Abstract
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.
Publication types
-
Research Support, Non-U.S. Gov't
MeSH terms
-
Afferent Pathways / cytology
-
Afferent Pathways / drug effects
-
Afferent Pathways / enzymology
-
Amygdala / cytology
-
Amygdala / drug effects
-
Amygdala / enzymology*
-
Androstadienes / pharmacology
-
Animals
-
Chromones / pharmacology
-
Colforsin / pharmacology
-
Conditioning, Psychological / drug effects
-
Conditioning, Psychological / physiology*
-
Cyclic AMP Response Element-Binding Protein / drug effects
-
Cyclic AMP Response Element-Binding Protein / metabolism
-
Dimethyl Sulfoxide / pharmacology
-
Electric Stimulation
-
Enzyme Inhibitors / pharmacology
-
Fear / drug effects
-
Fear / physiology*
-
Long-Term Potentiation / drug effects
-
Long-Term Potentiation / physiology
-
MAP Kinase Signaling System / drug effects
-
MAP Kinase Signaling System / physiology
-
Male
-
Memory / drug effects
-
Memory / physiology*
-
Morpholines / pharmacology
-
Neuronal Plasticity / drug effects
-
Neuronal Plasticity / physiology*
-
Neurons / cytology
-
Neurons / drug effects
-
Neurons / enzymology
-
Phosphatidylinositol 3-Kinases / metabolism*
-
Phosphoinositide-3 Kinase Inhibitors
-
Phosphorylation / drug effects
-
Rats
-
Rats, Sprague-Dawley
-
Signal Transduction / drug effects
-
Signal Transduction / physiology*
-
Synapses / drug effects
-
Synapses / enzymology
-
Synapses / ultrastructure
-
Wortmannin
Substances
-
Androstadienes
-
Chromones
-
Cyclic AMP Response Element-Binding Protein
-
Enzyme Inhibitors
-
Morpholines
-
Phosphoinositide-3 Kinase Inhibitors
-
Colforsin
-
2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one
-
Wortmannin
-
Dimethyl Sulfoxide