Visualization of Cyclic AMP–Regulated Presynaptic Activity at Cerebellar Granule Cells

Chavis, Pascale; Mollard, Patrice; Bockaert, Joël; Manzoni, Olivier J.

doi:10.1016/s0896-6273(00)81015-6

Cited by 105 publications

(93 citation statements)

References 40 publications

(29 reference statements)

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“…Reelin immunostaining and live uptake of anti-SytI antibodies (Calbiochem via VWR International, West Chester, PA) were performed as described previously (Chavis et al, 1998). Surface NR2A and NR2B subunits were stained by incubating live neurons with 10 g of affinity-purified polyclonal antibodies against the N-terminal domain of NR2A or NR2B (Groc et al, 2006b).…”

Section: Methodsmentioning

confidence: 99%

“…1 A). Active synapses were tagged in living neurons using the dynamic uptake of an antibody targeted against the luminal epitope of the vesicular protein synaptotagmin I (Syt I) (Chavis et al, 1998). Colabeling Reelin and active synapses revealed that, between 8 and 9 -12 div, a time critical for maturational processes, Reelin accumulates at developing synapses ( Fig.…”

Section: Reelin Is Sufficient To Induce the Maturation Of Synaptic Nmmentioning

confidence: 99%

See 1 more Smart Citation

NMDA Receptor Surface Trafficking and Synaptic Subunit Composition Are Developmentally Regulated by the Extracellular Matrix Protein Reelin

Groc¹,

Choquet²,

Stephenson³

et al. 2007

J. Neurosci.

190

165

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During postnatal development, changes in the subunit composition of glutamate receptors of the NMDA subtype (NMDARs) are key to the refinement of excitatory synapses. Hypotheses for maturation of synaptic NMDARs include regulation of their expression levels, membrane targeting, and surface movements. In addition, several members of extracellular matrix (ECM) proteins such as Reelin are involved in synaptic plasticity. However, it is not known whether and how ECM proteins regulate synaptic NMDAR maturation. To probe the participation of NMDARs to synaptic currents and NMDARs surface dynamics, we used electrophysiological recordings and singleparticle tracking in cultured hippocampal neurons. Our results show that, during maturation, Reelin orchestrates the regulation of subunit composition of synaptic NMDARs and controls the surface mobility of NR2B subunits. During postnatal maturation, we observed a marked decrease of NR1/NR2B receptor participation to NMDAR-mediated synaptic currents concomitant with the accumulation of Reelin at active synapses. Blockade of the function of Reelin prevented the maturation-dependent reduction in NR1/NR2B-mediated synaptic currents. The reduction of NR1/NR2B receptors was not inhibited by blocking synaptic activity but required ␤1-containing integrin receptors. Single-particle tracking showed that inhibition of Reelin decreased the surface mobility of native NR2B-containing NMDARs, whereas their synaptic dwell time increased. Conversely, recombinant Reelin dramatically reduced NR2B-mediated synaptic currents and the time spent by NR2B subunits within synapses. Our data reveal a new mode of control of synaptic NMDAR assembly at postnatal hippocampal synapses and an unprecedented role of ECM proteins in regulating glutamate receptor surface diffusion.

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Section: Methodsmentioning

confidence: 99%

Section: Reelin Is Sufficient To Induce the Maturation Of Synaptic Nmmentioning

confidence: 99%

NMDA Receptor Surface Trafficking and Synaptic Subunit Composition Are Developmentally Regulated by the Extracellular Matrix Protein Reelin

Groc¹,

Choquet²,

Stephenson³

et al. 2007

J. Neurosci.

190

165

View full text Add to dashboard Cite

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“…87 Similarly as it happens at the hippocampal mossy fibers, LTP in parallel fiberPurkinje cell synapses is mediated by presynaptic Ca 2 þ influx, which activates Ca 2 þ sensitive adenylyl cyclase to increase cAMP levels and activates PKA. 81,86,88,89 The potentiation of glutamate release putatively occurs upon the PKA-mediated phosphorylation of presynaptic proteins involved in neurotransmitter release, as it will be discussed below.…”

Section: Cerebellar Parallel-purkinje Cell Synapsesmentioning

confidence: 99%

Active zones for presynaptic plasticity in the brain

García-Junco-Clemente

Linares-Clemente

Fernández‐Chacón

2005

Mol Psychiatry

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Some of the most abundant synapses in the brain such as the synapses formed by the hippocampal mossy fibers, cerebellar parallel fibers and several types of cortical afferents express presynaptic forms of long-term potentiation (LTP), a putative cellular model for spatial, motor and fear learning. Those synapses often display presynaptic mechanisms of LTP induction, which are either NMDA receptor independent of dependent of presynaptic NMDA receptors. Recent investigations on the molecular mechanisms of neurotransmitter release modulation in short-and long-term synaptic plasticity in central synapses give a preponderant role to active zone proteins as Munc-13 and RIM1-alpha, and point toward the maturation process of synaptic vesicles prior to Ca 2 þ -dependent fusion as a key regulatory step of presynaptic plasticity.

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“…Modulation of synaptic transmission by variations in the cAMP levels has been observed in multiple neural networks, including the hippocampus, nodose ganglia, cerebellar granule cells, enteric plexus, and sympathetic ganglia. In cerebellar granule cells, it has been shown that activation of the cAMP/PKA pathway causes an increase in presynaptic vesicular turnover so that previously "silent" synapses show spontaneous transmitter release (9). Similarly, in other CNS areas, increases in the cAMP levels induce a pronounced augmentation of the exocytotic activity in synaptic terminals with low baseline vesicular activity (9,28).…”

Section: Perspective: Modulation Of Nts Transduction Mechanisms Equalmentioning

confidence: 99%

“…In cerebellar granule cells, it has been shown that activation of the cAMP/PKA pathway causes an increase in presynaptic vesicular turnover so that previously "silent" synapses show spontaneous transmitter release (9). Similarly, in other CNS areas, increases in the cAMP levels induce a pronounced augmentation of the exocytotic activity in synaptic terminals with low baseline vesicular activity (9,28). These factors suggest that cAMP levels may increase the response of synapses to numerous neuromodulatory substances.…”

Section: Perspective: Modulation Of Nts Transduction Mechanisms Equalmentioning

confidence: 99%

III. Activity-dependent plasticity in vago-vagal reflexes controlling the stomach

Travagli

Hermann

Browning³

et al. 2003

American Journal of Physiology-Gastrointestinal and Liver Physi

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.-Vago-vagal reflex circuits modulate digestive functions from the oral cavity to the transverse colon. Previous articles in this series have described events at the level of the sensory receptors encoding the peripheral stimuli, the transmission of information in the afferent vagus, and the conversion of this data within the dorsal vagal complex (DVC) to impulses in the preganglionic efferents. The control by vagal efferents of the postganglionic neurons impinging on the glands and smooth muscles of the target organs has also been illustrated. Here we focus on some of the mechanisms by which these apparently static reflex circuits can be made quite plastic as a consequence of the action of modulatory inputs from other central nervous system sources. A large body of evidence has shown that the neuronal elements that constitute these brain stem circuits have nonuniform properties and function differently according to status of their target organs and the level of activity in critical modulatory inputs. We propose that DVC circuits undergo a certain amount of short-term plasticity that allows the brain stem neuronal elements to act in harmony with neural systems that control behavioral and physiological homeostasis. dorsal motor nucleus of the vagus; nucleus of the solitary tract; brain stem; gastrointestinal motility VAGO-VAGAL REFLEXES CONSIST essentially of three components: sensory vagal afferents, second-order integrative neurons of the nucleus of the solitary tract (NTS), and efferent vagal neurons of the dorsal motor nucleus of the vagus (DMV). The sensory limb is comprised of chemo-and mechanosensory elements linked to vagal afferent nerves (reviewed in Refs. 27 and 37). Data received by these sensory elements are funneled mainly via glutamatergic synapses into the brain stem and converge on the NTS (13, 27, 32).The rat NTS is organized such that sensory information from the gastrointestinal (GI) tract is received and processed in distinct, viscerotopically organized subnuclei. Many of the gastric vagal afferents synapse at the level of the medial subnucleus of the solitary tract and in the subnucleus gelatinosus. Intestinal afferent vagal fibers terminate primarily in the subnucleus commissuralis (2), and esophageal sensory fibers terminate mainly in the subnucleus centralis (cNTS) (2, 14, 26). The NTS, then, sends projections to the efferent vagal neurons in the DMV. The NTS also sends a copy of this immense volume of visceral afferent activity to integrative structures in the pons and the diencephalon.The viscerotopic organization of the DMV is less rigid than that of the NTS. In fact, the DMV is organized in a mediolateral columnar manner such that neurons in the medial tips of the nucleus project to the stomach and neurons in the lateral tips project to the intestine. Most of the projections from the NTS to the DMV appear to be inhibitory. There are numerous phenotypes of neurons in the NTS that can contribute input to the DMV, although indirect evidence suggests that it consists mainly of a GABAergic...

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Visualization of Cyclic AMP–Regulated Presynaptic Activity at Cerebellar Granule Cells

Cited by 105 publications

References 40 publications

NMDA Receptor Surface Trafficking and Synaptic Subunit Composition Are Developmentally Regulated by the Extracellular Matrix Protein Reelin

NMDA Receptor Surface Trafficking and Synaptic Subunit Composition Are Developmentally Regulated by the Extracellular Matrix Protein Reelin

Active zones for presynaptic plasticity in the brain

III. Activity-dependent plasticity in vago-vagal reflexes controlling the stomach

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