Arbitration of Approach-Avoidance Conflict by Ventral Hippocampus

Abstract

When environmental cues or stimuli that represent both rewarding and aversive outcomes are presented, complex computations must be made in order to determine whether approach or avoidance is the better behavioral strategy. In many neuropsychiatric illnesses these computations can be skewed. In some instances, circumstances that may normally warrant avoidance instead promote approach, thus producing compulsive-like behavioral strategies that are inflexible in response to new or conflicting information. Alternatively, high sensitivity to aversion or low sensitivity to reward can result in the failure to achieve goals and loss of resilience that characterizes depressive disorders. Increases in compulsive-like behavior have been found to be associated with disrupted signaling in regions that regulate response to conflicting stimuli, including the hippocampus. Classic behavioral inhibition theories of hippocampus function in anxiety suggest that the hippocampus blocks aberrant behavior in response to anxiety related cues or stimuli. The hippocampus may act to block approach in the face of conflicting stimuli. Dysregulations of hippocampal function, as may be present in neuropsychiatric disorders, may therefore promote aberrant approach behavior. The ventral hippocampus (vHPC) subregion is key for coordinating this approach/avoidance conflict resolution, likely through its participation with cortico-striatal and mesolimbic circuits. We revisit Gray's behavioral inhibition theory of HPC function, first posited in the 1980s, and interpret in the context of new knowledge on vHPC function gained through modern technology. Taken together with the extant, classical literature on hippocampal function, we propose that these new findings suggest that vHPC circuits balance behavioral response to conflicting stimuli in a manner that is both state- and context-dependent and, further, that disruption of specific vHPC circuits tips the balance in favor of biased approach or avoidance behavioral strategies.

Keywords: arbitration; conflict; fear; reward; ventral hippocampus (vHPC).

Figure 1

Determining approach or avoidance strategies. Picking an appropriate behavioral strategy in response to conflicting stimuli requires the weighing and balancing of potential risks vs. benefits. In general, avoidance strategies are chosen in circumstances where negatively valenced stimuli hold more weight or the potential risks are greater than the potential benefits (A). In contrast, approach strategies are chosen in circumstances where positively valenced stimuli hold more weight or the potential benefits are greater than the potential risks (B). In neuropsychiatric illnesses and diseases, maladaptive strategies may be chosen because of changes in the weight of different stimuli, a change in the ratio of positively and negatively valenced stimuli, or biases toward certain response patterns.

Figure 2

Differences in dorsal and ventral hippocampal circuitry. The hippocampus contains extensive within-region micro circuitry between the dentate gyrus (DG), Cornu Ammonis 1 (CA1), CA2, CA3, and subiculum (SUB) subregions. Generally, input from the entorhinal cortex (EC) (inputs are simplified here) is received by the DG, which projects via mossy fibers to CA3, and then to CA1 via the Schaffer collaterals. Though the dHPC (A) and vHPC (B) share the same general micro circuitry, vCA1 and vSUB have more reciprocal connections and project to more cortical and subcortical structures than dCA1 and dSUB. ACC, anterior cingulate cortex; BLA, basolateral amygdala; BNST, bed nucleus of the stria terminalis; DLS, dorsolateral striatum; LHA, lateral hypothalamus; LS, lateral septum; NAcC, nucleus accumbens core; NAcS, nucleus accumbens shell; PFC, prefrontal cortex; RSC, retrosplenial cortex (Cenquizca and Swanson, ; Witter, ; McGinty et al., ; Arszovszki et al., ; Bienkowski et al., ; Besnard et al., ; Gergues et al., 2020).

Figure 3

Proposed roles of downstream vHPC targets. The vHPC is posited to be a region that compares conflicting stimuli and signals to inhibit aberrant behavior, but recent data has shown that vHPC can also promote behavioral action. This suggests that vHPC may still act as an arbitrator or comparator between conflicting stimuli, but promote different behavioral responses based on projection target. This review postulates that vHPC projections to orbitofrontal and accumbal regions generally support behavioral action, while those projections to septal and hypothalamic regions generally suppress behavioral action. Notably, the basolateral amygdala and medial prefrontal cortex in this context also act as a sort of arbitrator since they can drive either action or inaction depending on their projection targets. BLA, basolateral amygdala; CeA, central amygdala; dHPC, dorsal hippocampus; IfL, infralimbic prefrontal cortex; LHA, lateral hypothalamus; LS, lateral septum; NAc, nucleus accumbens; PrL, prelimbic prefrontal cortex; PFC, prefrontal cortex; OFC, orbitofrontal cortex; vHPC, ventral hippocampus.

Figure 4

Commonly used animal models of approach-avoidance conflict. Approach-avoidance conflict tasks typically have either general or discrete cues and contexts that are associated with positive or negative outcomes. Tasks that lack stimuli associated with specifically positive or negative outcomes include the elevated plus maze (A) and light-dark box (B). Tasks that involve discrete stimuli associated with specifically positive or negative outcomes includes the Vogel and Geller-Seifter (C) tasks and the modified Y-maze (D).