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Cerebral Cortex Advance Access originally published online on May 20, 2007
Cerebral Cortex 2008 18(1):151-161; doi:10.1093/cercor/bhm041
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© The Author 2007. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oxfordjournals.org

Activity-Dependent PSD Formation and Stabilization of Newly Formed Spines in Hippocampal Slice Cultures

Mathias De Roo, Paul Klauser, Pablo Mendez, Lorenzo Poglia and Dominique Muller

University of Geneva Medical School, Department of Neurosciences, Centre Médical Universitaire, 1211 Genève 4, Switzerland

Address correspondence to Dominique Muller, Department of Neuroscience, University of Geneva Medical School, 1211 Geneva, Switzerland. Email: dominique.muller{at}medecine.unige.ch.

Development and remodeling of synaptic networks occurs through a continuous turnover of dendritic spines. However, the mechanisms that regulate the formation and stabilization of newly formed spines remain poorly understood. Here, we applied repetitive confocal imaging to hippocampal slice cultures to address these issues. We find that, although the turnover rate of protrusions progressively decreased during development, the process of stabilization of new spines remained comparable both in terms of time course and low level of efficacy. Irrespective of the developmental stage, most new protrusions were quickly eliminated, in particular filopodia, which only occasionally lead to the formation of stable dendritic spines. We also found that the stabilization of new protrusions was determined within a critical period of 24 h and that this coincided with an enlargement of the spine head and the expression of tagged PSD-95. Blockade of postsynaptic AMPA and NMDA receptors significantly reduced the capacity of new spines to express tagged PSD-95 and decreased their probability to be stabilized. These results suggest a model in which synaptic development is associated with an extensive, nonspecific growth of protrusions followed by stabilization of a few of them through a mechanism that involves activity-driven formation of a postsynaptic density.

Key Words: confocal imaging • dendritic spine • hippocampus • plasticity • postsynaptic density • synaptogenesis

Mathias De Roo and Paul Klauser contributed equally to this work.


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