Mitsuko Watabe-Uchida
Profile
Welcome! I am a Research Fellow at the Center for Brain Science in Harvard University. I have been fascinated by animals since my childhood, and have a strong background in anatomy, behavior, molecular biology and awake electrophysiology. Since earning an independent position in Harvard University in 2013, my lab is interested in the functional organization of dopamine-striatum systems. Our current focuses include a unique subpopulation of dopamine neurons that project to the tail of the striatum (TS), computation of reward prediction error, and individual variability in the decision-making. My hobby now is to watch wild animals and to grow vegetables.
Research
Diversity of dopamine neurons
Our emphasis is on precise anatomical examination, combined with electrophysiology. When we started studying dopamine-striatum systems 15 years ago, there were many theories that modeled how dopamine neurons were regulated. Yet very little was known about the anatomical organization of dopamine systems, even the distribution pattern of presynaptic partners to dopamine neurons. Therefore, we first developed a systematic tracing method using rabies virus and light-sheet microscope to map the distribution of neurons presynaptic to dopamine neurons in the whole brain (Watabe-Uchida et al., 2012, Ogawa et al., 2014, Menegas et al., 2015). These studies systematically and quantitatively showed the anatomical diversity of dopamine neurons. In our signature paper (Menegas et al., 2015), we found that dopamine neurons that project to the tail of the striatum (TS) are anatomically distinct from many other dopamine neurons. Our follow-up studies (Menegas et al., 2017, 2018, Akiti et al., 2022) clearly demonstrated that TS-projecting dopamine neurons, unlike other dopamine neurons, convey information of stimulus intensity but not reward value, and are important for threat avoidance. In addition to the unique subset of dopamine neurons that project to TS, we also characterized quantitative difference in reward-related activity of other dopamine neurons across the striatal areas (Tsutsui-Kimura et al., 2020). Taken together, our works demonstrate the importance of acknowledging the diversity of and balance between dopamine systems in the striatum.
Computation in the dopamine system
In addition to establishing a new field of dopamine diversity, we presented new computational ideas in dopamine studies. Our recent publication demonstrated our emphasis in bridging computational theories and biology, such as finding a neuronal evidence supporting a learning theory that had been used in machine learning (Amo et al., 2022), applying a concept of shaping (default value) in machine learning to explain experimental data for dynamics and individual variability in novelty exploration (Akiti et al., 2022), and connecting uncertainty-related signals in dopamine neurons with temporal dynamics of machine learning signals (Tsutsui-Kimura et al., 2020). We continue to aim to understand behaviors and neural activity at an algorithmic level.
Individual variability in decision-making
In daily life, we continuously face complex sets of internal and environmental stimuli. How do people incorporate these various factors and decide what to do at a moment-by-moment basis? While behavioral outputs are diverse and complicated, there might be some fundamental rules in the brain to explain commonality and variability in behavioral choice across individuals. Our lab uses both naturalistic behavioral paradigms and simple artificial tasks to address these questions. Our current focuses include complex behaviors under conflicts between curiosity, threat, and reward (Matsumoto et al., 2016; Menegas et al., 2018; Akiti et al., 2022; Tsutsui-Kimura et al., 2022).