Evidence that brain-derived neurotrophic factor from presynaptic nerve terminals regulates the phenotype of calbindin-containing neurons in the lateral septum

Brain-derived neurotrophic factor (BDNF) is transported anterogradely in ne urons of the CNS and can be released by activity-dependent mechanisms to re gulate synaptic plasticity. However, few neural networks have been identifi ed in which the production, transport, and effects of BDNF on postsynaptic neurons can be analyzed in detail. In this study, we have identified such a network. BDNF has been colocalized by immunocytochemistry with tyrosine hy droxylase (TH) in nerve fibers and nerve terminals within the lateral septu m of rats. BDNF-containing nerve fibers terminate on a population of calbin din-containing neurons in lateral septum that contain TrkB, the high-affini ty receptor for BDNF. Overexpression of BDNF in noradrenergic neurons incre ased levels of calbindin in septum, as well as in whole-brain lysates. Sept al levels of calbindin and BDNF partially decreased after unilateral lesion s of the medial forebrain bundle (MFB), induced with 6-hydroxydopamine, a t reatment that abolished TH staining. These data suggest that BDNF is antero gradely transported within the MFB in catecholaminergic neurons arising fro m brainstem nuclei. To determine whether BDNF affects the production of cal bindin in lateral septal neurons directly, we tested the effects of BDNF on cultures of septal neurons from embryonic day 16-17 rats. BDNF promoted th e expression of calbindin, as well as the arborization of calbindin-contain ing neurons, but BDNF had no effect on cell division or survival. Together, these results suggest that BDNF, anterogradely transported in catecholamin ergic neurons, regulates calbindin expression within the lateral septum.