Changes in protein synthesis accompanying long-term potentiation in the dentate gyrus in vivo

Fazeli, Alireza; Corbet, J; Dunn, M. J.; Dolphin, AC; Bliss, TV

doi:10.1523/jneurosci.13-04-01346.1993

Cited by 101 publications

(39 citation statements)

References 18 publications

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“…Our localization of FMRP to the spine heads and bases raises the possibility that the spine dysmorphisms occurring in fragile X are related to local alterations in protein translation attributable to the loss of FMRP. It has been proposed that postsynaptic mRNAs and ribosomes may serve to synthesize components required for synapse development and plasticity (Steward and Levy, 1982;Steward, 1983;Steward and Falk, 1986) and for the induction and maintenance of long-term potentiation (Frey et al, 1991;Fazeli et al, 1993). Although direct evidence does not yet exist, we speculate that altered protein synthesis in dendrites and spines occurs in fragile X, leading to synaptic dysfunction and mental retardation.…”

Section: Fragile X Syndrome and Fmrpmentioning

confidence: 66%

Fragile X Mental Retardation Protein: Nucleocytoplasmic Shuttling and Association with Somatodendritic Ribosomes

et al. 1997

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Fragile X syndrome, a leading cause of inherited mental retardation, is attributable to the unstable expansion of a CGGrepeat within the FMR1 gene that results in the absence of the encoded protein. The fragile X mental retardation protein (FMRP) is a ribosome-associated RNA-binding protein of uncertain function that contains nuclear localization and export signals. We show here detailed cellular localization studies using both biochemical and immunocytochemical approaches. FMRP was highly expressed in neurons but not glia throughout the rat brain, as detected by light microscopy. Although certain structures, such as hippocampus, revealed a strong signal, the regional variation in staining intensity appeared to be related to neuron size and density. In human cell lines and mouse brain, FMRP co-fractionated primarily with polysomes and rough endoplasmic reticulum. Ultrastructural studies in rat brain revealed high levels of FMRP immunoreactivity in neuronal perikarya, where it is concentrated in regions rich in ribosomes, particularly near or between rough endoplasmic reticulum cisternae. Immunogold studies also provided evidence of nucleocytoplasmic shuttling of FMRP, which was localized in neuronal nucleoplasm and within nuclear pores. Moreover, labeling was observed in large-and small-caliber dendrites, in dendritic branch points, at the origins of spine necks, and in spine heads, all known locations of neuronal polysomes. Dendritic localization, which was confirmed by co-fractionation of FMRP with synaptosomal ribosomes, suggests a possible role of FMRP in the translation of proteins involved in dendritic structure or function and relevant for the mental retardation occurring in fragile X syndrome.

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Section: Fragile X Syndrome and Fmrpmentioning

confidence: 66%

Fragile X Mental Retardation Protein: Nucleocytoplasmic Shuttling and Association with Somatodendritic Ribosomes

et al. 1997

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“…These results suggest that critical phosphorylation events for LTP occur during the first 20 min after induction stimuli and ongoing protein kinase activity is not required during the later (30--80 min) stages of LTP. Increasing evidence indicates that phosphorylated substrates (e.g., B-50; Gianotti et al 1992;and AMPA receptor;Davies et al 1989) and new proteins (Otani et al 1992;Fazelli et al 1993) …”

Section: Discussionmentioning

confidence: 99%

A critical period of protein kinase activity after tetanic stimulation is required for the induction of long-term potentiation.

Huber¹,

Mauk²,

Thompson³

1995

Learn. Mem.

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A critical period of protein kinase activity required for the induction of long-term potentiation (LTP) was determined in area CA1 of hippocampal slices using the broad-range and potent protein kinase inhibitors K-252a and staurosporine. As reported previously, K-252a and staurosporine blocked LTP induction when applied before, during, and after high-frequency stimulation (HFS). In contrast, K-252a did not block LTP when applied only before and during HFS and washed out immediately after HFS. K-252a and staurosporine both attenuated LTP magnitude when applied immediately after or as late as 5 min after HFS. However, K-252a applications beginning 30-45 rain after HFS did not affect LTP expression significantly. K-252a had no detectable effect on isolated N-methyl-v-aspartate (NMDA) receptor-mediated EPSPs but significantly inhibited the in situ phosphorylation of specific hippocampal proteins (synapsin I, MARCKS, and B-50). In addition, K-252a attenuated 4~-phorbol-12,13-dibutyrate (PDBu)-enhanced synaptic transmission. Our results indicate that there is a critical period of protein kinase activity required for LTP induction that extends for ---20 min after HFS. In addition, our results suggest that protein kinase activity during and immediately after HFS is not sufficient for LTP induction. These results provide new information about the mechanisms that underlie LTP induction and expression and aCorresponding author.provide evidence for persistent and/or Ca2+-independent protein kinase activity involvement in LTP

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“…However, actinomycin D, an inhibitor of mRNA synthesis, exerted no significant effect during the first 3 h after tetanus (168, 474), although an inhibitory effect was observed after ϳ5 h (168), suggesting a dependence on transcription and translation at this time. Interestingly, there was evidence of newly synthesized proteins in the extracellular medium 3 h after induction of LTP (155), while increased synthesis of presynaptically located proteins was also reported within this time frame (359). Similar temporally distinct phases were distinguished with respect to learning in 1980 when it was reported that intrahippocampal injection of the protein synthesis inhibitor anisomycin inhibited retention in a brightness discrimination task but that the inhibition only occurred if the drug was administered before training or several hours after training; injection of anisomycin shortly after training failed to affect retention (206).…”

Section: F Protein Synthesis and Ltpmentioning

confidence: 99%

Long-Term Potentiation and Memory

Lynch

2004

Physiological Reviews

1,684

1,098

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Lynch, MA. Long-Term Potentiation and Memory. Physiol Rev 84: 87–136, 2004; 10.1152/physrev.00014.2003.—One of the most significant challenges in neuroscience is to identify the cellular and molecular processes that underlie learning and memory formation. The past decade has seen remarkable progress in understanding changes that accompany certain forms of acquisition and recall, particularly those forms which require activation of afferent pathways in the hippocampus. This progress can be attributed to a number of factors including well-characterized animal models, well-defined probes for analysis of cell signaling events and changes in gene transcription, and technology which has allowed gene knockout and overexpression in cells and animals. Of the several animal models used in identifying the changes which accompany plasticity in synaptic connections, long-term potentiation (LTP) has received most attention, and although it is not yet clear whether the changes that underlie maintenance of LTP also underlie memory consolidation, significant advances have been made in understanding cell signaling events that contribute to this form of synaptic plasticity. In this review, emphasis is focused on analysis of changes that occur after learning, especially spatial learning, and LTP and the value of assessing these changes in parallel is discussed. The effect of different stressors on spatial learning/memory and LTP is emphasized, and the review concludes with a brief analysis of the contribution of studies, in which transgenic animals were used, to the literature on memory/learning and LTP.

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Changes in protein synthesis accompanying long-term potentiation in the dentate gyrus in vivo

Cited by 101 publications

References 18 publications

Fragile X Mental Retardation Protein: Nucleocytoplasmic Shuttling and Association with Somatodendritic Ribosomes

Fragile X Mental Retardation Protein: Nucleocytoplasmic Shuttling and Association with Somatodendritic Ribosomes

A critical period of protein kinase activity after tetanic stimulation is required for the induction of long-term potentiation.

Long-Term Potentiation and Memory

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