SUMMARY

The role of TrkB/BDNF-signaling in the developing and immature brain is multifaceted. However, it has been difficult to study the effects of BDNF in the intact adult brain, without influencing the development of the brain. This thesis aims at elucidating the role of TrkB signaling in adult cortical plasticity to answer some of the following questions. What are the structural and functional effects of inhibiting TrkB signaling in the adult cortex? Are these effects different in a similar cell type from another brain area? Can the pre- and post-synaptic effects of TrkB signaling be discerned? Does TrkB signaling act as a competitive substrate for cortical plasticity? What are the mechanisms that bring about these effects? By generating transgenic mice expressing a dominant negative TrkB-EGFP in isolated excitatory neurons of the adult forebrain, we show that postsynaptic TrkB signaling is crucial for the maintenance of synaptic strength in the mature visual cortex but not in the hippocampus. However, spine maintenance is not compromised in transgenic mice that express TrkB-EGFP in a majority of excitatory neurons of the adult visual cortex, although they receive reduced inhibitory input. We hypothesize that synaptic maintenance by postsynaptic TrkB signaling is a competitive process controlled by the inhibitory system which, in turn, is triggered by population activity.