Author: Thomas Kilduff

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.

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.

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.

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).

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…

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.

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.

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.

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.

Arch may be better suited for long-term circuit inhibition, and may serve as an important tool for deciphering the role of Hcrt signaling in the maintenance of wakefulness.

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.

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.