NMDA receptor-dependent long-term potentiation and long-term depression (LTP/LTD).

In the paper

“Consistent with this idea, the spine density increases following LTP induction, and a significantly higher frequency of multiple-spine synapses (Toni et al. 1999) is observed, as well as a reduction of their turnover (De Roo et al. 2008).”

What the sources say

• ?Not checked — no full text of the sourcecites Toni et al. 1999 source
• Disputed

  The De Roo citation is attached to the claimed reduction in turnover. The Results section, “LTP Induction Results in a Lasting Increase in Protrusion Turnover” (page unavailable), reports that turnover increased for several days after LTP induction; the Discussion likewise calls it a lasting, enhanced turnover. The paper does report selective stabilization of stimulated spines, but not an overall reduction in turnover. (LLM, conf=0.88)

  Checked by a reasoning model — may be wrong.

  cites De Roo et al. 2008 sourceExperimental — accuracy not yet measured

In the paper

“Consistent with original ideas (Bienenstock et al. 1982), modest depolarization can elicit LTD, whereas stronger depolarization leads to LTP.”

What the sources say

• Partly supported

  Section II, “Modification of Cortical Synapses” (page unavailable), proposes that synaptic strength decreases when postsynaptic output is below a modification threshold and increases when it is above it. This supports the claim’s low-versus-high activity pattern, but the paper describes a theoretical rule based on postsynaptic response, not a finding that modest versus stronger depolarization elicits LTD and LTP. (LLM, conf=0.85)

  cites Bienenstock et al. 1982 sourceExperimental — accuracy not yet measured

In the paper

“Because the driving force for calcium entry is very large for a neuron at rest and the block of NMDARs by Mg 2þ is incomplete even at resting potentials (Jahr and Stevens 1993), significant Ca enters the cell in response to synaptic stimulation (Sabatini et al. 2002;Bloodgood and Sabatini 2007;Bloodgood et al. 2009) during low-frequency synaptic stimulation.”

What the sources say

• Partly supported

  Split into 2 atoms — 0 confirmed, 1 partially supported, 0 disputed, 0 misattributed, 1 unverifiable. Expand the claim to see per-atom verdicts.

  cites Jahr and Stevens 1993 sourceExperimental — accuracy not yet measured
• ?Not checked — no full text of the sourcecites Sabatini et al. 2002 source
• ?Not checked — no full text of the sourcecites Bloodgood and Sabatini 2007 source

In the paper

“These early drug-evoked changes in the properties of excitatory synapses on dopamine cells can be very long-lasting and are followed by many additional synaptic modifications in related structures.”

What the sources say

• ?Not checked — no full text of the sourcecites Thomas and Malenka 2003 source
• ?Not checked — no full text of the sourcecites Kauer and Malenka 2007 source
• Partly supported

  Section 5.3 (page unavailable) reports that early plasticity in VTA dopamine neurons is required for subsequent changes in nucleus accumbens AMPAR transmission, and discusses later adaptations in other VTA targets. It does not establish that the early synaptic changes themselves are very long-lasting; the changes it says persist after long withdrawal are in the nucleus accumbens. (LLM, conf=0.85)

  cites Wolf and Ferrario 2010 sourceExperimental — accuracy not yet measured

In the paper

“Through this mechanism NMDARs play the role of molecular coincidence detectors, which, as we will see below, is essential for several forms of synaptic plasticity.”

In the paper

“The workhorse of glutamatergic transmission is the AMPAR, which drives large and rapid synaptic signaling (Fig. 2).”

In the paper

“Both are ionotropic receptors that are permeable to Na þ and K þ .”

What the sources say

• ?Not checked — no full text of the sourcecites Dingledine et al. 1999 source

In the paper

“At these CA3-CA1 Schaffer collateral synapses, the loci of both induction and expression are situated in the postsynaptic neuron.”

In the paper

“The early phases of expression are mediated by a redistribution of AMPA-type glutamate receptors: More receptors are added to potentiate the synapse or receptors are removed to weaken synapses.”

• Also stated in: § EXPRESSION MECHANISM · boosted

  “A large body of experimental evidence now supports this hypothesis (Lu ¨scher et al. 2000;Lu ¨scher and Frerking 2001;Malinow and Malenka 2002;Nicoll 2003;Collingridge et al. 2004;Malenka and Bear 2004).”

What the sources say

• ?Not checked — no full text of the sourcecites Lledo et al. 1998 source
• ?Not matched

  Couldn’t be matched to a paper in Crossref, so it can’t be checked.

  cites Lu ¨scher et al. 1999

In the paper

“Activation of ionotropic glutamate receptors leads to strong influx of Na þ and only a small efflux of K þ , such that the net effect is the depolarization of the postsynaptic neuron.”

In the paper

“Some of these proteins modulate glutamate receptor function, whereas others control their membrane insertion and removal.”

What the sources say

• ?Not checked — no full text of the sourcecites Elias and Nicoll 2007 source

In the paper

“For LTP there is strong evidence that the opening of NMDARs increases calcium concentration sufficiently in the dendritic spine to activate calcium/calmodulin-dependent kinase II (CaMKII), which is found at very high concentrations in spines and which is clearly required for LTP (Lisman et al. 2002).”

What the sources say

• ?Not checked — no full text of the sourcecites Lisman et al. 2002 source

In the paper

“Because the latter have a higher conductance, this will potentiate the synapse even if the total number remains the same.”

In the paper

“However, this makes sense because high-frequency stimulation protocols cause a strong temporal summation of the excitatory postsynaptic potentials (EPSPs), and the resultant large depolarization of the postsynaptic cell is sufficient to relieve the Mg block of the NMDAR and allow a large amount of calcium to enter the postsynaptic cells during the induction protocol.”

In the paper

“Indeed, it is now fairly well accepted that modest activation of NMDARs leading to modest increases in postsynaptic calcium are optimal for triggering LTD, whereas much stronger activation of NMDARs leading to much larger increases in postsynaptic calcium are required to trigger LTP (Malenka 1994).”

What the sources say

• ?Not checked — no full text of the sourcecites Malenka 1994 source

In the paper

“From the perspective of the postsynaptic neuron (which is where the recordings are made), these manipulations lead to both a synaptic potential and an action potential that backpropagates into the dendrites, which presumably provides the additional depolarization required to facilitate calcium influx through the activated NMDARs (Stuart et al. 1997;Waters et al. 2005).”

What the sources say

• ?Not checked — no full text of the sourcecites Stuart et al. 1997 source
• ?Not checked — no full text of the sourcecites Waters et al. 2005 source

In the paper

“For LTP induction both pre-and postsynaptic neurons need to be active at the same time because the postsynaptic neuron must be depolarized when glutamate is released from the presynaptic bouton to fully relieve the Mg 2þ block of NMDARs.”

In the paper

“These ubiquitous forms of short-term synaptic plasticity are greatly influenced by the baseline release probability yet were unaffected by the generation of LTP (McNaughton 1982;Manabe et al. 1993; but see Schulz et al. 1995).”

What the sources say

• ?Not checked — no full text of the sourcecites McNaughton 1982 source
• ?Not checked — no full text of the sourcecites Manabe et al. 1993 source
• ?Not checked — no full text of the sourcecites Schulz et al. 1995 source

In the paper

“NMDAR-dependent LTP is therefore an associative form of plasticity and fulfills the criteria for correlated activity as the origin of the strengthening of the connection between two neurons proposed by Donald Hebb more than 60 years ago (Hebb 1949).”

What the sources say

• ?Not matched

  Couldn’t be matched to a paper in Crossref, so it can’t be checked.

  cites Hebb 1949

In the paper

“There is, however, no change in the size of these currents after induction of LTP even though other manipulations that affect transmitter release have clear effects.”

What the sources say

• ?Not checked — no full text of the sourcecites Diamond et al. 1998 source
• ?Not matched

  Couldn’t be matched to a paper in Crossref, so it can’t be checked.

  cites Lu ¨scher et al. 1998

In the paper

“Of particular interest are members of the TARP family, which interact with all AMPA receptor subunits and control not only membrane insertion but also lateral redistribution (Chen et al. 2000;Tomita et al. 2005; see Blakely and Edwards 2012).”

What the sources say

• ?Not checked — no full text of the sourcecites Chen et al. 2000 source
• ?Not checked — no full text of the sourcecites Tomita et al. 2005 source
• ?Not checked — no full text of the sourcecites Blakely and Edwards 2012 source

In the paper

“As a consequence of coincident depolarization and glutamate binding, calcium influx through NMDARs is maximal, which activates intracellular signaling cascades that ultimately are responsible for the altered synaptic efficacy.”

In the paper

“As the direction of synaptic plasticity depends on the timing between the presynaptic and postsynaptic spikes, this phenomenon has been named spike-timing-dependent plasticity (Dan and Poo 2006;Caporale and Dan 2008).”

What the sources say

• ?Not checked — no full text of the sourcecites Dan and Poo 2006 source
• ?Not checked — no full text of the sourcecites Caporale and Dan 2008 source

In the paper

“This causes only a modest amount of postsynaptic depolarization, resulting in a modest but prolonged increase in postsynaptic calcium due to modest and repetitive activation of NMDARs.”

In the paper

“Appropriate coincident activity of the pre-and postsynaptic neurons causes an influx of calcium through NMDARs, and depending on the quantitative characteristics of this calcium signal, AMPARs are either inserted into or removed from the synapses, resulting in LTP or LTD, respectively.”

In the paper

“Importantly, it was found that the rate of this decrease remains unaltered by LTP but is clearly affected by other manipulations that are known to influence the probability of transmitter release (Manabe and Nicoll 1994).”

What the sources say

• ?Not checked — no full text of the sourcecites Manabe and Nicoll 1994 source

In the paper

“This result immediately raised the possibility that at both silent synapses and synapses that already contain AMPARs, LTP involves the insertion of more AMPARs into the synapse, whereas conversely, LTD may involve the removal or endocytosis of synaptic AMPARs (Fig. 3) (Lledo et al. 1998;Lu ¨scher et al. 1999).”

What the sources say

• ?Not checked — no full text of the sourcecites Lledo et al. 1998 source
• ?Not matched

  Couldn’t be matched to a paper in Crossref, so it can’t be checked.

  cites Lu ¨scher et al. 1999

In the paper

“Furthermore, the toxic Ab also decreases synaptic NMDARs, a change that contributes to the impaired LTP (Kamenetz et al. 2003).”

What the sources say

• ?Not checked — no full text of the sourcecites Kamenetz et al. 2003 source

In the paper

“It is induced by activation of NMDARs (and sometimes voltagegated calcium channels) and modulated by GABA B receptors, which together drive an increase in cytoplasmic calcium, in part by triggering the release of calcium from intracellular stores.”

What the sources say

• ?Not checked — no full text of the sourcecites Inagaki et al. 2008 source

In the paper

“Such perforated synapses also contain a higher proportion of smooth endoplasmic reticulum and a spine apparatus (Lu ¨scher et al. 2000).”

What the sources say

• ?Not matched

  Couldn’t be matched to a paper in Crossref, so it can’t be checked.

  cites Lu ¨scher et al. 2000

In the paper

“Importantly, this manipulation occludes further LTP, suggesting a shared mechanism between the ways of increasing synaptic strength (Malenka and Nicoll 1999;Lisman et al. 2002).”

What the sources say

• ?Not checked — no full text of the sourcecites Malenka and Nicoll 1999 source
• ?Not checked — no full text of the sourcecites Lisman et al. 2002 source

In the paper

“The increase of this IPSP also depends on NMDAR activation and CaMKII, thus sharing two key properties with hippocampal LTP of AMPARs.”

What the sources say

• ?Not checked — no full text of the sourcecites Huang et al. 2005 source

In the paper

“This is a very attractive model because calcineurin has a much higher affinity for calcium/calmodulin than does CaMKII and thus will be preferentially activated by a modest increase in calcium, the exact trigger for LTD.”

In the paper

“Synaptic plasticity of GABAergic transmission needs the activation of glutamatergic synapses and a specific messenger that passes the signal from one type of synapses to the other.”

In the paper

“In this model NMDAR activation leads to postsynaptic release of BDNF, which functions as a retrograde messenger and causes an increase in GABA release through activation of presynaptic TrkB receptors.”

What the sources say

• ?Not checked — no full text of the sourcecites Inagaki et al. 2008 source

In the paper

“Indeed, a very influential model proposed that NMDAR-dependent LTD depends on the calcium/calmodulin-dependent protein phosphatase calcineurin as well as on protein phosphatase 1 (PP1) (Lisman 1989).”

What the sources say

• ?Not checked — no full text of the sourcecites Lisman 1989 source

In the paper

“This leads to activation of a Ca 2þ -dependent nitric oxide synthase, which generates nitric oxide, which acts as a retrograde messenger by diffusing back to presynaptic neurons.”

What the sources say

• ?Not checked — no full text of the sourcecites Nugent et al. 2007 source

In the paper

“Through these mechanisms LTP may guide the selective stabilization of synaptic inputs that show coincident activity, whereas nonactivated inputs may be removed and replaced by new spines.”

In the paper

“Direct application or overproduction of Ab oligomers both inhibits LTP and triggers LTD-like changes (Fig. 5).”

What the sources say

• ?Not matched

  Couldn’t be matched to a paper in Crossref, so it can’t be checked.

  cites Fig. 5

In the paper

“Soluble Ab oligomers strongly activate metabotropic glutamate receptors (mGluRs), which leads to the internalization of AMPARs and LTD.”

What the sources say

• ?Not matched

  Couldn’t be matched to a paper in Crossref, so it can’t be checked.

  cites Fig. 5

In the paper

“This drug-evoked plasticity requires activation of type 1 dopamine receptors along with NMDAR activation and is expressed by a redistribution of AMPARs and NMDARs.”

What the sources say

• ?Not checked — no full text of the sourcecites Ungless et al. 2001 source

In the paper

“In a second step synapses become thinner and some disappear.”

What the sources say

• ?Not matched

  Couldn’t be matched to a paper in Crossref, so it can’t be checked.

  cites Fig. 5

In the paper

“AMPA receptors have a linear I -V relationship when they contain the subunit GluA2, but are inward-rectifying (see text for definition) without GluA2.”

What the sources say

• ?Not matched

  Couldn’t be matched to a paper in Crossref, so it can’t be checked.

  cites Fig. 2

In the paper

“At the same time they inhibit NMDARs, precluding the induction of LTP.”

What the sources say

• ?Not matched

  Couldn’t be matched to a paper in Crossref, so it can’t be checked.

  cites Fig. 5