Long-Term Potentiation--A Decade of Progress?

Malenka, Robert C.; Nicoll, Roger A.

doi:10.1126/science.285.5435.1870

Cited by 2,428 publications

(1,786 citation statements)

References 128 publications

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“…Here, LTP is believed largely due to postsynaptic mechanisms (Malenka and Nicoll, 1999). However, in the mossy fiber-CA3 synapse, the endogenous inhibitory influence of the adenosine A 1 R is larger than in CA1, and LTP is largely presynaptic in nature.…”

Section: Discussionmentioning

confidence: 99%

Mice lacking the adenosine A₁ receptor have normal spatial learning and plasticity in the CA1 region of the hippocampus, but they habituate more slowly

Giménez-Llort

Masino

Diao

et al. 2005

Synapse

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Using mice with a targeted disruption of the adenosine A 1 receptor (A 1 R), we examined the role of A 1 Rs in hippocampal long-term potentiation (LTP), long-term depression (LTD), and memory formation. Recordings from the Shaffer collateral-CA1 pathway of hippocampal slices from adult mice showed no differences between theta burst and tetanic stimulation-induced LTP in adenosine A 1 receptor knockout (A 1 R −/− ), heterozygote (A 1 R +/− ), and wildtype (A 1 R +/+ ) mice. However, paired pulse facilitation was impaired significantly in A 1 R −/− slices as compared to (A 1 R +/+ ) slices. LTD in the CA1 region was unaffected by the genetic manipulation. The three genotypes showed similar memory acquisition patterns when assessed for spatial reference and working memory in the Morris water maze tasks at 9 months of age. However, 10 months later A 1 R −/− mice showed some deficits in the 6-arm radial tunnel maze test. The latter appeared, however, not due to memory deficits but to decreased habituation to the test environment. Taken together, we observe normal spatial learning and memory and hippocampal CA1 synaptic plasticity in adult adenosine A 1 R knockout mice, but find modifications in arousal-related processes, including habituation, in this knockout model.

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Section: Discussionmentioning

confidence: 99%

Mice lacking the adenosine A₁ receptor have normal spatial learning and plasticity in the CA1 region of the hippocampus, but they habituate more slowly

Giménez-Llort

Masino

Diao

et al. 2005

Synapse

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“…In particular, activity‐dependent secretion of BDNF plays a critical role in long‐term potentiation (LTP; Aicardi et al 2004; Lu et al 2005). LTP is an activity‐dependent, persistent enhancement of synaptic strength widely studied as a cellular model for learning and memory (Malenka & Nicoll 1999). However, fundamental aspects of the mechanistic relationship between caffeine and BDNF signaling are poorly defined, particularly at the level of synaptic plasticity.…”

Section: Introductionmentioning

confidence: 99%

Caffeine‐mediated BDNF release regulates long‐term synaptic plasticity through activation of IRS2 signaling

et al. 2016

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Caffeine has cognitive‐enhancing properties with effects on learning and memory, concentration, arousal and mood. These effects imply changes at circuital and synaptic level, but the mechanism by which caffeine modifies synaptic plasticity remains elusive. Here we report that caffeine, at concentrations representing moderate to high levels of consumption in humans, induces an NMDA receptor‐independent form of LTP (CAFLTP) in the CA1 region of the hippocampus by promoting calcium‐dependent secretion of BDNF, which subsequently activates TrkB‐mediated signaling required for the expression of CAFLTP. Our data include the novel observation that insulin receptor substrate 2 (IRS2) is phosphorylated during induction of CAFLTP, a process that requires cytosolic free Ca2+. Consistent with the involvement of IRS2 signals in caffeine‐mediated synaptic plasticity, phosphorylation of Akt (Ser473) in response to LTP induction is defective in Irs2−/− mice, demonstrating that these plasticity changes are associated with downstream targets of the phosphoinositide 3‐kinase (PI3K) pathway. These findings indicate that TrkB‐IRS2 signals are essential for activation of PI3K during the induction of LTP by caffeine.

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“…review Malenka and Nicoll, 1999). In vitro and fewer in vivo preparations have been used to demonstrate that NMDA receptors, too, are removed from or inserted into synaptic membrane (Rao and Craig, 1997;Liao et al, 1999;Quinlan et al, 1999;Heynen et al, 2000;Barria and Malinow, 2002;Grosshans et al, 2002;Tovar and Westbrook, 2002).…”

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confidence: 99%

In vivo blockade of N-methyl-d-aspartate receptors induces rapid trafficking of NR2B subunits away from synapses and out of spines and terminals in adult cortex

Fujisawa

Aoki

2003

Neuroscience

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We investigated the role of in vivo synaptic activity upon trafficking of the N-methyl-D-aspartate (NMDA) receptor subunit, NR2B, at mature synapses by electron microscopic immunocytochemistry. In vivo blockade of NMDA receptors was achieved by applying the NMDA receptor antagonist, D-2-amino-5-phosphonovalerate (D-APV), onto the cortical surface of one hemisphere of anesthetized adult rats. Inactive L-2-amino-5-phosphonovalerate (L-APV) was applied to the contralateral hemisphere for within-animal control and to assess basal level of NR2B subunits at synapses. Within 30 min of D-APV treatment, we observed a decrease in the number of layer I axospinous asymmetric synapses that are positively immuno-labeled for the NR2B subunits. This decrease was paralleled by reductions in the absolute number of immuno-gold particles found at these synapses. The decrease of NR2B labeling was detectable in all five animals examined. Significant reductions were seen not only at post-synaptic densities, but also within the cytoplasm of spines and axon terminals. The data demonstrate that blockade of NMDA receptors induces trafficking of NR2B subunits out of synaptic membranes, spines, and terminals. This is in sharp contrast to a previous observation that NR2A subunits move into spines and axon terminals following in vivo blockade with D-APV. These findings point to yet unknown, NMDA receptor activitydependent mechanisms that separately regulate the localization of NR2A and NR2B subunits at synapses. Keywordsactivity-dependent; D-APV; electron microscopy; immunocytochemistry; ultrastructure; postembedding colloidal gold labelingThe N-methyl-D-aspartate (NMDA) subtype of glutamate receptor plays an important role in experience-dependent plasticity. Calcium influx through this receptor can trigger a variety of downstream biochemical reactions, contributing to plasticity (Mori and Mishina, 1995;Kind and Neumann, 2001) and excitotoxicity (Lynch and Guttmann, 2002). One of many consequences of NMDA receptor activation is altered trafficking of proteins to and from the activated synapses. For example, long-term potentiation, in which the electrophysiological response to an input is augmented, is in part produced by NMDA receptor-dependent upregulation of synaptic α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptors (see NIH Public Access Author ManuscriptNeuroscience. Author manuscript; available in PMC 2010 May 24. Malenka and Nicoll, 1999). In vitro and fewer in vivo preparations have been used to demonstrate that NMDA receptors, too, are removed from or inserted into synaptic membrane (Rao and Craig, 1997;Liao et al., 1999;Quinlan et al., 1999;Heynen et al., 2000;Barria and Malinow, 2002;Grosshans et al., 2002;Tovar and Westbrook, 2002). However, since nearly all of these studies have used neonatal tissues, whether or not such dynamic properties of NMDA receptor subunits persist at mature synapses, in vivo, is a topic that remains relatively unexplored.Among the NMDA receptor subunits, the NR1 is necessary for NMD...

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Long-Term Potentiation--A Decade of Progress?

Cited by 2,428 publications

References 128 publications

Mice lacking the adenosine A₁ receptor have normal spatial learning and plasticity in the CA1 region of the hippocampus, but they habituate more slowly

Mice lacking the adenosine A₁ receptor have normal spatial learning and plasticity in the CA1 region of the hippocampus, but they habituate more slowly

Caffeine‐mediated BDNF release regulates long‐term synaptic plasticity through activation of IRS2 signaling

In vivo blockade of N-methyl-d-aspartate receptors induces rapid trafficking of NR2B subunits away from synapses and out of spines and terminals in adult cortex

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Long-Term Potentiation--A Decade of Progress?

Cited by 2,428 publications

References 128 publications

Mice lacking the adenosine A1 receptor have normal spatial learning and plasticity in the CA1 region of the hippocampus, but they habituate more slowly

Mice lacking the adenosine A1 receptor have normal spatial learning and plasticity in the CA1 region of the hippocampus, but they habituate more slowly

Caffeine‐mediated BDNF release regulates long‐term synaptic plasticity through activation of IRS2 signaling

In vivo blockade of N-methyl-d-aspartate receptors induces rapid trafficking of NR2B subunits away from synapses and out of spines and terminals in adult cortex

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Mice lacking the adenosine A₁ receptor have normal spatial learning and plasticity in the CA1 region of the hippocampus, but they habituate more slowly

Mice lacking the adenosine A₁ receptor have normal spatial learning and plasticity in the CA1 region of the hippocampus, but they habituate more slowly