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5-羟色胺依赖的前额叶皮层在出生后发育中的突触可塑性。

5-HT-dependent synaptic plasticity of the prefrontal cortex in postnatal development.

机构信息

Departamento de Fisiologia e Biofísica, Laboratório de Neurofisiologia, Universidade de São Paulo (USP), Butantã, São Paulo, SP, 05508-000, Brazil.

Laboratório de Neurogenética, Universidade Federal do ABC, São Bernardo do Campo, SP, 09606-045, Brazil.

出版信息

Sci Rep. 2022 Dec 5;12(1):21015. doi: 10.1038/s41598-022-23767-9.

DOI:10.1038/s41598-022-23767-9
PMID:36470912
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC9723183/
Abstract

Important functions of the prefrontal cortex (PFC) are established during early life, when neurons exhibit enhanced synaptic plasticity and synaptogenesis. This developmental stage drives the organization of cortical connectivity, responsible for establishing behavioral patterns. Serotonin (5-HT) emerges among the most significant factors that modulate brain activity during postnatal development. In the PFC, activated 5-HT receptors modify neuronal excitability and interact with intracellular signaling involved in synaptic modifications, thus suggesting that 5-HT might participate in early postnatal plasticity. To test this hypothesis, we employed intracellular electrophysiological recordings of PFC layer 5 neurons to study the modulatory effects of 5-HT on plasticity induced by theta-burst stimulation (TBS) in two postnatal periods of rats. Our results indicate that 5-HT is essential for TBS to result in synaptic changes during the third postnatal week, but not later. TBS coupled with 5-HT or 5-HT and 5-HT receptors stimulation leads to long-term depression (LTD). On the other hand, TBS and synergic activation of 5-HT, 5-HT, and 5-HT receptors lead to long-term potentiation (LTP). Finally, we also show that 5-HT dependent synaptic plasticity of the PFC is impaired in animals that are exposed to early-life chronic stress.

摘要

前额叶皮层（PFC）的重要功能是在生命早期建立的，此时神经元表现出增强的突触可塑性和突触发生。这个发育阶段推动了皮层连接的组织，负责建立行为模式。5-羟色胺（5-HT）是调节出生后大脑活动的最重要因素之一。在 PFC 中，激活的 5-HT 受体改变神经元的兴奋性，并与参与突触修饰的细胞内信号相互作用，这表明 5-HT 可能参与早期出生后的可塑性。为了验证这一假设，我们采用 PFC 第 5 层神经元的细胞内电生理记录来研究 5-HT 对两种出生后时期大鼠 TBS 诱导的可塑性的调制作用。我们的结果表明，5-HT 对于 TBS 在第三周出生后导致突触变化是必需的，但不是在更晚的时候。TBS 结合 5-HT 或 5-HT 和 5-HT 受体刺激导致长时程抑郁（LTD）。另一方面，TBS 和 5-HT、5-HT 和 5-HT 受体的协同激活导致长时程增强（LTP）。最后，我们还表明，暴露于早期生活慢性应激的动物中，PFC 的 5-HT 依赖性突触可塑性受损。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7381/9723183/bba6792c72ae/41598_2022_23767_Fig13_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7381/9723183/02e92768e3d6/41598_2022_23767_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7381/9723183/332bb7d2204c/41598_2022_23767_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7381/9723183/83a9c01e6df5/41598_2022_23767_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7381/9723183/6be6fe8b52de/41598_2022_23767_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7381/9723183/fbc2b8923001/41598_2022_23767_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7381/9723183/583d4383ce0a/41598_2022_23767_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7381/9723183/63ad1bb30545/41598_2022_23767_Fig7_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7381/9723183/4ac659a8e277/41598_2022_23767_Fig8_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7381/9723183/24f40b525257/41598_2022_23767_Fig9_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7381/9723183/db993a3d5ab2/41598_2022_23767_Fig10_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7381/9723183/a786b83c2c23/41598_2022_23767_Fig11_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7381/9723183/591da1c81e16/41598_2022_23767_Fig12_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7381/9723183/bba6792c72ae/41598_2022_23767_Fig13_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7381/9723183/02e92768e3d6/41598_2022_23767_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7381/9723183/332bb7d2204c/41598_2022_23767_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7381/9723183/83a9c01e6df5/41598_2022_23767_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7381/9723183/6be6fe8b52de/41598_2022_23767_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7381/9723183/fbc2b8923001/41598_2022_23767_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7381/9723183/583d4383ce0a/41598_2022_23767_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7381/9723183/63ad1bb30545/41598_2022_23767_Fig7_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7381/9723183/4ac659a8e277/41598_2022_23767_Fig8_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7381/9723183/24f40b525257/41598_2022_23767_Fig9_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7381/9723183/db993a3d5ab2/41598_2022_23767_Fig10_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7381/9723183/a786b83c2c23/41598_2022_23767_Fig11_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7381/9723183/591da1c81e16/41598_2022_23767_Fig12_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7381/9723183/bba6792c72ae/41598_2022_23767_Fig13_HTML.jpg

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