Medial prefrontal cortex neuronal ensembles plasticity during context-mediated renewal of responding to food cues

Abstract

Cues existing in the surrounding environment repeatedly paired with biologically relevant events can exert a powerful drive over behavior. When learned cues recurrently signal consumption, this can lead to eating in the absence of hunger or physiological need. The difficulties associated with resisting palatable foods and maintaining healthy habits may be related to the neurobiological underpinnings of pervasive responding to food cues. Behavioral flexibility through updating information about formed reward associations is vital to appropriately adapt to the surrounding environment and physiological need. Studying the renewal of responding of extinguished food-seeking behaviors can help us better understand the mechanisms mediating behavioral control over responding to learned reward cues. This dissertation aimed to explore behavioral sex differences and the neural substrates of renewal of responding to food cues after extinction by utilizing a context-mediated renewal of responding paradigm. The first chapter in this dissertation explored the effects of context habituation on context-induced renewal of responding to food cues in males and females. We investigated if increased familiarity with the behavioral contexts, and if presentation of food reward or not during these habituation sessions, would impact the strength of cue-food learning and renewal of responding after extinction differently in males and females. We discovered that when males received context habituation paired with food prior to training they exhibited elevated food-seeking behaviors throughout conditioning, as well as strengthened renewal. This suggests that for males the context habituation with food had a lasting, amplifying effect on cue-food learning. For females, however, increased context familiarity did not improve renewal of responding and, moreover, these experiments revealed evidence for resistance to extinguishing food-seeking behaviors in females. Then, in Chapter 2, we found neural evidence for potential plasticity mechanisms in the prelimbic (PL) and infralimbic (ILA) subregions, which were both recruited during context-mediated renewal of responding to food cues. Our findings are in line with evidence demonstrating that the PL and ILA are both recruited during appetitive learning and possibly provide overlapping contributions to encoding and responding in context-based reward learning. Taken together, the experiments outlined in this dissertation add to existing evidence of sex differences in appetitive motivated behaviors and the intricacies of the roles of the PL and ILA in cue-food learning and contextual processing. The findings from these studies advance our understanding of persistent food-seeking behaviors and highlight the importance of elucidating the neural substrates mediating behavioral responding to learned reward cues.