Plasticity of neuronal receptors

Klein, William L.; Sullivan, John A.; Skorupa, Annette F.; Aguilar, José S.

doi:10.1096/fasebj.3.10.2546848

Cited by 64 publications

(33 citation statements)

References 37 publications

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“…Plasticity of neurotransmitter receptor number or distribution is a key component of the compensatory neuronal response to denervation and changes in afferent activity (Klein et al, 1989). Although classically associated with the peripheral nervous system (Lømo and Rosenthal, 1972;Frank et al, 1975), receptor plasticity of this kind has also been demonstrated in the CNS.…”

Section: Abstract: Excitatory Amino Acid Receptors; Immunocytochemismentioning

confidence: 99%

Differential Subcellular Regulation of NMDAR1 Protein and mRNA in Dendrites of Dentate Gyrus Granule Cells after Perforant Path Transection

Gazzaley¹,

Benson²,

Huntley³

et al. 1997

J. Neurosci.

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Unilateral transection of the excitatory perforant path results in the acute deafferentation of a segregated zone on the distal dendrites of hippocampal dentate gyrus granule cells (i.e., outer molecular layer), followed by sprouting, reactive synaptogenesis, and a return of physiological and behavioral function. To investigate cellular mechanisms underlying NMDA receptor plasticity in response to such extensive synaptic reorganization, we quantitatively evaluated changes in intensity levels of NMDAR1 immunofluorescence and NMDAR1 mRNA hybridization within subcellular compartments of dentate gyrus granule cells 2, 5, and 9 d after perforant path lesions. There were no significant changes in either measure at 2 d postlesion. However, at 5 and 9 d postlesion, during the period of axonal sprouting and synaptogenesis, there was an increase in NMDAR1 immunolabeling that was restricted to the dendritic segments of the denervated outer molecular layer and the granule cell somata. In contrast, NMDAR1 mRNA levels at 5 and 9 d postlesion increased throughout the full extent of the molecular layer, including both denervated and nondenervated segments of granule cell dendrites. These findings reveal that NMDAR1 mRNA is one of a limited population of mRNAs that is transported into dendrites and further suggest that in response to terminal proliferation and sprouting, increased mRNA transport occurs throughout the full dendritic extent, whereas increased local protein synthesis is restricted to denervated regions of the dendrites whose afferent activity is perturbed. These results begin to elucidate the dynamic postsynaptic subcellular regulation of receptor subunits associated with synaptic plasticity after denervation.

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Section: Abstract: Excitatory Amino Acid Receptors; Immunocytochemismentioning

confidence: 99%

Differential Subcellular Regulation of NMDAR1 Protein and mRNA in Dendrites of Dentate Gyrus Granule Cells after Perforant Path Transection

Gazzaley¹,

Benson²,

Huntley³

et al. 1997

J. Neurosci.

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“…In addition to developmental changes of NMDA receptor subunit expression in culture, the adaptive changes in the number and/or the function of receptors following prolonged treatments with neurotransmitter (Klein et al, 1989;Hadcock and Malbon, 1991) were also reported for the NMDA receptor. In fact, treatment of cultured cerebellar granule cells at 5 days in vitro (DIV5) with 100 ,iM NMDA for 24 h evoked a pronounced decrease in NMDA-stimulated 45Ca2~fluxes accompanied by a reduction in NR 1, NR2A, and NR2B subunit mRNA levels and NR1 subunit protein (Resink et al, 1996).…”

mentioning

confidence: 99%

Up‐Regulation of NR2B Subunit of NMDA Receptors in Cerebellar Granule Neurons by Ca²⁺/Calmodulin Kinase Inhibitor KN93

Corsi¹,

Li²,

Krueger³

et al. 1998

Journal of Neurochemistry

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Abstract:Recordings of NMDA-activated currents from cerebellar granule neurons in culture revealed a developmental increase in current density accompanied by a slight decrease of the half-maximal effective concentration. At the same time, a decrease of NMDA receptors comprising NR2B subunits was demonstrated by the reduction in the antagonism of NMDA currents by ifenprodil. Ifenprodil antagonism increased after treatment for 24 h with KN93-and KN62-selective inhibitors of the Ca2~/calmodulin-dependentprotein kinases (CaM kinases), indicating a selective increase of receptor containing NR2B subunit. This increase was observed at all ages tested: 4 days in vitro (DIV4), DIV6, and DIV13. Western blot analysis with specific NMDA receptor antibodies performed at DIV6 confirmed the electrophysiological data. At this age, the negative control KN92 was ineffective. The increasing ifenprodil antagonism after KN93 treatment was proportionally greater in cells at DIV13 than at DIV4. Treatment with NMDA (100~tM) of cerebellar cultures for 24 h produced a decrease in the NMDA-induced current density by almost 50% at all ages tested. Ifenprodil antagonism, however, was unchanged. We propose that the expression of NR2B subunits in cerebellar granule cells is selectively stimulated by the inhibition of CaM kinases.

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“…Regulation of neurotransmitter signal transduction at the level of the synaptic receptor is a potentially important mechanism of synaptic plasticity. A substantial body of evidence now suggests that phosphorylation events regulate the functions of both G-protein<oupled receptors and ligand-gated ion channel receptors (reviewed by Sibley et al, 1987;Klein et al, 1989;Huganir and Greengard, 1990). The functional consequences of G-protein<oupled receptor phosphorylation have been extensively studied using the &adrenergic receptor (&AR)…”

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confidence: 99%

The G-protein-coupled receptor kinases beta ARK1 and beta ARK2 are widely distributed at synapses in rat brain

et al. 1992

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The beta-adrenergic receptor kinase (beta ARK) phosphorylates the agonist-occupied beta-adrenergic receptor to promote rapid receptor uncoupling from Gs, thereby attenuating adenylyl cyclase activity. Beta ARK-mediated receptor desensitization may reflect a general molecular mechanism operative on many G-protein-coupled receptor systems and, particularly, synaptic neurotransmitter receptors. Two distinct cDNAs encoding beta ARK isozymes were isolated from rat brain and sequenced. The regional and cellular distributions of these two gene products, termed beta ARK1 and beta ARK2, were determined in brain by in situ hybridization and by immunohistochemistry at the light and electron microscopic levels. The beta ARK isozymes were found to be expressed primarily in neurons distributed throughout the CNS. Ultrastructurally, beta ARK1 and beta ARK2 immunoreactivities were present both in association with postsynaptic densities and, presynaptically, with axon terminals. The beta ARK isozymes have a regional and subcellular distribution consistent with a general role in the desensitization of synaptic receptors.

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Plasticity of neuronal receptors

Cited by 64 publications

References 37 publications

Differential Subcellular Regulation of NMDAR1 Protein and mRNA in Dendrites of Dentate Gyrus Granule Cells after Perforant Path Transection

Differential Subcellular Regulation of NMDAR1 Protein and mRNA in Dendrites of Dentate Gyrus Granule Cells after Perforant Path Transection

Up‐Regulation of NR2B Subunit of NMDA Receptors in Cerebellar Granule Neurons by Ca²⁺/Calmodulin Kinase Inhibitor KN93

The G-protein-coupled receptor kinases beta ARK1 and beta ARK2 are widely distributed at synapses in rat brain

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Plasticity of neuronal receptors

Cited by 64 publications

References 37 publications

Differential Subcellular Regulation of NMDAR1 Protein and mRNA in Dendrites of Dentate Gyrus Granule Cells after Perforant Path Transection

Differential Subcellular Regulation of NMDAR1 Protein and mRNA in Dendrites of Dentate Gyrus Granule Cells after Perforant Path Transection

Up‐Regulation of NR2B Subunit of NMDA Receptors in Cerebellar Granule Neurons by Ca2+/Calmodulin Kinase Inhibitor KN93

The G-protein-coupled receptor kinases beta ARK1 and beta ARK2 are widely distributed at synapses in rat brain

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Up‐Regulation of NR2B Subunit of NMDA Receptors in Cerebellar Granule Neurons by Ca²⁺/Calmodulin Kinase Inhibitor KN93