一般口演
気分と不安 / 動機づけ
Mood and Anxiety / Motivation
座長：野村 洋（名古屋市立大学 大学院医学研究科 認知機能病態学） |
|---|
| 2022年7月2日 15:00～15:15 沖縄コンベンションセンター 会議場B2 第5会場
3O05a2-01
A reciprocal inhibition model to explain symptoms dynamics in patients with PTSD
*Toshinori Chiba(1,2,3), Kentaro Ide(1,4), Aurelio Cortese(1), Jessica E Taylor(1), Mitsuo Kawato(1), Ai Koizumi(5)
1. Advanced Telecommunications Research Institute International, 2. Self-Defense Forces Hanshin Hospital, 3. Kobe University Graduate School of Medicine, 4. Seven-mental clinic, 5. Sony Computer Science Laboratories, Inc.
Keyword: Posttraumatic stress disorder, symptoms dynamics, emotional modulation
Posttraumatic stress disorder (PTSD) is a heterogenous psychiatric disorder that includes two subtypes with opposing neural correlates. Typically, the non-dissociative subtype of PTSD is characterized by insufficient suppression of the amygdala by the ventromedial prefrontal cortex (vmPFC). In contrast, the dissociative subtype of PTSD is characterized by over-suppression of the amygdala by the vmPFC. However, despite diagnosis being binary, some patients display characteristics of both subtypes. To help explain this, we recently proposed a reciprocal inhibition model in which individual patients can switch between two opposing neural states via reciprocal inhibition between the amygdala and the vmPFC (Chiba et al., 2020). Here, in further support of our model, we provide additional empirical results that symptomatic and behavioral indicators of neural states exhibit dynamic fluctuations in short- and long-ranged frequencies. Since amygdala and vmPFC activity are strongly associated with the efficacy of first-line treatment of PTSD, precision medicine based on the dynamics of emotional modulatory state may possibly benefit current clinical strategy of PTSD treatment. In the conference, we will provide empirical results along with an overview of our model of PTSD. The potential therapeutic implications of our model will also be discussed. We also discuss potential therapeutic implications of our model in the hope to bridge the gap between neuroscientific findings and clinical practice. | | 2022年7月2日 15:15～15:30 沖縄コンベンションセンター 会議場B2 第5会場
3O05a2-02
視床下部ニューロンが引き起こすホームケージ特異的な新たな防御行動
ー強迫性障害との関連ー
Homecage-specific defensive behavior evoked by hypothalamic activation -Relation with obsessive-compulsive disorder-
*堀井 謹子(1)、西 真弓(1)
1. 奈良県立医科大学医学部
*Noriko Horii(1), Mayumi Nishi(1)
1. Nara Medical University
Keyword: anxiety, obsessive compulsive disorder, hypothalamus, serotonin
Home or territorial safety is essential for the survival of animals. Resident aggression toward intruders is one of the territorial defensive behaviors. Many researchers have eagerly investigated the neural mechanisms of aggression. Another behavior associated with territorial defense was reported by Calhoun in his wild rat study in 1963. He found that wild rats spontaneously plug entrances into their burrows with mud, rock, and vegetation from the inside by repetitive movements of the head and forepaws. Calhoun called this behavior "entrance sealing "or "hole-plugging" and he considered it a territorial defense to prevent potential invasion of enemy including conspecifics from outside. However, no additional studies have been reported so far since Calhoun initially described it. Thus, it is still unknown whether laboratory mice show similar behavior and which brain regions control the behavior. In this study, we found that chemogenetic activation of hypothalamic perifornical urocortin-3 (Ucn-3) neurons in mice evoked entrance sealing-like behavior with bedding material in homecage. The same manipulation also increased rodent behavioral indices for repetitive-stereotypic behavior such as burying and grooming. The activation of these neurons had no effects on anxiety levels measured by open-field, light-dark box, and elevated plus-maze tests, while it caused repetitive sniffing and risk assessment toward a novel object as representative behaviors to a potential threat. Entrance sealing-like behavior caused by the activation of hypothalamic Ucn-3 neurons was significantly reduced by prior treatment of selective serotonin reuptake inhibitors clinically used for the therapy for obsessive-compulsive disorder (OCD), anxiety disorders, and depression. These results suggest that entrance sealing is innately programmed in the hypothalamus for home protection from a potential threat and the hyperactivity of hypothalamic perifornical Ucn-3 neurons and/or the downstream of those neurons may be involved in home safety-related obsessions and compulsions in OCD patients. | | 2022年7月2日 15:30～15:45 沖縄コンベンションセンター 会議場B2 第5会場
3O05a2-03
下行性投射の異なる島皮質第5層ニューロン群が欲求行動において相反する役割を担う
Opposing roles for anatomically distinct neuronal populations of insular cortex layer 5 in appetitive behavior
*竹本 誠(1)、宋 文杰(1)
1. 熊本大学
*Makoto Takemoto(1), Wen-Jie Song(1)
1. Kumamoto University
Keyword: Insular cortex, Layer 5, Appetitive behavior
The insular cortex (insula) is known to play a top-down modulatory role in feeding and drinking. Despite its unique laminar structure, it remains elusive how each layer contributes to the behavioral modulation. In this study, we focused on layer 5, a major source of subcortical output, of the mouse dysgranular insula. By using neuron tracing techniques (cholera-toxin B subunit retrograde tracers and adeno-associated viruses with the Cre-lox system), we found two anatomically distinct neuron populations: one primarily in the upper layer 5 (L5a), projecting bilaterally to the lateral and capsular divisions of the central amygdala, and the other predominantly in the deeper layer 5 (L5b), projecting ipsilaterally to the parasubthalamic nucleus and the medial division of the central amygdala. The two populations were non-overlapping and distributed differently across the anterior-posterior axis of the insula.
To reveal the roles of these neuron populations in appetitive behavior, we first tested the effect of optogenetic activation of each population on licking of a single water spout in thirsty mice. We found that the activation of L5a and L5b populations suppressed and facilitated licking, respectively. To see whether the behavioral changes are attributed to emotional responses (i.e. avoidance or preference) to the optogenetic stimulation, we then examined the effect of the neuronal activation on the choice of spouts in a two-spout choice test in which the optogenetic stimulation was associated with one of the spouts. The activation of L5a neurons had no significant effect on the choice of spouts, although the activation of L5b neurons induced a modest preference to the spout associated with the optogenetic stimulation. A two-spout choice test with no water reward, however, resulted in similar choice of the spouts, it is therefore unlikely that the neuronal activation per se induces emotional valence. Taken together, our results suggest the opposing modulatory roles of distinct layer 5 neuron populations of insula in the motivational aspect of appetitive behavior. | | 2022年7月2日 15:45～16:00 沖縄コンベンションセンター 会議場B2 第5会場
3O05a2-04
ラットの報酬に基づく動機づけ行動におけるオレキシン神経の機能的役割
Functional roles of orexin neurons in reward-based motivative behavior in rats
*溝口 博之(1,2)、董 彧弢(1)、山中 章弘(3)、山田 清文(1)
1. 名古屋大学大学院医学系研究科医療薬学・附属病院薬剤部、2. 名古屋大学環境医学研究所MIRAIC、3. 名古屋大学環境医学研究所神経系分野Ⅱ
*Hiroyuki Mizoguchi(1,2), Yutao Dong(1), Akihiro Yamanaka(3), Kiyofumi Yamada(1)
1. Department of Neuropsychopharmacology and Hospital Pharmacy, Nagoya University Graduate School of Medicine, Nagoya, Japan, 2. Medical Interactive Research and Academia Industry collaboration Center, Research Institute of Environmental medicine, Nagoya university, Nagoya, Japan , 3. Department of Neuroscience II, Research Institute of Environmental Medicine, Nagoya University, Nagoya, Japan
Keyword: motivative behavior , orexin neuron
Orexin neurons in the hypothalamus regulate physiological functions, including energy homeostasis and wakefulness, and are also related to motivation. Here, we examined the roles of orexin neurons in motivated behaviors. We measured the activities of orexin neurons using fiber photometry under a free-moving condition, in which the rats were subjected to the fixed ratio (FR) or progressive ratio (PR) schedule of a touchscreen-based automated operant task. We found that breakpoint in PR test was increased when orexin neurons were activated by using chemogenetic approach, while the breakpoint was reduced when orexin neurons were disrupted by diphtheria toxin A. We also found that under FR5 conditions in which rats were able to obtain a food pellet by touching the screen consecutively five times, the activity in orexin neurons was increased after the fifth screen touch (after which one food pellet is delivered). The activity peaked before rats obtained reward, and then decreased after food intake. Next, we included non-reward trials in the FR5 test in which the rat was not able to earn reward even after touching the screen five times. The orexin activities in non-reward trials were also increased after the fifth screen touch, but the decrease after food intake was diminished compared to those in reward-trials. In the PR schedule test, the orexin activities were gradually increased. Together, these observations suggest that the orexin activities are associated with motivational behaviors, and that dynamic changes in activation of orexin neurons may be involved in craving and reward prediction, and satisfaction. | |
|
|
