Future experiments will be necessary to evaluate this possibility. At the molecular level, garcinol has been shown to be a potent inhibitor of the HAT activity of CREB-binding protein, E1A-associated protein, and the p300/CBP-associated factor. Each of these HATs has been widely studied in memory formation and synaptic plasticity, most notably using molecular genetic approaches with a focus on hippocampaldependent memory paradigms including object recognition, spatial memory and contextual fear memory. These studies have complemented existing pharmacological studies that have implicated HAT and HDAC activity in hippocampal longterm potentiation and hippocampal-dependent memory. To date, however, only two studies have implicated HATs in RO5185426 citations amygdala-dependent ��cued�� fear memory formation in a genetically modified mouse model while most have found no effect. These findings suggest that many of the existing mouse molecular genetic models may not be optimal to reveal a role for HATs in amygdala-dependent memory. In contrast, we have shown in the rat that auditory fear conditioning is associated with an increase in the acetylation of histone H3, but not H4, in the LA, and that intra-LA infusion of the HDAC inhibitor TSA enhances both H3 acetylation and the consolidation of an auditory fear memory; that is, STM is not affected, while LTM is significantly enhanced. Further, bath application of TSA to amygdala slices significantly enhances LTP at thalamic and cortical inputs to the LA. Consistent with these findings, in the LEE011 present study we show that intra-LA infusion of the HAT inhibitor garcinol significantly impairs training-related H3 acetylation and the consolidation of an auditory fear memory and associated neural plasticity in the LA; STM and short-term enhancements in tone-evoked neural activity in the LA are intact, while LTM and long-term training-related neural plasticity are significantly impaired. Collectively, our findings point to an important role for chromatin modifications in the consolidation of amygdala-dependent fear memories. Additional experiments will be required to examine the specific HATs that are targeted by garcinol after fear conditioning and the mechanisms by which they promote fear memory consolidation and long-term alterations in synaptic plasticity in the LA. This is the first study, of which we are aware, to systematically examine the role of a pharmacological inhibitor of HAT activity in memory reconsolidation processes. We show that intra-LA infusion of garcinol following auditory fear memory retrieval impairs retrieval-related histone H3 acetylation in the LA and significantly interferes with the reconsolidation of a fear memory and that of memory-related neural plasticity in the LA; that is, PR-STM and associated neural plasticity are unaffected, while PR-LTM is impaired together with a loss of memory-related plasticity in the LA.