LeDoux Lab 2004 SfN Abstracts

INHIBITION OF ERK/MAP KINASE IN THE AUDITORY THALAMUS IMPAIRS LONG-TERM POTENTIATION IN THE LATERAL AMYGDALA
A.M.Schoute1; J.Debiec1; J.LeDoux1; G.Schafe2*
1. NYU Ctr. for Neural Sci., New York, NY, USA
2. Dept. of Psychology, Yale Univ., New Haven, CT, USA

Much evidence indicates that memory formation of Pavlovian fear conditioning is encoded in neurons of the lateral amygdala (LA) by biochemical alterations in key signaling pathways. This includes the ERK/MAPK signaling pathway, which is thought to promote long-term memory formation in LA neurons by engaging transcriptional mechanisms that are necessary for long-term synaptic plasticity. We have recently demonstrated that bilateral infusion of the MAPK inhibitor U0126 into the auditory thalamus (MGm/PIN) impairs memory consolidation of fear conditioning. Intra-thalamic infusion of the protein synthesis inhibitor anisomycin, however, has no effect. These results suggest the intriguing possibility that the MGm/PIN contributes to memory formation, but is not itself a site of storage of Pavlovian fear conditioning. One possibility is that MAPK signaling in the MGm/PIN contributes to presynaptic aspects of plasticity in the LA. As a first test of this hypothesis, we ran in vivo electrophysiology experiments in which LTP was induced in the LA by stimulating the MGm/PIN with 3 series of theta-patterned 100 Hz tetani. Prior to LTP induction, we infused U0126 (1mg) or vehicle (50% DMSO) into the MGm/PIN through a cannula attached to the stimulation electrode. After LTP induction, we recorded LA field potentials for an additional 3 hrs. Relative to vehicle-treated animals, rats that received intra-thalamic infusions of U0126 had impaired amygdala LTP. The impairment was most evident in the last 2 hrs of the recording session. The effect was likely due to an effect on plasticity, since routine transmission in the LA was not significantly affected by thalamic infusion of U0126. Together these findings suggest that MAPK inhibition in the auditory thalamus impairs fear memory formation by interfering with synaptic plasticity in the LA.
Support Contributed By: MH38774, MH46516 & MH62519

Program No. 208.10
Poster presentation: Sunday, Oct. 24, 9:00 AM - 10:00 AM
Location: OO3