Skip Navigation



Cerebral Cortex Advance Access published online on November 19, 2008
Cerebral Cortex, doi:10.1093/cercor/bhn182
This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Supplementary Data
Right arrow All Versions of this Article:
19/6/1422    most recent
bhn182v1
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Add to My Personal Archive
Right arrow Download to citation manager
Right arrowRequest Permissions
Google Scholar
Right arrow Articles by Chiappalone, M.
Right arrow Articles by Benfenati, F.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Chiappalone, M.
Right arrow Articles by Benfenati, F.
Social Bookmarking
Add to CiteULike   Add to Connotea   Add to Del.icio.us  
What's this?

© The Author 2008. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oxfordjournals.org

Opposite Changes in Glutamatergic and GABAergic Transmission Underlie the Diffuse Hyperexcitability of Synapsin I–Deficient Cortical Networks

Michela Chiappalone1,2, Silvia Casagrande3, Mariateresa Tedesco2, Flavia Valtorta4,5, Pietro Baldelli1,3, Sergio Martinoia1,2 and Fabio Benfenati1,3,5

1 Department of Neuroscience and Brain Technologies, The Italian Institute of Technology, Genova, Italy, 2 Department of Biophysical and Electronic Engineering, University of Genova, Italy, 3 Department of Experimental Medicine, Section of Physiology, University of Genova, Italy, 4 S. Raffaele Scientific Institute/Vita-Salute University and IIT Unit of Molecular Neuroscience, Milano, Italy, 5 Italian Institute of Neuroscience, Genova, Italy

Address correspondence to Fabio Benfenati, MD, Department of Experimental Medicine, University of Genova, Viale Benedetto XV, 3 16132 Genova, Italy. Email: fabio.benfenati{at}unige.it.

Synapsins (Syns) are synaptic vesicle (SV) phosphoproteins that play a role in synaptic transmission and plasticity. Mutation of the SYN1 gene results in an epileptic phenotype in mouse and man, implicating SynI in the control of network excitability. We used microelectrode array and patch-clamp recordings to study network activity in primary cortical neurons from wild-type (WT) or SynI knockout (KO) mice. SYN1 deletion was associated with increased spontaneous and evoked activities, with more frequent and sustained bursts of action potentials and a high degree of synchronization. Blockade of GABAA ({gamma}-aminobutyric acidA) receptors with bicuculline attenuated, but did not completely abolish, the differences between WT and SynI KO networks in both spontaneous and evoked activities. Patch-clamp recordings on cortical autaptic neurons revealed a reduced amplitude of evoked inhibitory postsynaptic currents (PSCs) and a concomitantly increased amplitude of evoked excitatory PSCs in SynI KO neurons, in the absence of changes in miniature PSCs. Cumulative amplitude analysis revealed that these effects were attributable to opposite changes in the size of the readily releasable pool of SVs. The results indicate distinct roles of SynI in GABAergic and glutamatergic neurons and provide an explanation for the high susceptibility of SynI KO mice to epileptic seizures.

Key Words: epilepsy • GABA/glutamate release • knockout mice • network activity • synapsin

Michela Chiappalone and Silvia Casagrande contributed equally to this work.


Add to CiteULike CiteULike   Add to Connotea Connotea   Add to Del.icio.us Del.icio.us    What's this?




Disclaimer: Please note that abstracts for content published before 1996 were created through digital scanning and may therefore not exactly replicate the text of the original print issues. All efforts have been made to ensure accuracy, but the Publisher will not be held responsible for any remaining inaccuracies. If you require any further clarification, please contact our Customer Services Department.