DEVELOPMENTAL REGULATION OF MOSSY FIBER AFFERENT INTERACTIONS WITH TARGET GRANULE CELLS

In an in vitro model system based on purified target cerebellar granul e neurons and explants of afferents, pontine mossy fiber afferents sto p growing through contact-mediated mechanisms when they encounter gran ule neurons. Here we studied the developmental regulation of the stop signal posed by granule cells and the response of mossy fibers to the stop signal in two culture systems. Granule neurons presented in sl:ic es or as dissociated cells from postnatal day (P) 4 and P7 cerebellum were more potent in the arrest of PO pontine neurites than younger (P0 -P2) or older (up to P14) granule neurons. In contrast, pontine neurit es at embryonic day (E) 18, during their period of normal growth towar d the cerebellum, grew extensively on both cerebellar slices of all ag es from PO to P10 and dissociated P4 granule neurons. When E18 explant s were maintained for 2 days before plating in medium conditioned by n eonatal cerebellar cells, E18 pontine explants were rendered more resp onsive to the stop signal from P4 granule cells. These results indicat e that the stop signal, and the response of afferents to it, are devel opmentally regulated. Moreover, factors within the target region may i nitiate these interactions. (C) 1998 Academic Press.