Biology subjects

Tsutsui-Kimura, I.

Publications and source records attributed to Tsutsui-Kimura, I..

5 recordsLinked to original sources

bioRxiv2025

Competing valence-related roles of dopamine in the tail of the striatum

Understanding how the brain evaluates aversion and appetition to guide behavior remains an open question. Here, we investigated the role of dopamine signaling in the tail of the striatum (TS) in regulating competing valence-based behaviors and learning. TS dopamine dynamics were monitored as mice performed a classical conditioning task in which an odor cue predicted either an aversive air puff or a water reward. Initially, mice exhibited anticipatory blinking, which diminished over time, while anticipatory licking emerged later, coinciding with adaptation to the air puff. Dopamine responses in the TS to the air puff and its associated odor were initially elevated but declined with repeated exposure. Optogenetic disruption of this decline suppressed adaptation and hindered appetitive learning. These findings demonstrate that TS dopamine dynamics are essential for behavioral adaptation to aversive stimuli, which indirectly facilitates appetitive learning, underscoring a regulatory mechanism for shifting between defensive and reward-seeking behaviors.

neuroscience↗

bioRxiv2023

A Hypothalamic Circuit Underlying the Dynamic Control of Social Homeostasis

Social grouping increases survival in many species, including humans1,2. By contrast, social isolation generates an aversive state (loneliness) that motivates social seeking and heightens social interaction upon reunion3-5. The observed rebound in social interaction triggered by isolation suggests a homeostatic process underlying the control of social drive, similar to that observed for physiological needs such as hunger, thirst or sleep3,6. In this study, we assessed social responses in multiple mouse strains and identified the FVB/NJ line as exquisitely sensitive to social isolation. Using FVB/NJ mice, we uncovered two previously uncharacterized neuronal populations in the hypothalamic preoptic nucleus that are activated during social isolation and social rebound and that orchestrate the behavior display of social need and social satiety, respectively. We identified direct connectivity between these two populations of opposite function and with brain areas associated with social behavior, emotional state, reward, and physiological needs, and showed that animals require touch to assess the presence of others and fulfill their social need, thus revealing a brain-wide neural system underlying social homeostasis. These findings offer mechanistic insight into the nature and function of circuits controlling instinctive social need and for the understanding of healthy and diseased brain states associated with social context.

neuroscience↗

bioRxiv2022

Dynamical management of potential threats regulated by dopamine and direct- and indirect-pathway neurons in the tail of the striatum

Avoiding potential threats before experiencing an actual outcome is critical to prevent a disaster. Here we examined roles of the tail of the striatum (TS) and its dopamine input in threat management. Mice were presented with a potential threat (a moving object) while pursuing rewards. Mice initially failed to obtain rewards, but gradually successfully obtained rewards in later trials. We show that the initial failures depended on dopamine and direct-pathway neurons in TS, and variability in failure rate across trials and individuals was positively correlated with the activity of these neurons. In contrast, indirect-pathway neurons in TS were critical for eventual improvement in reward acquisition, and their activity was positively correlated with successful reward acquisition. These results demonstrate that direct- and indirect-pathway TS neurons promote and suppress threat avoidance, respectively, at different stages, providing a mechanism for overcoming a potential threat while maintaining the threat estimates.

neuroscience↗

bioRxiv2021

Striatal dopamine explains novelty-induced behavioral dynamics and individual variability in threat prediction

Animals exhibit diverse behavioral responses, such as exploration and avoidance, to novel cues in the environment. However, it remains unclear how dopamine neuron-related novelty responses influence behavior. Here, we characterized dynamics of novelty exploration using multi-point tracking (DeepLabCut) and behavioral segmentation (MoSeq). Novelty elicits a characteristic sequence of behavior, starting with investigatory approach and culminating in object engagement or avoidance. Dopamine in the tail of striatum (TS) suppresses engagement, and dopamine responses were predictive of individual variability in behavior. Behavioral dynamics and individual variability were explained by a novel reinforcement learning (RL) model of threat prediction, in which behavior arises from a novelty-induced initial threat prediction (akin to "shaping bonus"), and a threat prediction that is learned through dopamine-mediated threat prediction errors. These results uncover an algorithmic similarity between reward- and threat-related dopamine sub-systems. HighlightsO_LINovelty-induced behaviors are analyzed using modern machine-learning methods C_LIO_LINovelty induces risk assessment which develops into engagement or avoidance C_LIO_LIDopamine in the tail of striatum correlates with individual behavioral variability C_LIO_LIReinforcement learning with shaping bonus and uncertainty explains the data C_LI

neuroscience↗

bioRxiv2019

A unified framework for dopamine signals across timescales

Rapid phasic activity of midbrain dopamine neurons are thought to signal reward prediction errors (RPEs), resembling temporal difference errors used in machine learning. Recent studies describing slowly increasing dopamine signals have instead proposed that they represent state values and arise independently from somatic spiking activity. Here, we developed novel experimental paradigms using virtual reality that disambiguate RPEs from values. We examined the dopamine circuit activity at various stages including somatic spiking, axonal calcium signals, and striatal dopamine concentrations. Our results demonstrate that ramping dopamine signals are consistent with RPEs rather than value, and this ramping is observed at all the stages examined. We further show that ramping dopamine signals can be driven by a dynamic stimulus that indicates a gradual approach to a reward. We provide a unified computational understanding of rapid phasic and slowly ramping dopamine signals: dopamine neurons perform a derivative-like computation over values on a moment-by-moment basis.

neuroscience↗