85 research outputs found
Dissociating motor impairment from five-choice serial reaction time task performance in a mouse model of Angelman syndrome
Angelman syndrome (AS) is a single-gene neurodevelopmental disorder associated with cognitive and motor impairment, seizures, lack of speech, and disrupted sleep. AS is caused by loss-of-function mutations in the UBE3A gene, and approaches to reinstate functional UBE3A are currently in clinical trials in children. Behavioral testing in a mouse model of AS (Ube3am–/p+) represents an important tool to assess the effectiveness of current and future treatments preclinically. Existing behavioral tests effectively model motor impairments, but not cognitive impairments, in Ube3am–/p+ mice. Here we tested the hypothesis that the 5-choice serial reaction time task (5CSRTT) can be used to assess cognitive behaviors in Ube3am–/p+ mice. Ube3am–/p+ mice had more omissions during 5CSRTT training than wild-type littermate controls, but also showed impaired motor function including open field hypoactivity and delays in eating pellet rewards. Motor impairments thus presented an important confound for interpreting this group difference in omissions. We report that despite hypoactivity during habituation, Ube3am–/p+ mice had normal response latencies to retrieve rewards during 5CSRTT training. We also accounted for delays in eating pellet rewards by assessing omissions solely on trials where eating delays would not impact results. Thus, the increase in omissions in Ube3am–/p+ mice is likely not caused by concurrent motor impairments. This work underscores the importance of considering how known motor impairments in Ube3am–/p+ mice may affect behavioral performance in other domains. Our results also provide guidance on how to design a 5CSRTT protocol that is best suited for future studies in Ube3a mutants
GABAergic Neuron-Specific Loss of Ube3a Causes Angelman Syndrome-Like EEG Abnormalities and Enhances Seizure Susceptibility
Loss of maternal UBE3A causes Angelman syndrome (AS), a neurodevelopmental disorder associated with severe epilepsy. We previously implicated GABAergic deficits onto layer (L) 2/3 pyramidal neurons in the pathogenesis of neocortical hyperexcitability, and perhaps epilepsy, in AS model mice. Here we investigate consequences of selective Ube3a loss from either GABAergic or glutamatergic neurons, focusing on the development of hyperexcitability within L2/3 neocortex and in broader circuit and behavioral contexts. We find that GABAergic Ube3a loss causes AS-like increases in neocortical EEG delta power, enhances seizure susceptibility, and leads to presynaptic accumulation of clathrin-coated vesicles (CCVs) – all without decreasing GABAergic inhibition onto L2/3 pyramidal neurons. Conversely, glutamatergic Ube3a loss fails to yield EEG abnormalities, seizures, or associated CCV phenotypes, despite impairing tonic inhibition onto L2/3 pyramidal neurons. These results substantiate GABAergic Ube3a loss as the principal cause of circuit hyperexcitability in AS mice, lending insight into ictogenic mechanisms in AS
Erratum to: Delta rhythmicity is a reliable EEG biomarker in Angelman syndrome: a parallel mouse and human analysis
After publication of our article [1], we became aware that
there were two minor data loading and analysis scripting
errors in the human EEG data processing pipeline. These
errors affected the channel loading/grouping and sleep/
wake coding of EEG data. We have re-analysed all the
data affected by these errors. The errors do not affect any
interpretations or conclusions, thus no changes to the text
are required apart from correcting p values and raw values
affected by the errors. There are no changes to statistical
significance or lack-thereof. The errors affect data presented
in Fig. 3, Fig. 4, Fig. 5, and Additional file 3: Figure
S3 and thus we have re-plotted these figures (see below)
QCD
We discuss issues of QCD at the LHC including parton distributions, Monte
Carlo event generators, the available next-to-leading order calculations,
resummation, photon production, small x physics, double parton scattering, and
backgrounds to Higgs production.Comment: 115 pages, Latex, 47 figures, to appear in the Report of the ``1999
CERN Workshop on SM Physics (and more) at the LHC'', S. Catani, M. Dittmar,
D. Soper, W.J. Stirling, S. Tapprogge (convenors
Inflation and squeezed quantum states
The inflationary cosmology is analyzed from the point of view of squeezed
quantum states. As noted by Grishchuk and Sidorov, the amplification of quantum
fluctuations into macroscopic perturbations which occurs during cosmic
inflation is a process of quantum squeezing. We carefully develop the squeezed
state formalism and derive the equations that govern the evolution of a
gaussian initial state. We derive the power spectrum of density perturbations
for a simple inflationary model and discuss its features. We conclude that the
squeezed state formalism provides an interesting framework within which to
study the amplification process, but,in disagreement with the claims of
Grishchuk and Sidorov, that it does {\em not} provide us with any new physical
results.Comment: 33 pages, one section added, significant revisions, 6 figures (in
uuencoded file), Imperial/TP/92-93/2
The Physics of the B Factories
This work is on the Physics of the B Factories. Part A of this book contains a brief description of the SLAC and KEK B Factories as well as their detectors, BaBar and Belle, and data taking related issues. Part B discusses tools and methods used by the experiments in order to obtain results. The results themselves can be found in Part C
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