Bishop Georgia A
Department of Neuroscience, The Ohio State University, Columbus, 43210, USA.
Exp Neurol. 2002 Dec;178(2):165-74. doi: 10.1006/exnr.2002.8046.
Corticotropin-releasing factor (CRF), present in climbing and mossy fiber afferents to the adult mouse cerebellum, acts as a neuromodulator to enhance the spontaneous and amino-acid-induced firing rate of Purkinje cells. CRF also is present during development of the mouse cerebellum, at ages that precede synaptogenesis, which suggests that it may have a different function during development compared to its modulatory role in the adult. The intent of this study was to determine when CRF begins to affect the firing rate of Purkinje cells as well as the time course over which this effect matures. The earliest effect of CRF was elicited at postnatal day (P) 9 at which time a weak enhancement in the amplitude of the firing rate was recorded. However, the amplitude, time to peak, sustainability, and duration of the response were significantly different from that recorded in the older animals or adults. The excitatory effect of CRF became stronger and the duration of the response increased progressively from P9 until it was adult-like by P20. Purkinje cells in the posterior lobe vermis developed a mature response before those in the anterior lobe or hemispheres. Data from previous studies have shown that CRF and its type 1 receptor are present in the cerebellum before birth and that both undergo major reorganization around P10. Taken together, these immunohistochemical observations and the present physiologic data indicate that CRF does not modulate the activity of Purkinje cells until the peptide begins to assume an adult-like distribution in cerebellar afferents.
促肾上腺皮质激素释放因子(CRF)存在于成年小鼠小脑的攀缘纤维和苔藓纤维传入纤维中,作为一种神经调质,可增强浦肯野细胞的自发放电率和氨基酸诱导的放电率。CRF在小鼠小脑发育过程中也存在,即在突触形成之前的年龄阶段,这表明它在发育过程中的功能可能与其在成体中的调节作用不同。本研究的目的是确定CRF何时开始影响浦肯野细胞的放电率以及这种影响成熟的时间进程。CRF最早在出生后第9天(P9)产生作用,此时记录到放电率幅度有微弱增强。然而,其反应的幅度、达到峰值的时间、可持续性和持续时间与年长动物或成体中记录到的显著不同。从P9到P20,CRF的兴奋作用逐渐增强,反应持续时间逐渐增加,直到类似成体。小脑后叶蚓部的浦肯野细胞比前叶或半球的浦肯野细胞更早产生成熟反应。先前研究的数据表明,CRF及其1型受体在出生前就存在于小脑中,并且两者在P10左右都会发生重大重组。综合这些免疫组化观察结果和当前的生理学数据表明,在该肽在小脑传入纤维中开始呈现类似成体的分布之前,CRF不会调节浦肯野细胞的活性。