Pavlovian fear conditioning has received extensive experimental attention. Much of this work has focused on defining the neuroanatomical pathways and cellular events that underlie fear. In brief, studies have suggested that fear conditioning involves sensory transmission from thalamic and cortical areas to the lateral nucleus of the amygdala (LA), where alterations in synaptic transmission are thought to encode key aspects of the learning. In contrast to the progress that has been made at the systems level in fear conditioning, relatively little is known about the molecular mechanisms that underlie fear memory consolidation. To begin to define the molecular mechanisms that underlying conditioned fear, the following proposal is aimed at evaluating the role of mitogen-activated protein (MAP) kinase in both fear memory consolidation and in long-term potentiation (LTP) in the pathway between the auditory thalamus (MGm) and the LA, which is thought to undergo plastic changes that are necessary for fear conditioning. The first set of experiments will utilize behavioral, biochemical and immunohistochemical methods to determine whether activation of MAPK in the LA is necessary for fear memory consolidation. The second set of experiments will utilize in vivo electrophysiological, biochemical, and immunohistochemical methods to assess the involvement of MAPK activation in synaptic plasticity in the MGm-LA pathway. The third set of experiments will involve a MAPK activation in the LA impairs both memory consolidation of fear conditioning-induced neural plasticity in the LA in freely behaving animals. Investigation into the molecular mechanisms of conditioned fear in animals has both the potential to shed light on normal processes governing learning and memory in general, as well as implications for the etiology and treatment of various psychological disorders. In humans, including anxiety, phobic and panic disorders, in which fear is a prominent underlying symptom.
| Schafe, Glenn E; Swank, Michael W; Rodrigues, Sarina M et al. (2008) Phosphorylation of ERK/MAP kinase is required for long-term potentiation in anatomically restricted regions of the lateral amygdala in vivo. Learn Mem 15:55-62 |
| Apergis-Schoute, Annemieke M; Debiec, Jacek; Doyere, Valerie et al. (2005) Auditory fear conditioning and long-term potentiation in the lateral amygdala require ERK/MAP kinase signaling in the auditory thalamus: a role for presynaptic plasticity in the fear system. J Neurosci 25:5730-9 |
| Schafe, Glenn E; Doyere, Valerie; LeDoux, Joseph E (2005) Tracking the fear engram: the lateral amygdala is an essential locus of fear memory storage. J Neurosci 25:10010-4 |
| Schafe, Glenn E; Bauer, Elizabeth P; Rosis, Svetlana et al. (2005) Memory consolidation of Pavlovian fear conditioning requires nitric oxide signaling in the lateral amygdala. Eur J Neurosci 22:201-11 |
