Decision letter | Modulation of anxiety and fear via distinct intrahippocampal circuits

Open accessCopyright infoDownload PDFDownload figures

Modulation of anxiety and fear via distinct intrahippocampal circuits

Decision letter

Affiliation details

McLean Hospital, United States; Harvard Medical School, United States; The University of Tennessee Health Science Center, United States; Yale School of Medicine, United States; Russian Academy of Sciences, Russia; University of Zurich, Switzerland
Howard Eichenbaum, Reviewing editor, Boston University, United States

In the interests of transparency, eLife includes the editorial decision letter and accompanying author responses. A lightly edited version of the letter sent to the authors after peer review is shown, indicating the most substantive concerns; minor comments are not usually included.

Thank you for submitting your work entitled "Modulation of anxiety and fear via distinct intrahippocampal circuits" for consideration by eLife. Your article has been reviewed by two peer reviewers, Stephen Maren and Michael Fanselow, and the evaluation has been overseen by Howard Eichenbaum as Reviewing Editor and a Senior Editor.

The reviewers have discussed the reviews with one another and the Reviewing Editor has drafted this decision to help you prepare a revised submission.


The reviewers judged that this is an interesting report examining fear and anxiety in several mouse lines with selective knockouts of the GABAAR α2 subunit in specific hippocampal subregions, with results suggesting that hippocampal areas CA1 and CA3 and the dentate gyrus make different contributions to fear and anxiety.

Essential revisions:

1) The most robust loss of diazepam sensitivity on tests of anxiety (e.g., LDB) were performed in mice bred on a 129X1/SvJ background. This line of mice has been reported to show a high-anxiety phenotype (see Camp et al. 2009, Genes Brain Behav), which likely accounts for the lower levels of light-box time in this strain. Indeed, the differences in fear conditioning and extinction between C57 and 129S1 and 129X1 mice is well characterized. That said, the major concern is that all the measures (e.g., basal behavior, immunohistochemistry, RNA, in vivo and in vitro electrophysiology) used to establish the nature and pattern of α2 KO were performed in C57s (as near as I can tell). Of course, all of these parameters might differ markedly in the 129X1 animals (including the specificity for the KO).

2) In Figure 1, immunohistochemical evidence is reported to support the claim that the KOs exhibited selective patters of α2 KO. These data appear to indicate that amygdala protein expression is lower in the CA1 and CA3 KO (quite dramatic in Figure 1B, and apparent in the quantification in Figure 1C). Although this difference apparently was not statistically significant, it nonetheless appears pronounced and raises questions about how α2 KO in the amygdala either alone or in combination with the hippocampal KOs contributes to the observed effects.