Development of a corticotropin-releasing factor-mediated effect on the firing rate of Purkinje cells in the postnatal mouse cerebellum

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. (C) 2002 Elsevier Science (USA).