Cell type-specific effects of BDNF in modulating dendritic architecture of hippocampal neurons

Marta Zagrebelsky, N. Gödecke, A. Remus, Martin Korte

Brain-derived neurotrophin factor (BDNF) has been implicated in neuronal survival, differentiation and activity-dependent synaptic plasticity in the central nervous system. It was suggested that during postnatal development BDNF regulates neuronal architecture and spine morphology of neurons within certain brain areas but not others. Particularly striking are the differences between striatum, cortex and hippocampus. Whether this is due to region- or cell type-specific effects is so far not known. We address this question using conditional bdnf knock-out mice to analyze neuronal architecture and spine morphology of pyramidal cortical and hippocampal neurons as well as inhibitory neurons from these brain areas and excitatory granule neurons from the dentate gyrus. While hippocampal and cortical inhibitory neurons and granule cells of the dentate gyrus are strongly impaired in their architecture, pyramidal neurons within the same brain regions only show a mild phenotype. We found a reduced TrkB phosphorylation within hippocampal interneurons and granule cells of the dentate gyrus, accompanied by a significant decrease in dendritic complexity. In contrast, in pyramidal neurons both TrkB phosphorylation and neuronal architecture are not altered. The results suggest diverse levels of responsiveness to BDNF for different hippocampal and cortical neuronal populations within the same brain area. Among the possible mechanisms mediating these differences in BDNF function, we tested whether zinc might be involved in TrkB transactivation specifically in pyramidal neurons. We propose that a BDNF-independent transactivation of TrkB receptor may be able to compensate the lack of BDNF signaling to modulate neuronal morphology in a cell type-specific manner.