Some forms of cAMP-mediated long-lasting potentiation are associated with release of BDNF and nuclear translocation of phospho-MAP kinase.
Long-lasting forms of synaptic plasticity like the late phase of LTP (L-LTP) typically require an elevation of cAMP, the recruitment of the cAMP-dependent protein kinase (PKA), and ultimately the activation of transcription and translation; some forms also require brain-derived neurotrophic factor (BDNF). Both cAMP and BDNF can activate mitogen-activated protein kinase (MAPK/ERK), which also plays a role in LTP. However, little is known about the mechanisms whereby cAMP, BDNF, and MAPK interact. We find that increases in cAMP can rapidly activate the BDNF receptor TrkB and induce BDNF-dependent long-lasting potentiation at the Schaffer collateral-CA1 synapse in hippocampus. Surprisingly, in these BDNF-dependent forms of potentiation, which are also MAPK dependent, TrkB activation is not critical for the activation of MAPK but instead appears to modulate the subcellular distribution and nuclear translocation of the activated MAPK.
Patterson
S L
SL
Center for Neurobiology and Behavior, College of Physicians and Surgeons, Columbia University, New York, NY 10032, USA.
Pittenger
C
C
Morozov
A
A
Martin
K C
KC
Scanlin
H
H
Drake
C
C
Kandel
E R
ER
D021581:Active Transport, Cell Nucleus / Q000502:physiology; D000818:Animals; D019208:Brain-Derived Neurotrophic Factor / Q000235:genetics* / Q000378:metabolism*; D002467:Cell Nucleus / Q000201:enzymology; D005576:Colforsin / Q000494:pharmacology; D000242:Cyclic AMP / Q000378:metabolism*; D003712:Dendrites / Q000737:chemistry / Q000378:metabolism / Q000648:ultrastructure; D019706:Excitatory Postsynaptic Potentials / Q000187:drug effects / Q000502:physiology; D008024:Ligands; D017774:Long-Term Potentiation / Q000502:physiology*; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D016253:Microscopy, Immunoelectron; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism*; D009473:Neuronal Plasticity / Q000502:physiology; D010766:Phosphorylation; D017729:Presynaptic Terminals / Q000737:chemistry / Q000378:metabolism / Q000648:ultrastructure; D020813:Receptor, trkB / Q000032:analysis / Q000378:metabolism; D013826:Theta Rhythm
D019208:Brain-Derived Neurotrophic Factor; D008024:Ligands; D005576:Colforsin; D000242:Cyclic AMP; D020813:Receptor, trkB; D020928:Mitogen-Activated Protein Kinases