BRAIN-DERIVED NEUROTROPHIC FACTOR PROMOTES THE DIFFERENTIATION OF VARIOUS HIPPOCAMPAL NONPYRAMIDAL NEURONS, INCLUDING CAJAL-RETZIUS CELLS, IN ORGANOTYPIC SLICE CULTURES

Brain-derived neurotrophic factor (BDNF) is widely expressed in the ce ntral nervous system, where its function is poorly understood. The aim of this study was to investigate the effects of BDNF on the different iation of hippocampal nonpyramidal neurons using organotypic slice cul tures prepared from postnatal rats. The application of BDNF induced an increase in immunostaining for the microtubule-associated protein (MA P)-2 in nonpyramidal neurons of the stratum oriens. BDNF promotes the elongation of the dendrites of these neurons, as demonstrated by analy sis after biocytin labeling. Calbindin-D- and calretinin-containing su bgroups of nonpyramidal cells in the stratum oriens were responsive to BDNF but not to nerve growth factor, as shown by an increase in the n umber of neurons immunostained for these proteins. BDNF also induced a n increase in neuropeptide Y immunostaining of stratum oriens neurons. In contrast, BDNF had no effect on parvalbumin immunostaining, despit e the fact that these cells express the BDNF receptor trkB. In additio n, BDNF increased calretinin immunoreactivity in Cajal-Retzius cells s ituated around the hippocampal fissure. The Cajal-Retzius neurons pers isted in slices beyond the time at which they degenerate in vivo. Howe ver, BDNF is not required for the survival of these cells, because the y also persisted in slices from BDNF knock-out mice. The present resul ts indicate that BDNF exerts an effect on the morphology of stratum or iens nonpyramidal cells and their calcium-binding protein levels. BDNF also regulates the calretinin content of Cajal-Retzius cells but is n ot necessary for their survival.