In adult primary visual cortex (V1), dendritic spines are more persistent than during development. Brain-derived neurotrophic factor (BDNF) increases synaptic strength, and its levels rise during cortical development. We therefore asked whether postsynaptic BDNF signaling through its receptor TrkB regulates spine persistence in adult V1. This question has been difficult to address because most methods used to alter TrkB signaling in vivo affect cortical development or cannot distinguish between pre-and postsynaptic mechanisms. We circumvented these problems by employing transgenic mice expressing a dominant negative TrkB-EGFP fusion protein in sparse pyramidal neurons of the adult neocortex and hippocampus, producing a Golgi-staining-like pattern. In adult V1, expression of dominant negative TrkB-EGFP resulted in reduced mushroom spine maintenance and synaptic efficacy, accompanied by an increase in long and thin spines and filopodia. In contrast, mushroom spine maintenance was unaffected in CA1, indicating that TrkB plays fundamentally different roles in structural plasticity in these brain areas.adult cortical plasticity ͉ BDNF signaling ͉ synapse stability ͉ transgenic mice D uring development, synapse formation and elimination are regulated by molecular cues, spontaneous activity, and experience (1, 2). Most glutamatergic synapses on excitatory neurons are situated on dendritic spines. Live imaging of neurons expressing GFP has provided important information on the dynamics of spine formation and maintenance (3-8). Filopodia are short-lived fingershaped protrusions and believed to be precursors of dendritic spines (9, 10). Newly formed spines are often thin or long and appear and disappear within days. Some mature into mushroom or stubby spines, which are more stable and often persist for months (7,8). There are strong correlations between spine size, spine persistence, synaptic efficacy, and the number of ␣-amino-3-hydroxy-5-methyl-4-isoxazolepropionate receptors (AMPARs) at the postsynaptic density (8,11,12). With development and aging of the cortex, there is a shift toward larger and more persistent spine types (3,7,13).Spine dynamics are influenced by plasticity. Long-term potentiation in hippocampus is associated with an increase in spine size (14) and spine formation (15), whereas term depression is associated with spine elimination (16). Interestingly, reducing synaptic input results in an increase in spine numbers, probably due to homeostatic mechanisms (17)(18)(19).Ocular dominance plasticity in V1 is associated with initial pruning and later formation and stabilization of spines (20,21) and occurs predominantly during a critical period of development. Maturation of the extracellular matrix is a major factor in ending the critical period, probably by increasing spine and axon stability (20)(21)(22) BDNF signaling through TrkB receptors is a key player in visual plasticity (23,24). It drives the development of inhibitory innervation, an important factor in ocular dominance plasticity (25,26). BDNF is...