Sensory stimuli that have been associated with food, such as the sight of dessert, can increase eating behavior in the absence of caloric need. This phenomena of cue-induced eating can be maladaptive, resulting in overeating, weight gain and obesity. However, the neural circuits that enable external stimuli to override internal signals of satiety are unknown. Neurons in the basolateral amygdala (BLA) are known to respond selectively to sensory stimuli (conditioned stimuli, CS) depending on whether they are associated with rewarding or aversive stimuli. Furthermore, the function of BLA neurons depends on their projection target and neurons that project to the nucleus accumbens are preferentially involved in the representation of positive valence and reward-seeking behaviors. I hypothesize that the neural activity of BLA neurons that project to the accumbens represents appetitive stimuli and plays a causal role in cue-induced eating in satiated mice.
Aim 1 will use 1-photon calcium imaging to characterize the physiological response properties of BLA neurons during the cue-induced eating paradigm. This work will assess the extent to which neural activity represents a CS associated with liquid diet, a CS never paired with liquid diet, and the consumption of the reward.
Aim 2 will test whether BLA neurons project to the nucleus accumbens are involved in the representation of food stimuli and CSs by using retrograde tracing in combination with a molecular marker of neural activity, the immediate early gene c-fos.
Aim 2 will also assess the causal role of the BLA-to-accumbens pathway by optogenetically inactivating this pathway during cue-induced eating and eating behaviors more generally. The results of these experiments will provide insights to the neural circuits that drive eating behavior in the presence of a food-associated stimulus and the absence of caloric need. This data and behavioral paradigm could prove essential for discovering novel targets for therapeutic intervention in treating obesity.
Eating in the absence of caloric need can be maladaptive because overeating behaviors lead to weight gain and obesity. The neural circuits that underlie non-homeostatic eating remain poorly understood, yet elucidating this circuitry could prove essential for discovering novel targets for therapeutic intervention in treating obesity. The research proposed here will provide physiological and projection-specific data that elucidates neurocircuitry hypothesized to modulate cue-induced eating in the absence of hunger.
