Serotoninergic fine-tuning of the excitation-inhibition balance in rat visual cortical networks.
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.
Moreau
Alexandre William
AW
CNRS, Institut de Neurobiologie Alfred Fessard-FRC2118, Laboratoire de Neurobiologie Cellulaire et Moléculaire-UPR9040, F-91198 Gif sur Yvette, France.
Amar
Muriel
M
Le Roux
Nicolas
N
Morel
Nicolas
N
Fossier
Philippe
P
D000818:Animals; D001369:Axons / Q000378:metabolism* / Q000648:ultrastructure; D004558:Electric Stimulation; D004594:Electrophysiology; D019706:Excitatory Postsynaptic Potentials / Q000502:physiology*; D053444:Inhibitory Postsynaptic Potentials / Q000502:physiology*; D007395:Interneurons / Q000166:cytology / Q000378:metabolism; D009415:Nerve Net / Q000166:cytology / Q000378:metabolism*; D009924:Organ Culture Techniques; D018408:Patch-Clamp Techniques; D017966:Pyramidal Cells / Q000166:cytology / Q000378:metabolism; D012333:RNA, Messenger / Q000032:analysis / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D011985:Receptors, Serotonin / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012701:Serotonin / Q000378:metabolism*; D009435:Synaptic Transmission / Q000502:physiology; D014793:Visual Cortex / Q000166:cytology / Q000378:metabolism*; D014796:Visual Perception / Q000502:physiology
D012333:RNA, Messenger; D011985:Receptors, Serotonin; D012701:Serotonin