Rescue of Impaired Long-Term Facilitation at Sensorimotor Synapses of<i>Aplysia</i>following siRNA Knockdown of CREB1

Zhou, Lian; Zhang, Yili; Liu, Rong‐Yu; Smolen, Paul; Cleary, Leonard J.; Byrne, John H.

doi:10.1523/jneurosci.3330-14.2015

Cited by 13 publications

(22 citation statements)

References 52 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…A similar predicted rescue protocol of irregularly spaced intervals rescued a deficit in LTF that was produced by siRNA knockdown of CREB1 (REF. 97). …”

Section: Irregular Spacing Can Enhance Learningmentioning

confidence: 99%

The right time to learn: mechanisms and optimization of spaced learning

2016

View full text Add to dashboard Cite

For many types of learning, spaced training, which involves repeated long inter-trial intervals, leads to more robust memory formation than does massed training, which involves short or no intervals. Several cognitive theories have been proposed to explain this superiority, but only recently have data begun to delineate the underlying cellular and molecular mechanisms of spaced training, and we review these theories and data here. Computational models of the implicated signalling cascades have predicted that spaced training with irregular inter-trial intervals can enhance learning. This strategy of using models to predict optimal spaced training protocols, combined with pharmacotherapy, suggests novel ways to rescue impaired synaptic plasticity and learning.

show abstract

“…A similar predicted rescue protocol of irregularly spaced intervals rescued a deficit in LTF that was produced by siRNA knockdown of CREB1 (REF. 97). …”

Section: Irregular Spacing Can Enhance Learningmentioning

confidence: 99%

The right time to learn: mechanisms and optimization of spaced learning

2016

View full text Add to dashboard Cite

show abstract

“…96 h after injection, cultures were treated with the Standard protocol (RSK-siRNA + 5-HT, n = 6; Con-siRNA + 5-HT, n = 6) or vehicle control (RSK-siRNA + Veh, n = 6). Con-siRNA itself does not change basal synaptic strength 13,14,18,19 . Therefore, we omitted the Con-siRNA + Veh group in this experiment.…”

Section: Knockdown Of Rsk By Sirna Injection Also Reduced the 5-ht Inmentioning

confidence: 92%

“…siRNA knockdown of RSK. A custom ON-TARGET plus SMART pool of RSK siRNAs was designed and provided by Dharmacon to target an Aplysia homolog of RSK, which has been used in previous studies 13,16,19 . Non-targeting siRNA was used as a negative control.…”

Section: Methodsmentioning

confidence: 99%

“…Non-targeting siRNA was used as a negative control. Potential off-target effects were evaluated by examining biophysical properties (i.e., membrane resistance, resting membrane potential, cell excitability) to ensure the injections did not affect the health of the cells 13,16,19 . Before siRNA injection, cultures or co-cultures were allowed to grow for 2 d at 18 °C.…”

Section: Methodsmentioning

confidence: 99%

“…Before siRNA injection, cultures or co-cultures were allowed to grow for 2 d at 18 °C. siRNA (5 μM final concentration) was injected into SNs following established procedures 13,16,19 . Cultures and co-cultures were allowed to grow for another 4 d after siRNA injection at 18 °C.…”

Section: Methodsmentioning

confidence: 99%

See 2 more Smart Citations

Role of p90 ribosomal S6 kinase in long-term synaptic facilitation and enhanced neuronal excitability

Liu¹,

Zhang²,

Smolen³

et al. 2020

Sci Rep

View full text Add to dashboard Cite

Multiple kinases converge on the transcription factor cAMP response element-binding protein (CREB) to enhance the expression of proteins essential for long-term synaptic plasticity and memory. The p90 ribosomal S6 kinase (RSK) is one of these kinases, although its role is poorly understood. The present study exploited the technical advantages of the Aplysia sensorimotor culture system to examine the role of RSK in long-term synaptic facilitation (LTF) and long-term enhancement of neuronal excitability (LTEE), two correlates of long-term memory (LTM). Inhibition of RSK expression or RSK activity both significantly reduced CREB1 phosphorylation, LTF, and LTEE, suggesting RSK is required for learningrelated synaptic plasticity and enhancement in neuronal excitability. In addition, knock down of RSK by RNAi in Aplysia sensory neurons impairs LTF, suggesting that this may be a useful single-cell system to study aspects of defective synaptic plasticity in Coffin-Lowry Syndrome (CLS), a cognitive disorder that is caused by mutations in rsk2 and associated with deficits in learning and memory. We found that the impairments in LTF and LTEE can be rescued by a computationally designed spaced training protocol, which was previously demonstrated to augment normal LTF and LTM. In mammals, gene deletion studies have shown an essential role for the rsk2 gene in cognitive functions 1. In several animal models, the p90 isoform of RSK, expressed from rsk2, phosphorylates (i.e., activates) CREB after activation by the ERK isoform of MAP kinase (MAPK) 2-6. Coffin-Lowry Syndrome (CLS) is caused by X-linked mutations in rsk2, and is associated with human intellectual disability and skeletal abnormalities 7. A mouse rsk2-null model is deficient in fear memory consolidation and stimulus-induced CREB phosphorylation 1,8. CREB-mediated transcription is required for memory formation in vertebrates and invertebrates. In mammalian systems, many of the signaling pathways that lead to phosphorylation of CREB have been well characterized, including the cAMP/PKA pathway and the Ras/ERK pathway 9. However, the potential ERK/RSK/CREB pathway has received little attention as a potential contributor to synaptic plasticity, including long-term potentiation (LTP) and long-term synaptic facilitation (LTF), and also to long-term enhancement of neuronal excitability (LTEE). LTP, LTF, and LTEE are known correlates of long-term memory (LTM). To our knowledge, no study so far has examined the effects of RSK inhibitors on synaptic plasticity or excitability. One study examined the role of RSK2 in LTP using a RSK2 mutant mouse 8. A negative result was reported-LTP was normal in the mutant. The negative result may be explained by the effects of RSK activation not being expressed during the period of observation (120 minutes), or a different isoform of RSK may have compensated for the mutant. Consequently, the role of RSK in long-term synaptic plasticity and enhancement of excitability remains unsettled. The present study exploited advantages of the Aplysia sen...

show abstract