PREreview of Distinct Roles of Somatostatin and Parvalbumin Interneurons in Regulating Predictive Actions and Emotional Responses During Trace Eyeblink Conditioning

The work by Dai & Sun tackles the important question on differential roles of Parvalbumin-positive (PV) and Somatostatin-positive (SST) interneurons on the different phases of task learning. The authors used a combination of Trace Eyeblink Conditioning (TEC), where the mice learned to associate a whisker stimulus with an air puff on their eye, and two photon imaging to measure the activity of these two neuronal populations. They show how the activity in SST neurons is mostly involved in the learned anticipatory eyeblink, suggesting a role of these cells in the processing the learned association between the whisker stimulus and the air puff. On the contrary, PV neurons seem to be mostly involved in the emotional valence of the air puff. They also investigate the effect of cholinergic signalling on the two different neuronal populations.

The study uses an ingenious experimental design to monitor the live activity of SST and PV neurons while tracking the different learning phase. The authors provide a wonderful insight on the differential roles of the two major inhibitory neuron populations, adding a crucial piece to the puzzle of the role of inhibitory neurons on learning and memory.

Major issues

• Abstract: There seems to be a mismatch between the description of the cholinergic effect on PV and SST neurons in the abstract and what the results actually show. Rephrasing the abstract might help the reader grasp the take home message.

• Adding the strain of the mice used in the experiment would improve the reproducibility of the work

• It would be great if the authors would implement the FAIR principles regarding their data and analysis tools, by uploading their raw data to a common repository (for example Figshare. For a comprehensive list of repositories consider checking https://fairsharing.org ) and provide the link in the Materials & Methods section.

• The data and the graph presented often show a very clear difference between the experimental groups, making the results strong and reliable. However, the use of multiple Wilcoxon tests as statistical tests (for example in Fig. 1) might hinder the credibility of the analysis, since this type of test does not correct for multiple analysis. Using a more rigorous tests that compensate for multiple testing will sure making the results even more robust (for example a 2-way ANOVA followed by post-hoc tests).

• In Figure 2B, due to the low resolution of the figure, the shaded area of the curves is not visible. It would be very helpful to make it more visible since it represents the S.E.M.

• In Fig. 3 there is no mention of which statistical test was used. It would be very helpful to add this information.

• There seems to be no description for Fig.4E and Fig.5E.

• The bar graph on the right of Fig.4F shows a really interesting difference in the activity of SST neurons between resting and running trials. However, the size of the Y axis does not allow to fully appreciate this difference, nor the error bars. It would be very helpful to adjust the size of the Y axis within a range that highlights this difference

Minor issues

• At Page 4, at the end of the last sub-paragraph of the “Changes in Interneuron Population Activity during TEC Learning” paragraph, the acronym “UR” is presented without definition. It would be very helpful to describe the acronym the first time they are used.

• In the Discussion, in the paragraph “Locomotion-Dependent Modulation of Interneuron Activity” the authors conclude that “...SST-INs may suppress certain motor behaviours early in the learning process...”. It would be helpful to the reader if the authors could expand on this claim to better clarify the reasoning behind it.

• In the description of Fig.1C, the text refers to traces from 4 neurons, but the image only shows 3 traces. Correcting the typo might improve clarity.

Competing interests

The author declares that they have no competing interests.