Flexible Behavioral Adjustment to Frustrative Nonreward in Anticipatory Behavior, but Not in Consummatory Behavior, Requires the Dorsal Hippocampus.

The hippocampus (HC) is recognized for its pivotal role in memory-related plasticity and facilitating adaptive behavioral responses to reward shifts. However, the nature of its involvement in the response to reward downshifts remains to be determined. To bridge this knowledge gap, we explored the HC's function through a series of experiments in various tasks involving reward downshifts and using several neural manipulations in rats. In Experiment 1, complete excitotoxic lesions of the HC impaired choice performance in a modified T-maze after reducing the quantity of sugar pellet rewards. In Experiment 2, chemogenetic inhibition of the dorsal HC (dHC) disrupted anticipatory behavior following a food-pellet reward reduction. Experiments 3-5 impaired HC function by using peripheral lipopolysaccharide (LPS) administration. This treatment, which induces peripheral inflammation affecting HC function, significantly increased cytokine levels in the dHC (Experiment 3) and impaired anticipatory choice behavior (Experiment 4). None of these dorsal hippocampal manipulations affected consummatory responses in animals experiencing sucrose downshifts. Accordingly, we found no evidence of increased neural activation in either the dorsal or ventral HC, as measured by c-Fos expression, after a sucrose downshift task involving consummatory suppression (Experiment 6). The results highlight the HC's pivotal role in adaptively modulating anticipatory behavior in response to a variety of situations involving frustrative nonreward, while having no effect on adjustments on consummatory behavior. The data supporting this conclusion were obtained under heterogeneous experimental conditions derived from a multi-laboratory collaboration, ensuring the robustness and high reproducibility of our findings. Spatial orientation, memory update, choice of reward signals of different values, and anticipatory versus consummatory adjustments to reward downshift are discussed as potential mechanisms that could account for the specific effects observed from HC manipulations.

Frustrative nonreward: Detailed c-Fos expression patterns in the amygdala after consummatory successive negative contrast.

The amygdala has been implicated in frustrative nonreward induced by unexpected reward downshifts, using paradigms like consummatory successive negative contrast (cSNC). However, existing evidence comes from experiments involving the central and basolateral nuclei on a broad level. Moreover, whether the amygdala's involvement in reward downshift requires a cSNC effect (i.e., greater suppression in downshifted animals than in unshifted controls) or just consummatory suppression without a cSNC effect, remains unclear. Three groups were exposed to (1) a large reward disparity leading to a cSNC effect (32-to-2% sucrose), (2) a small reward disparity involving consummatory suppression in the absence of a cSNC effect (8-to-2% sucrose), and (3) an unshifted control (2% sucrose). Brains obtained after the first reward downshift session were processed for c-Fos expression, a protein often used as a marker for neural activation. c-Fos-positive cells were counted in the anterior, medial, and posterior portions (A/P axis) of ten regions of the rat basolateral, central, and medial amygdala. c-Fos expression was higher in 32-to-2% sucrose downshift animals than in the other two groups in four regions: the anterior and the medial lateral basal amygdala, the medial capsular central amygdala, and the anterior anterio-ventral medial amygdala. None of the areas exhibited differential c-Fos expression between the 8-to-2% sucrose downshift and the unshifted conditions. Thus, amygdala activation requires exposure to a substantial reward disparity. This approach has identified, for the first time, specific amygdala areas relevant to understand the cSNC effect, suggesting follow-up experiments aimed at testing the function of these regions in reward downshift.

Differential effects of naloxone on rewarding electrical stimulation of the central nucleus of the amygdala and parabrachial complex in a place preference study.

The central nucleus of the amygdala (CeA) is considered to be involved in different affective, sensory, regulatory, and acquisition processes. This study analyzed whether electrical stimulation of the PB-CeA system induces preferences in a concurrent place preference (cPP) task, as observed after stimulation of the parabrachial-insular cortex (PB-IC) axis. It also examined whether the rewarding effects are naloxone-dependent. The results show that electrical stimulation of the CeA and external lateral parabrachial subnucleus (LPBe) induces consistent preference behaviors in a cPP task. However, subcutaneous administration of an opiate antagonist (naloxone; 4mg/ml/kg) blocked the rewarding effect of the parabrachial stimulation but not that of the amygdala stimulation. These results are interpreted in the context of multiple brain reward systems that appear to differ both anatomically and neurochemically, notably with respect to the opiate system.

Naloxone impairs concurrent but not sequential flavor aversion: Resorting to a flexible/explicit learning.

The role of opiate systems has been extensively studied in relation to learning and memory. Naloxone (Nx), an opiate antagonist, was administrated in concurrent (Experiment 1) and sequential (Experiment 2) flavor aversion learning (FAL) tasks. The outcomes demonstrate that Nx impairs the acquisition of concurrent but not sequential FAL. In the concurrent learning (7 trials), both control (vehicle) and Nx2 (treated with Nx only on the first 2 days) groups learned the task. Furthermore, these 2 groups retained the learning in a discrimination test without drug administration (Day 8) but failed a reversal test (Day 9). In contrast, the Nx group (7 trials with Nx) showed no concurrent learning but correctly performed the discrimination test (Day 8) and, critically, the reversal test. These results suggest that Nx blocks concurrent (implicit) learning in these experiments but induces animals to resort to new strategies that are flexible, a characteristic of explicit learning.

Satiation and re-intake after partial withdrawal of gastric food contents: A dissociation effect in external lateral parabrachial lesioned rats.

Sensory information from the gastrointestinal system can be transmitted to the brain through the vagus nerve, the intermediate-caudal region of the nucleus of the solitary tract (NST), and various subnuclei of the parabrachial complex, notably the external lateral subnucleus (LPBe). The objective of the present study was to examine the relevance of this subnucleus in satiation and food reintake after gastrointestinal food removal. LPBe-lesioned animals were subjected to a re-intake task following the partial withdrawal of gastric food contents shortly after satiation. Lesioned and control animals ingested a similar amount of the initial liquid meal. However, after withdrawal of one-third of the food consumed, LPBe-lesioned rats were not able to compensate for the deficit created, and their re-intake of food was significantly lower than the amount withdrawn after the satiating meal. In contrast, the food re-intake of control animals was similar to the amount withdrawn. Hence, the LPBe does not appear to be critical in the satiation process under the present experimental conditions. However, the LPBe may be part of a system that is essential in rapid visceral adjustments related to short-term food intake, as also shown in other gastrointestinal regulatory behaviors that require immediate processing of visceral sensory information.

Lesions of the central nucleus of the amygdala only impair flavor aversion learning in the absence of olfactory information.

The amygdala is considered a crucial brain nucleus in different modalities of aversive conditioning, including flavor aversion learning (FAL). The importance attributed to the amygdala and its subnuclei has frequently depended on the different stimuli and procedures used in FAL tasks. In this study, FAL was impaired only in animals that had lesions in the central nucleus of the amygdala (CeA) area and also had their olfactory bulbs removed. However, this task was learned by neurologically intact animals, bulbectomized animals, and rats with lesions exclusively centered in the CeA area alone. These results suggest that the CeA area may be relevant in gustatory-gut associative learning but not in FAL, in which the olfactory system may counteract the deficit produced in taste-visceral convergence.