Web of Science: 20 citations, Scopus: 21 citations, Google Scholar: citations,
Learning improvement after PI3K activation correlates with de novo formation of functional small spines
Enriquez-Barreto, Lilian (Universitat Autònoma de Barcelona. Institut de Neurociències)
Cuesto, Germán (Centro de Investigación Biomédica (La Rioja))
Dominguez-Iturza, Nuria (Centro de Investigación Biomédica (La Rioja))
Gavilán, Elena (Universidad de Sevilla. Instituto de Biomedicina de Sevilla)
Ruano, Diego (Universidad de Sevilla. Instituto de Biomedicina de Sevilla)
Sandi, Carmen (École Polytechnique Fédérale de Lausanne. Brain Mind Institute)
Fernández-Ruiz, Antonio (Instituto Cajal-CSIC)
Martín-Vázquez, Gonzalo (Instituto Cajal-CSIC)
Herreras, Oscar (Instituto Cajal-CSIC)
Morales, Miguel (Centro de Investigación Biomédica (La Rioja))
Universitat Autònoma de Barcelona. Departament de Bioquímica i de Biologia Molecular

Date: 2014
Abstract: PI3K activation promotes the formation of synaptic contacts and dendritic spines, morphological features of glutamatergic synapses that are commonly known to be related to learning processes. In this report, we show that in vivo administration of a peptide that activates the PI3K signaling pathway increases spine density in the rat hippocampus and enhances the animals' cognitive abilities, while in vivo electrophysiological recordings show that PI3K activation results in synaptic enhancement of Schaffer and stratum lacunosum moleculare inputs. Morphological characterization of the spines reveals that subjecting the animals to contextual fear-conditioning training per se promotes the formation of large spines, while PI3K activation reverts this effect and favors a general change toward small head areas. Studies using hippocampal neuronal cultures show that the PI3K spinogenic process is NMDA-dependent and activity-independent. In culture, PI3K activation was followed by mRNA upregulation of glutamate receptor subunits and of the immediate-early gene Arc. Time-lapse studies confirmed the ability of PI3K to induce the formation of small spines. Finally, we demonstrate that the spinogenic effect of PI3K can be induced in the presence of neurodegeneration, such as in the Tg2576 Alzheimer's mouse model. These findings highlight that the PI3K pathway is an important regulator of neuronal connectivity and stress the relationship between spine size and learning processes.
Note: Número d'acord de subvenció MICINN/BFU2010-17537
Note: Número d'acord de subvenció MICINN/BFU2010-19192
Note: Número d'acord de subvenció ISCIII/PI12-00445
Rights: Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, la comunicació pública de l'obra i la creació d'obres derivades, fins i tot amb finalitats comercials, sempre i quan es reconegui l'autoria de l'obra original. Creative Commons
Language: Anglès
Document: article ; recerca ; publishedVersion
Subject: Dendritic spines ; Structural plasticity ; PI3K ; Hippocampus
Published in: Frontiers in molecular neuroscience, Vol. 6 (January 2014) , art. 54, ISSN 1662-5099

DOI: 10.3389/fnmol.2013.00054
PMID: 24427113

18 p, 3.4 MB

The record appears in these collections:
Research literature > UAB research groups literature > Research Centres and Groups (scientific output) > Health sciences and biosciences > Institut de Neurociències (INc)
Articles > Research articles
Articles > Published articles

 Record created 2018-01-29, last modified 2020-08-13

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