Inhibition of calcineurin facilitates the induction of memory for sensitization in Aplysia: requirement of mitogen-activated protein kinase.
The induction of both synaptic plasticity and memory is thought to depend on the balance between opposing molecular regulatory factors, such as protein kinases and phosphatases. Here we show that inhibition of protein phosphatase 2B (calcineurin, CaN) facilitates the induction of intermediate-term memory (ITM) and long-term memory (LTM) for tail shock-induced sensitization in Aplysia without any effect on short-term memory. To identify the molecular cascade underlying the improvement of memory by inhibition of CaN, we examined the role of extracellular signal-regulated kinase 1/2/mitogen-activated protein kinase (MAPK). Molecular experiments revealed that one pulse of serotonin, which by itself does not activate MAPK, leads to significant MAPK activation in the sensory neurons of the pleural ganglia when CaN is inhibited. Extending these observations, behavioral experiments showed that the facilitated induction of ITM and LTM produced by CaN inhibition depends on MAPK activity. These results demonstrate: (i) that CaN acts as an inhibitory constraint in the formation of long-lasting phases of memory, and (ii) that facilitated induction of ITM and LTM by CaN inhibition requires MAPK activity.
Sharma
Shiv K
SK
Department of Neurobiology and Behavior and Center for the Neurobiology of Learning and Memory, University of California, Irvine, CA 92697, USA.
Bagnall
Martha W
MW
Sutton
Michael A
MA
Carew
Thomas J
TJ
D000818:Animals; D001048:Aplysia / Q000502:physiology*; D019703:Calcineurin / Q000502:physiology; D065095:Calcineurin Inhibitors; D020935:MAP Kinase Signaling System; D008568:Memory / Q000187:drug effects / Q000502:physiology*; D008570:Memory, Short-Term / Q000187:drug effects / Q000502:physiology; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism*; D009473:Neuronal Plasticity; D013569:Synapses / Q000502:physiology; D016559:Tacrolimus / Q000494:pharmacology
D065095:Calcineurin Inhibitors; D020928:Mitogen-Activated Protein Kinases; D019703:Calcineurin; D016559:Tacrolimus