*M. H. MONFILS1, K. K. COWANSAGE1, M. V. CHAO2, J. E. LEDOUX1;
1Ctr. Neural Sci., 2Skirball Inst. of Biomolecular Med., New York Univ., New York, NY

Brain-derived neurotrophic factor (BDNF) and its main receptor, tyrosine kinase receptor B (TrkB), regulate activity-dependent plasticity in the hippocampus (Nagappan & Lu, 2005), as well as hippocampal- and amygdala-dependent learning and memory (Rattiner et al., 2004; Gean et al., 2006). Despite their established function in consolidation, it is yet unknown whether they also mediate fear memory acquisition, or synaptic plasticity in the amygdala. Here we evaluated whether modulating BDNF levels, or Trk activity, plays a role in fear learning, memory consolidation, and synaptic plasticity in the lateral nucleus of the amygdala (LA). Two sets of experiments were conducted. To assess fear acquisition and consolidation, rats were trained on a standard Pavlovian fear conditioning paradigm and tested for short- and long-term memory. Prior to training, BDNF, K252a (a trk receptor inhibitor), or Trk B IgG were infused bilaterally in the LA. Our results suggest that increasing LA BDNF before fear conditioning increased freezing to the tone relative to controls that received saline. Blocking Trk receptor activity via either K252a or the BDNF scavenger TrkB IgG blocked consolidation, but had no effect on short-term fear memory. To evaluate whether BDNF regulates synaptic plasticity in the LA, we tested long-term plasticity of the thalamo-amygdala pathway in anesthetized rats. We show that intra-LA infusion of BDNF induces a persistent potentiation at thalamo-amygdala synapses. The respective roles of BDNF and TrkB receptor on high-frequency stimulation-induced potentiation in the LA are currently being investigated. Together, our results show that BDNF plays a crucial role in fear memory consolidation, possibly through modulating synaptic plasticity in the LA, but is not necessary for short-term memory.

Support Contributed By: AHFMR; NSERC; CIHR; NIH grants R01; MH46516, R37 MH38774, K05 MH067048, P50 MH58911

Poster presentation:Sunday, Nov 04, 2007, 4:00 PM - 5:00 PM
Location: San Diego Convention Center: Halls B-H