Differential involvement of amygdala and cortical NMDA receptors activation upon encoding in odor fear memory

Abstract

Although the basolateral amygdala (BLA) plays a crucial role for the acquisition of fear memories, sensory cortices are involved in their long-term storage in rats. However, the time course of their respective involvement has received little investigation. Here we assessed the role of the glutamatergic N-methyl-D-aspartate (NMDA) receptors in the BLA and olfactory cortex at discrete moments of an odor fear conditioning session. We showed that NMDA receptors in BLA are critically involved in odor fear acquisition during the first association but not during the next ones. In the cortex, NMDA receptor activation at encoding is not necessary for recent odor fear memory while its role in remote memory storage needs further investigation.Although the amygdala plays a crucial role for the acquisition and storage of fear memories (for review, see LeDoux 2000;Maren 2001;Gale et al. 2004), sensory cortices were also shown to be involved in the long-term storage of the sensory attributes of remote fear memories in rats (Sacco and Sacchetti 2010). However, the precise time course of amygdala and sensory cortices involvement in fear conditioning remains to be clearly identified. In a recent study investigating hippocampal -cortical interactions, Lesburguères et al. (2011) showed that neurons in the rat cortex undergo a "tagging process" upon encoding to ensure the progressive rewiring of cortical networks that support remote memory storage. We reasoned that the same phenomenon might occur in amygdala-dependent memories and that the amygdala and cortical networks might be involved together at the time of encoding in order for fear memories to be stored in the long term.In a previous study using odor fear conditioning, we compared the dynamics of glutamate fluctuations between basolateral amygdala (BLA) and olfactory cortex (posterior piriform cortex: pPC) during the acquisition session (Hegoburu et al. 2009). In the BLA, we observed a transient increase in glutamate in response to the first odor-shock pairing only, whereas in the pPC increases in glutamate were seen after each pairing of the acquisition session. This led us to hypothesize that two parallel processes take place at encoding: the BLA might be critically involved early and transiently to encode unexpected stimulus-danger association; in parallel via a glutamatergic projection pathway, the BLA would trigger the involvement of the pPC which might be engaged regularly throughout the session to progressively build up the long-term engram as suggested by the literature (Sacco and Sacchetti 2010;Lesburguères et al. 2011). Because N-methyl-D-aspartate (NMDA) receptors play a major role in memory processes (for review, see Riedel et al. 2003), in this study we manipulated NMDA receptors in either the BLA or the pPC, at discrete moments of the acquisition session. We predicted that blocking NMDA receptors in the BLA before odor-shock training would prevent learning, while delaying the blockade to after the first pairing would not. In contrast, blocking NMDA receptors in t...

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