Flexible Use of Predictive Cues beyond the Orbitofrontal Cortex: Role of the Submedius Thalamic Nucleus

Abstract

The orbitofrontal cortex (OFC) is known to play a crucial role in learning the consequences of specific events. However, the contribution of OFC thalamic inputs to these processes is largely unknown. Using a tract-tracing approach, we first demonstrated that the submedius nucleus (Sub) shares extensive reciprocal connections with the OFC. We then compared the effects of excitotoxic lesions of the Sub or the OFC on the ability of rats to use outcome identity to direct responding. We found that neither OFC nor Sub lesions interfered with the basic differential outcomes effect. However, more specific tests revealed that OFC rats, but not Sub rats, were disproportionally relying on the outcome, rather than on the discriminative stimulus, to guide behavior, which is consistent with the view that the OFC integrates information about predictive cues. In subsequent experiments using a Pavlovian contingency degradation procedure, we found that both OFC and Sub lesions produced a severe deficit in the ability to update Pavlovian associations. Altogether, the submedius therefore appears as a functionally relevant thalamic component in a circuit dedicated to the integration of predictive cues to guide behavior, previously conceived as essentially dependent on orbitofrontal functions. Significance statement: In the present study, we identify a largely unknown thalamic region, the submedius nucleus, as a new functionally relevant component in a circuit supporting the flexible use of predictive cues. Such abilities were previously conceived as largely dependent on the orbitofrontal cortex. Interestingly, this echoes recent findings in the field showing, in research involving an instrumental setup, an additional involvement of another thalamic nuclei, the parafascicular nucleus, when correct responding requires an element of flexibility (Bradfield et al., 2013a). Therefore, the present contribution supports the emerging view that limbic thalamic nuclei may contribute critically to adaptive responding when an element of flexibility is required after the establishment of initial learning.

Keywords: Pavlovian associations; adaptive behaviors; degradation; differential outcome effect; rat.

Figure 1.

Tracing experiments. A, Top, Injection of dextrans in the VO and LO. The lower panels show the resulting retrograde labeling in the submedius at three different levels of the anteroposterior axis (indicated in millimeters relative to bregma). B, Top, Injection of a dextran at the level of the submedius. The three other panels show the retrograde labeling at the level of the prefrontal cortex. SubD, Dorsal part of the submedius; SubV, ventral part of the submedius; SubP, posterior part of the submedius; DLO, dorsolateral part of the orbitofrontal cortex; AI, insular area.

Figure 2.

Histology. A, Representative photomicrographs of the OFC (top) and Sub regions (bottom) in Sham (left) and lesioned rats (right). B, Representation of the included largest (gray) and smallest (black) OFC (left) and Sub (right) lesion at three different levels of the anteroposterior axis (indicated in millimeters relative to bregma).

Figure 3.

Percentage of correct responses during the acquisition phase of the conditional discrimination task. The performance of groups trained with the consistent (black) and inconsistent (white) procedures is shown for Sham (A), OFC (B) and Sub (C) rats. The gray area between black and white curves shows the differential outcome effect. Data are expressed as mean ± SEM.

Figure 4.

A, B, Percentage of correct responses during (A) the test without rewards and (B) the test without stimuli for Sham (left), Sub (middle), and OFC (right) groups. C, Percentage of correct responses during the last session of acquisition (S10) and the reversal test (reversal) conducted for Sham (white), Sub (black), and OFC (gray) rats trained with the consistent procedure. Data are expressed as mean ± SEM.

Figure 5.

Differential performance during the successive tests. Performance is expressed for each test relative to the last acquisition session (percentage). Results are shown for the consistent group only in Sham (white), Sub (black), and OFC (gray) rats. Data are expressed as mean ± SEM.

Figure 6.

Degradation of Pavlovian contingencies. A, B, Magazine visits expressed relative to the last session of acquisition (percentage) during (A) acquisition of the new contingencies (4 sessions) and (B) the test conducted without rewards. Results are shown for the nondegraded (white) as well as the degraded (black) contingencies for Sham (left), OFC (middle), and Sub (right) groups. Data are expressed as mean ± SEM. Degradation, *p < 0.05.

Figure 7.

A, B, Degradation of Pavlovian contingencies. Magazine visits expressed relative to the last session of acquisition (percentage) during (A) acquisition of the new contingencies (5 2-session blocks) and (B) the test conducted without rewards. Results are shown for the nondegraded (white) as well as the degraded (black) contingencies for Sham (left) and Sub (right) groups. Data are expressed as mean ± SEM. Degradation, *p < 0.05.