TY - JOUR T1 - Altered Balance of Glutamatergic/GABAergic Synaptic Input and Associated Changes in Dendrite Morphology after BDNF Expression in BDNF-Deficient Hippocampal Neurons JF - The Journal of Neuroscience JO - J. Neurosci. SP - 7189 LP - 7200 DO - 10.1523/JNEUROSCI.5474-05.2006 VL - 26 IS - 27 AU - B. Singh AU - C. Henneberger AU - D. Betances AU - M. A. Arevalo AU - A. Rodríguez-Tébar AU - J. C. Meier AU - R. Grantyn Y1 - 2006/07/05 UR - http://www.jneurosci.org/content/26/27/7189.abstract N2 - Cultured neurons from bdnf−/− mice display reduced densities of synaptic terminals, although in vivo these deficits are small or absent. Here we aimed at clarifying the local responses to postsynaptic brain-derived neurotrophic factor (BDNF). To this end, solitary enhanced green fluorescent protein (EGFP)-labeled hippocampal neurons from bdnf−/− mice were compared with bdnf−/− neurons after transfection with BDNF, bdnf−/− neurons after transient exposure to exogenous BDNF, and bdnf+/+ neurons in wild-type cultures. Synapse development was evaluated on the basis of presynaptic immunofluorescence and whole-cell patch-clamp recording of miniature postsynaptic currents. It was found that neurons expressing BDNF::EGFP for at least 16 h attracted a larger number of synaptic terminals than BDNF-deficient control neurons. Transfected BDNF formed clusters in the vicinity of glutamatergic terminals and produced a stronger upregulation of synaptic terminal numbers than high levels of ambient BDNF. Glutamatergic and GABAergic synapses reacted differently to postsynaptic BDNF: glutamatergic input increased, whereas GABAergic input decreased. BDNF::EGFP-expressing neurons also differed from BDNF-deficient neurons in their dendrite morphology: they exhibited weaker dendrite elongation and stronger dendrite initiation. The upregulation of glutamatergic synaptic input and the BDNF-induced downregulation of GABAergic synaptic terminal numbers by postsynaptic BDNF depended on tyrosine receptor kinase B activity, as deduced from the blocking effects of K252a. The suppression of dendrite elongation was also prevented by block of tyrosine receptor kinase B but required, in addition, glutamate receptor activity. Dendritic length decreased with the number of glutamatergic contacts. These results illuminate the role of BDNF as a retrograde synaptic regulator of synapse development and the dependence of dendrite elongation on glutamatergic input. ER -