A role for the PI-3 kinase signaling pathway in fear conditioning and synaptic plasticity in the amygdala.
Western blot analysis of neuronal tissues taken from fear-conditioned rats showed a selective activation of phosphatidylinositol 3-kinase (PI-3 kinase) in the amygdala. PI-3 kinase was also activated in response to long-term potentiation (LTP)-inducing tetanic stimulation. PI-3 kinase inhibitors blocked tetanus-induced LTP as well as PI-3 kinase activation. In parallel, these inhibitors interfered with long-term fear memory while leaving short-term memory intact. Tetanus and forskolin-induced activation of mitogen-activated protein kinase (MAPK) was blocked by PI-3 kinase inhibitors, which also inhibited cAMP response element binding protein (CREB) phosphorylation. These results provide novel evidence of a requirement of PI-3 kinase activation in the amygdala for synaptic plasticity and memory consolidation, and this activation may occur at a point upstream of MAPK activation.
Lin
C H
CH
Department of Pharmacology, College of Medicine, National Cheng Kung University, Tainan City, Taiwan.
Yeh
S H
SH
Lin
C H
CH
Lu
K T
KT
Leu
T H
TH
Chang
W C
WC
Gean
P W
PW
D000344:Afferent Pathways / Q000166:cytology / Q000187:drug effects / Q000201:enzymology; D000679:Amygdala / Q000166:cytology / Q000187:drug effects / Q000201:enzymology*; D000730:Androstadienes / Q000494:pharmacology; D000818:Animals; D002867:Chromones / Q000494:pharmacology; D005576:Colforsin / Q000494:pharmacology; D003213:Conditioning, Psychological / Q000187:drug effects / Q000502:physiology*; D017362:Cyclic AMP Response Element-Binding Protein / Q000187:drug effects / Q000378:metabolism; D004121:Dimethyl Sulfoxide / Q000494:pharmacology; D004558:Electric Stimulation; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005239:Fear / Q000187:drug effects / Q000502:physiology*; D017774:Long-Term Potentiation / Q000187:drug effects / Q000502:physiology; D020935:MAP Kinase Signaling System / Q000187:drug effects / Q000502:physiology; D008297:Male; D008568:Memory / Q000187:drug effects / Q000502:physiology*; D009025:Morpholines / Q000494:pharmacology; D009473:Neuronal Plasticity / Q000187:drug effects / Q000502:physiology*; D009474:Neurons / Q000166:cytology / Q000187:drug effects / Q000201:enzymology; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism*; D000081082:Phosphoinositide-3 Kinase Inhibitors; D010766:Phosphorylation / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology*; D013569:Synapses / Q000187:drug effects / Q000201:enzymology / Q000648:ultrastructure; D000077191:Wortmannin
D000730:Androstadienes; D002867:Chromones; D005576:Colforsin; D017362:Cyclic AMP Response Element-Binding Protein; D004121:Dimethyl Sulfoxide; D004791:Enzyme Inhibitors; D009025:Morpholines; D019869:Phosphatidylinositol 3-Kinases; D000081082:Phosphoinositide-3 Kinase Inhibitors; D000077191:Wortmannin; C085911:2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one