Detailed animal studies provide strong evidence that emotional memories are reconsolidated each time after retrieval, and that protein synthesis inhibitors or beta-adrenergic antagonists can impair this process (e.g., Nadar et al., 2000; Debiec and Ledoux, 2004). In contrast to the notion that memories are stable once they have passed the labile state of formation to being fully consolidated, this basic finding suggests there might be a window of opportunity to impair old emotional memories, and more importantly, traumatic memories. However, to date, there is no evidence that such a process exists in humans.
The aim of the current proposed research is to find evidence for reconsolidation of emotional memory in humans, and to elucidate its underlying brain mechanisms. Our strategy will be to examine reconsolidation in normal healthy human volunteers, using procedures that mirror those used in animals. These procedures will be aimed at detecting specific contributions of the amygdala and the hippocampus, two brain regions implicated in anxiety and emotional disorders, to reconsolidation processes. Specifically, we would attempt to provide the first evidence for reconsolidation of human amygdala and hippocampal dependent memories by examining the effects of the beta-adrenergic blocker propranolol on fear conditioning and its contextual modulation. There are two specific aims:
Specific Aim 1 : a) We will examine the effects of beta-adrenergic receptor blockade on reconsolidation of amygdala-dependent memories in humans, using a cue fear-conditioning paradigm; b) We will investigate the neural mechanisms underlying alterations in re-retrieval of amygdala-dependent memories induced by beta-adrenergic blockade effects on reconsolidation.
Specific Aim 2 : a) We will examine the effects of beta-adrenergic receptor blockade on reconsolidation of hippocampal-dependent memories in humans, using a context-mediated fear reinstatement paradigm; b) We will investigate the neural mechanisms underlying alterations in re-retrieval of hippocampal-dependent memories induced by beta-adrenergic blockade effects on reconsolidation. ? ? ?
| Schiller, Daniela; Kanen, Jonathan W; LeDoux, Joseph E et al. (2013) Extinction during reconsolidation of threat memory diminishes prefrontal cortex involvement. Proc Natl Acad Sci U S A 110:20040-5 |
