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 Citationer (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.

Originalsprog	Engelsk
Tidsskrift	P L o S Biology (Online)
Vol/bind	10
Udgave nummer	2
Sider (fra-til)	e1001262
ISSN	1545-7885
DOI	https://doi.org/10.1371/journal.pbio.1001262
Status	Udgivet - feb. 2012

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10.1371/journal.pbio.1001262

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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), bind 10, nr. 2, s. 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 - Knafo, Shira

AU - Venero, César

AU - Sánchez-Puelles, Cristina

AU - Pereda-Peréz, Inmaculada

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

N1 - Open Access

PY - 2012/2

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N2 - 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.

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.

KW - Analysis of Variance

KW - Animals

KW - Blotting, Western

KW - Calcium-Calmodulin-Dependent Protein Kinase Type 2

KW - Cognition

KW - Enzyme-Linked Immunosorbent Assay

KW - Hippocampus

KW - Long-Term Potentiation

KW - Male

KW - Maze Learning

KW - Microscopy, Electron

KW - Microscopy, Fluorescence

KW - Neural Cell Adhesion Molecules

KW - Neurons

KW - Patch-Clamp Techniques

KW - Phosphorylation

KW - Protein Kinase C

KW - Rats

KW - Rats, Wistar

KW - Receptor, Fibroblast Growth Factor, Type 1

KW - Receptors, AMPA

KW - Signal Transduction

KW - Synaptic Transmission

U2 - 10.1371/journal.pbio.1001262

DO - 10.1371/journal.pbio.1001262

M3 - Journal article

C2 - 22363206

SN - 1544-9173

VL - 10

SP - e1001262

JO - PLoS Biology

JF - PLoS Biology

IS - 2

ER -

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

Abstract

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