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Differential Regulation of the Excitability of Prefrontal Cortical Fast-Spiking Interneurons and Pyramidal Neurons by Serotonin and Fluoxetine

By Ping Zhong and Zhen Yan


Serotonin exerts a powerful influence on neuronal excitability. In this study, we investigated the effects of serotonin on different neuronal populations in prefrontal cortex (PFC), a major area controlling emotion and cognition. Using whole-cell recordings in PFC slices, we found that bath application of 5-HT dose-dependently increased the firing of FS (fast spiking) interneurons, and decreased the firing of pyramidal neurons. The enhancing effect of 5-HT in FS interneurons was mediated by 5-HT2 receptors, while the reducing effect of 5-HT in pyramidal neurons was mediated by 5-HT1 receptors. Fluoxetine, the selective serotonin reuptake inhibitor, also induced a concentration-dependent increase in the excitability of FS interneurons, but had little effect on pyramidal neurons. In rats with chronic fluoxetine treatment, the excitability of FS interneurons was significantly increased, while pyramidal neurons remained unchanged. Fluoxetine injection largely occluded the enhancing effect of 5-HT in FS interneurons, but did not alter the reducing effect of 5-HT in pyramidal neurons. These data suggest that the excitability of PFC interneurons and pyramidal neurons is regulated by exogenous 5-HT in an opposing manner, and FS interneurons are the major target of Fluoxetine. It provides a framework for understanding the action of 5-HT and antidepressants in altering PFC network activity

Topics: Research Article
Publisher: Public Library of Science
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Provided by: PubMed Central

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  31. (1994). Neuropsychological dysfunction in depression: the relationship to regional cerebral blood flow.
  32. (2002). Overcoming the effects of stress on synaptic plasticity in the intact hippocampus: rapid actions of serotonergic and antidepressant agents.
  33. (2009). Pascual-Leone A
  34. (1995). Prozac (fluoxetine, Lilly 110140), the first selective serotonin reuptake inhibitor and an antidepressant drug: twenty years since its first publication.
  35. (2001). Receptor-mediated inhibition of G protein-coupled inwardly rectifying potassium channels involves G(alpha)q family subunits, phospholipase C, and a readily diffusible messenger.
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  37. (1998). Regulation of membrane excitability in the central nervous system by serotonin receptor subtypes.
  38. (2000). Rhe prefrontal cortex and cognitive control.
  39. (2004). Serotonergic regulation of membrane potential in developing rat prefrontal cortex: coordinated expression of 5-hydroxytryptamine (5-HT)1A,5 - H T 2A,a n d 5-HT7 receptors.
  40. (2000). Serotonin induces EPSCs preferentially in layer V pyramidal neurons of the frontal cortex in the rat.
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  45. (1996). Serotonin modulates N- and P-type calcium currents in neocortical pyramidal neurons via a membrane-delimited pathway.
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  48. (2002). Serotonin1A receptor acts during development to establish normal anxiety-like behaviour in the adult.
  49. (1992). Structure and function of brain serotonin systems.
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  51. (2003). Synchronous neural oscillations and cognitive processes.
  52. (2006). T-Type calcium channels are inhibited by fluoxetine and its metabolite norfluoxetine.
  53. (1985). The pharmacologic profile of fluoxetine.
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  55. (2000). Timing of onset of antidepressant response with fluoxetine treatment.
  56. (1994). Working memory dysfunction in schizophrenia.