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.
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.