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

Gergely Komlósi, G. Molnár, Márton Rózsa, Szabolcs Oláh, P. Barzó, G. Tamás

Research output: Contribution to journalArticle

22 Citations (Scopus)

Abstract

Selective serotonin reuptake inhibitors are the most widely prescribed drugs targeting theCNSwith 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 down regulated by the acute action of selective serotonin reuptake inhibitors or serotonin at the site of pyramidal output in human microcircuits.

Original languageEnglish
Pages (from-to)16369-16378
Number of pages10
JournalJournal of Neuroscience
Volume32
Issue number46
DOIs
Publication statusPublished - Nov 14 2012

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Pyramidal Cells
Fluoxetine
Prefrontal Cortex
Synaptic Transmission
Serotonin
Serotonin Uptake Inhibitors
Neurons
Excitatory Postsynaptic Potentials
Interneurons
Drug Delivery Systems
Cerebral Cortex
Action Potentials

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

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abstract = "Selective serotonin reuptake inhibitors are the most widely prescribed drugs targeting theCNSwith 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 down regulated by the acute action of selective serotonin reuptake inhibitors or serotonin at the site of pyramidal output in human microcircuits.",
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AU - Oláh, Szabolcs

AU - Barzó, P.

AU - Tamás, G.

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