early embryos, but downregulated in neural progenitors concomitant with onset of neuronal differentiation in these cells. REST has been widely studied as a negative regulator of neuronal differentiation genes. Our recent work identified a novel role for REST in control of cell proliferation. However, the underlying molecular mechanism(s) are not known and is a focus of the current thesis project. Here, we provide evidence …

Psychological And Social Correlates Of Hiv Status Disclosure: The Significance Of Stigma Visibility, Sarah E. Sutterheim, Arjan E. R. Bos, John B. Pryor, Maartje Liebregts, Herman P. Schaalma, Ronald Brands

Faculty Publications – Psychology

HIV-related stigma, psychological distress, self-esteem, and social support were investigated in a sample comprising people who have concealed their HIV status to all but a selected few (limited disclosers), people who could conceal but chose to be open (full disclosers), and people who had visible symptoms that made concealing difficult (visibly stigmatized). The visibly stigmatized and full disclosers reported significantly more stigma experiences than limited disclosers, but only the visibly stigmatized reported more psychological distress, lower self-esteem, and less social support than limited disclosers. This suggests that having a visible stigma is more detrimental than having a concealable stigma. Differences …

Role Of Dopamine In Impulse Control, Paul Rafael Sabandal ^, Young-Cho Kim, Kyung-An Han *

COURI Symposium Abstracts, Summer 2011

No abstract provided.

Assembly Of Lamina-Specific Neuronal Connections By Slit Bound To Type Iv Collagen, Tong Xiao, Wendy Staub, Estuardo Robles, Nathan J. Gosse, Gregory J. Cole, Herwig Baier

Neuroscience: Faculty Publications

The mechanisms that generate specific neuronal connections in the brain are under intense investigation. In zebrafish, retinal ganglion cells project their axons into at least six layers within the neuropil of the midbrain tectum. Each axon elaborates a single, planar arbor in one of the target layers and forms synapses onto the dendrites of tectal neurons. We show that the laminar specificity of retinotectal connections does not depend on self-sorting interactions among RGC axons. Rather, tectum-derived Slit1, signaling through axonal Robo2, guides neurites to their target layer. Genetic and biochemical studies indicate that Slit binds to Dragnet (Col4a5), a type …

Dysfunctional Play And Dopamine Physiology In The Fischer 344 Rat, Stephen M. Siviy, Cynthia A. Crawford, Garnik Akopian, John P. Walsh

Psychology Faculty Publications

Juvenile Fischer 344 rats are known to be less playful than other inbred strains, although the neurobiological substrate(s) responsible for this phenotype is uncertain. In the present study, Fischer 344 rats were compared to the commonly used outbred Sprague-Dawley strain on several behavioral and physiological parameters in order to ascertain whether the lack of play may be related to compromised activity of brain dopamine (DA) systems. As expected, Fischer 344 rats were far less playful than Sprague-Dawley rats, with Fischer 344 rats less likely to initiate playful contacts with a playful partner and less likely to respond playfully to these …

Schizophrenia- Like Attentional Deficits Following Blockade Of Prefrontal Cortex Gaba(A) Receptors, Tracie A. Paine, Lauren E. Slipp, William A. Carlezon Jr.

Faculty & Staff Scholarship

Attentional deficits are a core symptom of schizophrenia. Post-mortem analyses of the brains of schizophrenics reveal consistent abnormalities in gamma-aminobutyric acid (GABA) interneurons indicative of reduced cortical GABA transmission, raising the possibility that this pathology contributes to attentional deficits. We examined whether blockade of prefrontal cortex (PFC) GABA(A) receptors with bicuculline (BMI) impairs attention in rats using the 5-choice serial reaction time task (5CSRTT). For comparison, we also examined whether administration of the GABA(A) receptor agonist muscimol (MUS) would improve attention. In parallel, we examined the effects of both manipulations on activity in an open field and on motivation using …

Investigation Of Mirnas Expression In A Citron-Kinase Mutant Model Of Microcephaly, Shan Parikh

Master's Theses

Mutation of Citron-Kinase (Cit-K) in rodents causes substantial reductions in the number of neurons generated in the CNS and results in a primary microcephaly-like phenotype. Evidence from drosophila genetics has further established a genetic link between Cit-K and a protein Argonaut 1 (AGO1), which is required for proper functioning of the miRNA machinery (2). Experiments characterizing the role of miRNAs in the developing cortex demonstrate the requirement of miRNAs for differentiation of neural progenitor cells starting at embryonic day 12.5 (3). Together, this evidence links the role of miRNAs to neurogenesis and thus this relationship warrants further investigation. Here miRNA …

Interictal Magnetoencephalographic Findings Related With Surgical Outcomes In Lesional And Nonlesional Neocortical Epilepsy, Rui Zhang, Ting Wu, Yingying Wang, Hongyi Liu, Yuanjie Zou, Wen Liu, Jing Xiang, Chaoyong Xiao, Lu Yang, Zhen Fu

Center for Brain, Biology, and Behavior: Faculty Publications

Purpose: To investigate whether interictal magnetoencephalography (MEG) concordant with other techniques can predict surgical outcome in patients with lesional and nonlesional refractory neocortical epilepsy (NE).

Methods: 23 Patients with lesional NE and 20 patients with nonlesional NE were studied. MEG was recorded for all patients with a 275 channel whole-head system. Synthetic aperture magnetometry (SAM) with excess kurtosis (g2) and conventional Equivalent Current Dipole (ECD) were used for MEG data analysis. 27 Patients underwent long-term extraoperative intracranial video electroencephalography (iVEEG) monitoring. Surgical outcomes were assessed based on more than 1-year of post-surgical follow-up using Engel classification system.

Results: As we …

“What” And “Where” In Auditory Sensory Processing: A High-Density Electrical Mapping Study Of Distinct Neural Processes Underlying Sound Object Recognition And Sound Localization, Victoria M. Leavitt, Sophie Molholm, Manuel Gomez-Ramirez, John J. Foxe

Publications and Research

Functionally distinct dorsal and ventral auditory pathways for sound localization (WHERE) and sound object recognition (WHAT) have been described in non-human primates. A handful of studies have explored differential processing within these streams in humans, with highly inconsistent findings. Stimuli employed have included simple tones, noise bursts, and speech sounds, with simulated left–right spatial manipulations, and in some cases participants were not required to actively discriminate the stimuli. Our contention is that these paradigms were not well suited to dissociating processing within the two streams. Our aim here was to determine how early in processing we …

Psychostimulants As Cognitive Enhancers: The Prefrontal Cortex, Catecholamines And Attention Deficit Hyperactivity Disorder, Craig Berridge, David M. Devilbiss

Rowan-Virtua School of Osteopathic Medicine Departmental Research

Psychostimulants exert behavioral-calming and cognition-enhancing actions in the treatment of attention deficit hyperactivity disorder (ADHD). Contrary to early views, extensive research demonstrates that these actions are not unique to ADHD. Specifically, when administered at low and clinically-relevant doses, psychostimulants improve a variety of behavioral and cognitive processes dependent on the prefrontal cortex (PFC) in subjects with and without ADHD. Despite the longstanding clinical use of these drugs, the neural mechanisms underlying their cognition-enhancing/therapeutic actions have only recently begun to be examined. At behaviorally-activating doses, psychostimulants produce large and widespread increases in extracellular levels of brain catecholamines. In contrast, cognition-enhancing doses …

Adaptive Significance Of Natural Variations In Maternal Care In Rats: A Translational Perspective, Annaliese K. Beery, Darlene D. Francis

Neuroscience: Faculty Publications

A wealth of data from the last fifty years documents the potency of early life experiences including maternal care on developing offspring. A majority of this research has focused on the developing stress axis and stress-sensitive behaviors in hopes of identifying factors impacting resilience and risk-sensitivity. The power of early life experience to shape later development is profound and has the potential to increase fitness of individuals for their environments. Current findings in a rat maternal care paradigm highlight the complex and dynamic relation between early experiences and a variety of outcomes. In this review we propose adaptive hypotheses for …

Pulsed Out Of Awareness: Eeg Alpha Oscillations Represent A Pulsed-Inhibition Of Ongoing Cortical Processing, Kyle E. Mathewson, Alejandro Lleras, Diane M. Beck, Monica Fabiani, Tony Ro, Gabriele Gratton

Publications and Research

Alpha oscillations are ubiquitous in the brain, but their role in cortical processing remains a matter of debate. Recently, evidence has begun to accumulate in support of a role for alpha oscillations in attention selection and control. Here we first review evidence that 8–12 Hz oscillations in the brain have a general inhibitory role in cognitive processing, with an emphasis on their role in visual processing. Then, we summarize the evidence in support of our recent proposal that alpha represents a pulsed-inhibition of ongoing neural activity. The phase of the ongoing electroencephalography can influence evoked activity and subsequent processing, and …

Intrinsic And Extrinsic Factors That Control Motor Neuron Vulnerability In Als, Pembe Hande Ozdinler

IMSA Great Minds Program ®

Even though there are millions of neurons in our brain, in neurodegenerative diseases only a select set of neurons show vulnerability and progressively degenerate. In amyotrophic lateral sclerosis (ALS), motor neurons in the cortex and spinal cord show selective vulnerability. Their progressive degeneration results in lack of control over voluntary movement, without affecting memory and cognitive function. We are developing novel approaches to understand cellular and molecular mechanisms responsible for motor neuron degeneration. Our findings will allow cell-based therapeutic interventions in the near future.

Synaptic Reorganization Of Inhibitory Hilar Interneuron Circuitry After Traumatic Brain Injury In Mice, Robert F. Hunt, Stephen W. Scheff, Bret N. Smith

Physiology Faculty Publications

Functional plasticity of synaptic networks in the dentate gyrus has been implicated in the development of posttraumatic epilepsy and in cognitive dysfunction after traumatic brain injury, but little is known about potentially pathogenic changes in inhibitory circuits. We examined synaptic inhibition of dentate granule cells and excitability of surviving GABAergic hilar interneurons 8–13 weeks after cortical contusion brain injury in transgenic mice that express enhanced green fluorescent protein in a subpopulation of inhibitory neurons. Whole-cell voltage-clamp recordings in granule cells revealed a reduction in spontaneous and miniature IPSC frequency after head injury; no concurrent change in paired-pulse ratio was found …

Modulation Of Hypoglossal Motoneurons By Nitric Oxide, Justin Philip Benoit

Master's Theses

Obstructive sleep apnea (OSA)- the occurrence of repetitive episodes of airway obstruction during sleep- is considered a major health problem affecting up to 9% of adults in the United States (Parish & Somers, 2004). The hypoglossal motor nucleus (HMN) controls genioglossus muscle tone and is critically important for maintaining airway patency; loss of excitatory input to the HMN during sleep results in disfacilitation of hypoglossal motoneurons, increased airway resistance and contributes to the development of OSA (Horner R. L., 2007). However, a fundamental question of sleep medicine that remains unresolved is what mechanisms help maintain airway patency during sleep? A …

Drosophila Model For Fetal Alcohol Syndrome Disorders: Role For The Insulin Pathway, Rachael L. French, K D. Mcclure, U Heberlein

Faculty Publications, Biological Sciences

Prenatal exposure to ethanol in humans results in a wide range of developmental abnormalities, including growth deficiency, developmental delay, reduced brain size, permanent neurobehavioral abnormalities and fetal death. Here we describe the use of Drosophila melanogaster as a model for exploring the effects of ethanol exposure on development and behavior. We show that developmental ethanol exposure causes reduced viability, developmental delay and reduced adult body size. We find that flies reared on ethanol-containing food have smaller brains and imaginal discs, which is due to reduced cell division rather than increased apoptosis. Additionally, we show that, as in mammals, flies reared …