Consolidation of auditory fear memories formed by weak unconditioned stimuli requires NMDA receptor activation and de novo protein synthesis in the striatum.

Background: Fear is one of the most potent emotional experiences and is an adaptive component of response to potentially threatening stimuli. Cumulative evidence suggests that the amygdala plays a central role in the acquisition, storage and expression of fear memory. We previously showed that the selective ablation of striatal neurons in the adult brain impairs the long-term, but not short-term, memory for auditory fear conditioning with a lower-intensity footshock. This finding raises an intriguing possibility that long-term auditory fear memory may be consolidated in the striatum.

Results: There was a significant difference in the freezing responses between two groups of mice subjected to paired and unpaired conditioning, indicating that the auditory fear conditioning with a lower-intensity footshock is an associative learning. Post-conditioning infusion of NMDA receptor inhibitors into the striatum suppressed the consolidation of auditory fear memory when mice were conditioned with a low-intensity footshock. Furthermore, intra-striatum infusion of protein synthesis blocker anisomycin immediately or 1 h after the conditioning prevented the formation of auditory fear memory. On the other hand, the infusion of anisomycin 3 h after conditioning exerted little effect on the auditory fear conditioning, consistent with the presence of a critical time window of protein synthesis for memory consolidation.

Conclusions: These results suggest that NMDA receptors and de novo protein synthesis in the striatum are crucial for the consolidation of auditory fear memory formed with a low-intensity unconditioned stimulus.