Research Topics
| David LindenSummaryAffiliation: Johns Hopkins University Country: USA Publications
Research Grants
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Detail Information
Publications
Characterizing the conductance underlying depolarization-induced slow current in cerebellar Purkinje cellsYu Shin Kim
Department of Neuroscience, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA
J Neurophysiol 109:1174-81. 2013..Thus, while the DISC conductance is Ca triggered, Na permeant, and Ca impermeant, suggesting a role for TRPM4 and TRPM5, these ion channels are not absolutely required for DISC...- A late phase of LTD in cultured cerebellar Purkinje cells requires persistent dynamin-mediated endocytosisDavid J Linden
The Solomon H Snyder Dept of Neuroscience, The Johns Hopkins Univ School of Medicine, 725 N Wolfe St, Baltimore, MD 21205, USA
J Neurophysiol 107:448-54. 2012.... 
Activation of presynaptic cAMP-dependent protein kinase is required for induction of cerebellar long-term potentiationD J Linden
Department of Neuroscience, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA
J Neurosci 19:10221-7. 1999....- Neuroscience. From molecules to memory in the cerebellumDavid J Linden
Department of Neuroscience, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA
Science 301:1682-5. 2003..suggesting that long-term depression in Purkinje cells mediated by protein kinase C signaling is responsible for motor memory in a task called associative eyelid conditioning... - The expression of cerebellar LTD in culture is not associated with changes in AMPA-receptor kinetics, agonist affinity, or unitary conductanceD J Linden
Department of Neuroscience, Johns Hopkins University School of Medicine, 725 North Wolfe Street, Baltimore, MD 21205, USA
Proc Natl Acad Sci U S A 98:14066-71. 2001..These results suggest that cerebellar LTD may be expressed solely as a reduction in the number of functional AMPA receptors in the postsynaptic density [Wang, Y.-T. & Linden, D. J. (2000) Neuron 25, 635-664]... - Requirement of AMPA receptor GluR2 phosphorylation for cerebellar long-term depressionHee Jung Chung
Howard Hughes Medical Institute, Johns Hopkins University School of Medicine, 725 North Wolfe Street, Baltimore, MD 21205 USA
Science 300:1751-5. 2003..In contrast, transfection with a point mutant that mimicked phosphorylation at Ser880 occluded subsequent LTD. Thus, PKC phosphorylation of GluR2 Ser880 is a critical event in the induction of cerebellar LTD... - N-ethylmaleimide-sensitive factor is required for the synaptic incorporation and removal of AMPA receptors during cerebellar long-term depressionJordan P Steinberg
Howard Hughes Medical Institute and Department of Neuroscience, The Johns Hopkins University School of Medicine, 725 North Wolfe Street, Baltimore, MD 21205, USA
Proc Natl Acad Sci U S A 101:18212-6. 2004..These findings demonstrate that interaction of AMPA receptors with N-ethylmaleimide-sensitive factor plays a critical role in incorporation of AMPA receptors into synapses and for their subsequent removal during cerebellar LTD... - Glutamate release during LTD at cerebellar climbing fiber-Purkinje cell synapsesYing Shen
Department of Neuroscience, Johns Hopkins University School of Medicine, 725 N. Wolfe Street, Baltimore, Maryland 21205, USA
Nat Neurosci 5:725-6. 2002..Here we report that LTD at the climbing fiber-Purkinje cell synapse in rat cerebellum was not associated with changes in a synaptic cleft glutamate transient, indicating that this type of LTD is most likely expressed postsynaptically... - Elongation factor 2 and fragile X mental retardation protein control the dynamic translation of Arc/Arg3.1 essential for mGluR-LTDSungjin Park
Department of Neuroscience, Johns Hopkins University School of Medicine, Baltimore, MD 20205, USA
Neuron 59:70-83. 2008..1. We propose a model in which eEF2K-eEF2 and FMRP coordinately control the dynamic translation of Arc/Arg3.1 mRNA in dendrites that is critical for synapse-specific LTD... - The glutamate receptor-interacting protein family of GluR2-binding proteins is required for long-term synaptic depression expression in cerebellar Purkinje cellsKogo Takamiya
Department of Neurosurgery, The Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA
J Neurosci 28:5752-5. 2008..These results indicate that the GRIP family comprises an essential molecular component for cerebellar LTD... - Targeted in vivo mutations of the AMPA receptor subunit GluR2 and its interacting protein PICK1 eliminate cerebellar long-term depressionJordan P Steinberg
Howard Hughes Medical Institute, Johns Hopkins School of Medicine, Baltimore, Maryland 21205, USA
Neuron 49:845-60. 2006..These results demonstrate that PICK1-GluR2 PDZ-based interactions and GluR2 phosphorylation are required for LTD expression in the cerebellum... - Activation of the TRPC1 cation channel by metabotropic glutamate receptor mGluR1Sang Jeong Kim
Department of Neuroscience, Johns Hopkins University School of Medicine, 725 N Wolfe Street, Baltimore, Maryland 21205, USA
Nature 426:285-91. 2003..Furthermore, co-expression of mGluR1 and TRPC1 in a heterologous system reconstituted a mGluR1-evoked conductance that closely resembles the slow EPSC in Purkinje cells... - SRF binding to SRE 6.9 in the Arc promoter is essential for LTD in cultured Purkinje cellsConstance Smith-Hicks
Solomon H Snyder Department of Neuroscience, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA
Nat Neurosci 13:1082-9. 2010..Co-transfection of wild-type Arc and SRF engineered to bind mutated SRE 6.9 restored late-phase LTD in Arc-/-, SRE 6.9 mutant BAC cells. Thus, SRF binding to SRE 6.9 in the Arc promoter is required for the late phase of cerebellar LTD... - Narp regulates homeostatic scaling of excitatory synapses on parvalbumin-expressing interneuronsMichael C Chang
The Solomon H Snyder Department of Neuroscience, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA
Nat Neurosci 13:1090-7. 2010..We propose that Narp recruits AMPARs at excitatory synapses onto PV-INs to rebalance network excitation/inhibition dynamics following episodes of increased circuit activity... - An NMDA receptor/nitric oxide cascade is involved in cerebellar LTD but is not localized to the parallel fiber terminalJung Hoon Shin
Department of Neuroscience, The Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA
J Neurophysiol 94:4281-9. 2005..These results are consistent with the hypothesis that an NMDA receptor/NO cascade involved in cerebellar LTD is localized to interneurons rather than parallel fibers... - Dendritic glutamate release produces autocrine activation of mGluR1 in cerebellar Purkinje cellsJung Hoon Shin
Department of Neuroscience, The Johns Hopkins University School of Medicine, 725 North Wolfe Street, 916 Hunterian Building, Baltimore, MD 21205, USA
Proc Natl Acad Sci U S A 105:746-50. 2008..These data suggest that Ca2+-dependent postsynaptic fusion of glutamate-loaded vesicles evokes a slow inward current produced by activation of postsynaptic mGluR1, thereby constituting a useful form of feedback regulation... - mGluR1/5-dependent long-term depression requires the regulated ectodomain cleavage of neuronal pentraxin NPR by TACERichard W Cho
Department of Neuroscience, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA
Neuron 57:858-71. 2008..These observations suggest that cleaved NPR functions to "capture" AMPAR for endocytosis and reveal a bifunctional role of NPs in both synapse strengthening and weakening... - Long-term depression at the mossy fiber-deep cerebellar nucleus synapseWei Zhang
Department of Neuroscience, The Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA
J Neurosci 26:6935-44. 2006..Unlike mGluR/translation-dependent LTD in other brain regions, this form of LTD requires mGluR1 and is mGluR5 independent... - Dopamine signaling is required for depolarization-induced slow current in cerebellar Purkinje cellsYu Shin Kim
Department of Neuroscience, The Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA
J Neurosci 29:8530-8. 2009..Together, these results suggest that strong Purkinje cell depolarization produces Ca-dependent release of vesicular postsynaptic dopamine that then excites Purkinje cells in an autocrine manner... - Neuromodulation at single presynaptic boutons of cerebellar parallel fibers is determined by bouton size and basal action potential-evoked Ca transient amplitudeWei Zhang
The Solomon H Snyder Department of Neuroscience, The Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA
J Neurosci 29:15586-94. 2009..These results suggest that boutons within brief segment of a single parallel fiber axon can have different sensitivities toward neuromodulators and may have different capacities for both short-term and long-term plasticities... - Axonal motility and its modulation by activity are branch-type specific in the intact adult cerebellumHiroshi Nishiyama
Department of Neuroscience, The Johns Hopkins University School of Medicine, 725 N Wolfe Street, Baltimore, MD 21205, USA
Neuron 56:472-87. 2007..Furthermore, dynamic changes in transverse branch length were almost completely suppressed by pharmacological stimulation of olivary firing... - Double dissociation between long-term depression and dendritic spine morphology in cerebellar Purkinje cellsAndrei D Sdrulla
Department of Neuroscience, Johns Hopkins University School of Medicine, 725 N Wolfe Street, 916 Hunterian Building, Baltimore, Maryland 21205, USA
Nat Neurosci 10:546-8. 2007..Conversely, a manipulation that evoked persistent dendritic spine retraction did not alter parallel fiber-evoked excitatory postsynaptic currents... - The other side of the engram: experience-driven changes in neuronal intrinsic excitabilityWei Zhang
Department of Neuroscience, The Johns Hopkins University School of Medicine, 725 North Wolfe Street, Baltimore, Maryland 21205, USA
Nat Rev Neurosci 4:885-900. 2003 - Cytosolic phospholipase A(2) alpha mediates electrophysiologic responses of hippocampal pyramidal neurons to neurotoxic NMDA treatmentYing Shen
Department of Neuroscience, Department of Anesthesiology and Critical Care Medicine, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA
Proc Natl Acad Sci U S A 104:6078-83. 2007..These results indicate that cPLA(2)alpha activity is required for development of aberrant electrophysiologic events triggered by NMDA receptor activation, in part through attenuation of K-channel function... - Differential maturation of climbing fiber innervation in cerebellar vermisHiroshi Nishiyama
Department of Neuroscience, The Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA
J Neurosci 24:3926-32. 2004..These findings suggest that the subdivisions of the cerebellar cortex produced by folding may create functionally distinct entities... - Dynamic imaging of cerebellar Purkinje cells reveals a population of filopodia which cross-link dendrites during early postnatal developmentAndrei D Sdrulla
Department of Neuroscience, The Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA
Cerebellum 5:105-15. 2006..While the functions of these novel structures are unknown it is attractive to speculate that they play an instructive role in Purkinje cell dendritic development... - Long-term potentiation of neuronal glutamate transportersYing Shen
Department of Neuroscience, The Johns Hopkins University School of Medicine, 725 North Wolfe Street, Baltimore, Maryland 21205, USA
Neuron 46:715-22. 2005.... - SRF mediates activity-induced gene expression and synaptic plasticity but not neuronal viabilityNarendrakumar Ramanan
Department of Neuroscience, 725 North Wolfe Street, Preclinical Teaching Building Room 1015, The Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA
Nat Neurosci 8:759-67. 2005..These findings indicate that the transcriptional events underlying neuronal survival and plasticity are dissociable and that SRF plays a prominent role in use-dependent modification of synaptic strength in the adult brain... - Phosphorylation of RIM1alpha by PKA triggers presynaptic long-term potentiation at cerebellar parallel fiber synapsesGYORGY LONART
Center for Basic Neuroscience, Department of Molecular Genetics and Howard Hughes Medical Institute, UT Southwestern Medical Center, 6000 Harry Hines Boulevard, Dallas, TX 75390, USA
Cell 115:49-60. 2003..Our findings suggest that PKA-mediated phosphorylation of the active zone protein RIM1alpha at a single N-terminal site induces presynaptic LTP... - Cerebellar long-term synaptic depression requires PKC-mediated activation of CPI-17, a myosin/moesin phosphatase inhibitorMasumi Eto
Center for Cell Signaling, University of Virginia School of Medicine, Charlottesville, VA 22908, USA
Neuron 36:1145-58. 2002..Thus, a biochemical circuit that involves PKC-mediated activation of CPI-17 modulates the distinct physiological processes of vascular contractility and cerebellar LTD... - Mechanisms underlying cerebellar motor deficits due to mGluR1-autoantibodiesMichiel Coesmans
Department of Neuroscience, Erasmus MC, Rotterdam, The Netherlands
Ann Neurol 53:325-36. 2003..We conclude that autoantibodies against mGluR1 can cause cerebellar motor coordination deficits caused by a combination of rapid effects on both acute and plastic responses of Purkinje cells and chronic degenerative effects... - Long-term depression of mGluR1 signalingYunju Jin
Department of Physiology, Seoul National University College of Medicine and Neuroscience Research Institute Medical Research Center, Korea
Neuron 55:277-87. 2007..Thus, different patterns of neural activity can evoke LTD of either fast ionotropic or slow mGluR1-mediated synaptic signaling... - A unique PDZ ligand in PKCalpha confers induction of cerebellar long-term synaptic depressionMichael Leitges
, Feodor-Lynen-Str. 7, 30625 Hannover, Germany
Neuron 44:585-94. 2004..When this motif is mutated, PKCalpha no longer supports LTD. Conversely, when this PDZ ligand is inserted in a nonpermissive isoform, PKCgamma, it confers the capacity for LTD induction... - Transient upregulation of postsynaptic IP3-gated Ca release underlies short-term potentiation of metabotropic glutamate receptor 1 signaling in cerebellar Purkinje cellsSang Jeong Kim
Department of Physiology, Seoul National University College of Medicine, Seoul 110 799, Korea
J Neurosci 28:4350-5. 2008..These data suggest that transient upregulation of postsynaptic IP(3)-gated Ca signaling constitutes a novel form of short-term synaptic plasticity... - Ubiquitous plasticity and memory storageSang Jeong Kim
Department of Physiology, Seoul National University College of Medicine, 110 799 Seoul, Korea
Neuron 56:582-92. 2007.... - Long-term depression of climbing fiber-evoked calcium transients in Purkinje cell dendritesJohn T Weber
Department of Neuroscience, Erasmus MC, 3000 DR, Rotterdam, The Netherlands
Proc Natl Acad Sci U S A 100:2878-83. 2003....
Research Grants
- Use-dependent intrinsic plasticity in the cerebellumDavid Linden; Fiscal Year: 2009..Because these cellular and molecular processes are not only involved in memory storage, this work has implications for other brain diseases as well, including epilepsy and addiction. ..
- CELLULAR SUBSTRATES OF CEREBELLAR INFORMATION STORAGEDavid Linden; Fiscal Year: 2007..In addition, they have potential clinical relevance for both cerebellar motor disorders and disorders of learning and memory generally...
- NEURONAL INFORMATION STORAGE IN CEREBELLAR DEEP NUCLEIDavid Linden; Fiscal Year: 2004..In addition, they have potential clinical relevance for both cerebellar motor disorders and disorders of learning and memory generally. ..
- LONG TERM POTENTIATION AND DEPRESSION IN THE CEREBELLUMDavid Linden; Fiscal Year: 2002..In addition, these investigations have potential clinical relevance not only for cerebellar motor disorders, but also for disorders of learning and memory generally. ..
- Use-dependent intrinsic plasticity in the cerebellumDavid J Linden; Fiscal Year: 2010..Because these cellular and molecular processes are not only involved in memory storage, this work has implications for other brain diseases as well, including epilepsy and addiction. ..