PDF(Pubmed)
Abstract：
Serotonergic neurons in the dorsal raphe nucleus (DRN) play important roles early in postnatal development in the maturation and modulation of higher-order emotional, sensory, and cognitive circuitry. The pivotal functions of these cells in brain development make them a critical substrate by which early experience can be wired into the brain. In this study, we investigated the maturation of synapses onto dorsal raphe serotonergic neurons in typically developing male and female mice using whole cell patch-clamp recordings in ex vivo brain slices. We show that while inhibition of these neurons is relatively stable across development, glutamatergic synapses greatly increase in strength between postnatal day 6 (P6) and P21-23. In contrast to forebrain regions, where the components making up glutamatergic synapses are dynamic across early life, we find that DRN excitatory synapses maintain a very high ratio of α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) to N-methyl-d-aspartate (NMDA) receptors and a rectifying component of the AMPA response until adulthood. Overall, these findings reveal that the development of serotonergic neurons is marked by a significant refinement of glutamatergic synapses during the first three postnatal weeks. This suggests this time is a sensitive period of heightened plasticity for the integration of information from upstream brain areas. Genetic and environmental insults during this period could lead to alterations in serotonergic output, impacting both the development of forebrain circuits and lifelong neuromodulatory actions.NEW & NOTEWORTHY Serotonergic neurons are regulators of both the development of and ongoing activity in neuronal circuits controlling affective, cognitive, and sensory processing. Here, we characterize the maturation of extrinsic synaptic inputs onto these cells, showing that the first three postnatal weeks are a period of synaptic refinement and a potential window for experience-dependent plasticity in response to both enrichment and adversity.
摘要：
中缝背核(DRN)中的5-羟色胺能神经元在出生后早期发育中在高级情感的成熟和调节中起重要作用,感官,和认知电路。这种独特的位置使这些细胞成为早期经验可以连接到大脑的基质。在这项研究中,我们使用离体脑切片中的全细胞膜片钳记录研究了通常发育中的雄性和雌性小鼠的背中缝血清素能神经元上突触的成熟。我们表明，虽然这些神经元的抑制在整个发育过程中相对稳定，谷氨酸能突触在P6和P21-23之间的强度大大增加。与前脑区域相反，组成谷氨酸能突触的成分在早期生命中是动态的，我们发现，这些突触在DRN血清素能神经元上的组成在P15后基本稳定。DRN兴奋性突触在整个生命周期中保持了很高的AMPA与NMDA受体的比例以及AMPA反应的整流成分。总的来说,这些发现表明，在出生后的前3周，5-羟色胺能神经元的发育以谷氨酸能突触的显着改善为标志。这表明这段时间是上游大脑区域信息整合的可塑性增强的敏感时期，并且在此期间的遗传和环境损害可能导致5-羟色胺能输出的改变，影响前脑回路的发育和终身神经调节作用。
