Summary:

In order to uncover the spinal mechanisms that underlie lasting sensorimotor adjustments, the
researchers conditioned a group of mice (learner mice) that associated nociceptive with
proprioceptive sensations. They then performed multiple experiments on those mice to narrow
down the spinal inhibitory neuron progenitors to the ones that are responsible for the learning
and adaptation property (and later one the specific mechanisms used by these narrowed down
neurons to facilitate the brain independent learning behavior). The gradual experimentation
went as such: 1. They found that ablation of Dorsal inhibitory neurons from Tlxs and PtflAlpha
progenitors perturbed learning. 2. They already knew that Tlxs neurons were involved in
nociceptive signal transmission, using markers; they managed to divide it into sub populations
of which one of them transmits conditional cues. 3. They also know that PtflAlpha is a potential
signal integrator through its presynaptic action on second order neurons (A Delta fibers) and
they then determined that this inhibition is higher in learner mice. 4. Finally, they singled out En1
ventral inhibitory neurons as mediators of the recollection of learned motor adaptation (post-
conditioning).

Main points of revision:

1. The use of shorter sentences in the abstract is recommended. For example (if I understood
the paper correctly): “These data reveal a circuit basis for lasting adaptive sensorimotor
behavior mediated by two molecularly and spatially distinct spinal inhibitory populations, each
regulating somatosensory-dependent learning and independent retention of learned behavior.”
could be written as “These data reveal a circuit basis for lasting adaptive sensorimotor behavior.
This behavior is mediated by two molecularly and spatially distinct spinal inhibitory populations,
each population regulating either somatosensory-dependent learning or independent retention
of learned behavior.”

2. More detailed depiction of the experimental setup in Figure 1. It would be very helpful to
visualize the state of the mouse, especially concerning the foot elevation post conditioning to
better understand the experimental setup.

3. Further elaboration of the term “Somatosensory modalities” would have been helpful in the
intro.

4. Increasing the number of more specific titles in the results section. For example: The text
under the title “A quantitative framework of limb kinematic analysis enables unbiased
characterization of cell type-specific contributions to spinal instrumental learning.” contains
many different results that are hard to derive out of that title (even vaguely so). Thus increasing
the number of titles and paragraphs would ease readability and text navigation.

5. Unclear what GAD2 neurons exactly are (could use better elaboration).

6. Adding a dedicated methods section.