LeDoux Lab 2004 SfN Abstracts

INHIBITION OF MYOSIN LIGHT CHAIN KINASE ACTIVITY IN LATERAL AMYGDALA ENHANCES FEAR-CONDITIONING MEMORY
R.Lamprecht; D.S.Margulies; J.E.LeDoux*
Ctr. for Neural Sci., New York Univ., New York, NY, USA
Synaptic plasticity in the lateral amygdala (LA) has been implicated in fear memory formation, and cytoskeletal rearrangements have been shown to contribute to synaptic plasticity. In order to determine whether cytoskeletal-regulating molecules in LA play a role in fear memory we inhibited the activity of myosin light chain kinase (MLCK) in LA of rats using the MLCK inhibitor ML-7 (1-(5-Iodonaphthalene-1-sulfonyl)-1H-hexahydro-l, 4-diazepineHCl). MLCK phosphorylates the myosin light chain, which activates myosin-based contractility and regulates cellular events such as neuronal morphogenesis and synaptic transmission. Microinjection of ML-7 immediately before a fear conditioning session involving tone-shock pairings significantly enhanced both short- and long-term fear memory, as measured by freezing responses elicited by the tone 1 hr or 24 hrs after conditioning. ML-7 did not affect freezing in animals given unpaired presentations of the tone and shock, ruling out sensitization to the tone by the shock or generalization of fear as the explanation of the enhanced memory in paired rats. We conclude that MLCK activity in LA suppresses fear memory formation possibly by affecting synaptic transmission or morphogenesis. Support Contributed By: NIH grants, P50 MH58911, R01 MH46516, K05 MH067048.
Program No. 208.8 Poster presentation:Sunday, Oct. 24, 11:00 AM - 12:00 PM Location: OO1