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Cerebral Cortex Advance Access published online on June 11, 2009
Cerebral Cortex, doi:10.1093/cercor/bhp114
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© The Author 2009. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oxfordjournals.org

Serotoninergic Fine-Tuning of the Excitation–Inhibition Balance in Rat Visual Cortical Networks

Alexandre William Moreau, Muriel Amar, Nicolas Le Roux, Nicolas Morel and Philippe Fossier

CNRS, Institut de Neurobiologie Alfred Fessard—FRC2118, Laboratoire de Neurobiologie Cellulaire et Moléculaire—UPR9040, F-91198 Gif sur Yvette, France

Address correspondence to Dr Philippe Fossier, CNRS, Laboratoire de Neurobiologie Cellulaire et Moléculaire, 1 Avenue de la Terrasse, F-91198 Gif sur Yvette Cedex, France. Email: fossier{at}nbcm.cnrs-gif.fr.

Fundamental brain functions depend on a balance between excitation (E) and inhibition (I) that is highly adjusted to a 20–80% set point in layer 5 pyramidal neurons (L5PNs) of rat visual cortex. Dysregulations of both the E–I balance and the serotonergic system in neocortical networks lead to serious neuronal diseases including depression, schizophrenia, and epilepsy. However, no link between the activation of neuronal 5-hydroxytryptamine receptors (5-HTRs) and the cortical E–I balance has yet been reported. Here we used a combination of patch-clamp recordings of composite stimulus-locked responses in L5PN following local electrical stimulations in either layer 2/3 or 6, simultaneous measurement of excitatory and inhibitory conductance dynamics, together with selective pharmacological targeting and single-cell reverse transcriptase-polymerase chain reaction. We show that cortical serotonin shifts the E–I balance in favor of more E and we reveal fine and differential modulations of the E–I balance between 5-HTR subtypes, in relation to whether layer 2/3 or 6 was stimulated and in concordance with the specific expression pattern of these subtypes in pyramidal cells and deep interneurons. This first evidence for the functional segregation of 5-HTR subtypes sheds new light on their coherent functioning in polysynaptic sensory circuits.

Key Words: 5-HT1A 5-HT2A 5-HT3 5-HT7Rs • patch clamp • pyramidal neuron • serotonin • synaptic integration


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