Behavioral strategy shapes activation of the Vip-Sst disinhibitory circuit in visual cortex

Abstract

In complex environments, animals can adopt diverse strategies to find rewards. How distinct strategies differentially engage brain circuits is not well understood. Here, we investigate this question, focusing on the cortical Vip-Sst disinhibitory circuit between vasoactive intestinal peptide-postive (Vip) interneurons and somatostatin-positive (Sst) interneurons. We characterize the behavioral strategies used by mice during a visual change detection task. Using a dynamic logistic regression model, we find that individual mice use mixtures of a visual comparison strategy and a statistical timing strategy. Separately, mice also have periods of task engagement and disengagement. Two-photon calcium imaging shows large strategy-dependent differences in neural activity in excitatory, Sst inhibitory, and Vip inhibitory cells in response to both image changes and image omissions. In contrast, task engagement has limited effects on neural population activity. We find that the diversity of neural correlates of strategy can be understood parsimoniously as the increased activation of the Vip-Sst disinhibitory circuit during the visual comparison strategy, which facilitates task-appropriate responses.

Keywords: behavior; cell type circuitry visual cortex; strategy models.

Figure 1:. Quantifying strategies during a change detection task.

(A) Head-fixed mice were shown repeating natural images and were rewarded for licking in response to image changes. Mice could perform this task using multiple strategies, including visually comparing images or learning statistical distributions of rewards. (B) Example lick rasters demonstrate multiple strategies. Each row is an epoch within one example session. Up to 20 examples for each strategy are shown. Gray bands show repeated images. Blue bands show “change images”, when the image changed from the previous image. Licks after change images generated water rewards (red markers). Dashed blue lines show omissions. Top left, licking aligned to image changes. Top right, licking aligned to omissions. Bottom left, licking aligned to post-omission images. Bottom right, licking aligned to a fixed time interval from the last licking bout, with epochs sorted into rewarded and unrewarded bouts. (C) Diagram of task structure, data processing, and strategies. Images were presented for 250ms with 500ms gray screens interleaved. 5% of all images were randomly omitted. Image changes were drawn from a geometric distribution. Individual licks were segmented into licking bouts. Bouts were assigned to the preceding image presentation. The model predicts whether a bout starts during each image interval, and therefore ignores images where the mouse was already licking. For each strategy we show the probability of starting a bout during each image interval. (D) Top, raster of licking, hits, and misses for full 1-hour session. Middle, time-varying strategy weights for each strategy. Bottom, licking probability in the data and model prediction smoothed with a one minute boxcar.

Figure 2:. Licking model reveals distinct task strategies

(A) Cross validated model performance (area under the ROC curve) for the dynamic model (blue) and static model (gray) (n=382 sessions). The red line marks the average dynamic model performance (0.83). (B-H) Dots indicate individual sessions (n=382), and (B-D) black bars are population averages. (B) Average strategy weights. (C) Learned smoothing prior σ. (D) Reduction in model evidence when removing each strategy. (E) Average weights of the visual and post-omission strategies. Red line shows a linear correlation (R² = 0.44). (F) Scatter plot of the absolute value of the reduction in model evidence (termed here as an index) for the visual and timing strategies. The strategy index is the difference between visual and timing indices. (G) Rewards per session compared with the strategy index. (H) Mice were sorted by their average strategy index. Each session from a mouse is shown in the same column. (I) 90 seconds of illustrative behavior for two example sessions with either a visual dominant strategy (top) or timing dominant strategy (bottom). Gray bands show image repeats, blue bands mark image changes, and dashed blue lines mark omissions.

Figure 3:. Strategy is distinct from engagement

(A) Contour plot of reward rate and lick bout rate from all imaging sessions (n=382 sessions, 1,804,462 image intervals). Red line: threshold for classifying engaged behavior (1 reward/120s, 1 lick bout/10s). 60.1% of image intervals are classified as engaged. (B) Example session showing lick bout rate (solid black), licking threshold (dashed black), reward rate (red), and reward rate threshold (dashed red). (C, D) Average value of the visual and timing strategy weights across a range of licking and reward rates. Both panels show data from all imaging sessions. (E) Percentage of sessions in an engaged state at each point in the hour long behavioral session. (F) Response latency, defined as the time from the start of each licking bout to the most recent image onset, split by engaged and disengaged epochs. (G-H) Response latency for engaged (G) or disengaged (H) periods, split by visual or timing strategy sessions.

Figure 4:. Neural correlates of behavioral strategy across multiple cell populations.

(A) Two-photon calcium imaging was performed in visual areas V1 and LM. (B) Cartoon of Vip-Sst microcircuit. Vip and Sst inhibitory neurons reciprocally inhibit each other. (C) Calcium events were regressed from the fluorescence traces. (D) Average calcium event magnitude of each cell class aligned to image omissions (left), hits (middle), and misses (right), split by dominant behavioral strategy. (E) Average calcium event magnitude ± hierarchically bootstrapped SEM in a interval around image changes split by strategy and whether the mouse responded. Excitatory and Sst cells show average events after image changes, (150, 250 ms) and (375, 750 ms) respectively. Vip cells show average events immediately before image changes (−375, 0 ms). (F) Average calcium event magnitude ± hb. SEM in the 750 ms interval after image presentations split by running speed and strategy. (G, H, I) Same as F after image omissions, hits, and misses. (All) Black stars indicates p<0.05 from a hierarchical bootstrap over imaging planes and cells, corrected for multiple comparisons. Gray stars indicate p<0.01

Figure 5:. Microcircuit disinhibition dynamics are amplified in the visual strategy

(A) Cartoon of Vip-Sst microcircuit. (B) Population response to image repeats, grouped by strategy. (C) Population response to image repeats plotted in 3D space. (D) Population response to image repeats for excitatory cells against Vip cells. (C,D) Arrow marks forward progression of time. Black circle marks image onset in B. (E) Same as B,D for image omissions. (F) Same as B,D for hits. (G) Same as B,D for misses.

Figure 6:. Stronger behavioral choice signals in cells from visual strategy sessions.

(A-C). Decoding was performed in the first 400ms after image presentation. Error bars are SEM over imaging planes. Each cell type is plotted as a separate color, with marker size indicating the number of cells used for decoding from each imaging plane. Black asterisks mark significant differences between visual and timing sessions (p < 0.05, t-test) (A) Cross validated random forest classifier performance at decoding image changes and repeats (% correct). (B) Correlation between decoder prediction on image changes (change vs repeat) and animal behavior (hit vs miss). (C) Cross validated random forest classifier performance at decoding hits and misses (% correct).

Figure 7:. Task engagement has minor effects on neural population activity.

(A) Population response from each dominant strategy, split by epochs of task engagement and disengagement, aligned to image omissions (left), or image change misses (right). Error bars are ± SEM. (B) Average calcium event magnitude ± hierarchically bootstrapped SEM in a interval (150ms, 250ms) around image changes split by strategy and whether the mouse responded. * indicates p<0.05 from a hierarchical bootstrap over imaging planes and cells, corrected for multiple comparisons.