Vesicle pools and synapsins: New insights into old enigmas

Fdez, Elena; Hilfiker, Sabine

doi:10.1007/s11068-007-9013-4

Cited by 70 publications

(63 citation statements)

References 56 publications

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“…We used a three-step strategy towards memory trace localization (Gerber et al, 2004b;Heisenberg and Gerber, 2008): (1) (Südhof et al, 1989;DeCamilli et al, 1990;Greengard et al, 1993;Südhof, 1995;Hilfiker et al, 1999;Kao et al, 1999;Ferreira and Rapoport, 2002;Fdez and Hilfiker, 2006;Cesca et al, 2010;Fornasiero et al, 2010;Benfenati, 2011)]. Vertebrates posses a three-member family of synapsin genes, while in invertebrates such as Drosophila only one synapsin gene is found (Klagges et al, 1996); from each gene, typically multiple protein isoforms are produced by alternative splicing.…”

Section: Synapsin Function Backgroundmentioning

confidence: 99%

Maggot learning and Synapsin function

Diegelmann

Klagges

Michels

et al. 2013

Journal of Experimental Biology

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SummaryDrosophila larvae are focused on feeding and have few neurons. Within these bounds, however, there still are behavioural degrees of freedom. This review is devoted to what these elements of flexibility are, and how they come about. Regarding odour-food associative learning, the emerging working hypothesis is that when a mushroom body neuron is activated as a part of an odour-specific set of mushroom body neurons, and coincidently receives a reinforcement signal carried by aminergic neurons, the AC-cAMP-PKA cascade is triggered. One substrate of this cascade is Synapsin, and therefore this review features a general and comparative discussion of Synapsin function. Phosphorylation of Synapsin ensures an alteration of synaptic strength between this mushroom body neuron and its target neuron(s). If the trained odour is encountered again, the pattern of mushroom body neurons coding this odour is activated, such that their modified output now allows conditioned behaviour. However, such an activated memory trace does not automatically cause conditioned behaviour. Rather, in a process that remains off-line from behaviour, the larvae compare the value of the testing situation (based on gustatory input) with the value of the odour-activated memory trace (based on mushroom body output). The circuit towards appetitive conditioned behaviour is closed only if the memory trace suggests that tracking down the learned odour will lead to a place better than the current one. It is this expectation of a positive outcome that is the immediate cause of appetitive conditioned behaviour. Such conditioned search for reward corresponds to a view of aversive conditioned behaviour as conditioned escape from punishment, which is enabled only if there is something to escape from -much in the same way as we only search for things that are not there, and run for the emergency exit only when there is an emergency. One may now ask whether beyond ʻvalueʼ additional information about reinforcement is contained in the memory trace, such as information about the kind and intensity of the reinforcer used. The Drosophila larva may allow us to develop satisfyingly detailed accounts of such mnemonic richness -if it exists.

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Section: Synapsin Function Backgroundmentioning

confidence: 99%

Maggot learning and Synapsin function

Diegelmann

Klagges

Michels

et al. 2013

Journal of Experimental Biology

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“…Syn I is 1 of the major ERK substrates in nerve terminals (18,19) and the other isoforms, Syn II and Syn III, also display potential consensus sequences for ERK phosphorylation (30,31). To investigate whether ERK exerts its presynaptic action through phosphorylation of Syn I, we examined both the phosphorylation state of Syn I at sites 4 and 5 during PTE and the effect of ERK blockade on PTE in Syn I-KO and Syn I/II/III-KO mice.…”

Section: Erk Modulation Of Mf-ca3 Short-term Plasticity Requires Synamentioning

confidence: 99%

“…One possibility is that at 100 Hz, a ceiling effect could exist which may be associated with the concomitant activation of calcineurin and calcineurin-dependent full dephosphorylation of synapsin I at ERK sites (32,33). Another hypothesis is that simultaneous activation of other protein kinases, for example, cAMP-dependent protein kinase or Ca2ϩ/calmodulin-dependent protein kinase II, could either occlude or overcome ERK action in this form of short-term plasticity (31).…”

Section: Molecular Mechanisms Of Presynaptic Short-term Plasticity Inmentioning

confidence: 99%

ERK activation in axonal varicosities modulates presynaptic plasticity in the CA3 region of the hippocampus through synapsin I

Vara

Onofri

Benfenati

et al. 2009

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

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Activity-dependent changes in the strength of synaptic connections in the hippocampus are central for cognitive processes such as learning and memory storage. In this study, we reveal an activity-dependent presynaptic mechanism that is related to the modulation of synaptic plasticity. In acute mouse hippocampal slices, high-frequency stimulation (HFS) of the mossy fiber (MF)-CA3 pathway induced a strong and transient activation of extracellular-regulated kinase (ERK) in MF giant presynaptic terminals. Remarkably, pharmacological blockade of ERK disclosed a negative role of this kinase in the regulation of a presynaptic form of plasticity at MF-CA3 contacts. This ERK-mediated inhibition of post-tetanic enhancement (PTE) of MF-CA3 synapses was both frequency-and pathway-specific and was observed only with HFS at 50 Hz. Importantly, blockade of ERK was virtually ineffective on PTE of MF-CA3 synapses in mice lacking synapsin I, 1 of the major presynaptic ERK substrates, and triple knockout mice lacking all synapsin isoforms displayed PTE kinetics resembling that of wildtype mice under ERK inhibition. These findings reveal a form of short-term synaptic plasticity that depends on ERK and is finely tuned by the firing frequency of presynaptic neurons. Our results also demonstrate that presynaptic activation of the ERK signaling pathway plays part in the activity-dependent modulation of synaptic vesicle mobilization and transmitter release.MAP kinase ͉ mossy fibers ͉ post-tetanic potentiation T he extracellular-regulated kinase (ERK) signaling pathway plays a crucial role in the regulation of activity-dependent changes in the strength of synaptic transmission in the hippocampus (1, 2). Indeed, multiple studies have shown that altering the normal function of ERK causes severe impairments of both short-and long-term forms of synaptic plasticity at hippocampal synapses (3-6, but see also ref. 7). Remarkably, behavioral analyses of animals with altered ERK signaling have revealed a crucial involvement of this cascade in learning and memory (8-10), supporting the idea that ERK-dependent synaptic plasticity is essential for cognitive processes.Because potential molecular substrates of ERK are present in distinct neuronal compartments (2), the precise subcellular location in which ERK activation occurs is a major determinant of ERK function. For example, phosphorylated ERK translocates into the nucleus and regulates gene expression in response to synaptic activity by directly or indirectly phosphorylating transcription factors (2,11,12). Moreover, there is increasing evidence that ERK phosphorylates target proteins in both dendritic (13-15) and axonal compartments (16,17). Synapsin I (Syn I), a synaptic vesicleassociated phosphoprotein implicated in the regulation of synaptic strength, is a major ERK substrate in nerve terminals and presents 3 ERK-dependent phosphorylation sites (18,19). Interestingly, it has been shown that ERK phosphorylation regulates the interaction of Syn I with the actin cytoskeleton, a mechanism that is...

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“…Synapsins are a family of synaptic vesicle (SV)-associated phosphoproteins that play a prominent role in synaptic transmission and plasticity Fdez and Hilfiker, 2006). Three distinct genes, SynI (Syn1), SynII (Syn2) and SynIII (Syn3), give rise in mammals to several differentially spliced isoforms sharing a high level of sequence similarity and whose expression is developmentally regulated.…”

Section: Introductionmentioning

confidence: 99%

Synapsin-I- and synapsin-II-null mice display an increased age-dependent cognitive impairment

Corradi¹,

Zanardi

Giacomini³

et al. 2008

Journal of Cell Science

103

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mice during aging. Both SynI-/-and SynII -/-mice displayed behavioural defects that emerged during aging and involved emotional memory in both mutants, and spatial memory in SynII -/-mice. These abnormalities, which were more pronounced in SynII -/-mice, were associated with neuronal loss and gliosis in the cerebral cortex and hippocampus. The data indicate that SynI and SynII have specific and non-redundant functions, and that synaptic dysfunctions associated with synapsin mutations negatively modulate cognitive performances and neuronal survival during senescence.

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Vesicle pools and synapsins: New insights into old enigmas

Cited by 70 publications

References 56 publications

Maggot learning and Synapsin function

Maggot learning and Synapsin function

ERK activation in axonal varicosities modulates presynaptic plasticity in the CA3 region of the hippocampus through synapsin I

Synapsin-I- and synapsin-II-null mice display an increased age-dependent cognitive impairment

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