Activation of a tyrosine kinase-MAPK cascade enhances the induction of long-term synaptic facilitation and long-term memory in Aplysia.
Tyrosine kinases have been implicated in cellular processes thought to underlie learning and memory. Here we show that tyrosine kinases play a direct role in long-term synaptic facilitation (LTF) and long-term memory (LTM) for sensitization in Aplysia. Tyrosine kinase activity is required for serotonin-induced LTF of sensorimotor (SN-MN) synapses, and enhancement of endogenous tyrosine kinase activity facilitates the induction of LTF. These effects are mediated, at least in part, through mitogen-activated protein kinase (MAPK) activation and are blocked by transcriptional and translational inhibitors. Moreover, brain-derived neurotrophic factor (BDNF) also enhances the induction of LTF in a MAPK-dependent fashion. Finally, activation of endogenous tyrosine kinases enhances the induction of long-term memory for sensitization, and this enhancement also requires MAPK activation. Thus, tyrosine kinases, acting through MAPK, play a pivotal role in LTF and LTM formation.
Purcell
Angela L
AL
Interdepartmental Neuroscience Program, Yale University, New Haven, CT 06520, USA.
Sharma
Shiv K
SK
Bagnall
Martha W
MW
Sutton
Michael A
MA
Carew
Thomas J
TJ
D000818:Animals; D001048:Aplysia; D019208:Brain-Derived Neurotrophic Factor / Q000494:pharmacology; D003609:Dactinomycin / Q000494:pharmacology; D004789:Enzyme Activation / Q000502:physiology; D017774:Long-Term Potentiation / Q000187:drug effects / Q000502:physiology*; D020935:MAP Kinase Signaling System / Q000502:physiology*; D008568:Memory / Q000502:physiology*; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D019384:Nucleic Acid Synthesis Inhibitors / Q000494:pharmacology; D014176:Protein Biosynthesis / Q000502:physiology; D011505:Protein-Tyrosine Kinases / Q000378:metabolism; D012701:Serotonin / Q000494:pharmacology; D009435:Synaptic Transmission / Q000187:drug effects / Q000502:physiology*; D014158:Transcription, Genetic / Q000502:physiology
D019208:Brain-Derived Neurotrophic Factor; D019384:Nucleic Acid Synthesis Inhibitors; D003609:Dactinomycin; D012701:Serotonin; D011505:Protein-Tyrosine Kinases; D020928:Mitogen-Activated Protein Kinases