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Published online on August 21, 2006, 10.1073/pnas.0604691103
PNAS | August 29, 2006 | vol. 103 | no. 35 | 13214-13219


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From the Cover
BIOLOGICAL SCIENCES / NEUROSCIENCE
Spontaneous and evoked synaptic rewiring in the neonatal neocortex

Jean-Vincent Le Bé, and Henry Markram*

Brain Mind Institute, Ecole Polytechnique Fédérale de Lausanne, CH-1015 Lausanne, Switzerland

Communicated by Michael M. Merzenich, University of California, San Francisco, CA, July 3, 2006 (received for review March 21, 2006)

The local microcircuitry of the neocortex is structurally a tabula rasa, with the axon of each pyramidal neuron having numerous submicrometer appositions with the dendrites of all neighboring pyramidal neurons, but is functionally highly selective, with synapses formed onto only a small proportion of these targets. This design leaves a vast potential for the microcircuit to rewire without extensive axonal or dendritic growth. To examine whether rewiring does take place, we used multineuron patch-clamp recordings on 12- to 14-day-old rat neocortical slices and studied long-term changes in synaptic connectivity within clusters of neurons. We found pyramidal neurons spontaneously connecting and disconnecting from each other and that exciting the slice with glutamate greatly increases the number of new connections established. Evoked emergence of new synaptic connections requires action potential activity and activation of metabotropic glutamate receptor 5, but not NMDA receptor or group II or group III metabotropic glutamate receptor activation. We also found that it is the weaker connections that are selectively eliminated. These results provide direct evidence for spontaneous and evoked rewiring of the neocortical microcircuitry involving entire functional multisynaptic connections. We speculate that this form of microcircuit plasticity enables an evolution of the microcircuit connectivity by natural selection as a function of experience.

plasticity | pyramidal neurons | synaptic connections


Author contributions: H.M. designed research; J.-V.L.B. performed research; J.-V.L.B. analyzed data; and J.-V.L.B. and H.M. wrote the paper.

Conflict of interest statement: No conflicts declared.

*To whom correspondence should be addressed. E-mail: henry.markram{at}epfl.ch

© 2006 by The National Academy of Sciences of the USA


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