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Facilitation of ampa receptor synaptic delivery as a molecular mechanism for cognitive enhancement
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نویسنده
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knafo s. ,venero c. ,sánchez-puelles c. ,pereda-peréz i. ,franco a. ,sandi c. ,suárez l.m. ,solís j. ,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.
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منبع
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plos biology - 2012 - دوره : 10 - شماره : 2
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چکیده
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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. © 2012 knafo et al.
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آدرس
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centro de biología molecular severo ochoa,consejo superior de investigaciones científicas,universidad autónoma de madrid,madrid,spain,instituto cajal (csic),centro de tecnología biomédica,universidad politécnica de madrid,centro de investigación biomédica en red sobre enfermedades neurodegenerativas,madrid, Spain, department of psychobiology,universidad nacional de educación a distancia,madrid, Spain, centro de biología molecular severo ochoa,consejo superior de investigaciones científicas,universidad autónoma de madrid,madrid, Spain, department of psychobiology,universidad nacional de educación a distancia,madrid, Spain, centro nacional biotecnología (csic),universidad autónoma de madrid,madrid, Spain, brain mind institute,ecole polytechnique federale de lausanne (epfl), Switzerland, instituto cajal (csic),centro de tecnología biomédica,universidad politécnica de madrid,centro de investigación biomédica en red sobre enfermedades neurodegenerativas,madrid,spain,servicio de neurobiología-investigación,hospital ramón y cajal,irycis,madrid, Spain, servicio de neurobiología-investigación,hospital ramón y cajal,irycis,madrid, Spain, instituto cajal (csic),centro de tecnología biomédica,universidad politécnica de madrid,centro de investigación biomédica en red sobre enfermedades neurodegenerativas,madrid, Spain, departamento de ciencias médicas,universidad de castilla-la mancha,albacete, Spain, instituto cajal (csic),centro de tecnología biomédica,universidad politécnica de madrid,centro de investigación biomédica en red sobre enfermedades neurodegenerativas,madrid, Spain, department of psychobiology,universidad nacional de educación a distancia,madrid, Spain, protein laboratory,department of neuroscience and pharmacology,faculty of health sciences,university of copenhagen,copenhagen, Denmark, protein laboratory,department of neuroscience and pharmacology,faculty of health sciences,university of copenhagen,copenhagen, Denmark, department of anatomy,faculty of veterinary medicine,complutense university,madrid, Spain, protein laboratory,department of neuroscience and pharmacology,faculty of health sciences,university of copenhagen,copenhagen, Denmark, protein laboratory,department of neuroscience and pharmacology,faculty of health sciences,university of copenhagen,copenhagen, Denmark, instituto cajal (csic),centro de tecnología biomédica,universidad politécnica de madrid,centro de investigación biomédica en red sobre enfermedades neurodegenerativas,madrid, Spain, centro de biología molecular severo ochoa,consejo superior de investigaciones científicas,universidad autónoma de madrid,madrid, Spain
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Authors
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