Time encoding migrates from prefrontal cortex to dorsal striatum during learning of a self-timed response duration task

Although time is a fundamental dimension of life, we do not know how brain areas cooperate to keep track and process time intervals. Notably, analyses of neural activity during learning are rare, mainly because timing tasks usually require training over many days. We investigated how the time encoding evolves when animals learn to time a 1.5 s interval. We designed a novel training protocol where rats go from naive- to proficient-level timing performance within a single session, allowing us to investigate neuronal activity from very early learning stages. We used pharmacological experiments and machine-learning algorithms to evaluate the level of time encoding in the medial prefrontal cortex and the dorsal striatum. Our results show a double dissociation between the medial prefrontal cortex and the dorsal striatum during temporal learning, where the former commits to early learning stages while the latter engages as animals become proficient in the task.

Please outline where this information can be found within the submission (e.g., sections or figure legends), or explain why this information doesn't apply to your submission:

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You should report how often each experiment was performed  You should include a definition of biological versus technical replication  The data obtained should be provided and sufficient information should be provided to indicate the number of independent biological and/or technical replicates  If you encountered any outliers, you should describe how these were handled  Criteria for exclusion/inclusion of data should be clearly stated  High-throughput sequence data should be uploaded before submission, with a private link for reviewers provided (these are available from both GEO and ArrayExpress) Please outline where this information can be found within the submission (e.g., sections or figure legends), or explain why this information doesn't apply to your submission: We used a novel behavioral task in an electrophysiological and pharmacological context. Hence, there was no reference to the results' experimental error, which was essential for the sample size estimate. Therefore, the sample size estimation was based on previous studies using the same behavioral task, published in: https://www.sciencedirect.com/science/article/abs/pii/S0376635719302086?via %3Dihub We also gaged our sample sizes based on similar timing tasks:

Statistical reporting
 Statistical analysis methods should be described and justified  Raw data should be presented in figures whenever informative to do so (typically when N per group is less than 10)  For each experiment, you should identify the statistical tests used, exact values of N, definitions of center, methods of multiple test correction, and dispersion and precision measures (e.g., mean, median, SD, SEM, confidence intervals; and, for the major substantive results, a measure of effect size (e.g., Pearson's r, Cohen's d)  Report exact p-values wherever possible alongside the summary statistics and 95% confidence intervals. These should be reported for all key questions and not only when the p-value is less than 0.05.
Please outline where this information can be found within the submission (e.g., sections or figure legends), or explain why this information doesn't apply to your submission: (For large datasets, or papers with a very large number of statistical tests, you may upload a single table file with tests, Ns, etc., with reference to sections in the manuscript.)

Group allocation
 Indicate how samples were allocated into experimental groups (in the case of clinical studies, please specify allocation to treatment method); if randomization was used, please also state if restricted randomization was applied  Indicate if masking was used during group allocation, data collection and/or data analysis Please outline where this information can be found within the submission (e.g., sections or figure legends), or explain why this information doesn't apply to your submission: We analyzed data from each animal separately for the behavioral and pharmacological results and, at the group level, compared them with statistical tests such as ANOVAs and ttests. For the electrophysiological data, we combined neurons' activity from different animals, a common approach in the area. We clearly stated so in the Results section.
All the other inclusion criteria were described in the methods session.
The results session show the complete explanation of the statistical tests used along with the effect sizes.
Raw data is presented in all figures in which it was possible. Effect sizes are reported in all analyses, together with the statistical tests used.