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

PLoS Biology
Shira KnafoJosé A Esteban

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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Citations

Sep 24, 2013·Journal of Neuroimmune Pharmacology : the Official Journal of the Society on NeuroImmune Pharmacology·Maya E Woodbury, Tsuneya Ikezu
Jan 10, 2014·Journal of Neural Transmission·Jessica A PanzerDavid R Lynch
Oct 11, 2013·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Wendy W WuJames Maylie
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Jun 29, 2016·Journal of Neuroimmune Pharmacology : the Official Journal of the Society on NeuroImmune Pharmacology·Rebecca KleinMichael Schroeter
Jul 14, 2018·Neurochemical Research·Chengyan ChuShen Li
May 29, 2021·Translational Psychiatry·María Calleja-FelipeShira Knafo
May 29, 2021·Frontiers in Synaptic Neuroscience·Marta Díaz GonzálezShira Knafo
Mar 14, 2021·Journal of Molecular Neuroscience : MN·Elif Emanetci, Tunahan Çakır

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Methods Mentioned

BETA
enzyme-linked immunosorbent assay
Fluorescence
confocal microscopy
ELISA
electron microscopy

Software Mentioned

Neurolucida
SPSS
IMARIS

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