Abstract:
:Molecular determinants of threshold sensitivity of mammalian mechanoreceptors are unknown. Here, we identify a mechanosensitive (MS) K(+) current (IKmech) that governs mechanical threshold and adaptation of distinct populations of mechanoreceptors. Toxin profiling and transgenic mouse studies indicate that IKmech is carried by Kv1.1-Kv1.2 heteromers. Mechanosensitivity is attributed to Kv1.1 subunits, through facilitation of voltage-dependent open probability. IKmech is expressed in high-threshold C-mechano-nociceptors (C-HTMRs) and Aβ-mechanoreceptors, but not in low-threshold C-mechanoreceptors. IKmech opposes depolarization induced by slow/ultraslow MS cation currents in C-HTMRs, thereby shifting mechanical threshold for firing to higher values. However, due to kinetics mismatch with rapidly-adapting MS cation currents, IKmech tunes firing adaptation but not mechanical threshold in Aβ-mechanoreceptors. Expression of Kv1.1 dominant negative or inhibition of Kv1.1/IKmech caused severe mechanical allodynia but not heat hyperalgesia. By balancing the activity of excitatory mechanotransducers, Kv1.1 acts as a mechanosensitive brake that regulates mechanical sensitivity of fibers associated with mechanical perception.
journal_name
Neuronjournal_title
Neuronauthors
Hao J,Padilla F,Dandonneau M,Lavebratt C,Lesage F,Noël J,Delmas Pdoi
10.1016/j.neuron.2012.12.035subject
Has Abstractpub_date
2013-03-06 00:00:00pages
899-914issue
5eissn
0896-6273issn
1097-4199pii
S0896-6273(13)00043-3journal_volume
77pub_type
杂志文章相关文献
NEURON文献大全abstract::Motor units comprise a pre-synaptic motor neuron and multiple post-synaptic muscle fibers. Many movement disorders disrupt motor unit contractile dynamics and the structure of sarcomeres, skeletal muscle's contractile units. Despite the motor unit's centrality to neuromuscular physiology, no extant technology can imag...
journal_title:Neuron
pub_type: 杂志文章
doi:10.1016/j.neuron.2015.11.022
更新日期:2015-12-16 00:00:00
abstract::Reversible silencing of neuronal activity is a powerful approach for isolating the roles of specific neuronal populations in circuit dynamics and behavior. In contrast with neuronal excitation, for which the majority of studies have used a limited number of optogenetic and chemogenetic tools, the number of genetically...
journal_title:Neuron
pub_type: 杂志文章,评审
doi:10.1016/j.neuron.2017.06.050
更新日期:2017-08-02 00:00:00
abstract::Hyperpolarization-activated cyclic nucleotide-gated (HCN) channels are key modulators of neuronal activity by providing the depolarizing cation current I(h) involved in rhythmogenesis, dendritic integration, and synaptic transmission. These tasks critically depend on the availability of HCN channels, which is dynamica...
journal_title:Neuron
pub_type: 杂志文章
doi:10.1016/j.neuron.2009.05.008
更新日期:2009-06-25 00:00:00
abstract::Commissural axons are attracted to the midline intermediate target by chemoattractants, but upon crossing the midline they switch off responsiveness to attractants and switch on responsiveness to midline repellents, which expel the axons from the midline and enable them to move on. Here we show that midline exit also ...
journal_title:Neuron
pub_type: 杂志文章
doi:10.1016/j.neuron.2008.01.006
更新日期:2008-02-28 00:00:00
abstract::Injection of inositol 1,4,5 trisphosphate (InsP3) into Limulus ventral photoreceptors elevates the concentration of intracellular calcium ions and as a consequence depolarizes the photoreceptor. This InsP3-induced elevation can be inhibited by a prior injection of calcium or InsP3 delivered 1 s earlier. Recovery from ...
journal_title:Neuron
pub_type: 杂志文章
doi:10.1016/0896-6273(90)90112-s
更新日期:1990-04-01 00:00:00
abstract::The Fragile X mental retardation protein (FMRP) regulates neuronal RNA metabolism, and its absence or mutations leads to the Fragile X syndrome (FXS). The β-amyloid precursor protein (APP) is involved in Alzheimer's disease, plays a role in synapse formation, and is upregulated in intellectual disabilities. Here, we s...
journal_title:Neuron
pub_type: 杂志文章
doi:10.1016/j.neuron.2015.06.032
更新日期:2015-07-15 00:00:00
abstract::Calcium/calmodulin-dependent protein kinase II (CaMKII) can be regulated by synaptic activity and could therefore be involved in activity-dependent control of neuronal growth. We tested whether increased CaMKII activity in postsynaptic optic tectal neurons can modify the development of retinotectal axons in Xenopus. T...
journal_title:Neuron
pub_type: 杂志文章
doi:10.1016/s0896-6273(00)80072-0
更新日期:1996-03-01 00:00:00
abstract::Ephrin signaling through Eph receptor tyrosine kinases can promote attraction or repulsion of axonal growth cones during development. However, the mechanisms that determine whether Eph signaling promotes attraction or repulsion are not known. We show here that the Rho family GEF Vav2 plays a key role in this process. ...
journal_title:Neuron
pub_type: 杂志文章
doi:10.1016/j.neuron.2005.03.019
更新日期:2005-04-21 00:00:00
abstract::The nicotinic acetylcholine receptor, a pentameric ligand-gated ion channel, converts the free energy of binding of the neurotransmitter acetylcholine into opening of its central pore. Here we present the first high-resolution structure of the receptor type found in muscle-endplate membrane and in the muscle-derived e...
journal_title:Neuron
pub_type: 杂志文章
doi:10.1016/j.neuron.2020.03.012
更新日期:2020-06-17 00:00:00
abstract::In the precedence effect, sounds emanating directly from the source are localized preferentially over their reflections. Although most studies have focused on the delay between the onset of a sound and its echo, humans still experience the precedence effect when this onset delay is removed. We tested in barn owls the ...
journal_title:Neuron
pub_type: 杂志文章
doi:10.1016/j.neuron.2010.07.014
更新日期:2010-08-26 00:00:00
abstract::Voltage-activated potassium (Kv) channels from mammalian brain are hetero-oligomers containing alpha and beta subunits. Coexpression of Kv1 alpha and Kv beta 1 subunits confers rapid A-type inactivation on noninactivating potassium channels (delayed rectifiers) in expression systems in vitro. We have delineated a Kv1....
journal_title:Neuron
pub_type: 杂志文章
doi:10.1016/s0896-6273(00)80063-x
更新日期:1996-02-01 00:00:00
abstract::To assess the role of exocytotic release in signaling by monoamines, we have disrupted the neuronal vesicular monoamine transporter 2 (VMAT2) gene. VMAT2-/- mice move little, feed poorly, and die within a few days after birth. Monoamine cell groups and their projections are indistinguishable from those of wild-type li...
journal_title:Neuron
pub_type: 杂志文章
doi:10.1016/s0896-6273(00)80418-3
更新日期:1997-12-01 00:00:00
abstract::The ability to classify visual objects into discrete categories ("friend" versus "foe"; "edible" versus "poisonous") is essential for survival and is a fundamental cognitive function. The cortical substrates that mediate this function, however, have not been identified in humans. To identify brain regions involved in ...
journal_title:Neuron
pub_type: 杂志文章
doi:10.1016/j.neuron.2006.01.032
更新日期:2006-03-02 00:00:00
abstract::Acetylcholine in the brain alters neuronal excitability, influences synaptic transmission, induces synaptic plasticity, and coordinates firing of groups of neurons. As a result, it changes the state of neuronal networks throughout the brain and modifies their response to internal and external inputs: the classical rol...
journal_title:Neuron
pub_type: 杂志文章,评审
doi:10.1016/j.neuron.2012.08.036
更新日期:2012-10-04 00:00:00
abstract::We recently reported that homozygous Presenilin-1 (Psen1) knockin (KI) mice carrying the familial Alzheimer's disease (FAD) mutation L435F or C410Y recapitulate the phenotypes of Psen1(-/-) mice. Production and steady-state levels of Aβ40 and Aβ42 are undetectable in KI/KI brains and reduced in KI/+ brains, though the...
journal_title:Neuron
pub_type: 评论,杂志文章
doi:10.1016/j.neuron.2016.03.009
更新日期:2016-04-20 00:00:00
abstract::Elucidating the molecular mechanisms underlying quantitative neurocognitive phenotypes will further our understanding of the brain's structural and functional architecture and advance the diagnosis and treatment of the psychiatric disorders that these traits underlie. Although many neurocognitive traits are highly her...
journal_title:Neuron
pub_type: 杂志文章,评审
doi:10.1016/j.neuron.2010.10.007
更新日期:2010-10-21 00:00:00
abstract::Rhythmic spontaneous electrical activity occurs in many parts of the developing nervous system, where it plays essential roles in the refinement of neural connections. By blocking or slowing this bursting activity, via in ovo drug applications at precise developmental periods, we show that such activity is also requir...
journal_title:Neuron
pub_type: 杂志文章
doi:10.1016/j.neuron.2004.08.018
更新日期:2004-09-02 00:00:00
abstract::The lateral mobility of neurotransmitter receptors has been shown to tune synaptic signals. Here we report that GABAA receptors (GABAARs) can diffuse between adjacent dendritic GABAergic synapses in long-living desensitized states, thus laterally spreading "activation memories" between inhibitory synapses. Glutamaterg...
journal_title:Neuron
pub_type: 杂志文章
doi:10.1016/j.neuron.2017.06.022
更新日期:2017-07-05 00:00:00
abstract::Local neuronal networks that are responsible for walking are poorly characterized in mammals. Using an innovative approach to identify interneuron inputs onto motorneuron populations in a neonatal rodent spinal cord preparation, we have investigated the network responsible for left-right coordination of the hindlimbs....
journal_title:Neuron
pub_type: 杂志文章
doi:10.1016/s0896-6273(03)00353-2
更新日期:2003-06-19 00:00:00
abstract::Several molecules involved in the development of the nervous system have specific binding sites for the glycosaminoglycan (GAG) side chains of proteoglycans. Exogenous GAGs should bind to these sites, competitively inhibit interactions with proteoglycans, and perturb development. GAGs added to the culture medium pertu...
journal_title:Neuron
pub_type: 杂志文章
doi:10.1016/0896-6273(92)90091-q
更新日期:1992-04-01 00:00:00
abstract::From the intracellularly recorded responses to small, rapidly flashed spots, we have quantitatively mapped the receptive fields of simple cells in the cat visual cortex. We then applied these maps to a feedforward model of orientation selectivity. Both the preferred orientation and the width of orientation tuning of t...
journal_title:Neuron
pub_type: 杂志文章
doi:10.1016/s0896-6273(01)00278-1
更新日期:2001-04-01 00:00:00
abstract::Fluorescence imaging has enabled us to decipher spatiotemporal information coded in complex tissues. Genetically encoded probes that enable fluorescence imaging of excitable cell activity have been constructed by fusing fluorescent proteins to functional proteins that are involved in physiological signaling. The probe...
journal_title:Neuron
pub_type: 杂志文章,评审
doi:10.1016/j.neuron.2005.10.003
更新日期:2005-10-20 00:00:00
abstract::The signaling mechanisms that control the survival of CNS neurons are poorly understood. Here we show that, in contrast to PNS neurons, the survival of purified postnatal rat retinal ganglion cells (RGCs) in vitro is not promoted by peptide trophic factors unless their intracellular cAMP is increased pharmacologically...
journal_title:Neuron
pub_type: 杂志文章
doi:10.1016/0896-6273(95)90172-8
更新日期:1995-10-01 00:00:00
abstract::Imaging large-scale circuit dynamics is crucial to understanding brain function, but most techniques have a limited depth of field. Here, we describe volumetric functional ultrasound imaging (vfUSI), a platform for brain-wide vfUSI of hemodynamic activity in awake head-fixed mice. We combined a high-frequency 1,024-ch...
journal_title:Neuron
pub_type: 杂志文章
doi:10.1016/j.neuron.2020.09.020
更新日期:2020-12-09 00:00:00
abstract::Spontaneous fluctuations in cortical excitability influence sensory processing and behavior. These fluctuations, long thought to reflect global changes in cortical state, were recently found to be modulated locally within a retinotopic map during spatially selective attention. We report that periods of vigorous (On) a...
journal_title:Neuron
pub_type: 杂志文章
doi:10.1016/j.neuron.2020.12.013
更新日期:2020-12-30 00:00:00
abstract::Functional neuroimaging uses activity-dependent changes in cerebral blood flow to map brain activity, but the contributions of presynaptic and postsynaptic activity are incompletely understood, as are the underlying cellular pathways. Using intravital multiphoton microscopy, we measured presynaptic activity, postsynap...
journal_title:Neuron
pub_type: 杂志文章
doi:10.1016/j.neuron.2008.04.029
更新日期:2008-06-26 00:00:00
abstract::Embryonic retinal ganglion cell (RGC) axons must extend toward and grow through the optic disc to exit the eye into the optic nerve. In the embryonic mouse eye, we found that immunoreactivity for the axon guidance molecule netrin-1 was specifically on neuroepithelial cells at the disk surrounding exiting RGC axons, an...
journal_title:Neuron
pub_type: 杂志文章
doi:10.1016/s0896-6273(00)80373-6
更新日期:1997-09-01 00:00:00
abstract::The carboxyl terminus of presenilin 1 and 2 (PS1 and PS2) binds to the neuron-specific cell adhesion molecule telencephalin (TLN) in the brain. PS1 deficiency results in the abnormal accumulation of TLN in a yet unidentified intracellular compartment. The first transmembrane domain and carboxyl terminus of PS1 form a ...
journal_title:Neuron
pub_type: 杂志文章
doi:10.1016/s0896-6273(01)00512-8
更新日期:2001-11-20 00:00:00
abstract::We have determined the sequences of isoforms of human tau protein, which differ from previously reported forms by insertions of 29 or 58 amino acids in the amino-terminal region. Complementary DNA cloning shows that the insertions occur in combination with both three and four tandem repeats. RNAase protection assays i...
journal_title:Neuron
pub_type: 杂志文章
doi:10.1016/0896-6273(89)90210-9
更新日期:1989-10-01 00:00:00
abstract::I(Ks) voltage-gated K(+) channels contain four pore-forming KCNQ1 subunits and MinK accessory subunits in a number that has been controversial. Here, I(Ks) channels assembled naturally by monomer subunits are compared to those with linked subunits that force defined stoichiometries. Two strategies that exploit charybd...
journal_title:Neuron
pub_type: 杂志文章
doi:10.1016/s0896-6273(03)00570-1
更新日期:2003-09-25 00:00:00