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 …

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 …

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 …

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 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 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 …

Transient And Selective Suppression Of Neural Activity With Infrared Light, Michael W. Jenkins, Hui Lu, Jeffrey M. Mcmanus, Hillel J. Chiel

Faculty Scholarship

Analysis and control of neural circuitry requires the ability to selectively activate or inhibit neurons. Previous work showed that infrared laser light selectively excited neural activity in endogenous unmyelinated and myelinated axons. However, inhibition of neuronal firing with infrared light was only observed in limited cases, is not well understood and was not precisely controlled. Using an experimentally tractable unmyelinated preparation for detailed investigation and a myelinated preparation for validation, we report that it is possible to selectively and transiently inhibit electrically- initiated axonal activation, as well as to both block or enhance the propagation of action potentials of specific …

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 …

Osteopontin Expression During The Acute Immune Response Mediates Reactive Synaptogenesis And Adaptive Outcome, Julie Chan

Theses and Dissertations

Traumatic brain injury (TBI) is a worldwide epidemic as the number of victims living with the resulting cognitive and physical impairment continues to rise, principally due to limited treatment options which fail to address its multifaceted sequelae. By approaching TBI therapy from a molecular standpoint, we have the opportunity to develop a better understanding of the mechanisms which prevent effective recovery. With this information, we can move toward the identification of novel therapeutic treatments which target specific molecules to improve patient outcome following TBI. Here, we have focused on the therapeutic potential of osteopontin (OPN), an extracellular matrix (ECM) protein …

A Multivariate Method To Determine The Dimensionality Of Neural Representation From Population Activity., Jörn Diedrichsen, Tobias Wiestler, Naveed Ejaz

Brain and Mind Institute Researchers' Publications

How do populations of neurons represent a variable of interest? The notion of feature spaces is a useful concept to approach this question: According to this model, the activation patterns across a neuronal population are composed of different pattern components. The strength of each of these components varies with one latent feature, which together are the dimensions along which the population represents the variable. Here we propose a new method to determine the number of feature dimensions that best describes the activation patterns. The method is based on Gaussian linear classifiers that use only the first d most important pattern …

Anticuerpos Contra El Virus De La Parainfluenza 3 En Cerdos De Crianza Tecnificada Y De Traspatio Beneficiados En Mataderos De Lima, Milagros P. Montesinos, Hermelinda G. Rivera, Mariluz Araínga

Journal Articles: Pharmacology & Experimental Neuroscience

Parainfluenza 3 antibodies against (PI3) virus in pigs were determined from commercial (n = 192) and backyard farms (n = 192). Blood samples were collected at the slaughter house from pigs of 2 to 6 months of age of any sex for detecting antibodies against the PI3 virus by viral neutralization test. The 5.5 ± 2.3% (21/384) of the pigs had antibodies against PI3 virus, where 5.2 ± 1.1% (10/192) and 5.7 ± 1.2% (11/192) were from commercial and backyard farms respectively. The antibody titres ranged from 4 to 64 and were detected in pigs older than 3 months of …

Expression Of C-Fos In Hilar Mossy Cells Of The Dentate Gyrus In Vivo., Aine M Duffy, Michael J Schaner, Jeannie Chin, Helen E Scharfman

Department of Neuroscience Faculty Papers

Granule cells (GCs) of the dentate gyrus (DG) are considered to be quiescent--they rarely fire action potentials. In contrast, the other glutamatergic cell type in the DG, hilar mossy cells (MCs) often have a high level of spontaneous activity based on recordings in hippocampal slices. MCs project to GCs, so activity in MCs could play an important role in activating GCs. Therefore, we investigated whether MCs were active under basal conditions in vivo, using the immediate early gene c-fos as a tool. We hypothesized that MCs would exhibit c-fos expression even if rats were examined randomly, under normal housing conditions. …

Network Dynamics Of Visual Naming, Christopher R. Conner

Dissertations and Theses (Open Access)

Recognition and naming of objects and actions are fundamental components of language. They involve several different systems working in coordination to accomplish a complex behavior. During visual naming, sensory and semantic processing are carried out by dedicated cortical substrates in the temporal and occipital lobes, while response selection and articulatory planning are handled by prefrontal cortex. Despite decades of research using lesion analysis, functional MRI and electro-encephalography, the precise dynamics involved remain unknown due to the inadequate spatio-temporal resolution of these methodologies. Of particular interest is the organization of semantic knowledge and the degree of serial and parallel organization of …

Environmental Circadian Disruption Elevates The Il-6 Response To Lipopolysaccharide In Blood, Kandis L. Adams, Oscar Castanon-Cervantes, Jennifer A. Evans, Alec J. Davidson

Biomedical Sciences Faculty Research and Publications

The immune system is regulated by circadian clocks within the brain and immune cells. Environmental circadian disruption (ECD), consisting of a 6-h phase advance of the light:dark cycle once a week for 4 weeks, elevates the inflammatory response to lipopolysaccharide (LPS) both in vivo and in vitro. This indicates that circadian disruption adversely affects immune function; however, it remains unclear how the circadian system regulates this response under ECD conditions. Here, we develop an assay using ex vivo whole-blood LPS challenge to investigate the circadian regulation of immune responses in mice and to determine the effects of ECD on these …

Alternations Of Nmda And Gabab Receptor Function In Development: A Potential Animal Model Of Schizophrenia, Monica Bolton

UNLV Theses, Dissertations, Professional Papers, and Capstones

Schizophrenia is a debilitating mental disorder that affects up to 3% of the world population. The behavioral symptoms are categorized into positive and negative symptoms, which appear during late adolescence/early adulthood. Unfortunately, the underlying cellular and molecular mechanisms of the disease are poorly understood. Several hypotheses exist to explain mechanisms contributing to these behavioral alterations. One model proposes that a reduced function of the NMDA glutamate receptor on specific GABAergic interneurons may be responsible for deficits in schizophrenia. Post-mortem investigations provide evidence of reductions in both glutamate and GABA-related proteins in patients with schizophrenia. Further, GABAergic interneurons that are activated …

Single-Trial Decoding Of Auditory Novelty Responses Facilitates The Detection Of Residual Consciousness, J. R. King, F. Faugeras, A. Gramfort, Aaron Schurger, I. El Karoui, J. D. Sitt, B. Rohaut, C. Wacongne, E. Labyt, T. Bekinschtein, L. Cohen, L. Naccache, S. Dehaene

Psychology Faculty Articles and Research

Detecting residual consciousness in unresponsive patients is a major clinical concern and a challenge for theoretical neuroscience. To tackle this issue, we recently designed a paradigm that dissociates two electro-encephalographic (EEG) responses to auditory novelty. Whereas a local change in pitch automatically elicits a mismatch negativity (MMN), a change in global sound sequence leads to a late P300b response. The latter component is thought to be present only when subjects consciously perceive the global novelty. Unfortunately, it can be difficult to detect because individual variability is high, especially in clinical recordings. Here, we show that multivariate pattern classifiers can extract …