Facilitation of AMPA receptor synaptic delivery as a molecular mechanism for cognitive enhancement

Shira Knafo; César Venero; Cristina Sánchez-Puelles; Inmaculada Pereda-Peréz; Ana Franco; Carmen Sandi; Luz M Suárez; José M Solís; Lidia Alonso-Nanclares; Eduardo D Martín; Paula Merino-Serrais; Erika Borcel; Shizhong Li; Yongshuo Chen; Juncal Gonzalez-Soriano; Vladimir Berezin; Elisabeth Bock; Javier Defelipe; José A Esteban

doi:10.1371/journal.pbio.1001262

Facilitation of AMPA receptor synaptic delivery as a molecular mechanism for cognitive enhancement

Shira Knafo, César Venero, Cristina Sánchez-Puelles, Inmaculada Pereda-Peréz, Ana Franco, Carmen Sandi, Luz M Suárez, José M Solís, Lidia Alonso-Nanclares, Eduardo D Martín, Paula Merino-Serrais, Erika Borcel, Shizhong Li, Yongshuo Chen, Juncal Gonzalez-Soriano, Vladimir Berezin, Elisabeth Bock, Javier Defelipe, José A Esteban

Eyepath Lab

37 Citations (Scopus)

Abstract

Cell adhesion molecules and downstream growth factor-dependent signaling are critical for brain development and synaptic plasticity, and they have been linked to cognitive function in adult animals. We have previously developed a mimetic peptide (FGL) from the neural cell adhesion molecule (NCAM) that enhances spatial learning and memory in rats. We have now investigated the cellular and molecular basis of this cognitive enhancement, using biochemical, morphological, electrophysiological, and behavioral analyses. We have found that FGL triggers a long-lasting enhancement of synaptic transmission in hippocampal CA1 neurons. This effect is mediated by a facilitated synaptic delivery of AMPA receptors, which is accompanied by enhanced NMDA receptor-dependent long-term potentiation (LTP). Both LTP and cognitive enhancement are mediated by an initial PKC activation, which is followed by persistent CaMKII activation. These results provide a mechanistic link between facilitation of AMPA receptor synaptic delivery and improved hippocampal-dependent learning, induced by a pharmacological cognitive enhancer.

Original language	English
Journal	P L o S Biology (Online)
Volume	10
Issue number	2
Pages (from-to)	e1001262
ISSN	1545-7885
DOIs	https://doi.org/10.1371/journal.pbio.1001262
Publication status	Published - Feb 2012

Keywords

Analysis of Variance
Animals
Blotting, Western
Calcium-Calmodulin-Dependent Protein Kinase Type 2
Cognition
Enzyme-Linked Immunosorbent Assay
Hippocampus
Long-Term Potentiation
Male
Maze Learning
Microscopy, Electron
Microscopy, Fluorescence
Neural Cell Adhesion Molecules
Neurons
Patch-Clamp Techniques
Phosphorylation
Protein Kinase C
Rats
Rats, Wistar
Receptor, Fibroblast Growth Factor, Type 1
Receptors, AMPA
Signal Transduction
Synaptic Transmission

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Knafo, S., Venero, C., Sánchez-Puelles, C., Pereda-Peréz, I., Franco, A., Sandi, C., Suárez, L. M., Solís, J. M., Alonso-Nanclares, L., Martín, E. D., Merino-Serrais, P., Borcel, E., Li, S., Chen, Y., Gonzalez-Soriano, J., Berezin, V., Bock, E., Defelipe, J., & Esteban, J. A. (2012). Facilitation of AMPA receptor synaptic delivery as a molecular mechanism for cognitive enhancement. P L o S Biology (Online), 10(2), e1001262. https://doi.org/10.1371/journal.pbio.1001262

Knafo, S, Venero, C, Sánchez-Puelles, C, Pereda-Peréz, I, Franco, A, Sandi, C, Suárez, LM, Solís, JM, Alonso-Nanclares, L, Martín, ED, Merino-Serrais, P, Borcel, E, Li, S, Chen, Y, Gonzalez-Soriano, J, Berezin, V, Bock, E, Defelipe, J & Esteban, JA 2012, 'Facilitation of AMPA receptor synaptic delivery as a molecular mechanism for cognitive enhancement', P L o S Biology (Online), vol. 10, no. 2, pp. e1001262. https://doi.org/10.1371/journal.pbio.1001262

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abstract = "Cell adhesion molecules and downstream growth factor-dependent signaling are critical for brain development and synaptic plasticity, and they have been linked to cognitive function in adult animals. We have previously developed a mimetic peptide (FGL) from the neural cell adhesion molecule (NCAM) that enhances spatial learning and memory in rats. We have now investigated the cellular and molecular basis of this cognitive enhancement, using biochemical, morphological, electrophysiological, and behavioral analyses. We have found that FGL triggers a long-lasting enhancement of synaptic transmission in hippocampal CA1 neurons. This effect is mediated by a facilitated synaptic delivery of AMPA receptors, which is accompanied by enhanced NMDA receptor-dependent long-term potentiation (LTP). Both LTP and cognitive enhancement are mediated by an initial PKC activation, which is followed by persistent CaMKII activation. These results provide a mechanistic link between facilitation of AMPA receptor synaptic delivery and improved hippocampal-dependent learning, induced by a pharmacological cognitive enhancer.",

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AU - Franco, Ana

AU - Sandi, Carmen

AU - Suárez, Luz M

AU - Solís, José M

AU - Alonso-Nanclares, Lidia

AU - Martín, Eduardo D

AU - Merino-Serrais, Paula

AU - Borcel, Erika

AU - Li, Shizhong

AU - Chen, Yongshuo

AU - Gonzalez-Soriano, Juncal

AU - Berezin, Vladimir

AU - Bock, Elisabeth

AU - Defelipe, Javier

AU - Esteban, José A

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AB - Cell adhesion molecules and downstream growth factor-dependent signaling are critical for brain development and synaptic plasticity, and they have been linked to cognitive function in adult animals. We have previously developed a mimetic peptide (FGL) from the neural cell adhesion molecule (NCAM) that enhances spatial learning and memory in rats. We have now investigated the cellular and molecular basis of this cognitive enhancement, using biochemical, morphological, electrophysiological, and behavioral analyses. We have found that FGL triggers a long-lasting enhancement of synaptic transmission in hippocampal CA1 neurons. This effect is mediated by a facilitated synaptic delivery of AMPA receptors, which is accompanied by enhanced NMDA receptor-dependent long-term potentiation (LTP). Both LTP and cognitive enhancement are mediated by an initial PKC activation, which is followed by persistent CaMKII activation. These results provide a mechanistic link between facilitation of AMPA receptor synaptic delivery and improved hippocampal-dependent learning, induced by a pharmacological cognitive enhancer.

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KW - Long-Term Potentiation

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KW - Neural Cell Adhesion Molecules

KW - Neurons

KW - Patch-Clamp Techniques

KW - Phosphorylation

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KW - Rats

KW - Rats, Wistar

KW - Receptor, Fibroblast Growth Factor, Type 1

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SP - e1001262

JO - PLoS Biology

JF - PLoS Biology

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ER -

Facilitation of AMPA receptor synaptic delivery as a molecular mechanism for cognitive enhancement

Abstract

Keywords

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