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5-HT-dependent synaptic plasticity of the prefrontal cortex in postnatal development
Guilherme Shigueto Vilar Higa1,2,3, José Francis-Oliveira4, Estevão Carlos-Lima4
1Departamento de Fisiologia e Biofísica, Laboratório de Neurofisiologia, Universidade de São Paulo (USP), Butantã, São Paulo, SP, 05508-000, Brazil. guisvhiga@gmail.com.
Scientific Reports
|December 5, 2022
Summary
Serotonin is crucial for synaptic plasticity in the developing prefrontal cortex (PFC) during the third postnatal week. Early-life stress impairs this serotonin-dependent plasticity, affecting brain development and function.
Area of Science:
- Neuroscience
- Developmental Biology
- Neuropharmacology
Background:
- The prefrontal cortex (PFC) is vital for cognitive functions, with critical development occurring early in life.
- Synaptic plasticity and synaptogenesis during early development shape neural circuits and behavioral patterns.
- Serotonin (5-HT) significantly modulates postnatal brain development and neuronal activity.
Purpose of the Study:
- To investigate the role of serotonin (5-HT) in modulating synaptic plasticity in the rat prefrontal cortex (PFC) during early postnatal development.
- To determine the specific 5-HT receptor subtypes involved in 5-HT-dependent plasticity.
- To examine the impact of early-life chronic stress on 5-HT-mediated synaptic plasticity in the PFC.
Main Methods:
- Intracellular electrophysiological recordings were used to study PFC layer 5 neurons in rats.
- Synaptic plasticity was induced using theta-burst stimulation (TBS).
- The modulatory effects of 5-HT and specific receptor agonists (5-HT2A, 5-HT1A, 5-HT7) were assessed.
Main Results:
- 5-HT was essential for TBS-induced synaptic changes in the third postnatal week, but not in later periods.
- Stimulation of 5-HT2A or 5-HT1A/5-HT7 receptors with TBS induced long-term depression (LTD).
- Synergistic activation of 5-HT1A, 5-HT2A, and 5-HT7 receptors with TBS induced long-term potentiation (LTP).
- Early-life chronic stress impaired 5-HT-dependent synaptic plasticity in the PFC.
Conclusions:
- Serotonin plays a critical role in establishing synaptic plasticity in the developing PFC.
- Specific 5-HT receptor combinations mediate either LTD or LTP during a critical developmental window.
- Early-life stress disrupts normal 5-HT signaling pathways, leading to impaired PFC synaptic plasticity and potentially affecting long-term cognitive function.
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