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Alterations of Adult Prefrontal Circuits Induced by Early Postnatal Fluoxetine Treatment Mediated by 5-HT7 Receptors

  • 0Sorbonne Université, ICM-Paris Brain Institute, CNRS, INSERM, Paris 75013, France.
The Journal of Neuroscience : the Official Journal of the Society for Neuroscience +

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February 5, 2025

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February 5, 2025

View abstract on PubMed

Summary

This summary is machine-generated.

Early life exposure to fluoxetine (FLX) alters prefrontal cortex (PFC) neuron firing, impacting adult mood disorders. Serotonin transporter (SERT) and 5-HT7 receptors are key in these neurodevelopmental effects.

Area Of Science

  • Neuroscience
  • Developmental Neuroscience
  • Psychiatry

Background

  • The prefrontal cortex (PFC) is crucial for cognitive and emotional functions, with alterations linked to depression and anxiety.
  • Early postnatal development is a sensitive period where serotonin (5-HT) regulates PFC neuronal wiring.
  • Early-life insults, including fluoxetine (FLX) exposure, can disrupt PFC development and lead to adult mood disorders.

Purpose Of The Study

  • To investigate the neurobiological mechanisms by which early postnatal FLX exposure affects PFC development and function.
  • To identify specific neuronal populations and molecular targets involved in FLX-induced neurodevelopmental changes.
  • To explore the role of serotonin transporter (SERT) and 5-HT7 receptors in mediating these effects.

Main Methods

  • In vivo and ex vivo electrophysiological recordings (in vivo and patch-clamp) in adult mice exposed to FLX during the first two postnatal weeks.
  • Analysis of neuronal firing properties in deep-layer medial PFC pyramidal neurons (PNs).
  • Genetic deletion and pharmacological blockade of 5-HT7 receptors (5-HT7Rs) to assess their role.

Main Results

  • Early postnatal FLX exposure (PNFLX) reduced overall and high-frequency firing of medial PFC PNs in adult mice.
  • PNFLX selectively impaired high-frequency firing in a subpopulation of deep-layer PNs expressing the serotonin transporter (SERT) during early development.
  • Genetic or pharmacological blockade of 5-HT7Rs partially rescued the firing deficits in PNs, suggesting a role for 5-HT7Rs in mediating these effects.

Conclusions

  • Early postnatal FLX exposure induces lasting alterations in PFC neuronal function, potentially contributing to depressive and anxiety-like behaviors.
  • SERT-expressing PNs in the deep medial PFC are a critical target of early-life 5-HT signaling during development.
  • 5-HT7 receptors play a significant role in the maturation of PFC circuits and mediate the detrimental effects of early-life 5-HT alterations.

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