Transsynaptic Expression of a Presynaptic Glutamate Receptor During Hippocampal Long-Term Potentiation

Smirnova, T.N.; Laroche, Serge; Er̀rington, M.L.; Hicks, Andrew A.; Bliss, T. V. P.; Mallet, Jacques

doi:10.1126/science.8105538

Cited by 58 publications

(26 citation statements)

References 18 publications

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“…Thus, changes in the postsynaptic expression of proteins that are targeted to the presynaptic terminals during LTP could represent a good candidate mechanism underlying the propagation of long-lasting increases in synaptic strength within hippocampal circuits, a process that would have wide implications for a molecular mechanism involved in learning. Indeed, there is a precedent for both these ideas in previous studies investigating changes in the expression of the presynaptic protein, syntaxin 1B, which functions in the docking and priming of vesicles for calcium-dependent neurotransmitter release (Stidhof 1995) after induction of LTP (Smirnova et al 1993) and learning . Smirnova et al (1993) found a rapid and transient increase in the expression of syntaxin 1B in dentate granule cells after the induction of LTP at the perforant path-dentate gyrus synapses.…”

Section: Discussionmentioning

confidence: 99%

“…Indeed, there is a precedent for both these ideas in previous studies investigating changes in the expression of the presynaptic protein, syntaxin 1B, which functions in the docking and priming of vesicles for calcium-dependent neurotransmitter release (Stidhof 1995) after induction of LTP (Smirnova et al 1993) and learning . Smirnova et al (1993) found a rapid and transient increase in the expression of syntaxin 1B in dentate granule cells after the induction of LTP at the perforant path-dentate gyrus synapses. Furthermore, an increase in the syntaxin 1B protein was observed in the terminal field of mossy fibers in CA3.…”

Section: Discussionmentioning

confidence: 99%

“…Within the first few hours of the induction of LTP, an increase in the expression of certain immediate early genes is observed (Cole et al 1989;Dragunow et al 1989;Wisden et al 1990;Abraham et al 1991 ). This is followed by expression of presynaptic vesicle proteins such as syntaxin (Smirnova et al 1993;Lynch et al 1994) and synapsin ) and calcium-dependent kinases such as e~CaMKII and ~/PKC (Thomas et al 1994b). At later time points, e.g., 24 hr after the induction of LTP, expression of the calcium-independent kinases ERK2 and raf-B occurs (Thomas et al 1994b), and at 48 hr, expression of the NMDA receptor subunit NR1 is increased (Thomas et al 1994a).…”

Section: Introductionmentioning

confidence: 99%

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Alterations in the expression of specific glutamate receptor subunits following hippocampal LTP in vivo.

Thomas¹,

Davis²,

Hunt³

et al. 1996

Learning & Memory

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Quantitative in situ hybridization revealed that following the induction of hippocampal long-term potentiation (LTP) in the dentate gyms of freely moving rats, specific increases in the expression of the NR2B subunit of the N-methyl-D-aspartate (NMDA) receptor and mGluRlc, a short splice variant of the metabotropic glutamate receptors that are linked intracellularly to phospholipase C (PLC) and protein kinase C (PKC), were seen in the postsynaptic dentate granule cells. There were no changes in the expression of NR2A; NR2C and NR2D NMDA receptor subunits; or mGluRla, mGluRlb, mGluR5a, and mGluR5b PLC-associated metabotropic receptors. The elevations in NR2B and mGluRlc mRNA were delayed, occurring days after LTP induction. NR2B expression was enhanced significantly by 48 hr after LTP but was starting to decrease toward basal levels by 96 hr. The transient increase in the expression of NR2B mirrored the increase in the expression of PKC-sensitive isoforms of the NR1 subunits of the NMDA 4Corresponding author. receptor we observed previously (Thomas et al. 1994a). The increase in mGluRlc expression was more persistent, showing a significant increase 96 hr after LTP. This study demonstrates that not only are there changes in the expression of individual glutamate receptor subunits but the increases in their expression occur days after the induction of LTP and may reflect so-called late-onset genes that may be important for the maintenance of LTP.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Alterations in the expression of specific glutamate receptor subunits following hippocampal LTP in vivo.

Thomas¹,

Davis²,

Hunt³

et al. 1996

Learning & Memory

View full text Add to dashboard Cite

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“…3B). Whereas most studies on syntaxin 1A have focused on its intracellular functions, several reports suggested that it can adopt an extracellular localization as well (Brimhall et al, 1999;Smirnova et al, 1993a;Smirnova et al, 1993b).…”

Section: Discussionmentioning

confidence: 99%

Non-classical export of epimorphin and its adhesion to αv-integrin in regulation of epithelial morphogenesis

Hirai

Nelson

Yamazaki

et al. 2007

Journal of Cell Science

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Epimorphin (also known as syntaxin 2) acts as an epithelial morphogen when secreted by stromal cells of the mammary gland, lung, liver, colon, pancreas and other tissues, but the same molecule functions within the cell to mediate membrane fusion. How this molecule, which lacks a signal sequence and contains a transmembrane domain at the C-terminus, translocates across the plasma membrane and is secreted to become a morphogen, and how it initiates morphogenic events is not clear. Here, we show that epimorphin is secreted through a non-classical mechanism, similar to that previously described for secretion of the leaderless protein FGF1, and we identify the key molecular elements responsible for translocation and secretion from the cell. We also show that secreted epimorphin binds to αv-integrin-containing receptors on target epithelial cells, leading to activation of specific downstream signaling pathways and induction of epithelial morphogenesis. These findings provide key insight into how epimorphin functions as an epithelial morphogen.

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“…The evidence came from two main sources: the fact that inhibitors of either protein synthesis (Krug et al 1984;Otani & Abraham 1989;Frey & Morris 1997) or transcription (Nguyen et al 1994) affect the duration of LTP; and the finding that LTP itself induces transcriptional regulation of a variety of genes, including inducible transcription factors (Cole et al 1989;Wisden et al 1990;Abraham et al 1993;Worley et al 1993;French et al 2001) and genes encoding synaptic proteins (e.g. Smirnova et al 1993;Thomas et al 1994Thomas et al , 1996Link et al 1995;Lyford et al 1995;Bramham et al 1996;Hicks et al 1997;Génin et al 2001). Remarkably, experimental evidence also indicates that the expression of long-term memories shares many characteristics with LTP, including similar molecular mechanisms, a requirement for protein synthesis (Davis & Squire 1984;Meiri & Rosenblum 1998) and, in specific areas of the brain, the regulated transcription of a variety of genes (Nikolaev et al 1992;Davis et al 1996Davis et al , 1998Okuno & Miyashita 1996;Guzowski et al 1999Guzowski et al , 2001Tischmeyer & Grimm 1999;Hall et al 2000;Zhao et al 2000;Cavallaro et al 2001).…”

Section: Introductionmentioning

confidence: 99%

MAPK, CREB andzif268are all required for the consolidation of recognition memory

Bozon

Kelly

Josselyn

et al. 2003

Phil. Trans. R. Soc. Lond. B

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285

211

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There has been nearly a century of interest in the idea that encoding and storage of information in the brain requires changes in the efficacy of synaptic connections between neurons that are activated during learning. Recent research into the molecular mechanisms of long-term potentiation (LTP) has brought about new knowledge that has provided valuable insights into the neural mechanisms of memory storage. The evidence indicates that rapid activation of the genetic machinery can be a key mechanism underlying the enduring modification of neural networks required for the stability of memories. In recent years, a wealth of experimental data has highlighted the importance of mitogen-activated protein kinase/ extracellular signal-regulated kinase (MAPK/ERK) signalling in the regulation of gene transcription in neurons. Here, we briefly review experiments that have shown MAPK/ERK, cAMP response elementbinding protein (CREB) and the immediate early gene (IEG) zif268 are essential components of a signalling cascade required for the expression of late phase LTP and of certain forms of long-term memory. We also present experiments in which we have assessed the role of these three molecules in recognition memory. We show that pharmacological blockade of MAPK/ERK phosphorylation, functional inactivation of CREB in an inducible transgenic mouse and inactivation of zif268 in a mutant mouse result in a similar deficit in long-term recognition memory. In the continuing debate about the role of LTP mechanisms in memory, these findings provide an important complement to the suggestion that synaptic changes brought about by LTP and memory consolidation and storage share, at least in part, common underlying molecular mechanisms.

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Transsynaptic Expression of a Presynaptic Glutamate Receptor During Hippocampal Long-Term Potentiation

Cited by 58 publications

References 18 publications

Alterations in the expression of specific glutamate receptor subunits following hippocampal LTP in vivo.

Alterations in the expression of specific glutamate receptor subunits following hippocampal LTP in vivo.

Non-classical export of epimorphin and its adhesion to αv-integrin in regulation of epithelial morphogenesis

MAPK, CREB andzif268are all required for the consolidation of recognition memory

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