Neurotrophins and Neuronal Plasticity

Thoenen, H.

doi:10.1126/science.270.5236.593

Cited by 1,833 publications

(1,092 citation statements)

References 105 publications

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“…In addition, recent results indicate that neurotrophins are also involved in the processes of neural plasticity (Thoenen, 1995). Here we have shown that NGF may in¯uence the program of gene expression which is under control of the cAMP signalling pathway.…”

Section: Discussionmentioning

confidence: 51%

Cross-talk in signal transduction: Ras-dependent induction of cAMP-responsive transcriptional repressor ICER by nerve growth factor

Monaco

Sassone–Corsi

1997

Oncogene

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The CREM gene encodes both activators and repressors of cAMP-induced transcription. By virtue of an alternative, intronic promoter within the gene, the ICER (Inducible cAMP Early Repressor) isoform is generated. ICER acts as a dominant negative regulator and is cAMP-inducible in various neuroendocrine cells and tissues. ICER negatively autoregulates its own expression, and appears to participate in the molecular events governing oscillatory hormonal regulations. Here we report that ICER is inducible with nerve growth factor (NGF). This is the ®rst example of cAMP-independent induction of ICER expression. Importantly, induction by NGF occurs via a subset of the CREs present in the ICER promoter which were previously shown to direct cAMP-inducibility. ICER induction correlates with a NGF-mediated phosphorylation of CREB. Both CREB phosphorylation and ICER inducibility require an intact Ras-dependent signalling pathway. We show that increased ICER levels result in the attenuation of c-fos expression. The activation of a powerful repressor of cAMP-responsive transcription by NGF, whose transduction signalling is cAMP-independent, constitutes a notable example of nuclear cross-talk and thus is likely to have relevant physiological implications.

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Section: Discussionmentioning

confidence: 51%

Cross-talk in signal transduction: Ras-dependent induction of cAMP-responsive transcriptional repressor ICER by nerve growth factor

Monaco

Sassone–Corsi

1997

Oncogene

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“…BDNF influences neuronal differentiation in development, as well as synaptic plasticity and neuronal survival in adulthood (Thoenen, 1995). Several results suggest that it may play a role in the pathophysiology of depression (Duman, 2002).…”

Section: Introductionmentioning

confidence: 99%

A BDNF Coding Variant is Associated with the NEO Personality Inventory Domain Neuroticism, a Risk Factor for Depression

Sen

Nesse

Stoltenberg

et al. 2002

Neuropsychopharmacol

311

229

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“…Mice overexpressing BDNF in the postnatal brain show a precocious critical period for ODP 18,19 . The prevailing hypothesis 8,17,20,21 has been that competition for limited amounts of BDNF, which acts on TrkB receptors, is the effector of activity-dependent plasticity in the cortex, and the conventional explanation for ODP is that the deprived eye fails to activate cortical cells as well as the open eye, thereby failing to stimulate them to release sufficient BDNF to sustain the deprived-eye pathway.…”

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confidence: 99%

TrkB kinase is required for recovery, but not loss, of cortical responses following monocular deprivation

et al. 2008

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Changes in visual cortical responses that are induced by monocular visual deprivation are a widely studied example of competitive, experience-dependent neural plasticity. It has been thought that the deprived-eye pathway will fail to compete against the open-eye pathway for limited amounts of brainderived neurotrophic factor, which acts on TrkB and is needed to sustain effective synaptic connections. We tested this model by using a chemical-genetic approach in mice to inhibit TrkB kinase activity rapidly and specifically during the induction of cortical plasticity in vivo. Contrary to the model, TrkB kinase activity was not required for any of the effects of monocular deprivation. When the deprived eye was re-opened during the critical period, cortical responses to it recovered. This recovery was blocked by TrkB inhibition. These findings suggest a more conventional trophic role for TrkB signaling in the enhancement of responses or growth of new connections, rather than a role in competition.During development, experience strongly influences the formation and maturation of neuronal connectivity in the mammalian cortex. In the visual system, closing one eye for even a few days during a critical period of heightened plasticity in early postnatal life leads to a pronounced decrease in the cortical representation of the deprived eye, which is observed both physiologically and anatomically 1 . The experience-dependent changes following such monocular deprivation, termed ocular dominance plasticity (ODP), operate through a competitive interaction between inputs from the two eyes and depend on the activity state of the postsynaptic neurons 1-5 . These features of ODP have suggested that a retrograde signal released by the postsynaptic neurons may mediate plasticity by affecting afferents from the two eyes differently.Brain-derived neurotrophic factor (BDNF), the cognate ligand for the TrkB receptor, has been proposed to be such a retrograde signal on the basis of a number of observations, including the Correspondence should be addressed to M.P.S. (stryker@phy.ucsf.edu). AUTHOR CONTRIBUTIONS M.K. carried out all of the biochemical analysis, optical imaging and single-unit recordings using TrkB F616A and their appropriate control mice, prepared all of the figures (except for Supplementary Fig. 3) and wrote the first draft of the manuscript. J.L.H. carried out experiments on K252a and TrkB-IgG mice. P.M.E. supplied mutant mice and 1NM-PP1. M.K., P.M.E. and M.P.S. designed the experiments and assisted with data analysis and revision of the manuscript.Reprints and permissions information is available online at

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Neurotrophins and Neuronal Plasticity

Cited by 1,833 publications

References 105 publications

Cross-talk in signal transduction: Ras-dependent induction of cAMP-responsive transcriptional repressor ICER by nerve growth factor

Cross-talk in signal transduction: Ras-dependent induction of cAMP-responsive transcriptional repressor ICER by nerve growth factor

A BDNF Coding Variant is Associated with the NEO Personality Inventory Domain Neuroticism, a Risk Factor for Depression

TrkB kinase is required for recovery, but not loss, of cortical responses following monocular deprivation

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