Long-lasting synapse formation in cultured rat hippocampal neurons after repeated PKA activation

Yamamoto, Megumi; Urakubo, Tomoyoshi; Tominaga-Yoshino, Keiko; Ogura, Akihiko

doi:10.1016/j.brainres.2005.01.102

Cited by 22 publications

(43 citation statements)

References 32 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…8). This is consistent with previous results that the repetitive activation of PKA by forskolin and Sp-cAMPS produced RISE in cultured slices and dissociated cultured neurons, respectively (Tominaga-Yoshino et al, 2002;Yamamoto et al, 2005). How-…”

Section: Possible Connection Between Pka and Protein Synthesissupporting

confidence: 93%

Repetitive induction of late‐phase LTP produces long‐lasting synaptic enhancement accompanied by synaptogenesis in cultured hippocampal slices

et al. 2007

Self Cite

View full text Add to dashboard Cite

Long-term plasticity of synaptic transmission is assumed to underlie the formation of long-term memory. Although the cellular mechanisms underlying short-term plasticity have been analyzed in detail, the mechanisms underlying the transformation from short-term to long-term plasticity remain largely unrevealed. We propose the novel long-lasting phenomenon as a model system for the analysis of long-term plasticity. We previously reported that the repetitive activation of cAMP-dependent protein kinase (PKA) by forskolin application led to an enhancement in synaptic strength coupled with synaptogenesis that lasted more than 3 weeks in cultured rat hippocampal slices. To elucidate whether this long-lasting synaptic enhancement depended on the induction of long-term potentiation (LTP) or on the pharmacological effect of forskolin, we applied glutamate (Glu) and correlated its dose with the production of the long-lasting synaptic enhancement. When the dose of Glu was low (10, 30 muM), only transient excitation or early-phase LTP (E-LTP) was induced by a single application and no long-lasting synaptic enhancement was produced by three applications. When the dose was raised to 100 or 300 muM, late-phase LTP (L-LTP) was induced by a single application and long-lasting synaptic enhancement was produced by three applications. The Glu-produced enhancement was accompanied by an increase in the frequency (but not the amplitude) of miniature EPSC and the number of synaptic structures. The enhancement depended on the interval of repetition and protein synthesis immediately after the Glu applications. These results indicate that the repetitive induction of L-LTP, but not E-LTP or transient excitation, triggers cellular processes leading to the long-lasting synaptic enhancement and the formation of new synapses.

show abstract

Section: Possible Connection Between Pka and Protein Synthesissupporting

confidence: 93%

Repetitive induction of late‐phase LTP produces long‐lasting synaptic enhancement accompanied by synaptogenesis in cultured hippocampal slices

et al. 2007

Self Cite

View full text Add to dashboard Cite

show abstract

“…Al could alter the excitability of (Impey et al, 1998;Grewal et al, 2000;Grzegorzewska et al, 2004). Furthermore, Al could also affect the formation of LTD, reduce synaptic plasticity range significantly (Yamamoto et al, 2005). E-LTP, which lasts about 1 hr, can be induced if one train of high frequency stimulation is input to the presynaptic area of CA1 region.…”

Section: Discussionmentioning

confidence: 99%

Effects of subchronic aluminum exposure on spatial memory, ultrastructure and L-LTP of hippocampus in rats

et al. 2013

View full text Add to dashboard Cite

-Epidemiological investigations have indicated that aluminum (Al), as an important environmental neurotoxicant, could cause damage to the cognitive function which was closely related with neurodegenerative diseases. Long-term potentiation (LTP) is one form of synaptic plasticity in association with cognitive function. Previous studies have demonstrated that Al impaired early phase long-term potentiation (E-LTP) in vivo and in vitro. However, Al-induced damage to late phase long-term potentiation (L-LTP) has poorly been studied. The present study was designed to observe the effects of subchronic Al exposure on the spatial memory, hippocampus ultrastructure and L-LTP in rats. Pregnant Wistar rats were assigned to four groups. Neonatal rats were exposed to Al by parental lactation from parturition to weaning for 3 weeks and then fed with the distilled water containing 0, 0.2%, 0.4% and 0.6% aluminum chloride (AlCl 3 ) respectively from weaning to postnatal 3 months. The levels of Al in blood and hippocampus were quantitated by atomic absorption spectrophotometer. Morris water maze test was performed to study spatial memory. The induction and maintenance of L-LTP in area of Schaffer collateral-CA1 synapse was recorded by extracellular microelectrode recording technology in hippocampus of experimental rats. Hippocampus was collected for transmission electron microscopy observation. The results showed that the Al concentrations in blood and hippocampus of Al-exposed rats were higher than those of the control rats. Al could impair spatial memory ability of rats. Neuronal and synaptic ultrastructure from Al-exposed rats presented pathological changes; the incidence of L-LTP has a decrease trend while population spike (PS) amplitude was much smaller significantly stimulated by high-frequency stimulation (HFS) in Al-exposed rats. Our findings showed that Al exposure caused spatial memory damage, under which the neuronal and synaptic ultrastructure changes maybe were their morphological basis and the impaired L-LTP of hippocampus could be their electrophysiological basis.

show abstract

“…In particular, a large body of experimental data suggests that PKA activity and neurotransmitter-induced signalling are correlated and strongly involved in synaptogenesis. In fact, the repeated activation of PKA by either a cAMP analogue or forskolin in primary rat hippocampal neurons (Yamamoto et al, 2005) or by glutamate in hippocampal slices (Tominaga-Yoshino et al, 2008) leads to a slowly developing long-lasting synaptogenesis. However, the expression of dominant-negative PKA in zebrafish olfactory sensory neurons in vivo prevents the formation of SV clusters in axon terminals during synaptogenesis (Yoshida and Mishina, 2005).…”

Section: Overexpression Of Wt Syn I Does Not Further Increase the Nummentioning

confidence: 99%

Effects of phosphorylation and neuronal activity on the control of synapse formation by synapsin I

Perlini

Botti

Fornasiero

et al. 2011

Journal of Cell Science

View full text Add to dashboard Cite

SummarySynapsins are synaptic vesicle (SV)-associated proteins that regulate synaptic transmission and neuronal differentiation. At early stages, Syn I and II phosphorylation at Ser9 by cAMP-dependent protein kinase (PKA) and Ca 2+ /calmodulin-dependent protein kinase I/IV modulates axon elongation and SV-precursor dynamics. We evaluated the requirement of Syn I for synapse formation by siRNAmediated knockdown as well as by overexpression of either its wild-type (WT) form or its phosphorylation mutants. Syn1 knockdown at 14 days in vitro caused a decrease in the number of synapses, accompanied by a reduction of SV recycling. Although overexpression of WT Syn I was ineffective, overexpression of its phosphorylation mutants resulted in a complex temporal regulation of synapse density. At early stages of synaptogenesis, phosphomimetic Syn I S9E significantly increased the number of synapses. Conversely, dephosphomimetic Syn I S9A decreased synapse number at more advanced stages. Overexpression of either WT Syn I or its phosphomimetic S9E mutant rescued the decrease in synapse number caused by chronic treatment with tetrodotoxin at early stages, suggesting that Syn I participates in an alternative PKA-dependent mechanism that can compensate for the impairment of the activitydependent synaptogenic pathway. Altogether these results indicate that Syn I is an important regulator of synapse formation, which adjusts synapse number in response to extracellular signals.

show abstract

Long-lasting synapse formation in cultured rat hippocampal neurons after repeated PKA activation

Cited by 22 publications

References 32 publications

Repetitive induction of late‐phase LTP produces long‐lasting synaptic enhancement accompanied by synaptogenesis in cultured hippocampal slices

Repetitive induction of late‐phase LTP produces long‐lasting synaptic enhancement accompanied by synaptogenesis in cultured hippocampal slices

Effects of subchronic aluminum exposure on spatial memory, ultrastructure and L-LTP of hippocampus in rats

Effects of phosphorylation and neuronal activity on the control of synapse formation by synapsin I

Contact Info

Product

Resources

About