Author: Thomas Kilduff
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Cortical nNOS/NK1 Neurons Are Regulated by Cholinergic Inputs
CCh has a network effect on excitability within the cortex, as both presynaptic and postsynaptic effects result in an oscillating pattern of nNOS/NK1 neuron excitability.
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Sleep/Wake Regulation and Cortical EEG Are Disturbed in the Neuroligin-3 Rat Model of Autism
This study demonstrates the presence of sleep/wake abnormalities in a model of ASD, consistent with the presence of sleep disruptions found in ASD. The observed decreases in NREM and increased wake consolidation are similar to findings of decreased sleep and hyperactivity in ASD individuals.
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Conditional Ablation of Orexin/Hypocretin Neurons: A New Mouse Model for the Study of Narcolepsy and Orexin System Function
The sleep disorder narcolepsy results from loss of hypothalamic orexin/hypocretin neurons. Although narcolepsy onset is usually postpubertal, current mouse models involve loss of either orexin peptides or orexin neurons from birth. To create a model of orexin/hypocretin deficiency with closer fidelity to human narcolepsy, diphtheria toxin A (DTA) was expressed in orexin neurons under control…
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Optogenetic Manipulation of Activity and Temporally Controlled Cell-Specific Ablation Reveal a Role for MCH Neurons in Sleep/Wake Regulation
To determine the physiological role of MCH neurons, newly developed transgenic mouse strains that enable manipulation of the activity and fate of MCH neurons in vivo were generated using the recently developed knockin-mediated enhanced gene expression by improved tetracycline-controlled gene induction system.
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GABAB Agonism Promotes Sleep and Reduces Cataplexy in Murine Narcolepsy
We evaluated the effects of chronic administration of GHB and the GABA B agonist R -baclofen ( R -BAC) on arousal state and cataplexy in two models of narcolepsy: orexin/ataxin-3 (Atax) and orexin/tTA; TetO diphtheria toxin mice (DTA).
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The Hypocretin/Orexin Antagonist Almorexant Promotes Sleep without Impairment of Performance in Rats
To test the hypothesis that less functional impairment results from HcrtR antagonist-induced sleep, we evaluated the performance of rats in the Morris Water Maze in the presence of ALM vs. ZOL.
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A Role for Cortical nNOS/NK1 Neurons in Coupling Homeostatic Sleep Drive to EEG Slow Wave Activity
These findings support the hypothesis that cortical nNOS/NK1 neurons translate homeostatic sleep drive into up-regulation of NREM δ power through an NO-dependent mechanism.
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Imaging Hippocampal Neuronal Activity across Sleep/Wake States in Freely Behaving Mice
We have utilized a combination of methodologies that collectively enable time-lapse imaging of CA1 neuronal calcium dynamics in behaving mice over periods of many weeks.
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Zolpidem Impairs Attention/Motivation in the Rodent Psychomotor Vigilance Task More Than Almorexant
Here, we tested the effects of ALM and ZOL on the Rodent Psychomotor Vigilance Task (rPVT), a sensitive test of attention and motivation. These results are consistent with the hypothesis that less functional impairment results from HcrtR antagonism than from BzRA-induced inhibition.
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Longitudinal Characterization of Diurnal Rhythms of Activity and Core Body Temperature in the zQ175 Knock-in Mouse Model of Huntington’s Disease: Genotype and Sex Interactions
These initial findings demonstrate that mutant huntington expression in this model causes progressive motor and thermoregulatory deficits with significant genotype and sex differences.
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Microinjections of the Hypocretin Antagonist Almorexant Vs. Gabaergic Agonist Zolpidem in Basal Forebrain Show Differential Effects on Cortical Adenosine Levels in Freely-Moving Rats
We used in vivo microdialysis and HPLC analysis to examine cortical adenosine (ADO) levels following BF microinjections of ZOL (0.6 µg/0.2 µl), ALM (1.0 µg/0.2 µl), or VEH (aCSF) combined with behavioral analyses. Preliminary analyses revealed a significant main effect of drug on ADO levels.
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Sleep-Wake Regulation Is Altered in Mice Lacking Trace Amine-Associated Receptor 1
Here, we tested the hypothesis that endogenous TAAR1 tone contributes to the normal regulation of sleep and wakefulness. Abnormal levels of TAs have long been associated with neuropsychiatric disorders; altered TAAR1 regulation of the monoamines may therefore underlie the sleep disturbances that are frequently comorbid with mental illness.