Abstract：
:The nanoscale topographical arrangement of voltage-gated calcium channels (VGCC) and synaptic vesicles (SVs) determines synaptic strength and plasticity, but whether distinct spatial distributions underpin diversity of synaptic function is unknown. We performed single bouton Ca2+ imaging, Ca2+ chelator competition, immunogold electron microscopic (EM) localization of VGCCs and the active zone (AZ) protein Munc13-1, at two cerebellar synapses. Unexpectedly, we found that weak synapses exhibited 3-fold more VGCCs than strong synapses, while the coupling distance was 5-fold longer. Reaction-diffusion modeling could explain both functional and structural data with two strikingly different nanotopographical motifs: strong synapses are composed of SVs that are tightly coupled (∼10 nm) to VGCC clusters, whereas at weak synapses VGCCs were excluded from the vicinity (∼50 nm) of docked vesicles. The distinct VGCC-SV topographical motifs also confer differential sensitivity to neuromodulation. Thus, VGCC-SV arrangements are not canonical, and their diversity could underlie functional heterogeneity across CNS synapses.
journal_name
Neuronjournal_title
Neuronauthors
Rebola N,Reva M,Kirizs T,Szoboszlay M,Lőrincz A,Moneron G,Nusser Z,DiGregorio DAdoi
10.1016/j.neuron.2019.08.014subject
Has Abstractpub_date
2019-11-20 00:00:00pages
693-710.e9issue
4eissn
0896-6273issn
1097-4199pii
S0896-6273(19)30698-1journal_volume
104pub_type
杂志文章相关文献
NEURON文献大全abstract：:Calcium/calmodulin-dependent protein kinase II (CaMKII) has been described as a biochemical switch that is turned on by increases in intracellular calcium to mediate synaptic plasticity. Here, we show that reductions in CaMKII activity trigger persistent increases in intrinsic excitability. In spontaneously firing ves...
journal_title：Neuron
pub_type： 杂志文章
doi：10.1016/j.neuron.2005.04.009
更新日期：2005-05-19 00:00:00
abstract：:The prefrontal cortex (PFC) and anterior cingulate cortex (ACC) have both been implicated in cognitive control, but their relative roles remain unclear. Here we recorded the activity of single neurons in both areas while monkeys performed a task that required them to switch between trials in which they had to look tow...
journal_title：Neuron
pub_type： 杂志文章
doi：10.1016/j.neuron.2006.12.023
更新日期：2007-02-01 00:00:00
abstract：:The role of cellular interactions in determining the fates of two identified motoneurons in the embryonic zebrafish was investigated by transplanting individual motoneurons from labeled donor embryos to unlabeled hosts. The results suggest that although these cells normally adopt different fates, they form an equivale...
journal_title：Neuron
pub_type： 杂志文章
doi：10.1016/0896-6273(92)90290-t
更新日期：1992-02-01 00:00:00
abstract：:Uptake and transneuronal passage of wild-type and attenuated strains of a swine alpha-herpesvirus (pseudorabies [PRV]) were examined in rat visual projections. Both strains of virus infected subpopulations of retinal ganglion cells and passed transneuronally to infect retino-recipient neurons in the forebrain. However...
journal_title：Neuron
pub_type： 杂志文章
doi：10.1016/0896-6273(91)90236-s
更新日期：1991-06-01 00:00:00
abstract：:mRNA coding for brain-derived neurotrophic factor (BDNF) has been detected in cultured L929 fibroblasts, rat dermal fibroblasts, and sciatic nerve Schwann cells, as well as in rat skin. Medium conditioned by cultured fibroblasts and Schwann cells also stimulates neurite growth from retinal explants and promotes the su...
journal_title：Neuron
pub_type： 杂志文章
doi：10.1016/0896-6273(91)90265-2
更新日期：1991-08-01 00:00:00
abstract：:The earliest stages of Alzheimer's disease (AD) are characterized by the formation of mature tangles in the entorhinal cortex and disorientation and confusion when navigating familiar places. The medial entorhinal cortex (MEC) contains specialized neurons called grid cells that form part of the spatial navigation syst...
journal_title：Neuron
pub_type： 杂志文章
doi：10.1016/j.neuron.2016.12.023
更新日期：2017-02-08 00:00:00
abstract：:Effective error-driven learning benefits from scaling of prediction errors to reward variability. Such behavioral adaptation may be facilitated by neurons coding prediction errors relative to the standard deviation (SD) of reward distributions. To investigate this hypothesis, we required participants to predict the ma...
journal_title：Neuron
pub_type： 杂志文章
doi：10.1016/j.neuron.2016.04.019
更新日期：2016-06-01 00:00:00
abstract：:We induced and characterized a recessive lethal mutation, nic-1, in zebrafish that blocks the function of muscle acetylcholine (ACh) receptors. Homozygous nic-1 embryos are nonmotile and fail to respond to exogenous application of cholinergic agonists, although their muscles contract in response to direct electrical s...
journal_title：Neuron
pub_type： 杂志文章
doi：10.1016/0896-6273(90)90139-7
更新日期：1990-06-01 00:00:00
abstract：:Heterotrimeric G proteins mediate a variety of signaling processes by coupling seven-transmembrane receptors to intracellular effector molecules. The Drosophila phototransduction cascade is a G protein-coupled signaling cascade that utilizes a phospholipase C (PLC beta) effector. PLC beta has been shown to be activate...
journal_title：Neuron
pub_type： 杂志文章
doi：10.1016/0896-6273(95)90182-5
更新日期：1995-10-01 00:00:00
abstract：:When faced with a crowded visual scene, observers must selectively attend to behaviorally relevant objects to avoid sensory overload. Often this selection process is guided by prior knowledge of a target-defining feature (e.g., the color red when looking for an apple), which enhances the firing rate of visual neurons ...
journal_title：Neuron
pub_type： 杂志文章
doi：10.1016/j.neuron.2007.06.015
更新日期：2007-07-19 00:00:00
abstract：:We show here that antisense MAP2 oligonucleotides inhibit neurite outgrowth in cultured cerebellar macroneurons. Unlike control neurons, which first extend a lamellipodial veil followed by a consolidation phase during which the cells extend minor neurites, MAP2-suppressed cells persist with lamellipodia and later beco...
journal_title：Neuron
pub_type： 杂志文章
doi：10.1016/0896-6273(92)90025-9
更新日期：1992-10-01 00:00:00
abstract：:Mesolimbic dopamine (DA) neurons play a central role in motivation and reward processing. Although the activity of these mesolimbic DA neurons is controlled by afferent inputs, little is known about the circuits in which they are embedded. Using retrograde tracing, electrophysiology, optogenetics, and behavioral assay...
journal_title：Neuron
pub_type： 杂志文章
doi：10.1016/j.neuron.2017.12.022
更新日期：2018-01-17 00:00:00
abstract：:In this issue of Neuron, Kraus et al. (2013) show that a population of "time cells" in the hippocampus responds to the passage of time rather than simply reflecting path integration. This study advances our understanding of how time is represented in the hippocampus. ...
journal_title：Neuron
pub_type： 评论,杂志文章
doi：10.1016/j.neuron.2013.05.039
更新日期：2013-06-19 00:00:00
abstract：:Light plays a pivotal role in the regulation of affective behaviors. However, the precise circuits that mediate the impact of light on depressive-like behaviors are not well understood. Here, we show that light influences depressive-like behaviors through a disynaptic circuit linking the retina and the lateral habenul...
journal_title：Neuron
pub_type： 杂志文章
doi：10.1016/j.neuron.2019.01.037
更新日期：2019-04-03 00:00:00
abstract：:In this issue of Neuron, Holz et al. (2019) show that the synaptic protein Homer1a switches mGluR5 signaling to increase AMPA receptor activity for the rapid antidepressant actions of sleep deprivation. ...
journal_title：Neuron
pub_type： 评论,杂志文章
doi：10.1016/j.neuron.2019.10.003
更新日期：2019-10-23 00:00:00
abstract：:The M current regulates neuronal excitability, with its amplitude resulting from high open probability modal M channel behavior. The M current is affected by changing intracellular calcium levels. It is proposed that internal calcium acts by regulating M channel modal gating. Intracellular application of a preactivate...
journal_title：Neuron
pub_type： 杂志文章
doi：10.1016/s0896-6273(00)80033-1
更新日期：1996-01-01 00:00:00
abstract：:Brain circuits endow behavioral flexibility. Here, we study circuits encoding flexible chemotaxis in C. elegans, where the animal navigates up or down NaCl gradients (positive or negative chemotaxis) to reach the salt concentration of previous growth (the set point). The ASER sensory neuron mediates positive and negat...
journal_title：Neuron
pub_type： 杂志文章
doi：10.1016/j.neuron.2014.05.010
更新日期：2014-06-04 00:00:00
abstract：:The size of the movement and the molecular identity of the moving parts of the voltage sensor of a voltage-gated ion channel are debated. In the helical-screw model, the positively charged fourth transmembrane segment S4 slides and rotates along negative counter charges in S2 and S3, while in the paddle model, S4 carr...
journal_title：Neuron
pub_type： 杂志文章
doi：10.1016/j.neuron.2008.07.008
更新日期：2008-09-11 00:00:00
abstract：:Recent advances in connectomics have led to a synthesis of perspectives regarding the brain's functional organization that reconciles classical concepts of localized specialization with an appreciation for properties that emerge from interactions across distributed functional networks. This provides a more comprehensi...
journal_title：Neuron
pub_type： 杂志文章,评审
doi：10.1016/j.neuron.2016.07.031
更新日期：2016-08-03 00:00:00
abstract：:A critical molecular requirement underlying many forms of long-lasting synaptic plasticity and memory is the de novo synthesis of mRNAs and proteins. In a recent paper in Cell, Costa-Mattioli et al. present data from a pharmacogenetic study that places a key regulatory event in the "neural decision" to undergo these p...
journal_title：Neuron
pub_type： 杂志文章
doi：10.1016/j.neuron.2007.04.003
更新日期：2007-04-19 00:00:00
abstract：:A study by Zhang et al. in this issue of Neuron reveals a novel mechanism of control of vestibular motor functions by the orexin (hypocretin) system in the perifornical/LH area through the lateral vestibular nucleus in the brainstem. This knowledge provides new insights into the understanding of brain circuitry that c...
journal_title：Neuron
pub_type： 评论,杂志文章
doi：10.1016/j.neuron.2011.02.017
更新日期：2011-02-24 00:00:00
abstract：:The cerebellum is well appreciated to impart speed, smoothness, and precision to skilled movements such as reaching. How these functions are executed by the final output stage of the cerebellum, the cerebellar nuclei, remains unknown. Here, we identify a causal relationship between cerebellar output and mouse reach ki...
journal_title：Neuron
pub_type： 杂志文章
doi：10.1016/j.neuron.2019.05.007
更新日期：2019-07-17 00:00:00
abstract：:Molecular determinants of Ca2+ channel responsiveness to inhibition by receptor-coupled G proteins were investigated in Xenopus oocytes. The inhibitory response of alpha1B (N-type) channels was much larger than alpha1A (P/Q-type) channels, while alpha1C (L-type) channels were unresponsive. Differences in both degree a...
journal_title：Neuron
pub_type： 杂志文章
doi：10.1016/s0896-6273(00)80229-9
更新日期：1996-11-01 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
abstract：:Although substantial advances have been made in behavioral and pharmacological treatments for addictions, moving treatment development to the next stage may require novel ways of approaching addictions, particularly ways based on new findings regarding the neurobiological underpinnings of addictions that also assimila...
journal_title：Neuron
pub_type： 杂志文章,评审
doi：10.1016/j.neuron.2011.02.009
更新日期：2011-02-24 00:00:00
abstract：:The visual perception of words is known to activate the auditory representation of their spoken forms automatically. We examined the neural mechanism for this phonological activation using transcranial magnetic stimulation (TMS) with a masked priming paradigm. The stimulation sites (left superior temporal gyrus [L-STG...
journal_title：Neuron
pub_type： 杂志文章
doi：10.1016/j.neuron.2006.09.030
更新日期：2006-11-09 00:00:00
abstract：:To characterize the role of rare complete human knockouts in autism spectrum disorders (ASDs), we identify genes with homozygous or compound heterozygous loss-of-function (LoF) variants (defined as nonsense and essential splice sites) from exome sequencing of 933 cases and 869 controls. We identify a 2-fold increase i...
journal_title：Neuron
pub_type： 杂志文章
doi：10.1016/j.neuron.2012.12.029
更新日期：2013-01-23 00:00:00
abstract：:The dopaminergic D3 receptor (D3R) is emerging as an antagonist of sensitized behavior induced by addictive drugs such as cocaine. New work by Wang and coworkers in this issue of Neuron now identifies CaMKII as an important negative regulator of the D3R. CaMKII relieves the D3R-mediated inhibition on sensitized behavi...
journal_title：Neuron
pub_type： 评论,杂志文章
doi：10.1016/j.neuron.2009.01.025
更新日期：2009-02-12 00:00:00
abstract：:Synaptic activity induces changes in the number of dendritic spines. Here, we report a pathway of regulated endocytosis triggered by arcadlin, a protocadherin induced by electroconvulsive and other excitatory stimuli in hippocampal neurons. The homophilic binding of extracellular arcadlin domains activates TAO2beta, a...
journal_title：Neuron
pub_type： 杂志文章
doi：10.1016/j.neuron.2007.08.020
更新日期：2007-11-08 00:00:00
abstract：:The mechanisms that constrain memory formation are of special interest because they provide insights into the brain's memory management systems and potential avenues for correcting cognitive disorders. RNAi knockdown in the Drosophila mushroom body neurons (MBn) of a newly discovered memory suppressor gene, Solute Car...
journal_title：Neuron
pub_type： 杂志文章
doi：10.1016/j.neuron.2016.03.017
更新日期：2016-05-04 00:00:00
