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对正中缝核或中缝背核进行电刺激可减少视交叉上核中光诱导的FOS蛋白,并引起昼夜活动节律的相位偏移。

Electrical stimulation of the median or dorsal raphe nuclei reduces light-induced FOS protein in the suprachiasmatic nucleus and causes circadian activity rhythm phase shifts.

作者信息

Meyer-Bernstein E L, Morin L P

机构信息

Graduate Program in Neurobiology and Behavior, State University of New York, Stony Brook 11794, USA.

出版信息

Neuroscience. 1999;92(1):267-79. doi: 10.1016/s0306-4522(98)00733-7.

Abstract

Several pharmacological studies have suggested that the large median raphe serotonergic projection to the circadian clock in the suprachiasmatic nucleus may modulate circadian rhythm phase. The present experiments studied the role of dorsal and median raphe nuclei as regulators of circadian rhythmicity by evaluating the ability of electrical stimulation to shift rhythm phase or to alter photic induction of FOS protein synthesis. Male hamsters implanted with bipolar electrodes in either the median or dorsal raphe nucleus were stimulated during the early subjective night coincident with exposure to a saturating light pulse. About 90 min later, animals were anesthetized, perfused and the brains processed for FOS protein immunoreactivity. As previously demonstrated, light alone induces FOS immunoreactivity in nuclei of suprachiasmatic nucleus neurons. This was significantly attenuated by stimulation of either the median or dorsal raphe nucleus, with the extent of attenuation proportional to the intensity of stimulation. Electrical stimulation without light exposure had no effect on FOS expression. The effect of light on FOS expression in the suprachiasmatic nucleus was not modified by pre-treatment with the 5-HT1/2 serotonin receptor antagonist, metergoline, although it greatly reduced electrical stimulation-induced FOS expression in the hippocampus. In a second experiment, hamsters housed with running wheels in constant light were electrically stimulated in the median or dorsal raphe nucleus 6 h prior to (CT6) or 2 h after (CT14) expected activity onset. Regardless of which raphe nucleus was electrically stimulated, approximately 22 min phase advances were elicited at CT6 and 36 min phase delays were elicited at CT14. Despite the fact that the sole direct projection from the raphe complex to the suprachiasmatic nucleus is from the median nucleus, the present data do not distinguish between the median and dorsal raphe with respect to their impact on circadian rhythm regulation. Instead, two possible roles for each raphe nucleus are demonstrated. One main effect is that both raphe nuclei modulate rhythm phase. The second is an interaction between raphe efferent activity and light which, in the present studies, is demonstrated by the ability of raphe stimulation to modulate the action of light on the circadian system. While serotonin is a likely neurotransmitter mediating one or both effects, alternatives such as GABA, must be considered.

摘要

多项药理学研究表明,中缝大核向视交叉上核生物钟发出的5-羟色胺能投射可能会调节昼夜节律相位。本实验通过评估电刺激改变节律相位或改变FOS蛋白合成的光诱导作用的能力,研究了中缝背核和中缝大核作为昼夜节律调节因子的作用。在早期主观夜间,给植入中缝大核或中缝背核双极电极的雄性仓鼠施加电刺激,同时给予饱和光脉冲。约90分钟后,将动物麻醉、灌注,然后对大脑进行处理以检测FOS蛋白免疫反应性。如先前所示,单独光照可诱导视交叉上核神经元细胞核中的FOS免疫反应性。中缝大核或中缝背核的刺激均能显著减弱这种反应,减弱程度与刺激强度成正比。无光暴露时的电刺激对FOS表达无影响。5-羟色胺1/2受体拮抗剂美替拉酮预处理并未改变光照对视交叉上核FOS表达的影响,尽管它能大大降低电刺激诱导的海马体FOS表达。在第二个实验中,将装有转轮的仓鼠置于持续光照下,在预期活动开始前6小时(CT6)或之后2小时(CT14)对中缝大核或中缝背核进行电刺激。无论刺激哪个中缝核,在CT6时都会引起约22分钟的相位提前,在CT14时会引起36分钟的相位延迟。尽管中缝复合体向视交叉上核的唯一直接投射来自中缝大核,但目前的数据并未区分中缝大核和中缝背核在昼夜节律调节方面的影响。相反,实验证明了每个中缝核对昼夜节律调节有两种可能的作用。一个主要作用是两个中缝核均能调节节律相位。第二个作用是中缝传出活动与光之间的相互作用,在本研究中,中缝刺激调节光对昼夜节律系统作用的能力证明了这种相互作用。虽然5-羟色胺可能是介导其中一种或两种作用的神经递质,但也必须考虑其他递质,如γ-氨基丁酸。

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