Publications by authors named "Laura Berkowitz"

Small-animal virtual reality (VR) systems have become invaluable tools in neuroscience for studying complex behavior during head-fixed neural recording, but they lag behind commercial human VR systems in terms of miniaturization, immersivity and advanced features such as eye tracking. Here we present MouseGoggles, a miniature VR headset for head-fixed mice that delivers independent, binocular visual stimulation over a wide field of view while enabling eye tracking and pupillometry in VR. Neural recordings in the visual cortex validate the quality of image presentation, while hippocampal recordings, associative reward learning and innate fear responses to virtual looming stimuli demonstrate an immersive VR experience.

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Differential RNA editing by adenosine deaminases that act on RNA (ADARs) has been implicated in several neurological disorders, including Parkinson's disease (PD). Here, we report results of a RNAi screen of genes differentially regulated in mutants, normally encoding the only catalytically active ADAR in , ADR-2. Subsequent analysis of candidate genes that alter the misfolding of human α-synuclein (α-syn) and dopaminergic neurodegeneration, two PD pathologies, reveal that reduced expression of , the ortholog of human xanthine dehydrogenase (XDH), is protective against α-synuclein-induced dopaminergic neurodegeneration.

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The fine-tuning of gene expression is critical for all cellular processes; aberrations in this activity can lead to pathology, and conversely, resilience. As their role in coordinating organismal responses to both internal and external factors have increasingly come into focus, small non-coding RNAs have emerged as an essential component to disease etiology. Using Systemic RNA interference Defective (SID) mutants of the nematode Caenorhabditis elegans, deficient in gene silencing, we examined the potential consequences of dysfunctional epigenomic regulation in the context of Parkinson's disease (PD).

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Prenatal alcohol exposure (PAE) leads to profound deficits in spatial memory and synaptic and cellular alterations to the hippocampus that last into adulthood. Neurons in the hippocampus called place cells discharge as an animal enters specific places in an environment, establish distinct ensemble codes for familiar and novel places, and are modulated by local theta rhythms. Spatial memory is thought to critically depend on the integrity of hippocampal place cell firing.

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Head direction (HD) cells, which fire action potentials whenever an animal points its head in a particular direction, are thought to subserve the animal's sense of spatial orientation. HD cells are found prominently in several thalamo-cortical regions including anterior thalamic nuclei, postsubiculum, medial entorhinal cortex, parasubiculum, and the parietal cortex. While a number of methods in neural decoding have been developed to assess the dynamics of spatial signals within thalamo-cortical regions, studies conducting a quantitative comparison of machine learning and statistical model-based decoding methods on HD cell activity are currently lacking.

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The consumption of alcohol during gestation is detrimental to the developing central nervous system. One functional outcome of this exposure is impaired spatial processing, defined as sensing and integrating information pertaining to spatial navigation and spatial memory. The hippocampus, entorhinal cortex, and anterior thalamus are brain regions implicated in spatial processing and are highly susceptible to the effects of developmental alcohol exposure.

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Allele-specific distinctions in the human apolipoprotein E () locus represent the best-characterized genetic predictor of Alzheimer's disease (AD) risk. Expression of isoform ε2 is associated with reduced risk, while ε3 is neutral and ε4 carriers exhibit increased susceptibility. Using , we generated a novel suite of humanized transgenic nematodes to facilitate neuronal modeling of amyloid-beta peptide (Aβ) co-expression in the context of distinct human alleles.

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Spatial navigation is impaired in early stages of Alzheimer's disease, and may be a defining behavioral marker of preclinical AD. A new rat model (TgF344-AD) of AD overcomes many limitations of other rodent models, though spatial navigation has not been comprehensively assessed. Using the hidden and cued platform variants of the Morris water task, a longitudinal assessment of spatial navigation was conducted on TgF344-AD (n = 16) and Fischer 344 (n = 12) male and female rats at three age ranges: 4 to 5 months, 7 to 8, and 10 to 11 months of age.

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Animals occupy territories in which resources such as food and shelter are often distributed unevenly. While studies of exploratory behavior have typically involved the laboratory rodent as an experimental subject, questions regarding what constitutes exploration have dominated. A recent line of research has utilized a descriptive approach to the study of rodent exploration, which has revealed that this behavior is organized into movement subsystems that can be readily quantified.

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The retrosplenial cortex is anatomically positioned to integrate sensory, motor, and visual information and is thought to have an important role in processing spatial information and guiding behavior through complex environments. Anatomical and theoretical work has argued that the retrosplenial cortex participates in spatial behavior in concert with input from the parietal cortex. Although the nature of these interactions is unknown, a central position is that the functional connectivity is hierarchical with egocentric spatial information processed in the parietal cortex and higher-level allocentric mappings generated in the retrosplenial cortex.

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Parkinson's disease is associated with intracellular α-synuclein accumulation and ventral midbrain dopaminergic neuronal death in the Substantia Nigra of brain patients. The Rho GTPase pathway, mainly linking surface receptors to the organization of the actin and microtubule cytoskeletons, has been suggested to participate to Parkinson's disease pathogenesis. Nevertheless, its exact contribution remains obscure.

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Alzheimer's disease (AD) is characterized by progressive cognitive decline and the presence of aggregates of amyloid beta (plaques) and hyperphosphorylated tau (tangles). Early diagnosis through neuropsychological testing is difficult due to comorbidity of symptoms between AD and other types of dementia. As a result, there is a need to identify the range of behavioral phenotypes expressed in AD.

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Head Direction (HD) cells of the rodent Papez circuit are thought to reflect the spatial orientation of the animal. Because NMDA transmission is important for spatial behavior, we sought to determine the effects of NMDA blockade on the basic directional signal carried by HD cells and on experience-dependent modification of this system. In Experiment 1, HD cells were recorded from the anterior dorsal thalamus in female Long-Evans rats while they foraged in a familiar enclosure following administration of the NMDA antagonist CPP or saline.

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Head direction (HD) cells, found in the rodent Papez circuit, are thought to form the neural circuitry responsible for directional orientation. Because NMDA transmission has been implicated in spatial tasks requiring directional orientation, we sought to determine if the NMDA antagonist dizocilpine (MK-801) would disrupt the directional signal carried by the HD network. Anterior thalamic HD cells were isolated in female Long-Evans rats and initially monitored for baseline directional activity while the animals foraged in a familiar enclosure.

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Early-onset torsion dystonia is the most severe heritable form of dystonia, a human movement disorder that typically starts during a developmental window in early adolescence. Deletion in the DYT1 gene, encoding the torsinA protein, is responsible for this dominantly inherited disorder, which is non-degenerative and exhibits reduced penetrance among carriers. Here, we explore the hypothesis that deficits in torsinA function result in an increased vulnerability to stress associated with protein folding and processing in the endoplasmic reticulum (ER), where torsinA is located.

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Improvements to the diagnosis and treatment of Parkinson's disease (PD) are dependent upon knowledge about susceptibility factors that render populations at risk. In the process of attempting to identify novel genetic factors associated with PD, scientists have generated many lists of candidate genes, polymorphisms, and proteins that represent important advances, but these leads remain mechanistically undefined. Our work is aimed toward significantly narrowing such lists by exploiting the advantages of a simple animal model system.

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Transgenic Caenorhabditis elegans can be readily created via microinjection of a DNA plasmid solution into the gonad. The plasmid DNA rearranges to form extrachromosomal concatamers that are stably inherited, though not with the same efficiency as actual chromosome. A gene of interest is co-injected with an obvious phenotypic marker, such as rol-6 or GFP, to allow selection of transgenic animals under a dissecting microscope.

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In early C. elegans embryos, signaling between a posterior blastomere, P2, and a ventral blastomere, EMS, specifies endoderm and orients the division axis of the EMS cell. Although Wnt signaling contributes to this polarizing interaction, no mutants identified to date abolish P2/EMS signaling.

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