Differential dynamics of activity changes in dorsolateral and dorsomedial striatal loops during learning

Abstract

The basal ganglia are implicated in a remarkable range of functions influencing emotion and cognition as well as motor behavior. Current models of basal ganglia function hypothesize that parallel limbic, associative, and motor cortico-basal ganglia loops contribute to this diverse set of functions, but little is yet known about how these loops operate and how their activities evolve during learning. To address these issues, we recorded simultaneously in sensorimotor and associative regions of the striatum as rats learned different versions of a conditional T-maze task. We found highly contrasting patterns of activity in these regions during task performance and found that these different patterns of structured activity developed concurrently, but with sharply different dynamics. Based on the region-specific dynamics of these patterns across learning, we suggest a working model whereby dorsomedial associative loops can modulate the access of dorsolateral sensorimotor loops to the control of action.

Figure 1. Behavioral training and neuronal recording

(A) Final tetrode locations for dorsolateral (top) and dorsomedial (bottom) recording sites. Different colors indicate sites from different animals. (B and C) Diagrams of T-maze task-versions (top) and percent correct performance across training sessions (bottom) for Group 1 (B, n = 5) and Group 2 (C, n = 3) animals. Dark gray denotes auditory instruction cue presenation, light gray, tactile instruction cue presentation. Only one animal in Group 1 continued training beyond 23 sessions, and session 25 for this animal was excluded from analysis as too few trials were performed. (D and E) Percent correct performance (D) and cue-to-goal running times (E) averaged across all rats, for auditory (dark gray) and tactile (light gray) task-versions. Stages denoted as: stage A1 = first 1 or 2 days of training; stage A2 = second 1 or 2 sessions of training; stages A3-A5 = evenly sampled 1 or 2 sessions of training prior to criterial performance (72.5%) on either task version; stages B1-B5: evenly sampled 1 or 2 sessions of training following criterial performance on the auditory version but prior to criterion on the tactile version; stages C1-C5: 2 consecutive sessions following criterial performance on both auditory and tactile task versions. Error bars indicate SEM. (F) Percent recorded units from dorsolateral (left, red) and dorsomedial (right, blue) striatum, classified as different putative neuronal subtypes. TRN = task-responsive medium spiny neurons; NTRN = non-task-responsive medium spiny neurons; FF = fast firing interneurons; TAN = tonically active neurons. (G) Percent of TRNs across training stages. See also Figure S1.

Figure 2. Ensemble neural activity differs between dorsolateral and dorsomedial striatal recording sites during T-maze training

(A) Ensemble z-score plots illustrating population activity across trial time and training stages for dorsolateral (top) and dorsomedial (bottom) TRNs. Scale for both plots shown in center. Numbers to the right of each row indicate the number of units included in that stage. (B and C) Mean z-scores (solid lines) and SEMs (shaded) plotted across task time for dorsolateral (red) and dorsomedial (blue) TRNs separately (B) and overlaid (C) for successive phases of training. Task events abbreviated as: BL = baseline (1 sec prior to warning click); W = warning click; Ga = gate opening; L = locomotion onset; S = out of start; C = cue onset; TS = turn start; TE = turn end; Go = goal reaching. Gray dots in C indicate significant difference between dorsolateral and dorsomedial activity during the corresponding 20-ms bin (p < 0.01, t-test). See also Table 1 and Figure S2.

Figure 3. Group 1 and Group 2 rats have similar ensemble TRN firing patterns

(A) Ensemble z-score plots for TRN populations in dorsolateral (left) and dorsomedial (right) striatum recorded from rats in Group 1 (top) and Group 2 (bottom). Conventions as in Figure 2A. (B) Mean z-scores and SEMs across task-time for Group 1 (light color) and Group 2 (dark color) neuronal populations in dorsolateral (left, red) and dorsomedial (right, blue) striatum during stages A1-A5 and stages B1-B5. Gray dots as in Figure 2C for Group 1 versus Group 2 activity. (C) Representative run trajectories during the performance of the two task versions recorded during the final training session for a Group 1 animal (left, D22 session 19) and a Group 2 animal (right, D25 session 33). (D) Mean z-scores for TRN ensembles recorded from each rat, left/red: dorsolateral, right/blue: dorsomedial. See also Table 2 and Figure S3.

Figure 4. Ensemble TRN activity displays different training-related dynamics in dorsolateral and dorsomedial striatum

(A and D) Mean entropy and 95% confidence interval of the ensemble firing distribution for each stage of training relative to stage A1 for dorsolateral (A) and dorsomedial (D) striatum. (B and E) Mean z-scores and 95% confidence interval around specific task events for dorsolateral (B) and dorsomedial (E) ensembles across training stages, relative to stage A1. Means and confidence intervals were computed using 1000 bootstrap samples over the neuronal population for each stage. (C and F) Z-score regression slopes for each 20 ms bin and 95% confidence intervals for dorsolateral striatum (C), using a single linear regression across all stages, and for dorsomedial striatum (F), using a segmented linear regression with a single breakpoint at training stage B1. (G) Overlaid 95% confidence intervals of dorsomedial regression slopes for stages A1-B1 and the negative of the regression slopes for stages B1-C5. See also Figure S4.

Figure 5. Ensemble TRN activity differs only around cue onset during auditory and tactile trials

(A) Pseudocolor z-score plots comparing dorsolateral (left) and dorsomedial (right) striatal TRN ensemble activity during auditory and tactile trials (as labeled). (B) Mean z-scores and SEMs across task-time for auditory (dark color) and tactile (light color) trials, plotted for each training block for dorsolateral (left, red) and dorsomedial (right, blue) ensembles. (C) Mean z-scores and SEM across all stages for dorsolateral (left) and dorsomedial (right) TRNs during ±300-ms around cue onset, (D) Percentage of units differentiating between auditory and tactile task-versions for dorsolateral (left, red) and dorsomedial (right, blue) TRNs. Dark and light bars indicate percentage of units with higher firing during auditory or tactile conditions, respectively. Solid and dashed black lines indicate percentage of auditory- and tactile-preferring neurons obtained after shuffling trials. (E) Percentages of modality-discriminative TRNs in dorsolateral (red) and dorsomedial (blue) striatal regions, plotted across training stage. (F) Percentage of TRNs responding with significant increases or decreases in firing to the onset of each of the four discriminative stimuli and the warning click in the dorsolateral (red) and the dorsomedial (blue) striatum. Dashed line indicates percentage expected by chance. See also Figure S5.

Figure 6. Dorsolateral and dorsomedial striatal TRNs similarly discriminate turn responses and trial outcomes

(A) Percentage of TRNs with higher peri-event firing rates during right or left turn resonses for dorsolateral (left, red) and dorsomedial (right, blue) striatum. Solid and dashed black lines indicate proportion of right- and left-preferring neurons obtained after shuffling trials. (B) Mean numbers of spikes and SEM with which turn-discriminative TRNs in dorsolateral (red) and dorsomedial (blue) striatum differentiate turn direction during each event-epoch. (C) Percentage of turn-discriminative TRNs across training. (D) Percentage of dorsolateral and dorsomedial TRNs differentiating correct and incorrect trials during each task epoch. Solid and dashed black lines as in A, for correct- and incorrect-preferring populations, respectively. (E) Percentage of outcome-discriminative TRNs across training. See also Figure S6.

Figure 7. The activity of non-task-responsive striatal ensembles is also modulated during training

(A and B) Pseudocolor z-score plots showing ensemble neural activity for dorsolateral (A) and dorsomedial (B) NTRNs. Conventions as in Figure 2A. (C) Entropy estimates and 95% confidence limints for dorsolateral (red) and dorsomedial (blue) NTRN ensembles across training, shown relative to stage A1.

Figure 8. Ensemble activity patterns of dorsolateral and dorsomedial striatal TRNs are correlated with different performance measures

(A) R² values for correlations between entropy of ensemble activity and behavioral parameters (as labeled), shown in red for dorsolateral TRN ensembles and in blue for dorsomedial TRN ensembles. *: p < 0.05, **: p < 0.01. (B) R² values for correlations between NTRN entropy and behavioral performance measures (conventions as in A). (C) Schematic model illustrating hypothesized dorsomedial and dorsolateral cortico-basal ganglia loop interactions across different phases of learning. Activity in both striatal regions and their corresponding loops becomes structured simultaneously during Phase 1. In Phase 3, the reduction in structured dorsomedial striatal activity permits sensorimotor circuits to drive execution of habitual behavior. Broken arrows indicate multisynaptic connections from striatum to neocortex through pallidum and thalamus. MC: motor cortex; PFC: prefrontal cortex; DLS: dorsolateral striatum; DMS: dorsomedial striatum. See also Figure S7 and Tables S1 and S2.