Medial Orbitofrontal Neurons Preferentially Signal Cues Predicting Changes in Reward during Unblocking

Abstract

The orbitofrontal cortex (OFC) has been broadly implicated in the ability to use the current value of expected outcomes to guide behavior. Although value correlates have been prominently reported in lateral OFC, they are more often associated with more medial areas. Further, recent studies in primates have suggested a dissociation in which the lateral OFC is involved in credit assignment and representation of reward identity and more medial areas are critical to representing value. Previously, we used unblocking to test more specifically what information about outcomes is represented by OFC neurons in rats; consistent with the proposed dichotomy between the lateral and medial OFC, we found relatively little linear value coding in the lateral OFC (Lopatina et al., 2015). Here we have repeated this experiment, recording in the medial OFC, to test whether such value signals might be found there. Neurons were recorded in an unblocking task as rats learned about cues that signaled either more, less, or the same amount of reward. We found that medial OFC neurons acquired responses to these cues; however, these responses did not signal different reward values across cues. Surprisingly, we found that cells developed responses to cues predicting a change, particularly a decrease, in reward value. This is consistent with a special role for medial OFC in representing current value to support devaluation/revaluation sensitive changes in behavior.

Significance statement: This study uniquely examines encoding in rodent mOFC at the single-unit level in response to cues that predict more, less, or no change in reward in rats during training in a Pavlovian unblocking task, finding more cells responding to change-predictive cues and stronger activity in response to cues predictive of less reward.

Keywords: Pavlovian; orbitofrontal; rat; single unit.

Figure 1.

Experimental outline, behavior summary, recording sites, and recorded cells. a, Thirsty rats were initially trained to enter an odor port after a house light lit up, then to go to the reward well below to receive a drop of chocolate milk. There were four trial types in the unblocking session. The first was a reminder of initial training. On the other three trial types, the originally trained odor was briefly presented, followed by one of three novel odors. The reward following the novel odors was unchanged (black; blocked trials), larger in size (blue; upshift trials), or smaller in size (green; downshift trials). In the probe test stage, we assessed learning by presenting the novel odors without a subsequent reward. b, Time in the reward well on the probe test trials. ANOVA for time spent in the reward well with odor (blocked, upshift, downshift), and trial (1–10) as factors found a significant effect of odor (ANOVA, F_(2,66) = 18.88, p = 3.27 × 10⁻⁷) and trial (ANOVA, F_(9,297) = 9.94, p = 2.43 × 10⁻¹³). Planned comparisons confirmed that, in the first two trial block, rats spent significantly more time in the reward well following the upshift odor (p = 0.0078) relative to the blocked odor. Rats also spent less time in the reward well following the downshift odor on Trials 3–8 relative to the blocked odor (p = 0.0306, p = 0.0009, and p = 0.0003, respectively). *p < 0.05. ^×p < 0.01. ⁺p < 0.001. Error bars indicate SEM. c, Single-unit activity was recorded from the medial orbital cortex with some recordings in or overlapping ventral orbital cortex. Locations are shown at 4.68 and 5.16 mm anterior to bregma. MO, Medial orbital cortex; VO, ventral orbital cortex. d, Theoretical firing pattern for cells that signal value monotonically (left) or are tuned to individual reward sizes (right). e–g, Activity of day 2 cells with a baseline firing rate <10 Hz sorted by when each cell reaches its maximal firing rate over the course of a trial on (e) downshift, (f) blocked, and (g) upshift trials. Cells are sorted independently in the order of earliest maximal firing rate within each trial type; thus, the cell numbers do not correspond between trial types.

Figure 2.

Recorded units not restricted to odor-responsive units. a, b, Classification accuracy for all cells with firing <10 Hz for day 1 cells (a) and day 2 cells (b). Dashed red line indicates chance. c, Classification accuracy over a sliding window of 6 trials for day 1 (left) and day 2 (right) cells. Classification accuracy significance above chance is indicated above time bins in a color matching the trial type. *p < 0.05. ^×p < 0.01. ⁺p < 0.001. Error bars indicate SEM.

Figure 3.

Single-unit and population firing of upshift-responsive neurons. a–c, Raster plots for firing of single units on initial (red), blocked (black), upshift (blue), and downshift (green) trials. First vertical line indicates odor onset (On). Second vertical line indicates novel odor onset (Novel). Third vertical line indicates odor offset (Off). Each tick represents a spike. Average activity across all trials is plotted by odor (bottom) showing the following: (a) selective firing to the upshift odor on day 2, (b) putative predictive firing to the upshift and downshift odors on day 2, (c) putative salience firing to all three novel odors but not the initially trained odor on day 1, and (d) mean neural activity (novel odor epoch, ITI) for the upshift-responsive population (n = 21) is plotted. Line colors as in raster plots. Shaded areas represent SEM. ANOVA with bin (50 ms) and odor as factors found significant effects of bin (F_(59,1180) = 6.18, p < 1 × 10⁻¹¹), odor (F_(3,60) = 3.31, p = 0.026), and a bin × odor interaction (F_(177,3540) = 1.88, p = 8.12 × 10⁻¹¹). ANOVA restricted to the novel odor period with odor and time (first 500 ms vs second 500 ms; top right, inset) as factors found a main effect of odor (F_(3,60) = 3.20, p = 0.0296). ANOVA restricted to only the three novel odors found no effect of odor (F_(2,40) = 0.79, p = 0.46). e, Scatter plot of blocked-cue and baseline-normalized upshift and downshift firing rate for all cells in the upshift-responsive population found a nonsignificant positive correlation between upshift and downshift firing. f, Baseline and initial cue-normalized firing to the upshift cue for the upshift-responsive population on the first 10 trials over both unblocking day (n = 21). Firing was calculated in a 150 ms sliding window for each 50 ms bin moving away from novel odor onset. The firing rate over ITI was then plotted, with dark red bins indicating maximal firing to the upshift cue and blue indicating minimal firing. Heat plot values shown on right of heat plot. g, The significance of the increased firing to the upshift cue was determined by performing a one-tailed t test comparing firing rate to 0, using a significance of p < 0.01 and a sliding window as in f. Black bins represent significant elevations in firing to the upshift cue.

Figure 4.

Single-unit and population firing of downshift-responsive neurons. a, b, Raster plots as in Figure 3a–c for day 1 cells showing (a) selective firing to the downshift cue and (b) putative anti-value firing, exhibiting a monotonic firing pattern negatively correlated with reward value. c, Mean neural activity (novel odor epoch, ITI) as in Figure 3d for the downshift-responsive population (n = 20). ANOVA with bin and odor as factors found significant effects of bin (F_(59,1121) = 9.44, p < 1 × 10⁻¹¹), odor (F_(3,57) = 6.75, p = 5.637 × 10⁻⁴), and the bin × odor interaction (F_(177,3363) = 2.49, p < 1 × 10⁻¹¹). ANOVA restricted to the novel odor period with odor and time (first 500 ms vs second 500 ms; top right, inset) as factors found a main effect of odor (F_(3,57) = 6.30, p = 9.2 × 10⁻⁴). ANOVA restricted to only the three novel odors found a main effect of odor (F_(2,38) = 3.25, p = 0.0498). d, Scatter plot of blocked-cue and baseline-normalized upshift and downshift firing rate for all cells in the downshift-responsive population as in Figure 3e. e, f, Heat plots and p value plots as in Figure 3f, g for all downshift-responsive cells on unblocking days 1 and 2 (n = 20).

Figure 5.

Single-unit and population firing of blocked-responsive neurons. a, Raster plots as in Figure 3a–c for firing of single units that are selective for the blocked cue. b, Mean neural activity (novel odor epoch, ITI) as in Figure 3d for the blocked-responsive population (n = 11). ANOVA with bin and odor as factors found significant effects of bin (F_(59,590) = 4.49, p < 1 × 10⁻¹¹), odor (F_(3,30) = 8.07, p = 4.36 × 10⁻⁴), and the bin × odor interaction (F(_177,1770) = 2.53, p < 1 × 10⁻¹¹). ANOVA restricted to the novel odor period with odor and time (first 500 ms vs second 500 ms, shown in top right, inset) as factors found a main effect of odor (F_(3,30) = 6.57, p < 0.01). ANOVA restricted to only the three novel odors found no effect of odor (F_(2,20) = 2.24, p = 0.1325). c, Scatter plot of blocked-cue and baseline-normalized upshift and downshift firing rate for all cells in the blocked-responsive population as in Figure 3e. d, e, Heat plots and p value plots as in Figure 3f, g for all blocked-responsive cells on unblocking days 1 and 2 (n = 11).

Figure 6.

lOFC and mOFC comparison. a, Venn diagram of lOFC response types. Each circle is proportionate to the number of cells that respond to each respective cue. Overlap between circles indicates cells that respond to multiple cues. Numbers represent the number of cells that respond to each cue or combination of cues. Curved lines indicate results of comparison of unique numbers in each group by χ². Inset, Population plots show mean neural activity (novel odor epoch, ITI) as in Figure 3d for populations in the lOFC that were as follows: Left, Upshift-responsive (n = 60). Right, Downshift-responsive (n = 56). Top, Blocked-responsive (n = 49). b, Venn diagram of mOFC response types as in a. Mean neural activity (novel odor epoch, ITI) as in Figure 3d for populations in the mOFC, replicated from previous figures, which were as follows: Left, Upshift-responsive (n = 21). Right, Downshift-responsive (n = 20). Top, Blocked-responsive (n = 11).