Synaptic evidence for the efficacy of spaced learning

In the paper

“A third train delayed by 60 min after TBS2 again increased potentiation, whereas a fourth and fifth had no effect (Fig. 1D).”

In the paper

“TBS2 caused short-term, but not additional long-term, response facilitation when delivered at 10 or 30 min after TBS1.”

In the paper

“Successive bouts of naturalistic theta burst stimulation of field CA1 afferents markedly enhanced previously saturated LTP if spaced apart by 1 h or longer, but were without effect when shorter intervals were used.”

In the paper

“Forty-minute treatments that immediately preceded TBS1, or that ended 10 min before the theta bursts, had no effect on baseline physiology or the induction of LTP1 (Fig. 4D, Left).”

In the paper

“However, as shown in Fig. 4D, brefeldin administered after TBS1 also produced a dramatic and unexpected result: it caused LTP1 to gradually decay back to baseline, again without affecting responses to a control input.”

In the paper

“Head volume changes did not occur in neighboring spines, confirming that the stimulation protocol produces plasticity at a single synapse.”

In the paper

“Indeed, the enlargement probability was significantly greater in young than in adult slices (P < 0.005) even though the targeted spines were of similar volume and the same induction protocol was used (Fig. 3D).”

In the paper

“Such an event would necessarily increase excitatory postsynaptic potentials (EPSPs) at 30–60 min after TBS1 and this is not observed.”

In the paper

“Regarding the cellular bases for the distinction between low and high threshold spines, we found that brief treatments with a drug that selectively enhances AMPA receptor-gated synaptic currents markedly increases both the number of spines in which TBS1 triggers actin polymerization and the magnitude of LTP1.”

In the paper

“Second, the glutamate-uncaging experiments were designed to produce maximal stimulation of NMDARs and yet detected two classes of spines in the proportions expected from the LTP studies.”

In the paper

“Activity-dependent synaptic plasticity, and, in particular, long-term potentiation (LTP) of glutamatergic transmission, is thought to underlie rapid storage of new information (5, 6).”

What the sources say

• Not checked yetcites [5] Lynch G, Rex CS, Chen LY, Gall CM. Synaptic mechanisms for encoding memory. In: Koob G, Thompson RF, Le Moal M, editors. Encyclopedia of Behavioral Neuroscience. London: Academic; 2009. pp. 356–366. section ed Shors T. [Google Scholar]
• Not checked yetcites [6] Morris RG. Long-term potentiation and memory. Philos Trans R Soc Lond B Biol Sci. 2003;358:643–647. doi: 10.1098/rstb.2002.1230. [DOI] [PMC free article] [PubMed] [Google Scholar] source

In the paper

“Other studies using variable stimulation intensities suggest that additional potentiation can be induced four hours after induction of LTP1 (10, 12).”

What the sources say

• Not checked yetcites [10] Frey U, Morris RG. Synaptic tagging: Implications for late maintenance of hippocampal long-term potentiation. Trends Neurosci. 1998;21:181–188. doi: 10.1016/s0166-2236(97)01189-2. [DOI] [PubMed] [Google Scholar] source
• Not checked yetcites [12] Frey U, Schollmeier K, Reymann KG, Seidenbecher T. Asymptotic hippocampal long-term potentiation in rats does not preclude additional potentiation at later phases. Neuroscience. 1995;67:799–807. doi: 10.1016/0306-4522(95)00117-2. [DOI] [PubMed] [Google Scholar] source

In the paper

“Low-frequency (5-Hz) stimulation erases LTP1 if applied shortly after TBS but then becomes progressively less effective over the following 30 min (8, 14);”

What the sources say

• Not checked yetcites [8] Huang CC, Liang YC, Hsu KS. A role for extracellular adenosine in time-dependent reversal of long-term potentiation by low-frequency stimulation at hippocampal CA1 synapses. J Neurosci. 1999;19:9728–9738. doi: 10.1523/JNEUROSCI.19-22-09728.1999. [DOI] [PMC free article] [PubMed] [Google Scholar] source
• Not checked yetcites [14] Barrionuevo G, Schottler F, Lynch G. The effects of repetitive low frequency stimulation on control and “potentiated” synaptic responses in the hippocampus. Life Sci. 1980;27:2385–2391. doi: 10.1016/0024-3205(80)90509-3. [DOI] [PubMed] [Google Scholar] source

In the paper

“In all, the present results show that LTP has a previously undetected refractory period, lasting for 30–60 min, which creates an analog of the behavioral spaced trials effect (13).”

What the sources say

• Not checked yetcites [13] Anderson MJ, Jablonski SA, Klimas DB. Spaced initial stimulus familiarization enhances novelty preference in Long-Evans rats. Behav Processes. 2008;78:481–486. doi: 10.1016/j.beproc.2008.02.005. [DOI] [PubMed] [Google Scholar] source

In the paper

“The mechanism underlying this phenomenon involves local spreading of signaling cascades from the activated spine to its neighbors, and some of these spreading signals are potent drivers of F-actin dynamics (24–26).”

What the sources say

• Not checked yetcites [24] Murakoshi H, Wang H, Yasuda R. Local, persistent activation of Rho GTPases during plasticity of single dendritic spines. Nature. 2011;472:100–104. doi: 10.1038/nature09823. [DOI] [PMC free article] [PubMed] [Google Scholar] source
• Not checked yetcites [25] Harvey CD, Yasuda R, Zhong H, Svoboda K. The spread of Ras activity triggered by activation of a single dendritic spine. Science. 2008;321:136–140. doi: 10.1126/science.1159675. [DOI] [PMC free article] [PubMed] [Google Scholar] source
• Not checked yetcites [26] Rex CS, et al. Different Rho GTPase-dependent signaling pathways initiate sequential steps in the consolidation of long-term potentiation. J Cell Biol. 2009;186:85–97. doi: 10.1083/jcb.200901084. [DOI] [PMC free article] [PubMed] [Google Scholar] source

In the paper

“The spaced-trial effect operates across multiple time frames, ranging from a few seconds to weeks (30).”

What the sources say

• Not checked yetcites [30] Cepeda NJ, Pashler H, Vul E, Wixted JT, Rohrer D. Distributed practice in verbal recall tasks: A review and quantitative synthesis. Psychol Bull. 2006;132:354–380. doi: 10.1037/0033-2909.132.3.354. [DOI] [PubMed] [Google Scholar] source

In the paper

“Previous efforts to find neurobiological explanations for the advantages of distributed practice obtained evidence that spaced trials can offset memory defects in mice lacking two variants of the transcription factor CREB (31, 32).”

What the sources say

• Not checked yetcites [31] Kogan JH, et al. Spaced training induces normal long-term memory in CREB mutant mice. Curr Biol. 1997;7:1–11. doi: 10.1016/s0960-9822(06)00022-4. [DOI] [PubMed] [Google Scholar] source
• Not checked yetcites [32] Yin JC, et al. Induction of a dominant negative CREB transgene specifically blocks long-term memory in Drosophila. Cell. 1994;79:49–58. doi: 10.1016/0092-8674(94)90399-9. [DOI] [PubMed] [Google Scholar] source

In the paper

“This form of plasticity shares many properties with Schaffer collateral LTP, including dependence on N-methyl-d-aspartate receptors (NMDARs), Rho GTPase signaling, Ca2+/calmodulin-dependent protein kinase II (CaMKII) phosphorylation, F-actin polymerization and synaptic AMPAR insertion (20–24).”

What the sources say

• Not checked yetcites [20] Harvey CD, Svoboda K. Locally dynamic synaptic learning rules in pyramidal neuron dendrites. Nature. 2007;450:1195–1200. doi: 10.1038/nature06416. [DOI] [PMC free article] [PubMed] [Google Scholar] source
• Not checked yetcites [21] Matsuzaki M, Honkura N, Ellis-Davies GC, Kasai H. Structural basis of long-term potentiation in single dendritic spines. Nature. 2004;429:761–766. doi: 10.1038/nature02617. [DOI] [PMC free article] [PubMed] [Google Scholar] source
• Not checked yetcites [22] Honkura N, Matsuzaki M, Noguchi J, Ellis-Davies GC, Kasai H. The subspine organization of actin fibers regulates the structure and plasticity of dendritic spines. Neuron. 2008;57:719–729. doi: 10.1016/j.neuron.2008.01.013. [DOI] [PubMed] [Google Scholar] source
• Not checked yetcites [23] Makino H, Malinow R. AMPA receptor incorporation into synapses during LTP: The role of lateral movement and exocytosis. Neuron. 2009;64:381–390. doi: 10.1016/j.neuron.2009.08.035. [DOI] [PMC free article] [PubMed] [Google Scholar] source
• Not checked yetcites [24] Murakoshi H, Wang H, Yasuda R. Local, persistent activation of Rho GTPases during plasticity of single dendritic spines. Nature. 2011;472:100–104. doi: 10.1038/nature09823. [DOI] [PMC free article] [PubMed] [Google Scholar] source

In the paper

“The latter finding points to a hypothesis in which similarly delayed events set in motion by TBS1 serve to anchor LTP in one set of spines and to provide ingredients needed for potentiation in a second.”

In the paper

“The low success rate in adults was unlikely related to technical issues because we used a strong induction protocol (20) that caused structural plasticity in >80% of young spines (Fig. 3C), a value in good agreement with previous studies (20, 21).”

What the sources say

• Not checked yetcites [20] Harvey CD, Svoboda K. Locally dynamic synaptic learning rules in pyramidal neuron dendrites. Nature. 2007;450:1195–1200. doi: 10.1038/nature06416. [DOI] [PMC free article] [PubMed] [Google Scholar] source
• Not checked yetcites [21] Matsuzaki M, Honkura N, Ellis-Davies GC, Kasai H. Structural basis of long-term potentiation in single dendritic spines. Nature. 2004;429:761–766. doi: 10.1038/nature02617. [DOI] [PMC free article] [PubMed] [Google Scholar] source

In the paper

“and (ii) conversion of TBS1-resistant spines into the low threshold state, which provides a refreshed pool of synapses capable of responding to TBS2.”

In the paper

“Precise alignment of the stimulation scanner to the image scanner was confirmed by ablation of a 0.5-μm tetraspec bead (Invitrogen) with a high-energy pulse of 720-nm light.”

In the paper

“several studies have shown that the kinase PKMζ is engaged at ≥1 h after induction and then contributes to maintenance of LTP (39).”

What the sources say

• Not checked yetcites [39] Sacktor TC. PKMzeta, LTP maintenance, and the dynamic molecular biology of memory storage. Prog Brain Res. 2008;169:27–40. doi: 10.1016/S0079-6123(07)00002-7. [DOI] [PubMed] [Google Scholar] source

In the paper

“One aspect of our data links the requirement for long delays to machinery that also serves to stabilize previously induced LTP and, thereby, supports consolidation explanations (43) for the behavioral effects.”

What the sources say

• Not checked yetcites [43] Glenberg AM. Component-levels theory of the effects of spacing of repetitions on recall and recognition. Mem Cognit. 1979;7:95–112. doi: 10.3758/bf03197590. [DOI] [PubMed] [Google Scholar] source

In the paper

“Prior work suggesting that strong stimulation of single synapses causes the spread of active GTPases to neighboring spines (24, 25) is of interest in this regard because these enzymes play critical roles in the production of stable LTP.”

What the sources say

• Not checked yetcites [24] Murakoshi H, Wang H, Yasuda R. Local, persistent activation of Rho GTPases during plasticity of single dendritic spines. Nature. 2011;472:100–104. doi: 10.1038/nature09823. [DOI] [PMC free article] [PubMed] [Google Scholar] source
• Not checked yetcites [25] Harvey CD, Yasuda R, Zhong H, Svoboda K. The spread of Ras activity triggered by activation of a single dendritic spine. Science. 2008;321:136–140. doi: 10.1126/science.1159675. [DOI] [PMC free article] [PubMed] [Google Scholar] source

In the paper

“because these enzymes play critical roles in the production of stable LTP.”

• Also stated in: § Discussion · plain

  “spines (24, 25) is of interest in this regard because these enzymes play critical roles in the production of stable LTP.”

What the sources say

• Not checked yetcites [24] Murakoshi H, Wang H, Yasuda R. Local, persistent activation of Rho GTPases during plasticity of single dendritic spines. Nature. 2011;472:100–104. doi: 10.1038/nature09823. [DOI] [PMC free article] [PubMed] [Google Scholar] source
• Not checked yetcites [25] Harvey CD, Yasuda R, Zhong H, Svoboda K. The spread of Ras activity triggered by activation of a single dendritic spine. Science. 2008;321:136–140. doi: 10.1126/science.1159675. [DOI] [PMC free article] [PubMed] [Google Scholar] source

In the paper

“First, it implies that the delayed membrane insertion step indicated by the brefeldin experiments involves delivery of AMPA receptors to synapses.”

In the paper

“This threshold was chosen before the experiments were conducted and was based on prior studies (21).”

What the sources say

• Not checked yetcites [21] Matsuzaki M, Honkura N, Ellis-Davies GC, Kasai H. Structural basis of long-term potentiation in single dendritic spines. Nature. 2004;429:761–766. doi: 10.1038/nature02617. [DOI] [PMC free article] [PubMed] [Google Scholar] source

In the paper

“Volume changes at nearby spines were also analyzed to ensure that laser targeting of individual spines was specific.”

In the paper

“Thus, previously undetected cellular mechanisms impose temporal spacing requirements for synaptic plasticity and, thereby, provide a neurobiological explanation for one temporal segment of a ubiquitous feature of learning.”

In the paper

“Reports that induction of LTP is accompanied by prolonged activation of CaMKII (38), a kinase localized to synapses, suggest a candidate for this role.”

What the sources say

• Not checked yetcites [38] Lisman J, Schulman H, Cline H. The molecular basis of CaMKII function in synaptic and behavioural memory. Nat Rev Neurosci. 2002;3:175–190. doi: 10.1038/nrn753. [DOI] [PubMed] [Google Scholar] source

In the paper

“The spine threshold component of the present results implies that spaced trials capture a greater percentage of the information carried by activated afferent systems, something that would allow for easier cue recognition during retention tests.”