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Original Research ARTICLE

Front. Neuroanat., 20 November 2009 | http://dx.doi.org/10.3389/neuro.05.028.2009

Diminished perisomatic GABAergic terminals on cortical neurons adjacent to amyloid plaques

1
Laboratorio de Circuitos Corticales, Centro de Tecnología Biomédica, Universidad Politécnica de Madrid, Madrid, Spain
2
Instituto Cajal, Madrid, Spain
3
Institut Neuropatologia, Servei Anatomia Patològica, IDIBELL-Hospital Universitari de Bellvitge, Universitat de Barcelona, Hospitalet de Llobregat, Spain
One of the main pathological hallmarks of Alzheimer’s disease (AD) is the accumulation of plaques in the cerebral cortex, which may appear either in the neuropil or in direct association with neuronal somata. Since different axonal systems innervate the dendritic (mostly glutamatergic) and perisomatic (mostly GABAergic) regions of neurons, the accumulation of plaques in the neuropil or associated with the soma might produce different alterations to synaptic circuits. We have used a variety of conventional light, confocal and electron microscopy techniques to study their relationship with neuronal somata in the cerebral cortex from AD patients and APP/PS1 transgenic mice. The main finding was that the membrane surfaces of neurons (mainly pyramidal cells) in contact with plaques lack GABAergic perisomatic synapses. Since these perisomatic synapses are thought to exert a strong influence on the output of pyramidal cells, their loss may lead to the hyperactivity of the neurons in contact with plaques. These results suggest that plaques modify circuits in a more selective manner than previously thought.
Keywords:
amyloid beta peptide, diffuse and neuritic plaques, electron microscopy, GABAergic perisomatic innervation, axo-somatic synapses, epilepsy
Citation:
Garcia-Marin V, Blazquez-Llorca L, Rodriguez JR, Boluda S, Muntane G, Ferrer I and DeFelipe J (2009). Diminished perisomatic GABAergic terminals on cortical neurons adjacent to amyloid plaques. Front. Neuroanat. 3:28. doi: 10.3389/neuro.05.028.2009
Received:
29 September 2009;
 Paper pending published:
06 October 2009;
Accepted:
06 November 2009;
 Published online:
20 November 2009.

Edited by:

Patrick R. Hof, Mount Sinai School of Medicine, USA

Reviewed by:

Stephen D. Ginsberg, Nathan Kline Institute, USA
James C. Vickers, University of Tasmania, Australia
Copyright:
© 2009 Garcia-Marin, Blazquez-Llorca, Rodriguez, Boluda, Muntane, Ferrer and DeFelipe. This is an open-access article subject to an exclusive license agreement between the authors and the Frontiers Research Foundation, which permits unrestricted use, distribution, and reproduction in any medium, provided the original authors and source are credited.
*Correspondence:
Javier DeFelipe, Laboratorio de Circuitos Corticales, Centro de Tecnología Biomédica, Universidad Politécnica de Madrid, Campus Montegancedo S/N, Pozuelo de Alarcón, 28223 Madrid, Spain; Instituto Cajal (CSIC), Avenida Doctor Arce 37, 28002 Madrid, Spain. e-mail: defelipe@cajal.csic.es