Appetite represents an important basis of internal energy and water homeostasis. We want to understand how the brain processes appetite and reward to drive goal-oriented behaviors. We employ rodent models to investigate the molecular and neural basis underlying appetite, primarily focusing on thirst and salt craving. Using variety of approaches: molecular biology, genetics, and neural manipulation tools (e.g. optogenetics and pharmacogenetics), we are currently pursuing the following questions;

Neural processing of appetite

Our goal is to understand where and how appetites are encoded in the brain. We recently found that water-drinking behavior can be instantly controlled by activation of genetically-defined neurons in the subfornical organ (SFO), a structure related to the hypothalamus (Oka et el., Nature 2015). Activation of nNOS/ETV-1 neurons in the SFO immediately induces robust drinking within seconds. On the other hand, activation of VGAT neurons quenches thirst in dehydrated animals. With these thirst-controlling neurons in hand, we are now exploring the downstream and upstream neural circuits to decipher how motivational signals are translated into behavioral outputs.

Detection of internal need by the brain

How does the brain sense need of the body? There are few brain regions including the SFO that lack the blood brain barrier. Because of this unique structural property, they serve as brain sensors detecting internal state. To gain insights into the interplay between the brain and the body at the molecular level, we employ single-cell transcriptomic analysis in SFO neurons. We believe that identifying molecules involved in internal sensing will help understand how body homeostasis is maintained through the brain-body interaction. 

Sensory perception of reward signals

Peripheral sensory signals also play an important role in appetitive behaviors. To engage in ingestive behaviors, animals first need to recognize external reward cues such as water or salt. For example, it has been shown that salt is detected through specific taste pathways (Chandrashekar et al., Nature 2010 and Oka et al., Nature 2013). Intake of salt is also finely regulated by these sensory pathways. The key questions we want to address here are 1) how do animals sense water and other reward cues? 2) why does a value of reward change depending on internal state? We combine genetics, electrophysiology and pharmacological tools to tackle these problems. 

 

Through the key questions above, our lab wants to understand the neural logic underlying central motivation and peripheral reward processing at the molecular, circuit, as well as behavioral levels.