Activation of p75NTR by proBDNF facilitates hippocampal long-term depression

Woo, Newton H.; Teng, Henry; Siao, Chia-Jen; Chiaruttini, Cristina; Pang, Petti T.; Milner, Teresa A.; Hempstead, Barbara L.; Lu, Bai

doi:10.1038/nn1510

Cited by 716 publications

(664 citation statements)

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“…Furthermore, this noncompetitive NMDA antagonist disrupts synaptic plasticity in the amygdala (Bauer et al, 2002). Of particular relevance to the present argument is the fact that NMDA NR2B receptor activation is required for the induction of LTD in vitro under some circumstances Liu et al, 2004;Woo et al, 2005;Izumi et al, 2006; but see Hendricson et al, 2002;Morishita et al, 2007) and for NMDA-induced AMPA receptor endocytosis in cultured neurons (Kim et al, 2001;Tigaret et al, 2006). Indeed, recent studies have demonstrated that systemic administration of Ro 25-6981 at the same dose used in the present study blocked selectively the induction of LTD while having no effect on LTP in the hippocampus in vivo (Fox et al, 2006;Wong et al, 2007).…”

Section: Manipulations That Disrupt Ltd Formation Disrupt Fear Extincmentioning

confidence: 69%

Disruption of AMPA Receptor Endocytosis Impairs the Extinction, but not Acquisition of Learned Fear

Dalton

Wang

Floresco

et al. 2007

Neuropsychopharmacol

144

135

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Synaptic plasticity in the form of long-term potentiation (LTP) plays a critical role in the formation of a Pavlovian fear association. However, the role that synaptic plasticity plays in the suppression of a learned fear response remains to be clarified. Here, we assessed the role that long-term depression (LTD) plays in the acquisition, expression, and extinction of a conditioned fear response. We report that blockade of LTD with a GluR2-derived peptide (Tat-GluR2 3Y ; 1.5 mmol/kg, i.v.) that blocks regulated a-amino-3-hydroxy-5-methyl-isoxazole-4-propionic acid (AMPA) receptor endocytosis during an initial extinction training session disrupted both the expression and recall of extinction learning. A similar impairment of extinction during training, but not recall, was observed when NMDA receptor-dependent LTD was inhibited through the selective blockade of NMDA NR2B receptors with Ro 25-6981. In contrast, blockade of LTD with Tat-GluR2 3Y during fear conditioning or during a fear recall test did not effect the expression or recall of either contextual or cue-induced conditioned fear. Similarly, administration of Tat-GluR2 3Y prior to an extinction recall test did not affect spontaneous recovery or rate of re-extinction in previously extinguished rats. These data demonstrate that AMPA receptor endocytosis does not mediate acquisition or expression of conditioned fear, but may play a role in the extinction of fear memories. Furthermore, these findings suggest that LTD may be a molecular mechanism that facilitates the selective modification of a learned association while leaving intact the ability to form a new memory.

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Section: Manipulations That Disrupt Ltd Formation Disrupt Fear Extincmentioning

confidence: 69%

Disruption of AMPA Receptor Endocytosis Impairs the Extinction, but not Acquisition of Learned Fear

Dalton

Wang

Floresco

et al. 2007

Neuropsychopharmacol

144

135

View full text Add to dashboard Cite

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“…Recent work suggests that BDNF is released in 'pro-forms' (estimated at 19-34 kD) that are cleaved to generate mature, 13-14 kD BDNF. Both pro-and mature BDNF proteins can mediate neurotrophin signaling but the mature form is argued to be the variant that supports LTP and neuronal viability (Pang et al, 2004;Lu et al, 2005;Woo et al, 2005). Because ELISA studies so far reported used antisera that detect both pro-and mature BDNF proteins, it is possible that age-related changes in the latter, LTP-related form of the neurotrophin, were obscured by relatively stable levels of its larger precursor.…”

Section: Causes Of Age-related Changes In Synaptic Plasticitymentioning

confidence: 99%

Synaptic plasticity in early aging

Lynch

Rex

Gall

2006

Ageing Research Reviews

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Studies of how aging affects brain plasticity have largely focused on old animals. However, deterioration of memory begins well in advance of old age in animals, including humans; the present review is concerned with the possibility that changes in synaptic plasticity, as found in the long-term potentiation (LTP) effect, are responsible for this. Recent results indicate that impairments to LTP are in fact present by early middle age in rats but only in certain dendritic domains. The search for the origins of these early aging effects necessarily involves ongoing analyses of how LTP is induced, expressed, and stabilized. Such work points to the conclusion that cellular mechanisms responsible for LTP are redundant and modulated both positively and negatively by factors released during induction of potentiation. Tests for causes of the localized failure of LTP during early aging suggest that the problem lies in excessive activity of a negative modulator. The view of LTP as having redundant and modulated substrates also suggests a number of approaches for reversing age-related losses. Particular attention will be given to the idea that induction of brain-derived neurotrophic factor, an extremely potent positive modulator, can be used to provide long periods of normal plasticity with very brief pharmacological interventions. The review concludes with a consideration of how the selective, regional deficits in LTP found in early middle age might be related to the global phenomenon of brain aging. #

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“…This isoform is not further processed into mBDNF and its function has not been elucidated yet. According to the "Ying and Yang" hypothesis (Lu et al, 2005), both mBDNF and proBDNF have particular neurobiological properties. In particular, proBDNF regulate neuronal survival Koshimizu et al, 2009;Woo et al, 2005) and boosts synaptic pruning whereas mBDNF improves the differentiation of new neurons.…”

Section: The Role Of Probdnf In Patients With Schizophreniamentioning

confidence: 99%

“…According to the "Ying and Yang" hypothesis (Lu et al, 2005), both mBDNF and proBDNF have particular neurobiological properties. In particular, proBDNF regulate neuronal survival Koshimizu et al, 2009;Woo et al, 2005) and boosts synaptic pruning whereas mBDNF improves the differentiation of new neurons. Also, the conversion of proBDNF into mBDNF seems to be decisive for signal transmission and synaptic plasticity.…”

Section: The Role Of Probdnf In Patients With Schizophreniamentioning

confidence: 99%

“…Mature BDNF is created intracellularly by furin (Mowla et al, 2001), or extracellularly, by plasmin or matrixmetalloprotease-7 (Lee et al, 2001), whereas truncated-BDNF is generated by a specific Ca 2+ dependent serine proteinase known as Membrane-bound transcription factor site-1 protease (MBTFS-1), also identified as Subtilisin/Kexin-Isozyme 1 (SKI-1) (Seidah et al, 1999); it is not further processed into the mature 14 kDa BDNF form representing a final proteolytic product whose role is ambiguous. Recent findings have established that mature and pro-BDNF elicit opposite biological functions Woo et al, 2005), leading to the hypothesis t h a t f r o m a n i n c o r r e c t b a l a n c i n g o f t h e d i verse isoforms may origin a pathological consequence. In recent times, Koshimizu et al (2009) pointed out that overexpression of pro-BDNF leads to apoptosis of cultured cerebellar granule neurons and produce a striking decrease in the number of cholinergic fibers of basal forebrain neurons and hippocampal dendritic spines, without disturbing the survival of these neurons.…”

Section: The Role Of Probdnf In Patients With Schizophreniamentioning

confidence: 99%

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