Tetanic Stimulation Recruits Vesicles from Reserve Pool via a cAMP-Mediated Process in Drosophila Synapses

Kuromi, Hiroshi; Kidokoro, Yoshiaki

doi:10.1016/s0896-6273(00)00015-5

Cited by 167 publications

(162 citation statements)

References 27 publications

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“…Some work has suggested that cAMP signaling increases the size of the recycling vesicle pool at already active synapses (Kuromi and Kidokoro, 2000;Menegon et al, 2006). With neither brief 30 min FSK stimulation nor our standard 4 h FSK stimulation paradigm did we observe reliable increases in the intensity of FM1-43FX labeling of synapses that might have indicated an increase in the recycling vesicle pool.…”

Section: Camp and Presynaptic Potentiationcontrasting

confidence: 59%

A Specific Role for Ca²⁺-Dependent Adenylyl Cyclases in Recovery from Adaptive Presynaptic Silencing

Moulder¹,

Jiang²,

Chang³

et al. 2008

J. Neurosci.

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Glutamate generates fast postsynaptic depolarization throughout the CNS. The positive-feedback nature of glutamate signaling likely necessitates flexible adaptive mechanisms that help prevent runaway excitation. We have previously explored presynaptic adaptive silencing, a form of synaptic plasticity produced by ongoing neuronal activity and by strong depolarization. Unsilencing mechanisms that maintain active synapses and restore normal function after adaptation are also important, but mechanisms underlying such presynaptic reactivation remain unexplored. Here we investigate the involvement of the cAMP pathway in the basal balance between silenced and active synapses, as well as the recovery of baseline function after depolarization-induced presynaptic silencing. Activation of the cAMP pathway activates synapses that are silent at rest, and pharmacological inhibition of cAMP signaling silences basally active synapses. Adenylyl cyclase (AC) 1 and AC8, the major Ca 2ϩ -sensitive AC isoforms, are not crucial for the baseline balance between silent and active synapses. In cells from mice doubly deficient in AC1 and AC8, the baseline percentage of active synapses was only modestly reduced compared with wild-type synapses, and forskolin unsilencing was similar in the two genotypes. Nevertheless, after strong presynaptic silencing, recovery of normal function was strongly inhibited in AC1/AC8-deficient synapses. The entire recovery phenotype of the double null was reproduced in AC8-deficient but not AC1-deficient cells. We conclude that, under normal conditions, redundant cyclase activity maintains the balance between presynaptically silent and active synapses, but AC8 plays a particularly important role in rapidly resetting the balance of active to silent synapses after adaptation to strong activity.

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Section: Camp and Presynaptic Potentiationcontrasting

confidence: 59%

A Specific Role for Ca²⁺-Dependent Adenylyl Cyclases in Recovery from Adaptive Presynaptic Silencing

Moulder¹,

Jiang²,

Chang³

et al. 2008

J. Neurosci.

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“…Short-term potentiation of Ca 2ϩ -regulated exocytosis by PKA has been reported previously in several types of secretory cells such as chromaffin cells, pancreatic ␤ cells, and neurons (O'Sullivan and Jamieson, 1992;Morgan et al, 1993;Ä mmälä et al, 1994;Trudeau et al, 1996;Kuromi and Kidokoro, 2000). In addition to these types of cells, it has been recently shown that PKA also potentiates Ca 2ϩ -regulated exocytosis of endosomes with lysosomal markers in normal rat kidney fibroblasts (Rodríguez et al, 1999).…”

Section: Early Potentiation Of Exocytosis and Facilitation Of Membranmentioning

confidence: 71%

Long-Term Potentiation of Exocytosis and Cell Membrane Repair in Fibroblasts

Togo

Alderton

Steinhardt

2003

MBoC

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We previously found that a microdisruption of the plasma membrane evokes Ca 2ϩ -regulated exocytosis near the wound site, which is essential for membrane resealing. We demonstrate herein that repeated membrane disruption reveals long-term potentiation of Ca 2ϩ -regulated exocytosis in 3T3 fibroblasts, which is closely correlated with faster membrane resealing rates. This potentiation of exocytosis is cAMP-dependent protein kinase A dependent in the early stages (minutes), in the intermediate term (hours) requires protein synthesis, and for long term (24 h) depends on the activation of cAMP response element-binding protein (CREB). We were able to demonstrate that wounding cells activated CREB within 3.5 h. In all three phases, the increase in the amount of exocytosis was correlated with an increase in the rate of membrane resealing. However, a brief treatment with forskolin, which is effective for short-term potentiation and which could also activate CREB, was not sufficient to induce long-term potentiation of resealing. These results imply that long-term potentiation by CREB required activation by another, cAMP-independent pathway.

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“…Elucidating whether cAMP signaling is involved is confounded by the facts that wholesale manipulations of cAMP levels through cAMP analogs and AC activation potently and bidirectionally affect release probability and result in diverse neurophysiological outputs at MFTs (48,49). Nevertheless, it is wellestablished that manipulating cAMP levels at various types of presynaptic terminals alters the dynamics of STP (50)(51)(52)(53). Of particular interest is that chronically elevated cAMP levels can affect synaptic facilitation through effects on vesicular pools (54), and animals lacking AC8, which acts as a presynaptic calcium sensor, have WM but not long-term memory deficits (55), similar to Disc1 Tm1Kara animals.…”

Section: Discussionmentioning

confidence: 99%

Altered axonal targeting and short-term plasticity in the hippocampus of Disc1 mutant mice

Kvajo

McKellar

et al. 2011

Proc. Natl. Acad. Sci. U.S.A.

106

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Carefully designed animal models of genetic risk factors are likely to aid our understanding of the pathogenesis of schizophrenia. Here, we study a mouse strain with a truncating lesion in the endogenous Disc1 ortholog designed to model the effects of a schizophreniapredisposing mutation and offer a detailed account of the consequences that this mutation has on the development and function of a hippocampal circuit. We uncover widespread and cumulative cytoarchitectural alterations in the dentate gyrus during neonatal and adult neurogenesis, which include errors in axonal targeting and are accompanied by changes in short-term plasticity at the mossy fiber/CA3 circuit. We also provide evidence that cAMP levels are elevated as a result of the Disc1 mutation, leading to altered axonal targeting and dendritic growth. The identified structural alterations are, for the most part, not consistent with the growthpromoting and premature maturation effects inferred from previous RNAi-based Disc1 knockdown. Our results provide support to the notion that modest disturbances of neuronal connectivity and accompanying deficits in short-term synaptic dynamics is a general feature of schizophrenia-predisposing mutations. psychiatric disease | rare mutation | mouse model T he schizophrenia (SCHZ) susceptibility gene DISC1 was identified through a balanced chromosomal translocation (1;11)(q42.1;q14.3) segregating with SCHZ and mood disorders in a large Scottish pedigree. This is the only confirmed disease risk allele within the DISC1 locus. The biology of DISC1 is being interrogated with a variety of approaches, such as acute RNAimediated gene knockdown (1-4), overexpression of truncated forms of the human DISC1 (5, 6), and chemical mutagenesis (7). Although they provide information about potential pathways related to DISC1, these approaches are not meant to recapitulate the integrated effects of the pathogenic translocation, and the relevance of these findings to SCHZ pathogenesis remains uncertain.We used a disease-focused knockin approach to introduce a truncating lesion in the endogenous murine Disc1 ortholog designed to model the effects of the (1;11) translocation (Mouse Genome Informatics nomenclature Disc1 Tm1Kara ) (8, 9). Although the divergence in the human and mouse Disc1 gene does not allow an exact replication of the human translocation, this mouse model approximates very closely the Scottish mutation. One advantage of our approach is that it retains endogenous levels as well as spatial and temporal patterns of Disc1 expression, and it preserves short N-terminal isoforms that are presumably unaffected by the Scottish translocation and seem to be expressed at relatively higher levels in the hippocampus (HPC) of patients with SCHZ (10). A comprehensive behavioral analysis has shown that Disc1 Tm1Kara mice display a unique profile of cognitive impairments, including specific and robust deficiencies in working memory (WM) tests (8, 9), which may relate to similar cognitive deficits prominent in psychotic disorders.DISC1 is...

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Tetanic Stimulation Recruits Vesicles from Reserve Pool via a cAMP-Mediated Process in Drosophila Synapses

Cited by 167 publications

References 27 publications

A Specific Role for Ca²⁺-Dependent Adenylyl Cyclases in Recovery from Adaptive Presynaptic Silencing

A Specific Role for Ca²⁺-Dependent Adenylyl Cyclases in Recovery from Adaptive Presynaptic Silencing

Long-Term Potentiation of Exocytosis and Cell Membrane Repair in Fibroblasts

Altered axonal targeting and short-term plasticity in the hippocampus of Disc1 mutant mice

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Tetanic Stimulation Recruits Vesicles from Reserve Pool via a cAMP-Mediated Process in Drosophila Synapses

Cited by 167 publications

References 27 publications

A Specific Role for Ca2+-Dependent Adenylyl Cyclases in Recovery from Adaptive Presynaptic Silencing

A Specific Role for Ca2+-Dependent Adenylyl Cyclases in Recovery from Adaptive Presynaptic Silencing

Long-Term Potentiation of Exocytosis and Cell Membrane Repair in Fibroblasts

Altered axonal targeting and short-term plasticity in the hippocampus of Disc1 mutant mice

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A Specific Role for Ca²⁺-Dependent Adenylyl Cyclases in Recovery from Adaptive Presynaptic Silencing

A Specific Role for Ca²⁺-Dependent Adenylyl Cyclases in Recovery from Adaptive Presynaptic Silencing