title: Fluoxetine (prozac) and serotonin act on excitatory synaptic transmission to suppress single layer 2/3 pyramidal neuron-triggered cell assemblies in the human prefrontal cortex.
abstract: Selective serotonin reuptake inhibitors are the most widely prescribed drugs targeting the CNS with acute and chronic effects in cognitive, emotional and behavioral processes. This suggests that microcircuits of the human cerebral cortex are powerfully modulated by selective serotonin reuptake inhibitors, however, direct measurements of serotonergic regulation on human synaptic interactions are missing. Using multiple whole-cell patch-clamp recordings from neurons in acute cortical slices derived from nonpathological human samples of the prefrontal cortex, we show that neuronal assemblies triggered by single action potentials of individual neurons in the human cortex are suppressed by therapeutic doses of fluoxetine (Prozac). This effect is boosted and can be mimicked by physiological concentrations of serotonin through 5HT-2A and 5HT-1A receptors. Monosynaptic excitatory connections from pyramidal cells to interneurons were suppressed by application of serotonin leaving the monosynaptic output of GABAergic cells unaffected. Changes in failure rate, in paired-pulse ratio, and in the coefficient of variation of the amplitude of EPSPs suggest a presynaptic action of serotonin. In conclusion, activation of neuronal assemblies, which were suggested as building blocks of high order cognitive processes, are effectively downregulated by the acute action of selective serotonin reuptake inhibitors or serotonin at the site of pyramidal output in human microcircuits.
authors.affiliation: Research Group for Cortical Microcircuits of the Hungarian Academy of Sciences, Department of Physiology, Anatomy and Neuroscience, University of Szeged, Szeged, H-6726, Hungary.
authors.forename: Gergely
authors.initials: G
authors.lastname: Komlósi
authors.forename: Gábor
authors.initials: G
authors.lastname: Molnár
authors.forename: Márton
authors.initials: M
authors.lastname: Rózsa
authors.forename: Szabolcs
authors.initials: S
authors.lastname: Oláh
authors.forename: Pál
authors.initials: P
authors.lastname: Barzó
authors.forename: Gábor
authors.initials: G
authors.lastname: Tamás
mesh_terms: D000328:Adult; D000368:Aged; D001932:Brain Neoplasms / Q000601:surgery; D018846:Excitatory Amino Acids / Q000502:physiology; D019706:Excitatory Postsynaptic Potentials / Q000187:drug effects; D005260:Female; D005473:Fluoxetine / Q000494:pharmacology*; D018698:Glutamic Acid / Q000502:physiology; D006801:Humans; D008297:Male; D008875:Middle Aged; D009415:Nerve Net / Q000166:cytology / Q000187:drug effects / Q000502:physiology; D017397:Prefrontal Cortex / Q000166:cytology / Q000187:drug effects / Q000502:physiology*; D017966:Pyramidal Cells / Q000502:physiology*; D044282:Receptor, Serotonin, 5-HT1A / Q000187:drug effects; D044402:Receptor, Serotonin, 5-HT2A / Q000187:drug effects; D012701:Serotonin / Q000494:pharmacology*; D017367:Selective Serotonin Reuptake Inhibitors / Q000494:pharmacology*; D009435:Synaptic Transmission / Q000502:physiology*
chemical_list: D018846:Excitatory Amino Acids; D005473:Fluoxetine; D018698:Glutamic Acid; D044282:Receptor, Serotonin, 5-HT1A; D044402:Receptor, Serotonin, 5-HT2A; D012701:Serotonin; D017367:Selective Serotonin Reuptake Inhibitors