Neurosciences Commons^™

Functional And Structural Changes Throughout The Auditory System Following Congenital And Early-Onset Deafness: Implications For Hearing Restoration, Blake E. Butler, Stephen G. Lombar

Brain and Mind Institute Researchers' Publications

The absence of auditory input, particularly during development, causes widespread changes in the structure and function of the auditory system, extending from peripheral structures into auditory cortex. In humans, the consequences of these changes are far-reaching and often include detriments to language acquisition, and associated psychosocial issues.Much of what is currently known about the nature of deafness-related changes to auditory structures comes from studies of congenitally deaf or early-deafened animal models. Fortunately, the mammalian auditory system shows a high degree of preservation among species, allowing for generalization from these models to the human auditory system. This review begins with a …

The Effects Of Pre- And Postnatal Administration Of Propionic Acid And Lipopolysaccharide On The Behaviour Of Adolescent Male And Female Rats, Kelly A. Foley

Electronic Thesis and Dissertation Repository

The gut microbiome plays an important role in immune functioning and neurodevelopment. Altered microbiome composition, leading to short chain fatty acid, and/or immune system dysfunction has been observed in children with autism spectrum disorders (ASD). This thesis describes the developmental influence of prenatal exposure to propionic acid (PPA), a metabolic fermentation product of enteric bacteria, or prenatal exposure to lipopolysaccharide (LPS), a bacterial mimetic and product of enteric bacteria, on a range of behaviours in male and female neonatal, adolescent and adult rats. Study one evaluated the effects of prenatal PPA and LPS, and postnatal PPA, on developmental milestones in …

A Novel Signal Processing Method For Intraoperative Neurophysiological Monitoring In Spinal Surgeries, Krishnatej Vedala

FIU Electronic Theses and Dissertations

Intraoperative neurophysiologic monitoring is an integral part of spinal surgeries and involves the recording of somatosensory evoked potentials (SSEP). However, clinical application of IONM still requires anywhere between 200 to 2000 trials to obtain an SSEP signal, which is excessive and introduces a significant delay during surgery to detect a possible neurological damage. The aim of this study is to develop a means to obtain the SSEP using a much less, twelve number of recordings. The preliminary step involved was to distinguish the SSEP with the ongoing brain activity. We first establish that the brain activity is indeed quasi-stationary whereas …

Bdnf In The Dentate Gyrus Is Required For Consolidation Of "Pattern-Separated" Memories., Pedro Bekinschtein, Brianne A Kent, Charlotte A Oomen, Gregory D Clemenson, Fred H Gage, Lisa M Saksida, Timothy J Bussey

Brain and Mind Institute Researchers' Publications

Successful memory involves not only remembering information over time, but also keeping memories distinct and less confusable. The computational process for making representations for similar input patterns more distinct from each other has been referred to as "pattern separation." In this work, we developed a set of behavioral conditions that allowed us to manipulate the load for pattern separation at different stages of memory. Thus, we provide experimental evidence that a brain-derived neurotrophic factor (BDNF)-dependent pattern separation process occurs during the encoding/storage/consolidation, but not the retrieval stage of memory processing. We also found that a spontaneous increase in BDNF in …

Proconvulsant Actions Of Intrahippocampal Botulinum Neurotoxin B In The Rat, Sonja Bröer, Dorota Zolkowska, Manuela Gernert, Michael A. Rogawski

Michael A. Rogawski

Botulinum neurotoxins (BoNTs) may affect the excitability of brain circuits by inhibiting neurotransmitter release at central synapses. There is evidence that local delivery of BoNT serotypes A and E, which target synaptosomal-associated protein 25, a component of the release machinery specific to excitatory synapses, can inhibit seizure generation. BoNT serotype B (BoNT/B) targets VAMP2, which is expressed in both excitatory and inhibitory terminals. Here we assessed the effects of unilateral intrahippocampal infusion of BoNT/B in the rat on intravenous pentylenetetrazol (PTZ) seizure thresholds, and on the expression of spontaneous behavioral and electrographic seizures. Infusion of BoNT/B (500 and 1000 Unit) …

Microrna-142 Reduces Monoamine Oxidase A Expression And Activity In Neuronal Cells By Downregulating Sirt1, Amrita Datta Chaudhuri, Sowmya V. Yelamanchili, Howard S. Fox

Journal Articles: Pharmacology & Experimental Neuroscience

Aberrant expression of microRNAs (miRs) has been implicated in the pathogenesis of several neurodegenerative disorders. In HIV-associated neurocognitive disorders (HAND), miR-142 was found to be upregulated in neurons and myeloid cells in the brain. We investigated the downstream effects of chronic miR-142 upregulation in neuronal cells by comparing gene expression in stable clones of the human neuroblastoma cell line BE(2)M17 expressing miR-142 to controls. Microarray analysis revealed that miR-142 expression led to a reduction in monoamine oxidase (MAO) A mRNA, which was validated by qRT-PCR. In addition to the mRNA, the MAOA protein level and enzyme activity were also reduced. …

A Molecular Mechanism Regulating The Timing Of Corticogeniculate Innervation, Justin Brooks

Theses and Dissertations

Visual system development requires the formation of precise circuitry in the dorsal lateral geniculate nucleus (dLGN) of the thalamus. Although much work has examined the molecular mechanisms by which retinal axons target and form synapses in dLGN, much less is known about the mechanisms that coordinate the formation of non-retinal inputs in dLGN. These non-retinal inputs represent ~90% of the terminals that form in dLGN. Interestingly, recently reports show that the targeting and formation of retinal and non-retinal inputs are temporally orchestrated. dLGN relay neurons are first innervated by retinal axons, and it is only after retinogeniculate synapses form that …

Reducing Multi-Sensor Data To A Single Time Course That Reveals Experimental Effects, Aaron Schurger, Sebastien Marti, Stanislas Dehaene

Psychology Faculty Articles and Research

Background: Multi-sensor technologies such as EEG, MEG, and ECoG result in high-dimensional data sets. Given the high temporal resolution of such techniques, scientific questions very often focus on the time-course of an experimental effect. In many studies, researchers focus on a single sensor or the average over a subset of sensors covering a “region of interest” (ROI). However, single-sensor or ROI analyses ignore the fact that the spatial focus of activity is constantly changing, and fail to make full use of the information distributed over the sensor array.

Methods: We describe a technique that exploits the optimality and …

Prolactin And Fmri Response To Skf38393 In The Baboon, Brad D. Miller, Lauren A. Marks, Jonathan M. Koller, Blake J. Newman, G Larry Bretthorst, Kevin J. Black

Kevin J. Black, MD

Background: This study’s goal was to provide dose-response data for a dopamine agonist in the baboon using standard methods (replicate measurements at each dose, across a range of doses), as a standard against which to subsequently validate a novel pharmacological MRI (phMRI) method. Dependent variables were functional MRI (fMRI) data from brain regions selected a priori, and systemic prolactin release. Necessary first steps included estimating the magnitude and time course of prolactin response to anesthesia alone and to various doses of agonist. These first steps (“time course studies”) were performed with three agonists, and the results were used to select …

Plasma Apolipoprotein E And Alzheimer Disease Risk: The Aibl Study Of Aging, Veer Bala Gupta, Simon Laws, Victor Villemagne, David Ames, Ashley Bush, Kathryn Ellis, James Lui, Colin Masters, Christopher Rowe, Cassandra Szoeke, Kevin Taddei, Ralph Martins

Simon Laws

Objective: There is mounting evidence for the contribution of apoE to the pathophysiology of Alzheimer disease (AD). Studies also indicate that plasma apoE levels may reflect disease status, suggesting that apoE is a potential AD biomarker. However, while some studies of apoE levels in plasma have presented correlations with AD pathology, others have not. Thus, there is a lack of consensus as to the suitability of plasma apoE as an AD biomarker. The major objective of this cross-sectional study was to investigate total plasma apoE as well as levels of the apoE4 form in a large, highly characterized cohort which …

Associatioin Of Plasma Aβ Peptides With Blood Pressure In The Elderly, Jean-Charles Lambert, Jean Dallongeville, Kathryn A. Ellis, Susanna Schraen-Maschke, James Lui, Simon Laws, Julie Dumont, Florence Richard, Dominque Cottel, Claudine Berr, David Ames, Colin L. Masters, Christopher C. Rowe, Cassandra Szoeke, Christophe Tzourio, Jean-Francois Dartigues, Luc Buee, Ralph Martins, Philippe Amouyel

Simon Laws

Background Aß peptides are often considered as catabolic by-products of the amyloid ß protein precursor (APP), with unknown physiological functions. However, several biological properties have been tentatively attributed to these peptides, including a role in vasomotion. We assess whether plasma Aß peptide levels might be associated with systolic and diastolic blood pressure values (SBP and DBP, respectively). Methodology/Principal Findings Plasma Aß1-40 and Aß1-42 levels were measured using an xMAP-based assay in 1,972 individuals (none of whom were taking antihypertensive drugs) from 3 independent studies: the French population-based 3C and MONA-LISA (Lille) studies (n = 627 and n = 769, respectively) …

The Touchscreen Operant Platform For Testing Working Memory And Pattern Separation In Rats And Mice., Charlotte A Oomen, Martha Hvoslef-Eide, Christopher J Heath, Adam C Mar, Alexa E Horner, Timothy J Bussey, Lisa M Saksida

Brain and Mind Institute Researchers' Publications

The automated touchscreen operant chamber for rats and mice allows for the assessment of multiple cognitive domains within the same testing environment. This protocol presents the location discrimination (LD) task and the trial-unique delayed nonmatching-to-location (TUNL) task, which both assess memory for location. During these tasks, animals are trained to a predefined criterion during ∼20-40 daily sessions. In LD sessions, touching the same location on the screen is rewarded on consecutive trials, followed by a reversal of location-reward contingencies. TUNL, a working memory task, requires animals to 'nonmatch' to a sample location after a delay. In both the LD and …

The Touchscreen Operant Platform For Testing Learning And Memory In Rats And Mice., Alexa E Horner, Christopher J Heath, Martha Hvoslef-Eide, Brianne A Kent, Chi Hun Kim, Simon R O Nilsson, Johan Alsiö, Charlotte A Oomen, Andrew Holmes, Lisa M Saksida, Timothy J Bussey

Brain and Mind Institute Researchers' Publications

An increasingly popular method of assessing cognitive functions in rodents is the automated touchscreen platform, on which a number of different cognitive tests can be run in a manner very similar to touchscreen methods currently used to test human subjects. This methodology is low stress (using appetitive rather than aversive reinforcement), has high translational potential and lends itself to a high degree of standardization and throughput. Applications include the study of cognition in rodent models of psychiatric and neurodegenerative diseases (e.g., Alzheimer's disease, schizophrenia, Huntington's disease, frontotemporal dementia), as well as the characterization of the role of select brain regions, …

The Touchscreen Operant Platform For Assessing Executive Function In Rats And Mice., Adam C Mar, Alexa E Horner, Simon R O Nilsson, Johan Alsiö, Brianne A Kent, Chi Hun Kim, Andrew Holmes, Lisa M Saksida, Timothy J Bussey

Brain and Mind Institute Researchers' Publications

This protocol details a subset of assays developed within the touchscreen platform to measure various aspects of executive function in rodents. Three main procedures are included: extinction, measuring the rate and extent of curtailing a response that was previously, but is no longer, associated with reward; reversal learning, measuring the rate and extent of switching a response toward a visual stimulus that was previously not, but has become, associated with reward (and away from a visual stimulus that was previously, but is no longer, rewarded); and the 5-choice serial reaction time (5-CSRT) task, gauging the ability to selectively detect and …

Latent Modulation Of Neuropathic Pain Intensity Via Hypothalamus-Pituitary-Thyroid Axis Of Psychogenic Stress, Roger J. Allen

All Faculty Scholarship

Background: In patients with complex regional pain syndrome (CRPS) delayed pain flares consistently occur ten days following salient psychogenic stress episodes. Timing of latent flares suggests pain modulation via hypothalamus-pituitary-thyroid (HPT) axis hormones.

Objective: To determine if thyroxine (T₄) may modulate latent stress-related neuropathic pain flare intensity, temporal relationships between daily stress, serum T₄ levels, and perceived pain intensity in patients with CRPS were investigated.

Patients and Methods: Daily, for ten weeks, three patients with type I CRPS and no thyroid pathology Hx provided blood samples for T₄ assay and ratings of stress and pain. Measures …

Er Stress Coupled Pannexin Channel Activation Via Stim Proteins, Ankur Bodalia

Electronic Thesis and Dissertation Repository

Many neurodegenerative diseases, including Alzheimer’s Disease, are associated with ER stress. It is suggested that plasma membrane channels contribute to the increased ionic influx and subsequent cell death in response to ER stress. Pannexin channels, which have been implicated in various pathophysiological conditions, are a suitable candidate for facilitating this response. However, mechanisms of pannexin channel activation are poorly defined. I investigated the potential regulation of pannexin activity by the ER stress sensor, STIM. It was hypothesized that pannexin channel activation during ER stress is contingent on the recruitment of STIM proteins. In neurons, pannexin activation was observed in response …

Combined Fluorescent In Situ Hybridization For Detection Of Micrornas And Immunofluorescent Labeling For Cell-Type Markers, Amrita Datta Chaudhuri, Sowmya V. Yelamanchili, Howard S. Fox

Journal Articles: Pharmacology & Experimental Neuroscience

Identification of the cell type of origin for normal or aberrant gene expression is critical for many studies, and poses a significant problem for some regulatory RNAs such as microRNAs. MicroRNAs are small non-coding RNAs that regulate cellular function by targeting specific mRNAs and reducing the level of their protein product. Aberrant expression of miRNAs in cell-types where they are not normally expressed occurs in several disease conditions. Therefore, it is important to determine not only the expression level of microRNAs, but also where they are expressed. Here we describe a detailed method for fluorescent in situ hybridization (FISH) combined …

Nf1 Loss And Ras Hyperactivation In Oligodendrocytes Induce Nos-Driven Defects In Myelin And Vasculature, Debra A. Mayes, Tilat A. Rizvi, Haley E. Titus-Mitchell, Rachel Oberst, Georgianne M. Ciraolo, Charles V. Vorhees, Andrew P. Robinson, Stephen D. Miller, Jose A. Cancelas, Anat O. Stemmer-Rachamimov, Nancy Ratner

Neuroscience, Cell Biology & Physiology Faculty Publications

Patients with neurofibromatosis type 1 (NF1) and Costello syndrome Rasopathy have behavioral deficits. In NF1 patients, these may correlate with white matter enlargement and aberrant myelin. To model these features, we induced Nf1 loss or HRas hyperactivation in mouse oligodendrocytes. Enlarged brain white matter tracts correlated with myelin decompaction, downregulation of claudin-11, and mislocalization of connexin-32. Surprisingly, non-cell-autonomous defects in perivascular astrocytes and the blood-brain barrier (BBB) developed, implicating a soluble mediator. Nitric oxide (NO) can disrupt tight junctions and gap junctions, and NO and NO synthases (NOS1-NOS3) were upregulated in mutant white matter. Treating mice with the NOS inhibitor …

The Hiv-1 Protein Vpr Targets The Endoribonuclease Dicer For Proteasomal Degradation To Boost Macrophage Infection, Laurieann Klockow, Hamayun J. Sharifi, Xiaoyun Wen, Meg Flagg, Andrea K.M. Furuya, Michael Nekorchuk, Carlos M.C. De Noronha

Biomedical Sciences Faculty Research and Publications

The HIV-1 protein Vpr enhances macrophage infection, triggers G2 cell cycle arrest, and targets cells for NK-cell killing. Vpr acts through the CRL4^DCAF1 ubiquitin ligase complex to cause G2 arrest and trigger expression of NK ligands. Corresponding ubiquitination targets have not been identified. UNG2 and SMUG1 are the only known substrates for Vpr-directed depletion through CRL4^DCAF1. Here we identify the endoribonuclease Dicer as a target of HIV-1 Vpr-directed proteasomal degradation through CRL4^DCAF1. We show that HIV-1 Vpr inhibits short hairpin RNA function as expected upon reduction of Dicer levels. Dicer inhibits HIV-1 replication in T …

Long-Lasting Attenuation Of Amygdala-Kindled Seizures After Convection-Enhanced Delivery Of Botulinum Neurotoxins A And B Into The Amygdala In Rats, Maciej Gasior, Rebecca Tang, Michael A. Rogawski

Michael A. Rogawski

Botulinum neurotoxins (BoNTs) are well recognized to cause potent, selective and long-lasting neuroparalytic actions by blocking cholinergic neurotransmission to muscles and glands. There is evidence that BoNT isoforms can also inhibit neurotransmission in the brain. Here we examined whether locally delivered BoNT/A and BoNT/B can attenuate kindling measures in amygdala-kindled rats. Male rats were implanted with a combination infusion cannula-stimulating electrode assembly into the right basolateral amygdala. Fully-kindled animals received a single infusion of vehicle or BoNT/A or BoNT/B at doses of 1, 3.2, or 10 ng over a 20-min period by convection enhanced delivery (CED). Electrographic (EEG) and behavioral …