Figure 2.

Scheme showing recent molecular and cellular mechanisms through which brain-derived neurotrophic factor (BDNF) regulates structural and functional synaptic plasticity in the hippocampus. (A) Schematic representation of rat Bdnf gene and splice variants derived from it, with different 5′untranslated region (UTR) and 3′UTR. The coding sequence (CDS) is indicated. Expression of BDNF generated by the different transcripts containing exons (Ex) is indicated according to Baj et al. (2011). (B) Illustration shows the extracellular proteolytic cleavage of pro-BDNF to give rise mature BDNF and the BDNF-prodomain, as well as the interaction of the different BDNF isoforms with specific receptors. The differences in the regulation of long-term depression (LTD) between the BDNF-prodomain polymorphisms: Val-pro-BDNF (Val-pBDNF) and Met-pro-BDNF (Met-pBDNF) are stated. (C) Model describing the endogenous inhibition of BDNF/TrkB signaling by the transmembrane protein Lrig1 and its implication for proximal dendrite development and spine formation in CA1-CA3 pyramidal neurons. (D) Model proposed for pre- vs. postsynaptic BDNF release and their contribution to long-term potentiation (LTP). Postsynaptic BDNF, as well as both presynaptic and postsynaptic TrkB, contribute to LTP maintenance (red arrows). Involvement of presynaptic BDNF and postsynaptic TrkB in LTP induction is also shown (blue arrows).