Article abstract


Nature Neuroscience 10, 702 - 711 (2007)
Published online: 21 May 2007 | doi:10.1038/nn1903

BDNF induces transport of PSD-95 to dendrites through PI3K-AKT signaling after NMDA receptor activation

Akira Yoshii1,2,3,4 & Martha Constantine-Paton1,2,3


The N-methyl-D-aspartate receptor (NMDAR), brain-derived neurotrophic factor (BDNF), postsynaptic density protein 95 (PSD-95) and phosphatidylinositol 3-kinase (PI3K) have all been implicated in long-term potentiation. Here we show that these molecules are involved in a single pathway for synaptic potentiation. In visual cortical neurons in young rodents, the neurotrophin receptor TrkB is associated with PSD-95. When BDNF is applied to cultured visual cortical neurons, PSD-95–labeled synaptic puncta enlarge, and fluorescent recovery after photobleaching (FRAP) reveals increased delivery of green fluorescent protein–tagged PSD-95 to the dendrites. The recovery of fluorescence requires TrkB, signaling through PI3K and the serine-threonine kinase Akt, and an intact Golgi apparatus. Stimulation of NMDARs mimics the PSD-95 trafficking that is induced by BDNF but requires active BDNF and PI3K. Furthermore, local dendritic contact with a BDNF-coated microsphere induces PSD-95 FRAP throughout the dendrites of the stimulated neuron, suggesting that this mechanism induces rapid neuron-wide synaptic increases in PSD-95 and refinement whenever a few robust inputs activate the NMDAR-BDNF-PI3K pathway.

Top
  1. Department of Biology, Massachusetts Institute of Technology, 77 Massachusetts Avenue, Cambridge, Massachusetts 02139-4307, USA.
  2. Department of Brain and Cognitive Science, Massachusetts Institute of Technology, 77 Massachusetts Avenue, Cambridge, Massachusetts 02139-4307, USA.
  3. McGovern Institute for Brain Research, Massachusetts Institute of Technology, 77 Massachusetts Avenue, Cambridge, Massachusetts 02139-4307, USA.
  4. Department of Neurology, Massachusetts General Hospital, 55 Fruit Street, Boston, Massachusetts 02114, USA.

Correspondence to: Akira Yoshii1,2,3,4 e-mail: ayoshii@mit.edu

MORE ARTICLES LIKE THIS

These links to content published by NPG are automatically generated.

NEWS AND VIEWS

Pins for spines

Nature Cell Biology News and Views (01 Dec 2005)

Pins for spines

Nature Cell Biology News and Views (01 Dec 2005)

See all 3 matches for News And Views

Extra navigation

Subscribe to Nature Neuroscience

Subscribe

Open Innovation Challenges

naturejobs

ADVERTISEMENT