Our research group aims to understand how the brain and the body cooperate to achieve appropriate internal balance. Maintaining biological balance requires complex regulations involving central nervous systems, peripheral chemosensory systems, and gut-brain communication. We use rodents as model organisms to identify 1) what types of central and peripheral signals are involved in internal state regulation, 2) when these signals are triggered, and 3) how they contribute to behavioral outputs. Some of the current directions in our laboratory are listed below;

Balance between water and sodium
Fine regulation of internal sodium and water balance is critical for body fluid homeostasis and survival for any organisms. Imbalance of these two nutrients can cause serious health issues such as dehydration and renal dysfunction. We study the neural mechanisms by which the brain controls appetite toward water and sodium. Our recent studies identified neural circuits that regulate water intake in the forebrain lamina terminalis (Oka et al., Nature 2015) and sodium ingestion in a hind brain structure (Lee et al., Nature 2019). Following up these findings, we are interested in 1) how individual appetites are processed throughout the brain, and 2) how sodium appetite and thirst circuits interact each other to balance internal osmolality environment.

Relationship among appetite, satiation, and reward
How does the brain regulate initiation and termination of behavior? This question is particularly important for nutrient ingestion because animals need to ingest right amounts of each nutrient factor. Either too much or too little eating/drinking poses risks to our health. To achieve this fine balance, the brain monitors the internal need as well as ingestive behaviors on a real-time basis. For instance, when thirsty animals drink water, both liquid gulping action and gut osmolality change send rapid satiation signals to the brain, which in turn suppress the thirst drive prior to water absorption to the body (Augustine et al., Nature 2018, Augustine et al., Neuron 2019).

Interestingly, sodium ingestion is regulated by an entirely different strategy. Appetite for sodium is rapidly alleviated by sodium taste on the tongue, rather than post-oral mechanisms (Lee et al., Nature 2019). Thus, our studies revealed distinct appetite and satiation mechanisms for different nutrient factors. Our current work is focused on how peripheral satiation and depletion signals are transmitted to and processed in the brain.

Balance between positive and negative valence (value)
Eating and drinking become much more enjoyable when we are hungry and thirsty compared to sated state. This is because the valence of water and energy changes depending on our internal state. It appears that both peripheral and central mechanisms are involved in this valence regulation. For example, sodium taste is not very attractive under sated state (Chandrashekar et al., Nature 2010 and Oka et al., Nature 2013). However, when the body loses sodium, brain appetite neurons become activated, which increases the hedonic value of sodium. The valence of oral water detection signals exhibits the similar valence shift depending on dehydration status of the body (Zocchi et al., Nat. Neurosci. 2017).  We seek to dissect the logic behind internal-state-dependent valence change of sensory inputs such as water and sodium signals. 

We tackle these key questions in neuroscience using modern techniques including neural manipulation, optical recording/imaging, and tracing. We actively collaborate with engineering, chemistry, and neurobiology labs inside and outside Caltech to complement our technical expertise.