RGS4-dependent attenuation of M4 autoreceptor function in striatal cholinergic interneurons following dopamine depletion.

Abstract:

:Parkinson disease is a neurodegenerative disorder whose symptoms are caused by the loss of dopaminergic neurons innervating the striatum. As striatal dopamine levels fall, striatal acetylcholine release rises, exacerbating motor symptoms. This adaptation is commonly attributed to the loss of interneuronal regulation by inhibitory D(2) dopamine receptors. Our results point to a completely different, new mechanism. After striatal dopamine depletion, D(2) dopamine receptor modulation of calcium (Ca(2+)) channels controlling vesicular acetylcholine release in interneurons was unchanged, but M(4) muscarinic autoreceptor coupling to these same channels was markedly attenuated. This adaptation was attributable to the upregulation of RGS4-an autoreceptor-associated, GTPase-accelerating protein. This specific signaling adaptation extended to a broader loss of autoreceptor control of interneuron spiking. These observations suggest that RGS4-dependent attenuation of interneuronal autoreceptor signaling is a major factor in the elevation of striatal acetylcholine release in Parkinson disease.

journal_name

Nat Neurosci

journal_title

Nature neuroscience

authors

Ding J,Guzman JN,Tkatch T,Chen S,Goldberg JA,Ebert PJ,Levitt P,Wilson CJ,Hamm HE,Surmeier DJ

doi

10.1038/nn1700

subject

Has Abstract

pub_date

2006-06-01 00:00:00

pages

832-42

issue

6

eissn

1097-6256

issn

1546-1726

pii

nn1700

journal_volume

9

pub_type

杂志文章
  • Functional connectivity between simple cells and complex cells in cat striate cortex.

    abstract::In the cat primary visual cortex, neurons are classified into the two main categories of simple cells and complex cells based on their response properties. According to the hierarchical model, complex receptive fields derive from convergent inputs of simple cells with similar orientation preferences. This model receiv...

    journal_title:Nature neuroscience

    pub_type: 杂志文章

    doi:10.1038/1609

    authors: Alonso JM,Martinez LM

    更新日期:1998-09-01 00:00:00

  • Reward expectation differentially modulates attentional behavior and activity in visual area V4.

    abstract::Neural activity in visual area V4 is enhanced when attention is directed into neuronal receptive fields. However, the source of this enhancement is unclear, as most physiological studies have manipulated attention by changing the absolute reward associated with a particular location as well as its value relative to ot...

    journal_title:Nature neuroscience

    pub_type: 杂志文章

    doi:10.1038/nn.4141

    authors: Baruni JK,Lau B,Salzman CD

    更新日期:2015-11-01 00:00:00

  • Functional and structural underpinnings of neuronal assembly formation in learning.

    abstract::Learning and memory are associated with the formation and modification of neuronal assemblies: populations of neurons that encode what has been learned and mediate memory retrieval upon recall. Functional studies of neuronal assemblies have progressed dramatically thanks to recent technological advances. Here we discu...

    journal_title:Nature neuroscience

    pub_type: 杂志文章,评审

    doi:10.1038/nn.4418

    authors: Holtmaat A,Caroni P

    更新日期:2016-12-01 00:00:00

  • Drug-induced GABA transporter currents enhance GABA release to induce opioid withdrawal behaviors.

    abstract::Neurotransmitter transporters can affect neuronal excitability indirectly via modulation of neurotransmitter concentrations or directly via transporter currents. A physiological or pathophysiological role for transporter currents has not been described. We found that GABA transporter 1 (GAT-1) cation currents directly...

    journal_title:Nature neuroscience

    pub_type: 杂志文章

    doi:10.1038/nn.2940

    authors: Bagley EE,Hacker J,Chefer VI,Mallet C,McNally GP,Chieng BC,Perroud J,Shippenberg TS,Christie MJ

    更新日期:2011-10-30 00:00:00

  • Retinotopic activity in V1 reflects the perceived and not the retinal size of an afterimage.

    abstract::An afterimage looks larger when one fixates on a distant than on a closer surface. We show that the retinotopic activity in the primary visual cortex (V1) associated with viewing an afterimage is modulated by perceived size, even when the size of the retinal image remains constant. This suggests that V1 has an importa...

    journal_title:Nature neuroscience

    pub_type: 杂志文章

    doi:10.1038/nn.3069

    authors: Sperandio I,Chouinard PA,Goodale MA

    更新日期:2012-03-11 00:00:00

  • A GABAergic nigrotectal pathway for coordination of drinking behavior.

    abstract::The contribution of basal ganglia outputs to consummatory behavior remains poorly understood. We recorded from the substantia nigra pars reticulata (SNR), the major basal ganglia output nucleus, during self-initiated drinking in mice. The firing rates of many lateral SNR neurons were time-locked to individual licks. T...

    journal_title:Nature neuroscience

    pub_type: 杂志文章

    doi:10.1038/nn.4285

    authors: Rossi MA,Li HE,Lu D,Kim IH,Bartholomew RA,Gaidis E,Barter JW,Kim N,Cai MT,Soderling SH,Yin HH

    更新日期:2016-05-01 00:00:00

  • The MEC-4 DEG/ENaC channel of Caenorhabditis elegans touch receptor neurons transduces mechanical signals.

    abstract::Transformation of mechanical energy into ionic currents is essential for touch, hearing and nociception. Although DEG/ENaC proteins are believed to form sensory mechanotransduction channels, the evidence for this role remains indirect. By recording from C. elegans touch receptor neurons in vivo, we found that external...

    journal_title:Nature neuroscience

    pub_type: 杂志文章

    doi:10.1038/nn1362

    authors: O'Hagan R,Chalfie M,Goodman MB

    更新日期:2005-01-01 00:00:00

  • Genome-wide association study implicates CHRNA2 in cannabis use disorder.

    abstract::Cannabis is the most frequently used illicit psychoactive substance worldwide; around one in ten users become dependent. The risk for cannabis use disorder (CUD) has a strong genetic component, with twin heritability estimates ranging from 51 to 70%. Here we performed a genome-wide association study of CUD in 2,387 ca...

    journal_title:Nature neuroscience

    pub_type: 杂志文章

    doi:10.1038/s41593-019-0416-1

    authors: Demontis D,Rajagopal VM,Thorgeirsson TE,Als TD,Grove J,Leppälä K,Gudbjartsson DF,Pallesen J,Hjorthøj C,Reginsson GW,Tyrfingsson T,Runarsdottir V,Qvist P,Christensen JH,Bybjerg-Grauholm J,Bækvad-Hansen M,Huckins LM,Stahl

    更新日期:2019-07-01 00:00:00

  • From neuroanatomy to behavior: central integration of peripheral signals regulating feeding behavior.

    abstract::Over the past two centuries, prevalent models of energy and glucose homeostasis have emerged from careful anatomical descriptions in tandem with an understanding of cellular physiology. More recent technological advances have culminated in the identification of peripheral and central factors that influence neural circ...

    journal_title:Nature neuroscience

    pub_type: 杂志文章,评审

    doi:10.1038/nn.3217

    authors: Williams KW,Elmquist JK

    更新日期:2012-10-01 00:00:00

  • The representation of economic value in the orbitofrontal cortex is invariant for changes of menu.

    abstract::Economic choice entails assigning values to the available options and is impaired by lesions to the orbitofrontal cortex (OFC). Recent results show that some neurons in the OFC encode the values that monkeys (Macaca mulatta) assign to different goods when they choose between them. A broad and fundamental question is h...

    journal_title:Nature neuroscience

    pub_type: 杂志文章

    doi:10.1038/nn2020

    authors: Padoa-Schioppa C,Assad JA

    更新日期:2008-01-01 00:00:00

  • Neural encoding of opposing strategy values in anterior and posterior cingulate cortex.

    abstract::Humans, and animals, often encounter ambiguous situations that require a decision on whether to take an offense or a defense strategy. Behavioral studies suggest that a strategy decision is frequently made before concrete options are evaluated. It remains enigmatic, however, how a strategy is determined without explor...

    journal_title:Nature neuroscience

    pub_type: 杂志文章

    doi:10.1038/nn.3999

    authors: Wan X,Cheng K,Tanaka K

    更新日期:2015-05-01 00:00:00

  • p75NTR-dependent, myelin-mediated axonal degeneration regulates neural connectivity in the adult brain.

    abstract::Axonal degeneration is important during development but has not been thought to function in the intact mature nervous system. Here, we provide evidence that degeneration of adult axons occurs in the intact rodent brain through a p75 neurotrophin receptor (p75NTR)- and myelin-dependent mechanism. Specifically, we show ...

    journal_title:Nature neuroscience

    pub_type: 杂志文章

    doi:10.1038/nn.2513

    authors: Park KJ,Grosso CA,Aubert I,Kaplan DR,Miller FD

    更新日期:2010-05-01 00:00:00

  • High frequency, synchronized bursting drives eye-specific segregation of retinogeniculate projections.

    abstract::Blockade of retinal waves prevents the segregation of retinogeniculate afferents into eye-specific layers in the visual thalamus. However, the key features of retinal waves that drive this refinement are controversial. Some manipulations of retinal waves lead to normal eye-specific segregation but others do not. By co...

    journal_title:Nature neuroscience

    pub_type: 杂志文章

    doi:10.1038/nn1376

    authors: Torborg CL,Hansen KA,Feller MB

    更新日期:2005-01-01 00:00:00

  • Exome sequencing in schizophrenia-affected parent-offspring trios reveals risk conferred by protein-coding de novo mutations.

    abstract::Protein-coding de novo mutations (DNMs) are significant risk factors in many neurodevelopmental disorders, whereas schizophrenia (SCZ) risk associated with DNMs has thus far been shown to be modest. We analyzed DNMs from 1,695 SCZ-affected trios and 1,077 published SCZ-affected trios to better understand the contribut...

    journal_title:Nature neuroscience

    pub_type: 杂志文章

    doi:10.1038/s41593-019-0564-3

    authors: Howrigan DP,Rose SA,Samocha KE,Fromer M,Cerrato F,Chen WJ,Churchhouse C,Chambert K,Chandler SD,Daly MJ,Dumont A,Genovese G,Hwu HG,Laird N,Kosmicki JA,Moran JL,Roe C,Singh T,Wang SH,Faraone SV,Glatt SJ,McCarroll

    更新日期:2020-02-01 00:00:00

  • Contribution of mGluR5 to pathophysiology in a mouse model of human chromosome 16p11.2 microdeletion.

    abstract::Human chromosome 16p11.2 microdeletion is the most common gene copy number variation in autism, but the synaptic pathophysiology caused by this mutation is largely unknown. Using a mouse with the same genetic deficiency, we found that metabotropic glutamate receptor 5 (mGluR5)-dependent synaptic plasticity and protein...

    journal_title:Nature neuroscience

    pub_type: 杂志文章

    doi:10.1038/nn.3911

    authors: Tian D,Stoppel LJ,Heynen AJ,Lindemann L,Jaeschke G,Mills AA,Bear MF

    更新日期:2015-02-01 00:00:00

  • Trajectory events across hippocampal place cells require previous experience.

    abstract::Replay of hippocampal place cell sequences has been proposed as a fundamental mechanism of learning and memory. However, the standard interpretation of replay has been challenged by reports that similar activity is observed before experience ('preplay'). By the preplay account, pre-existing temporal sequences are mapp...

    journal_title:Nature neuroscience

    pub_type: 杂志文章

    doi:10.1038/nn.4151

    authors: Silva D,Feng T,Foster DJ

    更新日期:2015-12-01 00:00:00

  • Continuous shifts in the active set of spinal interneurons during changes in locomotor speed.

    abstract::The classic 'size principle' of motor control describes how increasingly forceful movements arise by the recruitment of motoneurons of progressively larger size and force output into the active pool. We explored the activity of pools of spinal interneurons in larval zebrafish and found that increases in swimming speed...

    journal_title:Nature neuroscience

    pub_type: 杂志文章

    doi:10.1038/nn.2225

    authors: McLean DL,Masino MA,Koh IY,Lindquist WB,Fetcho JR

    更新日期:2008-12-01 00:00:00

  • Heterogeneity of CNS myeloid cells and their roles in neurodegeneration.

    abstract::The diseased brain hosts a heterogeneous population of myeloid cells, including parenchymal microglia, perivascular cells, meningeal macrophages and blood-borne monocytes. To date, the different types of brain myeloid cells have been discriminated solely on the basis of their localization, morphology and surface epito...

    journal_title:Nature neuroscience

    pub_type: 杂志文章,评审

    doi:10.1038/nn.2923

    authors: Prinz M,Priller J,Sisodia SS,Ransohoff RM

    更新日期:2011-09-27 00:00:00

  • Rapid redistribution of glutamate receptors contributes to long-term depression in hippocampal cultures.

    abstract::Synaptic strength can be altered by a variety of pre- or postsynaptic modifications. Here we test the hypothesis that long-term depression (LTD) involves a decrease in the number of glutamate receptors that are clustered at individual synapses in primary cultures of hippocampal neurons. Similar to a prominent form of ...

    journal_title:Nature neuroscience

    pub_type: 杂志文章

    doi:10.1038/8123

    authors: Carroll RC,Lissin DV,von Zastrow M,Nicoll RA,Malenka RC

    更新日期:1999-05-01 00:00:00

  • Unique functional properties of somatostatin-expressing GABAergic neurons in mouse barrel cortex.

    abstract::Neocortical GABAergic neurons have diverse molecular, structural and electrophysiological features, but the functional correlates of this diversity are largely unknown. We found unique membrane potential dynamics of somatostatin-expressing (SOM) neurons in layer 2/3 of the primary somatosensory barrel cortex of awake ...

    journal_title:Nature neuroscience

    pub_type: 杂志文章

    doi:10.1038/nn.3051

    authors: Gentet LJ,Kremer Y,Taniguchi H,Huang ZJ,Staiger JF,Petersen CC

    更新日期:2012-02-26 00:00:00

  • GluA1 phosphorylation at serine 831 in the lateral amygdala is required for fear renewal.

    abstract::Fear renewal, a widely pursued model of post-traumatic stress disorder and phobias, refers to the context-specific relapse of conditioned fear after extinction. However, its molecular mechanisms are largely unknown. We found that renewal-inducing stimuli, generally believed to be insufficient to induce synaptic plasti...

    journal_title:Nature neuroscience

    pub_type: 杂志文章

    doi:10.1038/nn.3491

    authors: Lee S,Song B,Kim J,Park K,Hong I,An B,Song S,Lee J,Park S,Kim J,Park D,Lee CJ,Kim K,Shin KS,Tsien RW,Choi S

    更新日期:2013-10-01 00:00:00

  • A hierarchy of intrinsic timescales across primate cortex.

    abstract::Specialization and hierarchy are organizing principles for primate cortex, yet there is little direct evidence for how cortical areas are specialized in the temporal domain. We measured timescales of intrinsic fluctuations in spiking activity across areas and found a hierarchical ordering, with sensory and prefrontal ...

    journal_title:Nature neuroscience

    pub_type: 杂志文章

    doi:10.1038/nn.3862

    authors: Murray JD,Bernacchia A,Freedman DJ,Romo R,Wallis JD,Cai X,Padoa-Schioppa C,Pasternak T,Seo H,Lee D,Wang XJ

    更新日期:2014-12-01 00:00:00

  • Cortical specialization for attended versus unattended working memory.

    abstract::Items held in working memory can be either attended or not, depending on their current behavioral relevance. It has been suggested that unattended contents might be solely retained in an activity-silent form. Instead, we demonstrate here that encoding unattended contents involves a division of labor. While visual cort...

    journal_title:Nature neuroscience

    pub_type: 杂志文章

    doi:10.1038/s41593-018-0094-4

    authors: Christophel TB,Iamshchinina P,Yan C,Allefeld C,Haynes JD

    更新日期:2018-04-01 00:00:00

  • Integration of diverse information in working memory within the frontal lobe.

    abstract::Ability to integrate diverse forms of information in current thought, or working memory, is essential for human reasoning and problem solving. We used functional imaging to identify brain regions preferentially involved in maintaining integrated versus unintegrated information in working memory. For equal amounts of v...

    journal_title:Nature neuroscience

    pub_type: 临床试验,杂志文章

    doi:10.1038/71156

    authors: Prabhakaran V,Narayanan K,Zhao Z,Gabrieli JD

    更新日期:2000-01-01 00:00:00

  • Phosphodiesterase 1C is dispensable for rapid response termination of olfactory sensory neurons.

    abstract::In the nose, odorants are detected on the cilia of olfactory sensory neurons (OSNs), where a cAMP-mediated signaling pathway transforms odor stimulation into electrical responses. Phosphodiesterase (PDE) activity in OSN cilia has long been thought to account for rapid response termination by degrading odor-induced cAM...

    journal_title:Nature neuroscience

    pub_type: 杂志文章

    doi:10.1038/nn.2289

    authors: Cygnar KD,Zhao H

    更新日期:2009-04-01 00:00:00

  • Octopamine fuels fighting flies.

    abstract::The neural basis of aggression is poorly understood. A study in this issue used genetic scalpels to dissect the circuitry of the fly brain and identified a small cluster of octopaminergic neurons that can make a fly fighting mad. ...

    journal_title:Nature neuroscience

    pub_type: 评论,杂志文章,评审

    doi:10.1038/nn0908-989

    authors: Potter CJ,Luo L

    更新日期:2008-09-01 00:00:00

  • Spike timing of dendrite-targeting bistratified cells during hippocampal network oscillations in vivo.

    abstract::Behavior-contingent network oscillations bring about transient, functionally coherent neuronal assemblies in the cerebral cortex, including the hippocampus. Inhibitory input on and close to the soma is believed to phase intrinsic oscillations and output of pyramidal cells, but the function of GABA release to pyramidal...

    journal_title:Nature neuroscience

    pub_type: 杂志文章

    doi:10.1038/nn1159

    authors: Klausberger T,Márton LF,Baude A,Roberts JD,Magill PJ,Somogyi P

    更新日期:2004-01-01 00:00:00

  • Conscious awareness, memory and the hippocampus.

    abstract::Declarative memory, the conscious recollection of past experiences, is known to involve the hippocampus. Now a study of amnesic patients shows that hippocampus-dependent learning can occur in the absence of conscious awareness. ...

    journal_title:Nature neuroscience

    pub_type: 评论,新闻

    doi:10.1038/12137

    authors: Eichenbaum H

    更新日期:1999-09-01 00:00:00

  • Extrasynaptic NMDARs oppose synaptic NMDARs by triggering CREB shut-off and cell death pathways.

    abstract::Here we report that synaptic and extrasynaptic NMDA (N-methyl-D-aspartate) receptors have opposite effects on CREB (cAMP response element binding protein) function, gene regulation and neuron survival. Calcium entry through synaptic NMDA receptors induced CREB activity and brain-derived neurotrophic factor (BDNF) gene...

    journal_title:Nature neuroscience

    pub_type: 杂志文章

    doi:10.1038/nn835

    authors: Hardingham GE,Fukunaga Y,Bading H

    更新日期:2002-05-01 00:00:00

  • Social signals of safety and risk confer utility and have asymmetric effects on observers' choices.

    abstract::Individuals' risk attitudes are known to guide choices about uncertain options. However, in the presence of others' decisions, these choices can be swayed and manifest as riskier or safer behavior than one would express alone. To test the mechanisms underlying effective social 'nudges' in human decision-making, we use...

    journal_title:Nature neuroscience

    pub_type: 杂志文章

    doi:10.1038/nn.4022

    authors: Chung D,Christopoulos GI,King-Casas B,Ball SB,Chiu PH

    更新日期:2015-06-01 00:00:00