Tandem-pore K+ channels mediate inhibition of orexin neurons by glucose.


:Glucose-inhibited neurons orchestrate behavior and metabolism according to body energy levels, but how glucose inhibits these cells is unknown. We studied glucose inhibition of orexin/hypocretin neurons, which promote wakefulness (their loss causes narcolepsy) and also regulate metabolism and reward. Here we demonstrate that their inhibition by glucose is mediated by ion channels not previously implicated in central or peripheral glucose sensing: tandem-pore K(+) (K(2P)) channels. Importantly, we show that this electrical mechanism is sufficiently sensitive to encode variations in glucose levels reflecting those occurring physiologically between normal meals. Moreover, we provide evidence that glucose acts at an extracellular site on orexin neurons, and this information is transmitted to the channels by an intracellular intermediary that is not ATP, Ca(2+), or glucose itself. These results reveal an unexpected energy-sensing pathway in neurons that regulate states of consciousness and energy balance.






Burdakov D,Jensen LT,Alexopoulos H,Williams RH,Fearon IM,O'Kelly I,Gerasimenko O,Fugger L,Verkhratsky A




Has Abstract


2006-06-01 00:00:00
















  • Neuroanatomical correlates of veridical and illusory recognition memory: evidence from positron emission tomography.

    abstract::Memory distortions and illusions have been thoroughly documented in psychological studies, but little is known about the neuroanatomical correlates of true and false memories. Vivid but illusory memories can be induced by asking people whether they recall or recognize words that were not previously presented, but are ...


    pub_type: 杂志文章


    authors: Schacter DL,Reiman E,Curran T,Yun LS,Bandy D,McDermott KB,Roediger HL 3rd

    更新日期:1996-08-01 00:00:00

  • A monoclonal antibody that defines rostrocaudal gradients in the mammalian nervous system.

    abstract::Spinal cord axons display a rostrocaudal, positional bias in their innervation of sympathetic ganglia and intercostal skeletal muscles. In an effort to examine the molecular basis of this positional specificity, we used the cyclophosphamide immunosuppression method to produce monoclonal antibodies that bind preferenti...


    pub_type: 杂志文章


    authors: Suzue T,Kaprielian Z,Patterson PH

    更新日期:1990-10-01 00:00:00

  • A Circuit for Integration of Head- and Visual-Motion Signals in Layer 6 of Mouse Primary Visual Cortex.

    abstract::To interpret visual-motion events, the underlying computation must involve internal reference to the motion status of the observer's head. We show here that layer 6 (L6) principal neurons in mouse primary visual cortex (V1) receive a diffuse, vestibular-mediated synaptic input that signals the angular velocity of hori...


    pub_type: 杂志文章


    authors: Vélez-Fort M,Bracey EF,Keshavarzi S,Rousseau CV,Cossell L,Lenzi SC,Strom M,Margrie TW

    更新日期:2018-04-04 00:00:00

  • New roles for ubiquitin in the assembly and function of neuronal circuits.

    abstract::A series of recent papers highlight a prominent role for ubiquitin in the formation and function of neural circuits. These new results focus attention on the molecular remodeling that occurs at various decision points in the life of growth cones and synapses. ...


    pub_type: 杂志文章,评审


    authors: Murphey RK,Godenschwege TA

    更新日期:2002-09-26 00:00:00

  • Learning How Neurons Fail Inside of Networks: Nonhuman Primates Provide Critical Data for Psychiatry.

    abstract::Advancing psychiatry requires understanding brain malfunction at a microscopic scale, where neurons and synapses operate under constraints imposed by behavior, cognition, and neural architecture. Nonhuman primates are unmatched in approximating the structural and computational environment of the human brain. ...


    pub_type: 杂志文章,评审


    authors: Heilbronner SR,Chafee MV

    更新日期:2019-04-03 00:00:00

  • TREM2 and Amyloid Beta: A Love-Hate Relationship.

    abstract::Mutations in TREM2 increase risk for late-onset AD. In this issue of Neuron, Zhao et al. (2018) show that TREM2 binds Aβ to enhance its clearance and Lee et al. (2018) demonstrate that human TREM2 expression in AD mice ameliorates Aβ-associated deficits. ...


    pub_type: 评论,杂志文章


    authors: Udeochu J,Sayed FA,Gan L

    更新日期:2018-03-07 00:00:00

  • A Cacna1a knockin migraine mouse model with increased susceptibility to cortical spreading depression.

    abstract::Migraine is a common, disabling, multifactorial, episodic neurovascular disorder of unknown etiology. Familial hemiplegic migraine type 1 (FHM-1) is a Mendelian subtype of migraine with aura that is caused by missense mutations in the CACNA1A gene that encodes the alpha(1) subunit of neuronal Ca(v)2.1 Ca(2+) channels....


    pub_type: 杂志文章


    authors: van den Maagdenberg AM,Pietrobon D,Pizzorusso T,Kaja S,Broos LA,Cesetti T,van de Ven RC,Tottene A,van der Kaa J,Plomp JJ,Frants RR,Ferrari MD

    更新日期:2004-03-04 00:00:00

  • Cognitive association formation in human memory revealed by spatiotemporal brain imaging.

    abstract::Cognitive theory posits association by juxtaposition or by fusion. We employed the measurement of event-related brain potentials (ERPs) to a concept fusion task in order to explore memory encoding of these two types of associations between word pairs, followed by a memory test for original pair order. Encoding process...


    pub_type: 临床试验,杂志文章


    authors: Kounios J,Smith RW,Yang W,Bachman P,D'Esposito M

    更新日期:2001-01-01 00:00:00

  • Anterior regions of monkey parietal cortex process visual 3D shape.

    abstract::The intraparietal cortex is involved in the control of visually guided actions, like reach-to-grasp movements, which require extracting the 3D shape and position of objects from 2D retinal images. Using fMRI in behaving monkeys, we investigated the role of the intraparietal cortex in processing stereoscopic informatio...


    pub_type: 杂志文章


    authors: Durand JB,Nelissen K,Joly O,Wardak C,Todd JT,Norman JF,Janssen P,Vanduffel W,Orban GA

    更新日期:2007-08-02 00:00:00

  • Dopamine Does Double Duty in Motivating Cognitive Effort.

    abstract::Cognitive control is subjectively costly, suggesting that engagement is modulated in relationship to incentive state. Dopamine appears to play key roles. In particular, dopamine may mediate cognitive effort by two broad classes of functions: (1) modulating the functional parameters of working memory circuits subservin...


    pub_type: 杂志文章,评审


    authors: Westbrook A,Braver TS

    更新日期:2016-02-17 00:00:00

  • Curbing the excesses of youth: molecular insights into axonal pruning.

    abstract::The embryonic nervous system is refined over the course of development as a result of the twin processes of naturally occurring cell death and selective axon pruning. Recent studies provide new insights into the molecular events that underlie axon pruning and underscore the diversity of refinement processes employed b...


    pub_type: 评论,杂志文章,评审


    authors: Kantor DB,Kolodkin AL

    更新日期:2003-06-19 00:00:00

  • The Hitchhiker's Guide to a Neuroscience Career.

    abstract::Neuroscience is an exciting and vibrant field, but building an academic career is not always easy. What are critical success indicators? Which tools help talented young neuroscientists conquer the challenges? In this NeuroView, we discuss instruments and steps that can help people progress through the ranks. ...


    pub_type: 杂志文章


    authors: Joëls M,Hoogenraad CC,Poirazi P,Di Luca M

    更新日期:2015-05-06 00:00:00

  • The nematode degenerin UNC-105 forms ion channels that are activated by degeneration- or hypercontraction-causing mutations.

    abstract::Nematode degenerins have been implicated in touch sensitivity and other forms of mechanosensation. Certain mutations in several degenerin genes cause the swelling, vacuolation, and death of neurons, and other mutations in the muscle degenerin gene unc-105 cause hypercontraction. Here, we confirm that unc-105 encodes a...


    pub_type: 杂志文章


    authors: García-Añoveros J,García JA,Liu JD,Corey DP

    更新日期:1998-06-01 00:00:00

  • Encoding of Articulatory Kinematic Trajectories in Human Speech Sensorimotor Cortex.

    abstract::When speaking, we dynamically coordinate movements of our jaw, tongue, lips, and larynx. To investigate the neural mechanisms underlying articulation, we used direct cortical recordings from human sensorimotor cortex while participants spoke natural sentences that included sounds spanning the entire English phonetic i...


    pub_type: 杂志文章


    authors: Chartier J,Anumanchipalli GK,Johnson K,Chang EF

    更新日期:2018-06-06 00:00:00

  • Amyloid Beta Peptides Block New Synapse Assembly by Nogo Receptor-Mediated Inhibition of T-Type Calcium Channels.

    abstract::Compelling evidence links amyloid beta (Aβ) peptide accumulation in the brains of Alzheimer's disease (AD) patients with the emergence of learning and memory deficits, yet a clear understanding of the events that drive this synaptic pathology are lacking. We present evidence that neurons exposed to Aβ are unable to fo...


    pub_type: 杂志文章


    authors: Zhao Y,Sivaji S,Chiang MC,Ali H,Zukowski M,Ali S,Kennedy B,Sklyar A,Cheng A,Guo Z,Reed AK,Kodali R,Borowski J,Frost G,Beukema P,Wills ZP

    更新日期:2017-10-11 00:00:00

  • Dynactin is necessary for synapse stabilization.

    abstract::We present evidence that synapse retraction occurs during normal synaptic growth at the Drosophila neuromuscular junction (NMJ). An RNAi-based screen to identify the molecular mechanisms that regulate synapse retraction identified Arp-1/centractin, a subunit of the dynactin complex. Arp-1 dsRNA enhances synapse retrac...


    pub_type: 杂志文章


    authors: Eaton BA,Fetter RD,Davis GW

    更新日期:2002-05-30 00:00:00

  • G protein-coupled receptor kinase function is essential for chemosensation in C. elegans.

    abstract::G protein-coupled receptors (GPCRs) mediate diverse signaling processes, including olfaction. G protein-coupled receptor kinases (GRKs) are important regulators of G protein signal transduction that specifically phosphorylate activated GPCRs to terminate signaling. Despite previously described roles for GRKs in GPCR s...


    pub_type: 杂志文章


    authors: Fukuto HS,Ferkey DM,Apicella AJ,Lans H,Sharmeen T,Chen W,Lefkowitz RJ,Jansen G,Schafer WR,Hart AC

    更新日期:2004-05-27 00:00:00

  • Neuropilin-2 is required in vivo for selective axon guidance responses to secreted semaphorins.

    abstract::Neuropilins are receptors for class 3 secreted semaphorins, most of which can function as potent repulsive axon guidance cues. We have generated mice with a targeted deletion in the neuropilin-2 (Npn-2) locus. Many Npn-2 mutant mice are viable into adulthood, allowing us to assess the role of Npn-2 in axon guidance ev...


    pub_type: 杂志文章


    authors: Giger RJ,Cloutier JF,Sahay A,Prinjha RK,Levengood DV,Moore SE,Pickering S,Simmons D,Rastan S,Walsh FS,Kolodkin AL,Ginty DD,Geppert M

    更新日期:2000-01-01 00:00:00

  • Peri-Synaptic Glia Recycles Brain-Derived Neurotrophic Factor for LTP Stabilization and Memory Retention.

    abstract::Glial cells respond to neuronal activation and release neuroactive molecules (termed "gliotransmitters") that can affect synaptic activity and modulate plasticity. In this study, we used molecular genetic tools, ultra-structural microscopy, and electrophysiology to assess the role of brain-derived neurotrophic factor ...


    pub_type: 杂志文章


    authors: Vignoli B,Battistini G,Melani R,Blum R,Santi S,Berardi N,Canossa M

    更新日期:2016-11-23 00:00:00

  • Injury-Induced Inhibition of Bystander Neurons Requires dSarm and Signaling from Glia.

    abstract::Nervous system injury and disease have broad effects on the functional connectivity of the nervous system, but how injury signals are spread across neural circuits remains unclear. We explored how axotomy changes the physiology of severed axons and adjacent uninjured "bystander" neurons in a simple in vivo nerve prepa...


    pub_type: 杂志文章


    authors: Hsu JM,Kang Y,Corty MM,Mathieson D,Peters OM,Freeman MR

    更新日期:2020-12-02 00:00:00

  • Network Dynamics Mediate Circadian Clock Plasticity.

    abstract::A circadian clock governs most aspects of mammalian behavior. Although its properties are in part genetically determined, altered light-dark environment can change circadian period length through a mechanism requiring de novo DNA methylation. We show here that this mechanism is mediated not via cell-autonomous clock p...


    pub_type: 杂志文章


    authors: Azzi A,Evans JA,Leise T,Myung J,Takumi T,Davidson AJ,Brown SA

    更新日期:2017-01-18 00:00:00

  • Is top-down control from prefrontal cortex necessary for visual categorization?

    abstract::The brain mechanisms underlying visual object categorization remain unclear. In this issue of Neuron, Minamimoto and colleagues introduce a novel task that associates each category with a different incentive value, and they demonstrate that it can be learned within a single session even after ablation of the lateral p...


    pub_type: 评论,杂志文章


    authors: Buckley MJ,Sigala N

    更新日期:2010-05-27 00:00:00

  • Seeing Anew through Interneuron Transplantation.

    abstract::Critical periods are developmental time windows during which neuronal connections are shaped by experience. In this issue of Neuron, Davis et al. (2015) show that transplantation of embryonic inhibitory interneurons can reactivate critical period plasticity and reverse amblyopia in the visual cortex of adult mice. ...


    pub_type: 评论,杂志文章


    authors: Levine JN,Gu Y,Cang J

    更新日期:2015-05-20 00:00:00

  • Locus Coeruleus, Noradrenaline, and Behavior: Network Effect, Network Effects?

    abstract::How does the noradrenergic nucleus locus coeruleus act on target networks to regulate behavior? In this issue of Neuron, Zerbi et al. (2019) combine functional neuroimaging and pharmacogenetics in mice to tackle that question, uncovering a network action underlying stress. And providing insight for cognition? ...


    pub_type: 评论,杂志文章


    authors: Bouret S

    更新日期:2019-08-21 00:00:00

  • In vivo release of dopa and dopamine from genetically engineered cells grafted to the denervated rat striatum.

    abstract::Fibroblastic 3T3 and endocrine RIN cells were genetically modified by infection with a recombinant retrovirus encoding the form I of human tyrosine hydroxylase (TH) and selection in tyrosine-free medium. These cells were grafted to rats unilaterally lesioned with 6-hydroxy-dopamine. Both cell types survived implantati...


    pub_type: 杂志文章


    authors: Horellou P,Brundin P,Kalén P,Mallet J,Björklund A

    更新日期:1990-10-01 00:00:00

  • TMC Proteins Modulate Egg Laying and Membrane Excitability through a Background Leak Conductance in C. elegans.

    abstract::Membrane excitability is a fundamentally important feature for all excitable cells including both neurons and muscle cells. However, the background depolarizing conductances in excitable cells, especially in muscle cells, are not well characterized. Although mutations in transmembrane channel-like (TMC) proteins TMC1 ...


    pub_type: 杂志文章


    authors: Yue X,Zhao J,Li X,Fan Y,Duan D,Zhang X,Zou W,Sheng Y,Zhang T,Yang Q,Luo J,Duan S,Xiao R,Kang L

    更新日期:2018-02-07 00:00:00

  • Serines 13 and 16 are critical determinants of full-length human mutant huntingtin induced disease pathogenesis in HD mice.

    abstract::The N-terminal 17 amino acids of huntingtin (NT17) can be phosphorylated on serines 13 and 16; however, the significance of these modifications in Huntington's disease pathogenesis remains unknown. In this study, we developed BAC transgenic mice expressing full-length mutant huntingtin (fl-mhtt) with serines 13 and 16...


    pub_type: 杂志文章


    authors: Gu X,Greiner ER,Mishra R,Kodali R,Osmand A,Finkbeiner S,Steffan JS,Thompson LM,Wetzel R,Yang XW

    更新日期:2009-12-24 00:00:00

  • Sensory Cortical Control of a Visually Induced Arrest Behavior via Corticotectal Projections.

    abstract::Innate defense behaviors (IDBs) evoked by threatening sensory stimuli are essential for animal survival. Although subcortical circuits are implicated in IDBs, it remains largely unclear whether sensory cortex modulates IDBs and what the underlying neural pathways are. Here, we show that optogenetic silencing of cortic...


    pub_type: 杂志文章


    authors: Liang F,Xiong XR,Zingg B,Ji XY,Zhang LI,Tao HW

    更新日期:2015-05-06 00:00:00

  • Molecular basis for K(ATP) assembly: transmembrane interactions mediate association of a K+ channel with an ABC transporter.

    abstract::K(ATP) channels are large heteromultimeric complexes containing four subunits from the inwardly rectifying K+ channel family (Kir6.2) and four regulatory sulphonylurea receptor subunits from the ATP-binding cassette (ABC) transporter family (SUR1 and SUR2A/B). The molecular basis for interactions between these two unr...


    pub_type: 杂志文章


    authors: Schwappach B,Zerangue N,Jan YN,Jan LY

    更新日期:2000-04-01 00:00:00

  • Localization of the alpha 1 and alpha 2 subunits of the dihydropyridine receptor and ankyrin in skeletal muscle triads.

    abstract::We have studied the subcellular distribution of the alpha 1 and alpha 2 subunits of the dihydropyridine (DHP) receptor and ankyrin in rat skeletal muscle with immunofluorescence and immunogold labeling techniques. All three proteins were concentrated in the triad junction formed between the T-tubules and sarcoplasmic ...


    pub_type: 杂志文章


    authors: Flucher BE,Morton ME,Froehner SC,Daniels MP

    更新日期:1990-09-01 00:00:00