Basolateral amygdala and orbitofrontal cortex, but not dorsal hippocampus, are necessary for the control of reward-seeking by occasion setters

Abstract

Reward-seeking in the world is driven by cues that can have ambiguous predictive and motivational value. To produce adaptive, flexible reward-seeking, it is necessary to exploit occasion setters, other distinct features in the environment, to resolve the ambiguity of Pavlovian reward-paired cues. Despite this, very little research has investigated the neurobiological underpinnings of occasion setting, and as a result little is known about which brain regions are critical for occasion setting. To address this, we exploited a recently developed task that was amenable to neurobiological inquiry where a conditioned stimulus is only predictive of reward delivery if preceded in time by the non-overlapping presentation of a separate cue-an occasion setter. This task required male rats to maintain and link cue-triggered expectations across time to produce adaptive reward-seeking. We interrogated the contributions of the basolateral amygdala and orbitofrontal cortex to occasion setting as these regions are thought to be critical for the computation and exploitation of state value, respectively. Reversible inactivation of either structure prior to the occasion-setting task resulted in a profound inability of rats to use the occasion setter to guide reward-seeking. In contrast, inactivation of the dorsal hippocampus, a region fundamental for context-specific responding was without effect nor did inactivation of the basolateral amygdala or orbitofrontal cortex in a standard Pavlovian conditioning preparation affect conditioned responding. We conclude that neural activity within the orbitofrontal cortex and basolateral amygdala circuit is necessary to update and resolve ambiguity in the environment to promote cue-driven reward-seeking.

Keywords: Amygdala; Context; Motivation; Orbitofrontal cortex; Pavlovian conditioning.

Figure 1.. Experimental design and histological verification of microinjector tips.

A, Schematic of the occasion setting task. B, Cannula placements for rats in the BLA group (n=10). C, Cannula placements for rats in the OFC group (n=16). Numbers indicate distance from bregma in millimeters and the coronal sections were obtained from (Paxinos and Watson, 2007).

Figure 2.. Reversible inactivation of the basolateral amygdala impairs occasion setting.

A, Average time in port during the conditioned stimulus period for both test sessions. B, Individual differences in time in port during the conditioned stimulus period on reinforced trials minus either conditioned stimulus alone or occasion setter alone trials. C, Intertrial port entries during the behavioral session. D, Intertrial port time during the behavioral session. For all figures bars indicate mean ± SEM. Empty bars represent data from the saline session and filled bars from the inactivation session. Individual rats are overlaid and represented by the colored lines. OS, occasion setter. CS, conditioned stimulus. *p<0.05.

Figure 3.. Reversible inactivation of the orbitofrontal cortex impairs occasion setting.

A, Average time in port during the conditioned stimulus period for each trial type. B, Individual differences in time in port during the conditioned stimulus period on reinforced trials minus either conditioned stimulus alone or occasion setter alone trials. C, Intertrial port entries during the behavioral session. D, Intertrial port time during the behavioral session. For all figures bars indicate mean + SEM. Empty bars represent data from the saline session and filled bars data from the inactivation session. Individual rats are overlaid and represented by the colored lines. OS, occasion setter. CS, conditioned stimulus. *p<0.05.

Figure 4.. Dorsal hippocampus inactivation is without effect on occasion setting.

A, Average time in port during the conditioned stimulus period for each trial type. B, Individual differences in time in port during the conditioned stimulus period on reinforced trials minus either conditioned stimulus alone or occasion setter alone trials. C, Intertrial port entries during the behavioral session. D, Intertrial port time during the behavioral session. E, Cannula placements for DH rats (n=10). Numbers indicate distance from bregma in millimeters and the coronal sections were obtained from (Paxinos and Watson, 2007). For all figures bars indicate mean + SEM. Empty bars represent data from the saline session and filled bars data from the inactivation session. Individual rats are overlaid and represented by the colored lines. OS, occasion setter. CS, conditioned stimulus. *p<0.05.

Figure 5.. Inactivation of neither basolateral amygdala nor orbitofrontal cortex alters Pavlovian conditioned approach.

A, Schematic of task design where 30 trials per session were presented with each trial being the presentation of white noise for 5 s followed by 5 s activation of a pump containing 15% sucrose. B, Time in port expressed as a percentage during the white noise. C, Intertrial time in the port during the behavioral session. D, Cannula placements for BLA rats (n=8). E, Time in port expressed as a percentage during the white noise. F, Intertrial time in the port during the behavioral session. G, Cannula placements for OFC rats (n=11). Numbers indicate distance from bregma in millimeters and the coronal sections were obtained from (Paxinos and Watson, 2007). For all figures bars indicate mean + SEM. Empty bars represent data from the saline session and filled bars data from the inactivation session. Individual rats are overlaid and represented by the colored lines. *p<0.05.