Abstract:
:Classical feed-forward inhibition involves an excitation-inhibition sequence that enhances the temporal precision of neuronal responses by narrowing the window for synaptic integration. In the input layer of the cerebellum, feed-forward inhibition is thought to preserve the temporal fidelity of granule cell spikes during mossy fiber stimulation. Although this classical feed-forward inhibitory circuit has been demonstrated in vitro, the extent to which inhibition shapes granule cell sensory responses in vivo remains unresolved. Here we combined whole-cell patch-clamp recordings in vivo and dynamic clamp recordings in vitro to directly assess the impact of Golgi cell inhibition on sensory information transmission in the granule cell layer of the cerebellum. We show that the majority of granule cells in Crus II of the cerebrocerebellum receive sensory-evoked phasic and spillover inhibition prior to mossy fiber excitation. This preceding inhibition reduces granule cell excitability and sensory-evoked spike precision, but enhances sensory response reproducibility across the granule cell population. Our findings suggest that neighboring granule cells and Golgi cells can receive segregated and functionally distinct mossy fiber inputs, enabling Golgi cells to regulate the size and reproducibility of sensory responses.
journal_name
Proc Natl Acad Sci U S Aauthors
Duguid I,Branco T,Chadderton P,Arlt C,Powell K,Häusser Mdoi
10.1073/pnas.1510249112subject
Has Abstractpub_date
2015-10-20 00:00:00pages
13099-104issue
42eissn
0027-8424issn
1091-6490pii
1510249112journal_volume
112pub_type
杂志文章abstract::Antibodies can be developed to directly inhibit almost any protein, but their inability to enter the cytosol limits inhibitory antibodies to membrane-associated or extracellular targets. Developing a cytosolic antibody delivery system would offer unique opportunities to directly inhibit and study intracellular protein...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.1913973116
更新日期:2019-10-29 00:00:00
abstract::By manufacturing a single-particle system in two particulate forms (i.e., micrometer size and nanometer size), we have designed a bacterial vaccine form that exhibits improved efficacy of immunization. Microstructural properties are adapted to alter dispersive and aerosol properties independently. Dried "nanomicropart...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.0800043105
更新日期:2008-03-25 00:00:00
abstract::Spontaneous liposome formation is predicted in binary mixtures of fluid phase phospholipids and poly(n)ethylene oxide (PEO)-bearing lipids by using single chain mean field theory. The range of stability of the spontaneous liposomes is determined as a function of percentage of PEO-conjugated lipids and polymer molecula...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.95.3.1032
更新日期:1998-02-03 00:00:00
abstract::The rotational strengths of the four longer wavelength transitions, B(2u), B(1u), and the two E(1u), of adenosine derivatives constrained in the syn form have been investigated theoretically and experimentally. The theory combines a complete neglect of differential overlap version S (CNDO/S) description of the base wi...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.77.6.3398
更新日期:1980-06-01 00:00:00
abstract::High-throughput metagenomic sequencing offers an unbiased approach to identify pathogens in clinical samples. Conventional metagenomic sequencing, however, does not integrate information about the host, which is often critical to distinguish infection from infectious disease, and to assess the severity of disease. Her...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.1906320116
更新日期:2019-09-10 00:00:00
abstract::Given their relatively small area, mangroves and their organic sediments are of disproportionate importance to global carbon sequestration and carbon storage. Peat deposition and preservation allows some mangroves to accrete vertically and keep pace with sea-level rise by growing on their own root remains. In this stu...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.1519774113
更新日期:2016-04-19 00:00:00
abstract::The unfolded protein response (UPR) is an evolutionarily conserved mechanism by which all eukaryotic cells adapt to the accumulation of unfolded proteins in the endoplasmic reticulum (ER). Inositol-requiring kinase 1 (IRE1) and PKR-related ER kinase (PERK) are two type I transmembrane ER-localized protein kinase recep...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.0606480103
更新日期:2006-09-26 00:00:00
abstract::Replication of complementary-strand DNA in filamentous phages is initiated by a primer RNA that is synthesized at the minus-strand origin on the viral single-stranded DNA by Escherichia coli RNA polymerase holoenzyme containing the sigma70 subunit. We have demonstrated that the affinity of RNA polymerase in vitro to t...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.94.7.2909
更新日期:1997-04-01 00:00:00
abstract::Many changes have been described in the brains of Alzheimer's disease (AD) patients, including loss of neurons and formation of senile plaques and neurofibrillary tangles. The molecular mechanisms underlying these pathologies are unclear. Northern blot, dot-blot, and reverse transcription-coupled PCR analyses have dem...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.95.16.9620
更新日期:1998-08-04 00:00:00
abstract::Time series data on arthropod populations are critical for understanding the magnitude, direction, and drivers of change. However, most arthropod monitoring programs are short-lived and restricted in taxonomic resolution. Monitoring data from the Arctic are especially underrepresented, yet critical to uncovering and u...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.2002557117
更新日期:2021-01-12 00:00:00
abstract::There are certain genes on the sex chromosome of Drosophila for which the female contains twice as many copies as the male. Some of the genes in this group produce the same phenotype in each sex despite the dosage difference and are said, therefore, to manifest dosage compensation. The structural genes for glucose-6-p...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.62.2.528
更新日期:1969-02-01 00:00:00
abstract::An integral mitochondrial membrane protein (p32) of yeast has previously been molecularly cloned and sequenced and suggested to function as a mitochondrial import receptor. However, this protein has also been proposed to function as phosphate translocator [Guérin, B., Bukusoglu, C., Rakotomanana, F. & Wohlrab, H. (199...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.90.8.3358
更新日期:1993-04-15 00:00:00
abstract::The eukaryotic small ribosomal subunit carries only four ribosomal (r) RNA methylated bases, all close to important functional sites. N(7)-methylguanosine (m(7)G) introduced at position 1575 on 18S rRNA by Bud23-Trm112 is at a ridge forming a steric block between P- and E-site tRNAs. Here we report atomic resolution s...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.1413089111
更新日期:2014-12-23 00:00:00
abstract::Understanding the origin, nature, and functional significance of complex patterns of neural activity, as recorded by diverse electrophysiological and neuroimaging techniques, is a central challenge in neuroscience. Such patterns include collective oscillations emerging out of neural synchronization as well as highly h...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.1712989115
更新日期:2018-02-13 00:00:00
abstract::Herpes simplex virus type 2 (HSV-2) DNA was treated with four restriction endonucleases (EcoRI, HincIII, Bgl II, and Xba I) and eight fragments were purified and labeled with 32P in vitro. The kinetics of renaturation of each of the fragments was measured in the presence of DNA extracted from 333-8-9, a hamster cell l...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.77.2.880
更新日期:1980-02-01 00:00:00
abstract::We report free-standing atomic crystals that are strictly 2D and can be viewed as individual atomic planes pulled out of bulk crystals or as unrolled single-wall nanotubes. By using micromechanical cleavage, we have prepared and studied a variety of 2D crystals including single layers of boron nitride, graphite, sever...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.0502848102
更新日期:2005-07-26 00:00:00
abstract::Protein phosphorylation is a ubiquitous and one of the most effective means of regulating protein activity. Receptor phosphorylation is a key event in signal transduction. The question, therefore, that arises is whether this modulatory mechanism might produce functional changes in a membrane receptor in the absence of...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.88.22.10213
更新日期:1991-11-15 00:00:00
abstract::Recent single-molecule experiments reveal that mechanical tension on DNA can control both the speed and direction of the DNA polymerase motor. We present a theoretical description of this tension-induced "tuning" and "switching." The internal conformational states of the enzyme motor are represented as nodes, and the ...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.1033134100
更新日期:2003-08-19 00:00:00
abstract::A unique neuronal system was detected in the rat central nervous system by immunohistochemistry and radioimmunoassay with antibodies to salmon melanin-concentrating hormone (MCH). MCH-like immunoreactive (MCH-LI) cell bodies were confined to the hypothalamus. MCH-LI fibers were found throughout the brain but were most...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.83.5.1528
更新日期:1986-03-01 00:00:00
abstract::Circadian rhythms modulate many aspects of physiology. Knowledge of the molecular basis of these rhythms has exploded in the last 20 years. However, most of these data are from model organisms, and translation to clinical practice has been limited. Here, we present an approach to identify molecular rhythms in humans f...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.1619320114
更新日期:2017-05-16 00:00:00
abstract::Although common in birds, social monogamy, or pair-living, is rare among mammals because internal gestation and lactation in mammals makes it advantageous for males to seek additional mating opportunities. A number of hypotheses have been proposed to explain the evolution of social monogamy among mammals: as a male ma...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.1307903110
更新日期:2013-08-13 00:00:00
abstract::Two-electron oxidation of cobaltous octaethylporphyrin [Co(II)(Et)(8)P] yields a stable pi-cation radical [Co(III)(Et)(8)P](2+.), the optical spectrum of which exhibits spectral changes dependent upon the nature of the counterion. Comparison of these spectra with those of Compounds I of horseradish peroxidase and cata...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.68.3.614
更新日期:1971-03-01 00:00:00
abstract::Photosynthesis has recently gained considerable attention for its potential role in the development of renewable energy sources. Optimizing photosynthetic organisms for biomass or biofuel production will therefore require a systems understanding of photosynthetic processes. We reconstructed a high-quality genome-scale...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.1117907109
更新日期:2012-02-14 00:00:00
abstract::The conservation of endangered fish is of critical importance. Cryobanking could provide an effective backup measure for use in conjunction with the conservation of natural populations; however, methodology for cryopreservation of fish eggs and embryos has not yet been developed. The present study established a method...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.1218468110
更新日期:2013-01-29 00:00:00
abstract::Myoglobin-mediated oxygen delivery to intracellular mitochondria is demonstrated in cardiac myocytes isolated from the hearts of mature rats. Myocytes are held at high ambient oxygen pressure, 40-340 torr (5-45 kPa); sarcoplasmic myoglobin is fully oxygenated. In this condition oxygen availability does not limit respi...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.84.21.7503
更新日期:1987-11-01 00:00:00
abstract::We advance a theory of resilience as it applies to the challenges of international development. The conceptualization we advance for development resilience focuses on the stochastic dynamics of individual and collective human well-being, especially on the avoidance of and escape from chronic poverty over time in the f...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.1320880111
更新日期:2014-10-07 00:00:00
abstract::Engineered calmodulins (CaMs), rendered Ca2+-insensitive by mutations, function as dominant negatives in heterologous systems, and have revealed mechanisms of ion channel modulation by Ca2+/CaM. The use of these CaMs in native mammalian cells now emerges as a strategy to unmask the biology of such Ca2+ feedback. Here,...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.262372999
更新日期:2002-12-24 00:00:00
abstract::Calpains are Ca(2+)-dependent intracellular proteases. We show here that calpain-generated natural C-terminal fragments of proteins that include G protein-coupled receptors, transmembrane ion channels, transcriptional regulators, apoptosis controllers, kinases, and phosphatases (Phe-GluN2a, Lys-Ica512, Arg-Ankrd2, Tyr...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.1401639111
更新日期:2014-03-04 00:00:00
abstract::A human craniofacial cDNA library was screened with a degenerate oligonucleotide probe based on the conserved third helix of homeobox genes. From this screening, we identified a homeobox gene, H6, which shared only 57-65% amino acid identity to previously reported homeodomains. H6 was physically mapped to the 4p16.1 r...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.89.23.11579
更新日期:1992-12-01 00:00:00
abstract::The plasma concentration of the major vitamin D metabolites; 25-hydroxyvitamin D, 1,25-dihydroxyvitamin D, and 24,25-dihydroxyvitamin D were measured during pregnancy and lactation in the adult female rat. The concentrations of these metabolites were also measured in rat pups during lactation and after weaning. The pl...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.76.11.5549
更新日期:1979-11-01 00:00:00