Symposium
Bridging emotion and decision making: a view through neural circuits
シンポジウム
Bridging emotion and decision making: a view through neural circuits
理化学研究所 |
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| 7月26日（金）15:10～15:34 第3会場（朱鷺メッセ 2F メインホールB）
2S03a-1
The nature of dopamine signals during spatial navigation
Naoshige Uchida（Uchida Naoshige）
Harvard University
Dopamine plays an essential role in motivation, learning and motor control. Decades of experimental and theoretical work has shown that these phasic dopamine responses can be approximated by temporal difference reward prediction errors (TD RPEs) used in reinforcement learning algorithms. However, many of these experiments have employed relatively simple behavioral paradigms using discrete stimuli or outcomes. Whether the same principle apply to more complex behavioral contexts remains to be examined. Recent studies that used freely moving animals have shown that dopamine concentrations in the striatum ramp up over the time scale of seconds. Some authors have argued that these slow dopamine fluctuations cannot be readily explained by TD RPEs, and it has alternatively been proposed that they represent state values and drive motivation to move (Howe et al., 2013; Hamid et al., 2016). As proposed originally (Sutton & Barto, 1990), TD RPEs are approximately the derivative of the value function. The idea that dopamine represents value is, therefore, incompatible with the canonical view that dopamine represents TD RPEs.
To test whether dopamine represents RPEs or state values during spatial navigation, we developed a set of experimental tests using virtual reality. In these experiments, teleportation and manipulation of scene speed make distinct predictions between the two hypotheses. I will discuss the results of these experiments and broader implications regarding the nature of dopamine signals as well as the diversity of dopamine neurons. | | 7月26日（金）15:34～15:58 第3会場（朱鷺メッセ 2F メインホールB）
2S03a-2
Prefrontal-thalamic pathways involved in emotional regulation
Stephen Maren（Maren Stephen）
Texas A&M University
The nucleus reuniens (RE) is a midline thalamic region that is an anatomical interface between the medial prefrontal cortex (mPFC) and the hippocampus (HPC). Previous work reveals a critical role for this structure forms of learning and memory that require coordinated activity between the mPFC and HPC, such as spatial working memory. Coordinated HPC and mPFC activity has also been suggested to be involved in emotional regulation, including the regulating the expression of conditioned fear memories. In particular, this circuit has shown to be involved in fear extinction, a form of learning in which animals learn to suppress conditioned fear responses, such as freezing behavior. Critically, extinction learning is context-dependent and is preferentially expressed in the extinction context; outside the extinction context, fear to an extinguished conditioned stimulus returns or renews. Here we hypothesize that RE may be an important hub by which the mPFC might and HPC interact to acquire context-dependent extinction memories to regulate the expression of conditioned fear. Consistent with this hypothesis, our results reveal that that the RE and its mPFC afferents are critical for the extinction of Pavlovian fear memories in rats. Pharmacological inactivation of the RE during extinction learning or retrieval increases freezing to an extinguished conditioned stimulus (CS), however renewal of extinguished fear to the CS outside the extinction context was unaffected. In the extinction context, c-fos expression and spike firing in RE neurons were increased by the extinguished CS when fear was suppressed. The role for the RE in suppressing extinguished fear requires the mPFC, insofar as pharmacogenetically silencing mPFC->RE projection neurons or mPFC terminals in the RE impairs the expression of extinction memory. These results reveal that mPFC-RE projections inhibit the expression of fear, a function that is essential for adaptive emotional regulation. | | 7月26日（金）15:58～16:22 第3会場（朱鷺メッセ 2F メインホールB）
2S03a-3
Cerebral and systemic integration mechanisms to elicit the crisis-response state
Reiko Kobayakawa（Kobayakawa Reiko），Ko Kobayakawa（Kobayakawa Ko）
Kansai Medical University
The highest priority for living organisms is protecting their own lives. When organisms face life-threatening dangers, they are likely to pursue all possible strategies for survival by using their latent bioprotective capabilities. Fear is evoked when the brain perceives life-threatening danger, having evolved to induce behavioural and physiological responses that increase an individual's chance of survival. However, the protective effects conferred by fear are not fully understood. Elucidating these effects is important not only for understanding the evolution of fear, but also for utilising these potential protective effects for medical applications. Early ethological studies revealed that innate behaviours are induced more robustly by artificial, exaggerated stimuli (i.e., supernormal stimuli) than by natural stimuli. For example, chicks will peck a stick, which has exaggerated shape and colour of their parents' beak, more frequently than the real one. Furthermore, parent birds will incubate much larger artificial model eggs rather than their own eggs, if they have similar markings. Given this context, we have optimised the chemical structure of a predator odorant to develop artificial thiazoline-related fear odours (tFOs) with more than 10 times greater innate freezing behaviour inducing activities compared to any other previously identified innate fear odours. Thus, indeed tFOs such as 2-methyl-2-thiazoline (2MT) can be utilised as unique supernormal stimuli to induce robust innate fear in mice. In the present study, we took advantage of this technology to decipher biological significances of innate fear and successfully discovered series of unexpected protective effects intrinsic to innate fear which determine life-or-death in various aspects. | | 7月26日（金）16:22～16:46 第3会場（朱鷺メッセ 2F メインホールB）
2S03a-4
Function of Basal Ganglia Circuitry in Motivation and Decision Making
Anatol C Kreitzer（Kreitzer Anatol C）
Gladstone Institutes/UCSF
In healthy animals, decision costs and benefits have a profound influence on the speed or vigor of action execution. Previous work has largely implicated dopaminergic innervation of the ventral striatum as critical for allowing animals to generate effort necessary to overcome response cost. In contrast, there have been few studies investigating how motivational variables affect response vigor in the dorsal striatum, even though activation of specific cell-types have a profound effect on speeding or slowing of motor responses. To examine the mechanisms underlying motivated behavior, we developed a set of novel tasks for mice that allows for quantitative dissection of the effects of effort and reward magnitude on response vigor. In this task, mice move repeatedly back-and-forth between a center port and a side port to receive reward. The number of repetitions can be varied to receive reward, and this can occur either in a block structure (enabling mice to predict when reward is received) or randomly (mice cannot predict when reward will be received, although the average reward rate remains the same across the session). Using a combination of optogenetic control of dopamine neurons, imaging of striatal dopamine release with the genetically-encoded dopamine sensor GRAB-DA, and imaging or photometry of activity in striatal MSN subtypes with GCaMP6f, we have identified a key role for dopaminergic control of indirect-pathway striatal projection neurons in the allocation of effort to receive reward. | | 7月26日（金）16:46～17:11 第3会場（朱鷺メッセ 2F メインホールB）
2S03a-5
Parallel brainstem-to-amygdala projections control aversive emotional learning
Joshua P. Johansen（Johansen Joshua P.）
RIKEN Center for Brain Science
Aversive experiences are powerful triggers for memory formation and alter neural circuits to adaptively shape behavior. Understanding how aversive events are transduced by the nervous system into neural signals which engage learning is thus critical to understanding how and why memories form and behavior is adaptively altered. I will discuss our recent studies examining how aversive information reaches the lateral amygdala (LA) through parallel brainstem neural circuits to trigger aversive associative learning. Using cutting edge cell type specific optogenetic, neural recording, anatomical tracing and molecular manipulation approaches, we examined neuromodulatory and glutamatergic projections to the LA during fear and reward learning. We found that locus coeruleus noradrenaline neurons projecting to the lateral amygdala were activated by shock and that this activity was necessary for fear learning to occur. Furthermore, beta-adrenergic receptor activation in a specific population of LA pyramidal neurons was necessary for normal fear learning. Importantly, activation of locus coeruleus projections to the LA was not important for associative reward learning. Finally, I will discuss recent findings showing that a specific glutamatergic mesencephalic reticular formation pathway functions in parallel with the noradrenergic circuit to convey aversive information to the LA and trigger fear learning. Together, these findings reveal the neural mechanisms through which neural circuits coordinate extrinsic salient experiences to produce emotional memories. | | | |
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