Ventral Hippocampal CA1 and CA3 Differentially Mediate Learned Approach-Avoidance Conflict Processing

Abstract

Approach-avoidance conflict arises when an animal encounters a stimulus that is associated simultaneously with positive and negative valences [1]. The effective resolution of approach-avoidance conflict is critical for survival and is believed to go awry in a number of mental disorders, such as anxiety and addiction. An accumulation of evidence from both rodents and humans suggests that the ventral hippocampus (anterior in humans) plays a key role in approach-avoidance conflict processing [2-8], with one influential model proposing that this structure modulates behavioral inhibition in the face of conflicting goals by increasing the influence of negative valences [9]. Very little is known, however, about the contributions of specific hippocampal subregions to this process-an important issue given the functional and anatomical heterogeneity of this structure. Using a non-spatial cue-based paradigm in rats, we found that transient pharmacological inactivation of ventral CA1 produced an avoidance of a conflict cue imbued with both learned positive and learned negative outcomes, whereas inactivation of the ventral CA3 resulted in the opposite pattern of behavior, with significant preference for the conflict cue. In contrast, dorsal CA1- and CA3-inactivated rats showed no change in conflict behavior, and furthermore, additional behavioral tasks confirmed that the observed pattern of approach-avoidance findings could not be explained by other factors, such as differential alterations in novelty detection or locomotor activity. Our data demonstrate that ventral CA1 and CA3 subserve distinct and opposing roles in approach-avoidance conflict processing and provide important insight into the functions and circuitry of the ventral hippocampus.

Examining the Effects of Exercise on Frustration-Induced Anxiety-Like Behavior in Rats

“…The hippocampus is a brain area involved in the perception of stressful contexts and the production of anxious behavior (Adhikari, Topiwala, & Gordon, 2010) and is implicated as a key brain area for devel oping new interventions to treat anxiety disorders (Gorman, 2003). All three major subregions of the hippocampus (i.e., the dentate gyrus (DG) and areas CA3 and CA1) form the trisynaptic circuit and each have been functionally implicated in moderating anxious behavior (Jimenez et al, 2018;Kheirbek et al, 2013;Schumacher et al, 2018). Interestingly, these areas are all highly plastic and undergo many structural changes in response to environmental stimuli.…”

From Isolated Emotional Memories to Their Competition During Conflict

“…A currently popular notion of PFC suggests its key role in emotional processing and decision making (Damasio, 1996;Miller and Cohen, 2001) which often depends on weighing information about aversion and reward memories to control behavior. The PFC may exert its conflict resolution function through connections with other structures, such as the striatum (Berendse et al, 1992), thalamus (Choi et al, 2019), ventral hippocampus (Schumacher et al, 2018) and amygdala (McDonald et al, 1996;Gabbott et al, 2005), to name a few. A broad range of studies has shown that medial PFC (mPFC) encodes both rewarding (Otis et al, 2015) and aversive stimuli (Burgos-Robles et al, 2009).…”

“…This involves considering the weights of each emotional memory because animals choose what behavior to execute guided by the relative weighs of opposing memories. Both early and recent works have made efforts to characterize approach-avoidance conflict (Miller, 1944;Choi and Kim, 2010;Friedman et al, 2015;Burgos-Robles et al, 2017;Schumacher et al, 2018;Choi et al, 2019;Verharen et al, 2019;Walters et al, 2019). We recently developed two related approach-avoidance conflict animal models that are set to separate discrete variables (reward memory retrieval, threat memory retrieval and their competition) in the same individual by putting variable weigh on reward-or threat-related memories through training, and therefore are amenable to study both sides of the coin: when reward has higher relative value than threat and vice versa.…”

The Effects of Conflicting Dietary Information on Dieting Self-Efficacy and Motivation

“…The hippocampus is a brain area involved in the perception of stressful contexts and the production of anxious behavior (Adhikari, Topiwala, & Gordon, 2010) and is implicated as a key brain area for devel oping new interventions to treat anxiety disorders (Gorman, 2003). All three major subregions of the hippocampus (i.e., the dentate gyrus (DG) and areas CA3 and CA1) form the trisynaptic circuit and each have been functionally implicated in moderating anxious behavior (Jimenez et al, 2018;Kheirbek et al, 2013;Schumacher et al, 2018). Interestingly, these areas are all highly plastic and undergo many structural changes in response to environmental stimuli.…”