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.

A circuit from the ventral subiculum to anterior hypothalamic nucleus GABAergic neurons essential for anxiety-like behavioral avoidance

“…Psychologists have long postulated that the hippocampal formation is a center for computing, comparing, and arbitrating “safety” and “threat” signals to coordinate approach vs. avoidance in anxiety-provoking situations 2 , 58 , 59 . Here, we identified vSub of the hippocampal formation as the primary hippocampal input to AHN Vgat+ neurons.…”

Measuring Anxiety-Like Behaviors in Rodent Models of Traumatic Brain Injury

“…The authors reported that only about 13% of the injured animals were found to be "vulnerable, " showing increased exploration of anxiogenic regions during testing compared to baseline behavior and to sham-treated animals (Popovitz et al, 2021). The behavior of the vulnerable mice had neurobiological correlates in the medial prefrontal cortex, basolateral amygdala, and ventral hippocampus; all areas that are associated with stress and anxiety (Almeida-Suhett et al, 2014;Bryant and Barker, 2020;Kenwood et al, 2021;Liu et al, 2021;McCorkle et al, 2021;Pentkowski et al, 2021). Statz et al employed a different "affective profiling" technique to identify "affected" and "unaffected" rats 3 weeks or 6 months following exposure to repeated blast overpressure (Statz et al, 2019).…”

A hippocampal-hypothalamic circuit essential for anxiety-related behavioral avoidance

“…Psychologists have long postulated that the hippocampal formation is a center for computing, comparing, and arbitrating “safety” and “threat” signals to coordinate approach vs. avoidance in anxiety-provoking situations 2, 43, 44 . Rodent studies have consistently shown that the ventral hippocampus, particularly vCA1, regulates anxiety-related behaviors in various paradigms 9, 45–50 .…”