OUR
RESEARCH
- 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.
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