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 .