The Influence of the Basolateral Amygdala-medial Prefrontal Cortex Circuitry in Appetitive Cue Learning and Valuation

Abstract

Environmental cues that are neutral in respect to hunger and feeding can come to predict food through Pavlovian appetitive conditioning. These learned cues can drive food seeking and eating independent of physiological hunger leading to overeating and obesity. However, the food outcome, and thus the value of the cues, can change due to environmental alterations. A change in the values of learned cues requires altering behavioral responses to accurately reflect the cue’s new outcome. This behavioral flexibility is necessary to respond appropriately to changes in the environment and, as such, is an adaptive trait. The aim of this dissertation was to determine critical neural mechanisms specifically within the basolateral amygdala (BLA) and also with its interactions with the medial prefrontal cortex (mPFC) during behavioral flexibility when outcomes of learned appetitive cues change using the appetitive reversal learning paradigm. The main focus was on the BLA (Chapter 2) and its connection with the mPFC (Chapters 3 and 4) since both of these areas are critical in appetitive cue learning and valuation and subsequent behavioral modifications. The first study in this dissertation examined if separate neuronal ensembles within the BLA respond to different learned cues, a cue that signals food availability and a cue that does not. Additionally, we investigated if these potentially distinct neuronal ensembles are necessary during periods of behavioral flexibility when the value of the specific learned cues are changed during reversal learning. We determined that there are distinct neuronal ensembles within the BLA that respond to different learned cues, and that the cue-specific ensembles are necessary for updating the value of each specific cue (Chapter 2). Next, we examined a projection target of the BLA, the mPFC, to determine if BLA-projecting neurons are activated during learning (Chapter 3). Using retrograde tract tracing combined with Fos detection, we found recruitment of the anterior BLA to prelimbic area of the mPFC across cue-food learning, signifying that the BLA can inform the mPFC of the value of learned cues. Then to establish that communication between the BLA and mPFC is necessary for cue value learning and updating (Chapter 4), we functionally disconnected communication between these regions and examined appetitive learning using discriminative conditioning, reversal learning, and devaluation paradigms. We found impairments in cue value recall and subsequent updating of the cues’ values during reversal learning. Together, these studies indicate the BLA may be important in informing the mPFC of the value of learned cues, and their interaction is critical to optimally guide behavioral responding. The findings from these experiments are valuable for our understanding of the neural mechanisms that motivate eating behavior under the control of learned food cues and to understand the mechanisms necessary for behavioral flexibility when the outcomes of learned cues are changed.