The functional forebrain circuitry of fear-cue inhibited feeding in food-deprived rats

Abstract

The drive to eat, like most motivated behaviors, is controlled by both intrinsic signals from the body as well as extrinsic signals from the environment. Although these factors often act in concert, in some instances environmental cues can override the body’s homeostatic signals. Prior work investigating the ability of learned cues to promote overeating in the absence of hunger identified a critical forebrain network composed of the amygdala, medial prefrontal cortex (mPFC), and lateral hypothalamus (LHA). We hypothesized that a similar forebrain network may also be critical when learned fear-cues inhibit eating despite hunger. The amygdala, mPFC and LHA are each anatomically and functionally positioned to influence feeding, and evidence suggests they could work together to support the fear-cue’s ability to inhibit feeding by overriding homeostatic hunger signals triggered by food-deprivation. Prior anatomical work identified direct pathways between these three large, heterogeneous regions; however, less is known about the organization of the underlying circuitries, especially between distinct nuclei and/or subdivisions that comprise these structures. Study 1 used a dual retrograde tract tracing design to map the topographical organization of the connections between the amygdala, mPFC, and LHA in detail, and to determine whether amygdalar pathways to the mPFC and to LHA originated from the same or different neurons. We found evidence for multiple, topographically organized, direct pathways from the amygdala to the LHA, and separate pathways from the amygdala to areas of the mPFC that send direct projections to the LHA. Importantly, nearly all amygdalar projections to the mPFC and to the LHA originated from different neurons, suggesting that amygdala and amygdala-mPFC processing influence the LHA independently. Study 2 used immediate early gene induction to map the patterns of functional activation within this amygdala-prefrontal-lateral hypothalamic network during the expression of fear-cue inhibited feeding behavior, and to assess whether these patterns were similar in males and females. We found differential activation across the network, and activation patterns related to the presentation of fear-cues, the presence of food-related cues, and the amount of food consumed were associated within distinct cell groups in the amygdala, mPFC, and LHA. Together, the studies presented in this dissertation provide anatomical and functional maps for future interrogation of the circuitry underlying fear-cue inhibited feeding.