BDNF is produced from many transcripts that display distinct subcellular localization, suggesting that spatially restricted effects occur as a function of genetic and physiological regulation. Different BDNF 5' splice variants give a restricted localization in the cell body or the proximal and distal compartments of dendrites; however, the functional consequences are not known. Silencing individual endogenous transcripts or overexpressing BDNF-GFP transcripts in cultured neurons demonstrated that whereas some transcripts (1 and 4) selectively affected proximal dendrites, others (2C and 6) affected distal dendrites. Moreover, segregation of BDNF transcripts resulted in a highly selective activation of the BDNF TrkB receptor. These studies indicate that spatial segregation of BDNF transcripts enables BDNF to differentially shape distinct dendritic compartments.