シンポジウム
32 Integrating emotion and cognition in the brain
座長：Johansen Joshua Patrick（RIKEN Center for Brain Science）・Paz Rony（Professor and Head Department of Brain Sciences, Weizmann Instituteof Science） |
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| 2022年7月2日 9:00～9:20 ラグナガーデンホテル 羽衣：東 第8会場
3S08m-01
Mechanisms of averive learning in primate amygdala networks
*Paz Rony(1)
*Rony Paz(1)
1. Weizmann Institute of Science
Keyword: Averive Learning, Primate, Amygdala
We will describe the implementation of neural circuits in the primate brain that underlies the modulation of learning via aversive and appetitive feedback, and how learning in these systems affects the generalization of stimuli and the balance between exploration and exploitation. The evidence comes from electrophysiological recordings in primates (animal models and humans) and imaging studies in humans, and demonstrate a critical role for the amygdala and its communication with the prefrontal cortex, both at the population level and at the single-cell computations. | | 2022年7月2日 9:20～9:40 ラグナガーデンホテル 羽衣：東 第8会場
3S08m-02
The interplay of anxiety and hunger in anorexia nervosa
*Mark Andermann(1)
1. Beth Israel Deaconess Medical , Harvard Medical School
Keyword: Anorexia nervosa, Arcuate nucleus of the hypothalamus, Anxiety and hunger, Optogenetics
Anorexia nervosa (AN) is a severe psychiatric disorder with high rates of mortality and relapse. AN is characterized by food restriction and is accompanied by stress and anxiety. Treatments to date are inadequate and do not treat the root cause. In recent years, knowledge of how the brain controls hunger and eating has expanded tremendously. However, we lack fundamental information about how hunger interacts with other internal states such as stress and anxiety. This knowledge is critical if we are to make progress on understanding and treating AN. Unfortunately, current animal models fail to recapitulate a core feature of AN: willful starvation despite the physiological need to eat. In this talk, I will describe a novel behavioral paradigm that addresses the intriguing hypothesis that a voluntary state of hunger is maintained in AN as a means of coping with stress. This paradigm uses real-time place-preference assays in which head-fixed mice in a virtual reality can choose to remain in or avoid environments associated with optogenetic stimulation of genetically-defined hunger-promoting neurons in the hypothalamus. This model may provide a useful platform for defining the neural basis of voluntary seeking of a starvation state, as a potential means of self-medication following chronic stress. | | 2022年7月2日 9:40～10:00 ラグナガーデンホテル 羽衣：東 第8会場
3S08m-03 | | 2022年7月2日 10:00～10:20 ラグナガーデンホテル 羽衣：東 第8会場
3S08m-04
Cholinergic Mechanisms of Retrieval-Based Generalization of Aversive Memories
*Radulovic Jelena(1)、Ren Lynn 、Cicvaric Ana(1)、Zhang Hui (1)、Petrovic Zorica(1)、Gao Pan、Lin Yingxi、Sun Xiaochen
*Jelena Radulovic(1), Lynn Ren, Ana Cicvaric(1), Hui Zhang(1), Zorica Petrovic(1), Pan Gao, Yingxi Lin, Xiaochen Sun
1. Albert Einstein Medical College
Keyword: generalization, cholinergic, stress, robust activity marker
Generalization, the process of applying knowledge acquired in one context to other contexts, often drives the expression of similar behaviors in related situations. At the cellular level, generalization is thought to depend on the activity of overlapping neurons that represent shared features between contexts (general representations). Using contextual fear conditioning in mice, we demonstrate that generalization can also occur in response to stress and result from reactivation of specific context representations in ambiguous situations. We found that generalization emerges during memory retrieval, along with stress-induced changes of septohippocampal oscillatory activity and acetylcholine release. In hippocampal neurons that represent aversive memories and drive generalization, cholinergic septohippocampal afferents contributed to a unique reactivation pattern of cFos, Npas4, and repressor element-1 silencing transcription factor (REST).
Together, our findings support the view that neuromodulatory systems significantly contribute to memory generalization. The cholinergic mechanism described here is robust, enduring, and involves both network and cellular changes in the septohippocampal circuit. Importantly, the transcription factors cFos, Npas4, and REST are also important regulators of neuronal gene expression associated with synaptic plasticity and memory. Their recurring co-activation with neurons representing aversive contexts (NRAM) likely results in the update of initially non-aversive memory representations to fit the cholinergic-mediated negative affective state through a state-dependent reinterpretation of current, as well as past, experiences. Thus, through promoting the reactivation of aversive memories and their interference with ongoing behavior, abnormal cholinergic signaling could underlie maladaptive cognitive and behavioral generalization linked to negative affective states. | | 2022年7月2日 10:20～10:40 ラグナガーデンホテル 羽衣：東 第8会場
3S08m-05
The primate model of decision making under stress
*Kae Nakamura(1), Masaharu Yasuda(1)
1. Dept. Physiology, Kansai Medical University
Keyword: dorsal raphe, stress, decision making, primate
Emotional contexts such as stress may influence decision-making to pursue rewards, and the process may yield aspects of neuropsychiatric disorders. The normal function of monoamine neurotransmitters would play a crucial role in successful decision-making under varying emotional contexts. Neurons in the primate dorsal raphe nucleus (DRN), the primary source of serotonin, encode positive and negative emotional context by sustained neuronal activity. There is also a causal relationship between the serotonin system and performance on cognitive tasks. To examine how the emotional signal is integrated with the decision process in the DRN, we analyzed the activity of single neurons in the DRN while macaque monkeys performed a choice saccade task under different emotional contexts. In the task, after fixation on a central fixation point (FP), the monkey chose one of two visual cues: ‘correct’ and ‘wrong’, presented simultaneously in the left and right of the FP by a saccade. Correct and wrong cues were associated with a reward with a higher (80 or 100%) or lower (20 or 0 %) probability. The cue-reward association switched when the proportion of the correct choice reached the criterion (80% correct in the preceding 13 trials). During the inter-trial interval (ITI), the visual stimuli conditioned to appetitive reward or aversive air puff were presented repeatedly. This procedure made the animals perform the choice task under distinct emotional context, verified by sympathetic reactions by larger pupil diameter and higher heart rate during the aversive context. We confirmed that many DRN neurons exhibited sustained activity during the ITI and fixation periods with appetitive or aversive-context preference. This emotional-context coding was observed consistently among aversive-context preferring neurons across epochs in the choice task and different tasks such as Pavlovian conditioning. Further, a group of DRN neurons with distinct modulation in the fixation-period activity predicted forthcoming choice. Specifically, stronger fixation-period activity predicted correct choice under the aversive context for aversive-context preferring neurons. Conversely, the same neurons showed weaker fixation-period activity before choosing a correct cue under the appetitive context. Such dynamic emotion-performance interaction in the DRN may be the neuronal substrates for optimum decision-making under different emotional contexts. | | 2022年7月2日 10:40～11:00 ラグナガーデンホテル 羽衣：東 第8会場
3S08m-06
Prefrontal cortex neurons encode an internal model for emotional inference
*Joshua Johansen Johansen(1)
1. RIKEN Center for Brain Science
Keyword: Emotion, Cognition, Amygdala, Prefrontal cortex
To survive in an ever changing world, organisms need to learn which stimuli predict danger and mount appropriate defensive responses. Brain systems mediating aversive emotion have evolved to perform this function and decades of work has revealed the neural circuits which control simple forms of associative learning. However, emotions in humans and other species relies on cognitive processes in which interpretative internal models of the world are used to determine whether emotional responses are appropriate. For example, a central aspect of emotion is the use of inference to extrapolate the features of a directly experienced aversive events to other, related contexts and sensory patterns which weren’t a part of the original aversive experience. Despite the importance of inference in emotion, how brain systems mediating cognition and emotion interact to perform this function is not known. To address this question, we’ve adapted a behavioral model to study the neural mechanisms of emotional inference in rodents. Using this model, we found that rodents perform emotional inference and use it to flexibly control defensive behavior. We then performed in-vivo calcium imaging in the medial prefrontal cortex (mPFC, a region important in cognition and emotional control) and amygdala (a brain which controls simple associative emotional learning) and used optogenetics to manipulate the projections of the mPFC to the amygdala. We found that mPFC and amygdala neurons come to encode simple and higher order associations through learning. Notably, mPFC neuronal populations encode directly experienced and inferred aversive memories orthogonally following learning through a reorganization and enhancement of sensory selectivity in mPFC neurons. Furthermore, mPFC neurons projecting to the amygdala are necessary for the expression of inferred, but not directly experienced, emotional responses. This suggests that mPFC neurons encode a rich internal model of emotional associations and that this information is used to guide inference through projections to the amygdala where both directly experienced and inferred associations are expressed. This study reveals how higher order emotional processing is organized in the brain with important implications for our understanding of trauma related psychiatric conditions which are associated with disturbances in cognitive appraisals of threat leading to inappropriate emotional expression. | |
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