Site-Specific Synapsin I Phosphorylation Participates in the Expression of Post-Tetanic Potentiation and Its Enhancement by BDNF

Valente, Pierluigi; Casagrande, Silvia; Nieus, Thierry; Verstegen, Anne M.J.; Valtorta, Flavia; Benfenati, Fabio; Baldelli, Pietro

doi:10.1523/jneurosci.5275-11.2012

Cited by 58 publications

(56 citation statements)

References 56 publications

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“…Synapsin I isoforms are likely to be important for the presynaptic BDNF response, because BDNF causes synapsin Ia to be phosphorylated at MAPK phosphorylation sites Ser 62, Ser 67 and Ser 549 (Jovanovic et al, 1996) and deletion of the synapsin I gene abolishes the enhancement of glutamate release by BDNF in synaptosomes (Jovanovic et al, 2000). It remains possible that isoforms other than synapsin I may also be involved: the acute enhancement of evoked EPSCs by BDNF is intact in synapsin I KO neurons, as well as in synapsin I KO neurons expressing loss-of-function mutations in synapsin I MAPK phosphorylation sites (S62A, S67A; Valente et al, 2012). Ser 470 in synapsin IIIa has also been determined to be a substrate for MAPK (Porton et al, 2004), though whether this site is phosphorylated in response to BDNF is not yet known.…”

Section: Discussionmentioning

confidence: 99%

Calcium-Dependent and Synapsin-Dependent Pathways for the Presynaptic Actions of BDNF

Cheng

Song

Augustine

2017

Front. Cell. Neurosci.

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We used cultured hippocampal neurons to determine the signaling pathways mediating brain-derived neurotrophic factor (BDNF) regulation of spontaneous glutamate and GABA release. BDNF treatment elevated calcium concentration in presynaptic terminals; this calcium signal reached a peak within 1 min and declined in the sustained presence of BDNF. This BDNF-induced transient rise in presynaptic calcium was reduced by SKF96365, indicating that BDNF causes presynaptic calcium influx via TRPC channels. BDNF treatment increased the frequency of miniature excitatory postsynaptic currents (mEPSCs). This response consisted of two components: a transient component that peaked within 1 min of initiating BDNF application and a second component that was sustained, at a lower mEPSC frequency, for the duration of BDNF application. The initial transient component was greatly reduced by removing external calcium or by treatment with SKF96365, as well as by Pyr3, a selective blocker of TRPC3 channels. In contrast, the sustained component was unaffected in these conditions but was eliminated by U0126, an inhibitor of the MAP kinase (MAPK) pathway, as well as by genetic deletion of synapsins in neurons from a synapsin triple knock-out (TKO) mouse. Thus, two pathways mediate the ability of BDNF to enhance spontaneous glutamate release: the transient component arises from calcium influx through TRPC3 channels, while the sustained component is mediated by MAPK phosphorylation of synapsins. We also examined the ability of these two BDNF-dependent pathways to regulate spontaneous release of the inhibitory neurotransmitter, GABA. BDNF had no effect on the frequency of spontaneous miniature inhibitory postsynaptic currents (mIPSCs) in neurons from wild-type (WT) mice, but surprisingly did increase mIPSC frequency in synapsin TKO mice. This covert BDNF response was blocked by removal of external calcium or by treatment with SKF96365 or Pyr3, indicating that it results from calcium influx mediated by TRPC3 channels. Thus, the BDNF-activated calcium signaling pathway can also enhance spontaneous GABA release, though this effect is suppressed by synapsins under normal physiological conditions.

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Section: Discussionmentioning

confidence: 99%

Calcium-Dependent and Synapsin-Dependent Pathways for the Presynaptic Actions of BDNF

Cheng

Song

Augustine

2017

Front. Cell. Neurosci.

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“…Patch-clamp recordings from dissociated cultured hippocampal neurons and acute hippocampal slices Patch-clamp recordings were performed on cultured pyramidal neurons as previously described (Valente et al, 2012). Cultured pyramidal neurons were morphologically identified by their teardrop-shaped somata and characteristic apical dendrite after 12-16 div (Watt et al, 2000;Pratt et al, 2003).…”

Section: Mea Recordings and Analysis Of Neuronal Network Firing Activitymentioning

confidence: 99%

Cell adhesion molecule L1 contributes to neuronal excitability regulating the function of voltage-gated Na+ channels

Valente

Lignani

Medrihan

et al. 2016

Journal of Cell Science

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L1 (also known as L1CAM) is a trans-membrane glycoprotein mediating neuron-neuron adhesion through homophilic and heterophilic interactions. Although experimental evidence has implicated L1 in axonal outgrowth, fasciculation and pathfinding, its contribution to voltage-gated Na + channel function and membrane excitability has remained unknown. Here, we show that firing rate, single cell spiking frequency and Na + current density are all reduced in hippocampal excitatory neurons from L1-deficient mice both in culture and in slices owing to an overall reduced membrane expression of Na + channels. Remarkably, normal firing activity was restored when L1 was reintroduced into L1-deficient excitatory neurons, indicating that abnormal firing patterns are not related to developmental abnormalities, but are a direct consequence of L1 deletion. Moreover, L1 deficiency leads to impairment of action potential initiation, most likely due to the loss of the interaction of L1 with ankyrin G that produces the delocalization of Na + channels at the axonal initial segment. We conclude that L1 contributes to functional expression and localization of Na + channels to the neuronal plasma membrane, ensuring correct initiation of action potential and normal firing activity.

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“…The C domain likewise contains such a candidate membrane-binding region, while other sites within the C domain appear responsible for binding to Actin filaments. These insights into Synapsin function were subsequently enriched in a number of ways (Benfenati, 2011): (1) Concomitant with the discovery of the requirement of Synapsin in non-associative short-term plasticity in Aplysia (Humeau et al, 2001), it was shown that serotonin induces Synapsin phosphorylation in Aplysia (Angers et al, 2002), likely via the cAMP-PKA pathway (Fiumara et al, 2004; see also Dolphin and Greengard, 1981) and/or the MAP kinase pathway (Giachello et al, 2010), and that these processes impact nonassociative short-term plasticity (Fioravante et al, 2007;Doussau et al, 2010;Giachello et al, 2010;Valente et al, 2012). Strikingly, it was recently reported that the synapsin gene of Aplysia features a CRE-recognition site, that serotonin induces de novo synthesis of Synapsin via the CREB1 pathway, and that this is required for nonassociative long-term plasticity (Hart et al, 2011).…”

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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Site-Specific Synapsin I Phosphorylation Participates in the Expression of Post-Tetanic Potentiation and Its Enhancement by BDNF

Cited by 58 publications

References 56 publications

Calcium-Dependent and Synapsin-Dependent Pathways for the Presynaptic Actions of BDNF

Calcium-Dependent and Synapsin-Dependent Pathways for the Presynaptic Actions of BDNF

Cell adhesion molecule L1 contributes to neuronal excitability regulating the function of voltage-gated Na+ channels

Maggot learning and Synapsin function

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