Spacing Effect: SHP2 Phosphatase Regulates Resting Intervals Between Learning Trials in Long-Term Memory Induction

By M. R. Pagani, Kimihiko Oishi, B. Gelb, Yi Zhong. 2009

153 citations recorded by the source corpus.

SUMMARY A common property of long-term memory (LTM) induction is the requirement for repeated training sessions spaced over time. The phenomena of better memory being formed with resting intervals between training sessions is called the spacing effect, for which the underlying molecular and neural bases are largely unknown. Our study reveals that the duration of resting intervals required for inducing LTM can be regulated by activity levels of the protein tyrosine phosphatase corkscrew (CSW) in Drosophila. Our studies demonstrate that wild-type CSW overexpression dramatically shortens the inter-trial interval required for LTM induction. In contrast, overexpression of gain-of-function CSWs prolong the resting interval for induction of LTM formation. Further biochemical analysis reveals that LTM-inducing training regimens generate repetitive waves of CSW-dependent mitogen-activated protein kinase activation. The length of that kinase activity wave appears to define the duration of the resting interval. Thus, we establish that the spacing effect has a molecular basis and CSW/SHP2 is key in its regulation.

Subfields: Cellular and Molecular Neuroscience, Molecular Biology

How researchers see this paper

The researchers whose trusted networks rank it highest, strongest advocate first. Every researcher gets a different order.

In Cellular and Molecular Neuroscience

1. Qian Li
2. Liyuan Wang
3. Yi Zhong
4. Edgar Körner
5. Xuchen Zhang
6. Friedrich T. Sommer
7. Ursula Körner
8. Wantong Hu

In Molecular Biology

1. Qian Li
2. Xuchen Zhang
3. A. Yarali
4. Liyuan Wang
5. Andreas Knoblauch
6. Yi Zhong
7. Hiromu Tanimoto

Citations in the corpus

• Structural Synaptic Plasticity Has High Memory Capacity and Can Explain Graded Amnesia, Catastrophic Forgetting, and the Spacing Effect (2014, methodology): “While previous models based on delayed synaptic consolidation induced by molecular signaling cascades [52,141] may account for short-term spacing effects on the time-scale of minutes, structural plasticity can also explain long-term spacing effects on the time scale of months to years [110,111].”
• Genetic dissection of mutual interference between two consecutive learning tasks in Drosophila (2022, methodology): “And the regulation of CSW on the “time interval” effect in LTM formation is also thought to be via the MAPK pathway (Pagani et al., 2009).”
• Forgetting is regulated through Rac activity in Drosophila. (2010, unknown): “1Department of Biological Sciences and Biotechnology, Tsinghua University, Beijing 100084, P.R. China 2Cold Spring Harbor Laboratory, Cold Spring Harbor, NY 11724, USA *Correspondence: zhongyi@cshl.edu DOI 10.1016/j.cell.2009.12.044”
• Active Protection: Learning-Activated Raf/MAPK Activity Protects Labile Memory from Rac1-Independent Forgetting. (2018, unknown): “Consistent with our previous study (Pagani et al., 2009), we observed no training-dependent activation of MAPK 15 min after unpaired or backward training, which does not produce associative learning (Tully and Quinn, 1985) (Figures S1A and S1B).”
• Mg2+ Block of Drosophila (2012, unknown): “, 2005) and for ERK (MAPK) and pERK (pMAPK) (Pagani et al., 2009) have been previously described.”
• Event Timing in Associative Learning: From Biochemical Reaction Dynamics to Behavioural Observations (2012, background): “Also, degradation of cAMP [35] and de-phosphorylation of key downstream proteins [61] is likely critical for restricting the effects of learning both during training and thereafter.”
• How can memories last for days, years, or a lifetime? Proposed mechanisms for maintaining synaptic potentiation and memory (2019, background): “Inhibition of an atypical PKC isoform homologous to PKM ζ also impaired maintenance of LTM in Drosophila (Drier et al. 2002).”
• Spaced Training Forms Complementary Long-Term Memories of Opposite Valence in Drosophila (2019, unknown): “The 15 min ITI required for optimal spaced training coincides with the peak of training-induced activity of the extracellular signal-regulated kinase (ERK, aka MAPK) (Pagani et al., 2009; Miyashita et al., 2018).”
• Reward signal in a recurrent circuit drives appetitive long-term memory formation (2015, unknown): “While there has been progress on the molecular and cellular mechanisms underlying LTM formation resulting from repetitive conditioning (Pagani et al., 2009; Placais et al., 2012; Philips et al., 2013), how a single presentation of a reward can trigger LTM remains to be understood.”