Content of review 1, reviewed on April 06, 2021

Bruce and colleagues show how projection neurons from the mice dorsal striatum can enhance their temporal encoding during an interval timing task. This lab has shown previously how is the temporal encoding of the striatal projection neurons, but in this work, they show how this temporal encoding is enhanced through the experience. Additionally, they mentioned that some neurons responded differently during erroneous animal trial responses.

  1. The title seems to mismatch the study. Should it be more appropriated to say “enhance” instead of “remap”? Also, I am not sure one could say that “striatal ensembles” were analyzed here, rather there are single-neuron and decoding population analyses, and specifically, of spiny projection neurons.

  2. The scheme of the switch interval timing task in Figure 1A is not so clear. It seems that lamps are both on during the task. Also, it seems that the long trial has two sound cues. Do animals have a second sound cue for the long trials?

  3. Figure 2A is not so clear. Are rows representing a single trial? Does each dot correspond to a single trial response? How do you count a response? What response are you referring to when you quantify response modulation in Figure 3B?

  4. In Figure 3C, the authors claim that either ramping or response neurons increased significantly. However, in the pie chart neurons modulated by both ramping and response show a high increase (from 10% to 25%) meanwhile ramping or response neurons show a low increase (from 18% to 19% and 17% to 20%, respectively). Do you think either response or ramping neurons during early training became both response and ramping neurons during experienced trials? Could it be possible that unrelated neurons became related to both response and ramping during experienced trials?

  5. Is Figure 4A an example mouse? is it a representative example? I suggest indicating it in Figure 4C. Also, it is not explicit in the text what represents each dot in Figure 4C. Is high decoding accuracy intermingled between mice? What do you think is happening on low decoding accuracy experienced sessions? Are there fewer neurons?

  6. In Figure 4C, from 0 s to 6 s animals were performing the same behavior they were previously doing. Should not it be a better comparison of computing decoding from time 6 s to 18 s between early trained and experienced mice?

  7. The authors mentioned that decoding without ramping neurons was low (Figure 4D), but the neurons related to ramping and/or response were selected statistically, was not it expected?

  8. The firing rate was binned at 200 ms to quantify the neuronal modulation (line 151) and at 1 s to examine decoding (line 171). How much do the results change when you vary the time window either for modulation or decoding?

  9. What do you mean by error-trial modulated neurons? Could you predict that the animal will fail with the activity of those neurons? How is the activity of a non-error-modulated neuron?

  10. The authors mentioned they could not dissect the ramping activity from movements (line 326), but it could be useful to see how trajectories change over experience. How do these trajectories change from early training to experienced mice? Do spatial trajectories become stereotyped on experienced mice? For example, during temporal habits animals perform stereotyped movements and striatal neurons encode sequential events (https://doi.org/10.1038/s41467-019-12075-y).

  11. The authors based this study on its important relation to diseases, such a Parkinson's disease. They claim that this task readily translates to humans (line 329), but they did not show results to support this idea. Does temporal encoding of striatal neurons is disrupted in Parkinsonian subjects? Authors should cite more studies of striatal ensembles in Parkinsonian subjects to bring support to their hypothesis (for example, https://doi.org/10.1016/j.neuroscience.2019.04.058 or https://doi.org/10.1111/ejn.14344).

  12. Putative striatal projection neuronal activity was analyzed. Besides, I suggest adding what happened with the putative fast-spiking interneurons, are they modulated?. Some studies suggest striatal interneurons are disrupted in Parkinsonian subjects (https://doi.org/10.5772/intechopen.70601).

Minor details:

  • I suggest putting that you are using microelectrode-array recordings in the abstract

  • Change “@” to “at” in line 102.

  • Figures 2B and 2C should have the same scale.

  • In line 249 correct “increase” and remove “together”.

Source

    © 2021 the Reviewer.

Content of review 2, reviewed on May 24, 2021

The authors addressed all the inquiries requested and commented appropriately about the limitations of their work. Although the authors removed the word "ensembles" from the title, they did not justify their extensive use in the manuscript.

Nevertheless, I may have a bias about the concept of neuronal ensembles. So, I recommend accepting the manuscript.

Source

    © 2021 the Reviewer.

References

    A., B. R., A., W. M., A., V. R., Mayu, O., B., E. E., Youngcho, K., S., N. N. 2021. Experience-related enhancements in striatal temporal encoding. European Journal of Neuroscience.