Weaver D R, Reppert S M
Laboratory of Developmental Chronobiology, Massachusetts General Hospital, Boston, MA 02114, USA.
Brain Res Mol Brain Res. 1995 Oct;33(1):136-48. doi: 10.1016/0169-328x(95)00117-b.
D1-dopamine receptor stimulation induces c-fos gene expression in the fetal suprachiasmatic nucleus (SCN), but not in the adult rat SCN. Light exposure at night induces c-fos gene expression in the adult SCN. The present experiments were designed to define the developmental transition from dopaminergic to photic regulation of c-fos gene expression in the SCN. Treatment with the D1-dopamine receptor agonist SKF 38393 (10 mg/kg) increased SCN c-fos gene expression during both day and night on postnatal day (PD) 0, 1, and at night on PD 2, but the c-fos response disappeared by PD 4. Photic induction of c-fos gene expression was apparent during both day and night at each age examined, from PD 0 through PD 6. The magnitude and distribution of c-fos expression following light during the daytime was distinguishable from the response to light at night beginning on PD 2, indicating that the circadian clock regulates (gates) the c-fos response by PD 2. Orbital enucleation prevents the induction of c-fos by light at night on PD 2, indicating retinal mediation. Developmental loss of the c-fos response to SKF is not precipitated by the arrival of the retinohypothalamic tract; animals enucleated on PD 0 were insensitive to SKF on PD 6, as were visually intact controls. The results demonstrate that both dopaminergic and photic inputs can regulate SCN c-fos gene expression early in the neonatal period, and that the developmental loss of sensitivity to SKF is not due to the arrival of photic input to the SCN. The developmental transition from dopaminergic to photic regulation of c-fos gene expression roughly parallels the developmental transition from maternal to photic entrainment of the developing biological clock.
D1 - 多巴胺受体刺激可诱导胎鼠视交叉上核(SCN)中c - fos基因表达,但对成年大鼠SCN无此作用。夜间光照可诱导成年SCN中c - fos基因表达。本实验旨在确定SCN中c - fos基因表达从多巴胺能调节向光调节的发育转变。用D1 - 多巴胺受体激动剂SKF 38393(10 mg/kg)处理,在出生后第(PD)0、1天的白天和黑夜以及PD 2的黑夜均可增加SCN中c - fos基因表达,但到PD 4时c - fos反应消失。从PD 0到PD 6的每个检查年龄,白天和黑夜的光照均可明显诱导c - fos基因表达。从PD 2开始,白天光照后c - fos表达的幅度和分布与夜间光照反应不同,表明昼夜节律时钟在PD 2时调节(控制)c - fos反应。眼眶摘除可阻止PD 2夜间光照诱导的c - fos表达,表明是视网膜介导的。视网膜下丘脑束的到达并不会导致对SKF的c - fos反应在发育过程中丧失;PD 0摘除眼球的动物在PD 6时对SKF不敏感,视觉完整的对照动物也是如此。结果表明,多巴胺能和光输入在新生儿期早期均可调节SCN中c - fos基因表达,且对SKF敏感性的发育性丧失并非由于光输入到达SCN所致。c - fos基因表达从多巴胺能调节向光调节的发育转变大致与发育中的生物钟从母体调节向光调节的发育转变平行。