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 blo cked tetanus-induced LTP as well as PI-3 kinase activation. In parallel, th ese inhibitors interfered with long-term fear memory while leaving short-te rm memory intact. Tetanus and forskolin-induced activation of mitogen-activ ated protein kinase (MAPK) was blocked by PI-3 kinase inhibitors, which als o inhibited cAMP response element binding protein (CREB) phosphorylation. T hese results provide novel evidence of a requirement of PI-3 kinase activat ion in the amygdala for synaptic plasticity and memory consolidation, and t his activation may occur at a point upstream of MAPK activation.