Neural Circuits of Fear Memory Retrieval Accuracy Over Time
Gabrielle Pollack ’17 and Hadley Bergstrom (Psychology)
Fear memory for contextual stimuli is well-known to generalize over time. However, it is not understood how auditory cued fear memory generalizes at remote time frames following learning. Further, how neuronal activity patterns in the prelimbic (PL) cortex track fear memory performance is unknown. The present study sought to establish an auditory fear memory stimulus discrimination gradient at 1-day (recent) and 30-days (remote) following learning. Adult male C57BL/6 mice were fear conditioned with three auditory conditioned stimuli (CS; 75 dB, 5 kHz, 20 s) that each coterminated with a foot shock unconditioned stimulus (US; 0.5 s, 0.6 mA) in context A. One day after fear conditioning, mice were assigned to one of five different tone frequencies (2, 3, 5, 8, or 12 kHz), placed into a novel context (context B), and played the stimulus (75 dB, 20s). 30 days later, the mice were placed into context B again and replayed the stimulus at the same frequency (2, 3, 5, 8, or 12 kHz) and strength (75 dB, 20s) as 30 days prior. 60 min following the CS test, brains were taken for activity-regulated cytoskeletal-associated protein (Arc/Arg 3.1) immunohistochemistry. Behavioral results showed mice discriminated auditory frequencies over remote time frames, with no evidence for incubation, suggesting a high degree of retrieval accuracy over time. However, mice exhibited both generalization and incubation of contextual fear memory over time, confirming previous work. Arc+ cells were found to be elevated in the 5 kHz, but not 3 kHz, groups at recent time points compared to controls, suggesting the PL tracks fear memory performance. Arc+ cell density decreased from recent to remote time frames, indicating PL circuit refinement over time. Future studies are in progress to determine whether the early reminder cue improved discrimination accuracy at the remote time point. Brain wide Arc/Arg 3.1 mapping is ongoing in the infralimbic cortex and basolateral amygdala complex.