Brain-derived neurotrophic factor induces rapid morphological changes in dendritic spines of olfactory bulb granule cells in cultured slices through the modulation of glutamatergic signaling

Abstract

While the acute physiological effects of brain-derived neurotrophic factor (BDNF) have been well demonstrated, little is known regarding possible morphological effects that occur within a short period of time. The acute effects of BDNF on dendritic spine morphology were examined in granule cells in cultured main olfactory bulb slices. Organotypic slices prepared from 7-day-old rats were cultured for 1 day, and BDNF was applied at varying time points prior to fixation. Granule cell dendrites were labeled with a membrane dye and observed with a confocal laser scanning microscope. The addition of BDNF into the culture medium 6 h before fixation decreased the mean diameter of the dendritic processes (filopodia/spines), but the length and density of the processes were not affected. Both filopodia/spines in the external plexiform layer and those in the granule cell layer exhibited similar changes. Considering the slow penetration into the slices, BDNF was then applied to the top of each slice. When applied 1 h before fixation, 5 ng and 0.5 ng of BDNF induced the same changes in the external plexiform layer and the granule cell layer, respectively. The changes became detectable as early as 30 min when 50 ng of BDNF was applied. The pretreatment with tetanus toxin or an N-methyl- d-aspartate receptor antagonist abolished the acute effects of BDNF on spine morphology. These results indicate that BDNF can alter spine morphology within a shorter period of time than previously observed and that the effects are mediated by enhanced glutamatergic signaling.