Saturday, September 7, 2024
9/7/2024
Project Summary/Abstract: When an animal is hungry, it will undergo several behavioral adaptations, including increasing its exploration of the environment. This adaptation of increased exploration is presumably critical for an animal to increase its probability of rectifying its homeostatic imbalance and is an adaptation which is altered in eating disorders such as anorexia nervosa. The neural process of sensing this internal state disturbance is thought to be mediated by hypothalamic neurons while the process of changing exploratory behavior is thought to be mediated by midbrain dopaminergic neurons that project to the striatum. These hypothalamic neurons project disynaptically to midbrain dopaminergic neurons and are known to modulate the response of these neurons to calorically rewarding substances, i.e., food. However, it is unknown how the state of hunger exactly changes the exploratory behavior of an animal in response to non-calorically rewarding substances, and whether these changes are mediated by connections between hypothalamic neurons and midbrain dopaminergic neurons. I will examine and answer this gap in knowledge by studying how caloric state and hypothalamic neurons modulates mouse exploratory behavior and midbrain dopaminergic neural activity in the absence of food. I will focus on studying hypothalamic agouti-related peptide (AgRP) neurons and midbrain dopaminergic neurons which release dopamine at the tail of the striatum. To study this question, I will use freely-moving mouse behavioral assays with fiber photometry and optogenetics/chemogenetics to monitor and perturb the neural activity of an animal, respectively. First, I will study how caloric deprivation affects the exploratory behavior of hungry animals, and whether these changes are mediated by differences in dopamine release at the tail of the striatum. Next, I will shift my view upstream and investigate how AgRP neurons change the exploratory behavior of calorically replete animals and whether these neurons modulate the activity of midbrain dopaminergic neurons that project to the tail of striatum when an animal explores a non-obviously rewarding substance. If successful, this project will elucidate the neural pathways by which hunger modulates the exploratory behavior of animals and provide new understandings of the circuitry underlying an ethologically important behavior .
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