Symposium
Diverse functions of the reward system: from sleep regulation to executive function
シンポジウム
報酬系の多様な役割:睡眠制御から高次脳機能まで |
|---|
| 7月28日（日）10:55～11:18 第3会場（朱鷺メッセ 2F メインホールB）
4S03a-1
異なる情動下の意思決定における霊長類線条体の役割
Kae Nakamura（中村 加枝），Yasumasa Ueda（上田 康雅），Masaharu Yasuda（安田 正治）
関西医大生理学
Decision making is often influenced by emotional contexts. For example, irrational choice may occur due to anxiety and autonomic arousal caused by imminent threats. To investigate neuronal mechanisms by which decision making is modulated by distinct emotion, we developed an experimental model in which monkeys (Macaca fascicularis n=2; mulatta n=1) performed saccade tasks under different emotional context. In the task whereby monkeys chose one of a pair of cues associated with appetitive, neutral, or aversive outcomes, blocks of cues selectively and progressively influenced their emotional state assessed by task performance and autonomic responses. When an aversive outcome was possible, the frequency of non-optimal choices, which were often associated with too-short reaction times, increased significantly; decrease in skin temperature around the nose and larger pupil size was also evident.
The striatum, the input stage of the basal ganglia, has been recognized as a critical neuronal substrate for decision making. We hypothesized that alternation of information processing in the striatum, caused by distinct emotional context, would result in changes in behavior and autonomic responses. To this end, we recorded activity of single neurons in the caudate, a part of the striatum, while monkeys (n = 3) performed a choice saccade task. We found that neurons exhibited differential activity depending on whether the upcoming cue-pairs included either an appetitive (42% of neurons) , an aversive (32%) or both (6%) cues. The activity changed temporally coherent to autonomic responses and task performance. The same neurons' activity did not show consistent modulation in the passive conditioning task indicating that the activity was associated with subsequent choices and response speed under specific emotional contexts, rather than the emotional context per se. Causal role of the caudate for emotion-dependent modulation in behavior was confirmed by local injections of dopamine D1 (SCH23390 10μg/μL, n=9) or D2 (Eticlopride hydrochloride 6μg/μL, n=7) antagonists. Drug injections in the caudate caused difficulty in controlling of response execution, characterized by too fast, premature responses, non-optimal choices, and larger pupil size, particularly under an aversive context.
These data suggest that the striatum, with dopamine projections, plays causal roles in flexible adjustment for successful decision making under diverse emotional contexts. | | 7月28日（日）11:18～11:41 第3会場（朱鷺メッセ 2F メインホールB）
4S03a-2
環境に依存した行動切り替えにおける線条体局所回路の役割
Jun Kunimatsu（國松 淳）1,2，Okihide Hikosaka（彦坂 興秀）2
1Faculty of Med, Univ Tsukuba, Tsukuba, Japan
2National Eye Institute, NIH, MD, U.S.A.
Learning and memorizing the values of objects are crucial for survival. Previous studies showed that the striatum tail contributes to this function by encoding reward values of many visual objects stably for a long time. In our daily life, however, the object values may change in different environments and we can choose different objects accordingly. We asked whether the striatum tail change its stable value coding depending on the environment. To address this question, we devised a new value procedure: scene-based value task. The monkey viewed 8 fractal objects in 2 scenes (A and B), repeatedly across days; 4 of them were good (with large-reward) in scene A and bad (with small-reward) in scene B, while the other 4 were good in scene B and bad in scene A. After experiencing this procedure repeatedly, the monkey became able to choose whichever objects were good. Since scenes A and B were presented in a random sequence, the monkey's choice was switched abruptly depending on the scene-context.
We then recorded neuronal activity in striatum tail while the monkey passively viewed these objects in different scenes. We found differences between medium spiny neurons (MSNs) and fast spiking interneurons (FSIs). Many of MSNs responded to the fractal objects differently depending on their values. Importantly, this object-value coding was stronger in either scene A or B. In contrast, FSIs showed no object-value coding. Instead, many of them responded to the scenes selectively (stronger to scene A or B). These results suggested that the object-value coding of MSNs, which is basically stable, is modulated by the inhibitory inputs from the scene-selective FSIs. Our neuronal circuit model suggested that two groups of MSNs (scene A-preferring and scene B-preferring), together, provide object-value information that is reversed by the scene change.
To test these hypotheses experimentally, we locally injected IEM-1460, an inhibitor of GluA2-lacking AMPARs, in the recording sites to selectively block the excitation of FSIs but not MSNs. After injection, monkeys were unable to learn new scene-object value association. On the other hand, object-value learning (no scene) was not affected. This result indicated that the local network of striatum tail regulates the scene-object association learning. These mechanisms may support the monkey's flexible switching based on stable long-term experiences of various environments. | | 7月28日（日）11:41～12:04 第3会場（朱鷺メッセ 2F メインホールB）
4S03a-3
Why do we fall asleep when bored - The gating of sleep by motivated behaviors
Michael Lazarus（Lazarus Michael）
University of Tsukuba
The brain mechanisms governing the regulation of sleep by cognitive and emotional factors are not well understood. As humans, we often defy sleepiness and stay awake when attention is necessary, but also experience an inescapable desire to sleep in boring situations. The mesolimbic dopamine pathway from the ventral medial midbrain to the nucleus accumbens (NAc) plays a central role in motivated behavior. We reported that the NAc also can produce sleep. We used chemo-genetic and optical techniques to remotely control the activities of NAc neurons that express adenosine A receptors (A2AR), also known as indirect pathway neurons. As a result, we discovered that NAc A2AR neurons have an extremely strong ability to induce sleep that is indistinguishable from the major component of natural sleep, known as slow-wave sleep, as it is characterized by slow and high-voltage brain waves. Moreover, we identified a GABAergic population in the ventral medial midbrain/pons area that is necessary to control the daily amount of sleep and wakefulness in mice. We also found that these inhibitory neurons control wakefulness by suppressing dopaminergic systems. Surprisingly, chemogenetic activation of these neurons strongly induced slow-wave sleep while suppressing wakefulness. Our findings reveal new brain mechanisms critical for sleep-wake regulation and may explain why we have the tendency to fall asleep in the absence of motivating stimuli, i.e., when bored. | | 7月28日（日）12:04～12:27 第3会場（朱鷺メッセ 2F メインホールB）
4S03a-4
Why would you want to know? The neuronal mechanisms of uncertainty reduction in primates
Ilya E Monosov（Monosov Ilya E）
Washington Univerisity in St Louis
Humans and other animals often show a strong desire to know the uncertain rewards their future has in store, even when they cannot use this information to influence the outcome. However, it is unknown how the brain predicts opportunities to gain information and how it motivates this information seeking behavior. Does the brain contain a distinct mechanism to drive our desire to know the future? I will discuss work from our Laboratory that uncovered a novel function of a brain network of interconnected subregions of primate anterior cingulate cortex and the basal ganglia, including internal capsule bordering regions of the anterior striatum and the ventral pallidum. Single neurons in this network predict the moment of gaining information about uncertain rewards. Importantly, spontaneous increases in their information prediction related activity are followed by gaze shifts toward objects associated with resolving uncertainty suggesting that they may have a direct role in the control of uncertainty-reducing information seeking behavior. Furthermore, consistently with this notion, pharmacologically disrupting this network reduces the motivation to seek information. These findings demonstrate a cortico-basal ganglia mechanism responsible for motivating actions to resolve uncertainty by seeking knowledge about the future. | | 7月28日（日）12:27～12:50 第3会場（朱鷺メッセ 2F メインホールB）
4S03a-5
ドーパミンによる報酬予測と脅威予測の制御
Mitsuko Watabe-Uchida（渡部内田 光子）
ハーバード大学
Animals including human beings learn from reward and punishment. It was widely accepted that dopamine plays a role in reward-related learning by signaling reward prediction error (RPE), discrepancy between predicted reward and actual reward. However, recent studies showed diversity of dopamine neurons, although it is controversial how dopamine neurons are functionally diverse.
Dopamine neurons in midbrain project most heavily to the striatum. The striatum receives inputs from cortex and thalamus, and dopamine is believed to modulate information flow from cortex and thalamus through the striatum, by adding reward information. We examined diversity of dopamine neurons that project to subareas of the striatum and other brain areas, and found that dopamine neurons that project to the tail of the striatum (TS) are outliers both anatomically and functionally. TS-projecting dopamine neurons do not encode reward value, but instead signal environmental threats, potentially reinforcing threat prediction in the brain. Without these dopamine neurons, mice could learn from reward but could not learn to avoid a threatening stimulus. These results indicate that there are at least two axes of dopamine systems in the striatum in mice. Although importance of proper amounts of dopamine is often emphasized, our findings point out that the balance between different dopamine systems would be critical for normal adaptive behaviors. I will further discuss importance of multiple axes of evaluation systems for learning in general. | | | |
|
|
