Herry et al

Herry et al

            While some aspects of this paper contained convincing evidence I found that certain paradigm designs were confounded. The fear renewal experiment and related figures were understandable; extinction recall for CS- and CS+ were found to be approximately equal while there was a sharp spike in freezing for CS+ implying that those who had been fear conditioned recognized context-dependent information. Additionally, there were inverse results for extinction neurons during extinction recall as compared to fear neurons during fear renewal.

          However, I question some of the validity of the first two experiments as demonstrated by figures 1 and 2. As seen in figure 1a, on “Day 2: Post-FC” mice in the CS+ condition received 12 CS as opposed to 4 CS in the CS- group. While figure 1c points out that freezing was measured in blocks of 4, rather than generally measured, I wonder how the additional CS presentation could have affected the extinction process. Additionally, extinction for CS+ was 12 CS as compared to 4 CS in CS-. The authors’ results would appear less confounded had they used a consistent presentation of the CS.

            The same confound appears in figure 2a. While the discriminative fear-conditioning paradigm dictates that only one CS of CS1 and CS2 should be extinguished, I question why they did not even present CS2 prior to extinction on “Day 2: Post-FC.” Furthermore, they do present the CS2 group with 4 CS during CS1 extinction (day 3). Although the experimenters appropriately found that on “Day 3: Ext.” there was a significant difference in the CS2 level of freezing (no extinction; CS2 froze more) I would argue that they did not subject their mice to the same conditions prior to extinction. To add a human analogy, it’s as if you were attacked in a park and for many weeks you avoided that park before deciding to attempt to walk through it again. I would imagine there would still be trepidations about doing so.

            Overall, I felt the paper did, in some respects demonstrate that the BA is constituted of distinct neurons for fear conditioning, extinction and renewal as well as the transitions between them, however, their results seem confounded and a bit noisy. It would have been good to see more consistent use of CS pairings between groups.