神経化学
優秀賞受賞者企画シンポジウム
モノアミン研究の最前線 |
|---|
| 7月7日（金） 10:40-12:40 Room F
2SY⑤-1
記憶の想起と忘却を調節するヒスタミン神経の活動
Histamine neuronal activity modulates a transition between retrieval and forgetting
野村 洋
名古屋市立大学 医学 認知機能病態学
Hiroshi Nomura
Dept. of Cog. Func. Patho., Nagoya City Univ., Nagoya, Japan
As time passes after experiences, it becomes difficult to recall memories. In addition, various cognitive impairments, including dementia, make it difficult for people to recall memories they had in the past. However, even after the memories fade over time, the forgotten memories may occasionally be recollected spontaneously. Nevertheless, the neural mechanisms underlying the transition between forgetting and retrieval remain elusive. Histamine in the central nervous system is produced mainly in the tuberomammillary nucleus and is implicated in learning and memory, sleep and wakefulness, feeding and drinking, and neuroendocrine regulation. We previously demonstrated that histamine H3 receptor antagonists/inverse agonists, which augment histamine neurotransmission, induced the recall of forgotten memories even 1 week and 1 month after training in mice. A human clinical trial revealed that treatment of H3 receptor inverse agonists is specifically more effective for items that are more difficult to remember for subjects with poorer performance. More recently, we have been studying the activity of histamine neurons during memory retrieval and have observed that the dynamics of histamine neuronal activity modulate memory retrieval performance. These findings suggest that histamine is a key neuromodulator of memory retrieval. | | 7月7日（金） 10:40-12:40 Room F
2SY⑤-2
セロトニン神経による情動制御およびストレス適応とその神経機序
On the serotonin neurons underlying reward, aversion, and stress resiliency
永安 一樹
京都大学 薬学研究科 生体機能解析学
Kazuki Nagayasu
Dept. Mol. Pharm., Grad Sch Pharm Sci., Kyoto Univ., Kyoto, Japan
Serotonin neurons are involved in various brain functions including rewarding and aversive stimuli processing. Specifically, naturally rewarding stimuli such as sucrose intake and social interaction activate serotonin neurons in the dorsal raphe nucleus (DRN), whereas optogenetic stimulation of DRN serotonin neurons elicits reward-like effect; however, pharmacological enhancement of serotonin neurotransmission in a whole body exerts neither reward-like effect nor aversion. These findings strongly suggest the presence of serotonin neurons controlling preference and aversion but opposite direction to the DRN. In this symposium, we would like to present our recent findings on the opposite roles of serotonin neurons in the DRN and median raphe nucleus (MRN) in processing reward and aversive stimuli (Kawai et al., Nat Commun. 2022). Additionally, serotonin neurons are involved in mood regulation and stress resiliency. We found that repeated stimulation of DRN serotonin neurons reversed sociality deficit and increased passive coping behavior induced by chronic social defeat stress, similar to positive experience associated-hippocampal neurons. We want to share our recent results on the relationship between DRN serotonin neurons and positive experience-associated neuronal ensembles and its role in stress resiliency (Nagai et al., Cell Rep. 2023). | | 7月7日（金） 10:40-12:40 Room F
2SY⑤-3
恐怖条件づけ中のマウス脳内における領域特異的なドーパミン放出動態
Brain region-specific dopamine dynamics during fear conditioning in mice
小澤 貴明, 梅本 和宏, 岩本 涼太郎, 中村 萌, 松本 悠真, 柴田 智弘, 尾山 賀信, マクファーソン トム, 疋田 貴俊
大阪大学 蛋白質研究所
Takaaki Ozawa, Kazuhiro Umemoto, Ryotaro Iwamoto, Moe Nakamura, Yuma Matsumoto, Tomohiro Shibata, Yoshinobu Oyama, Tom Macpherson, Takatoshi Hikida
Institute for protein research, Osaka University, Osaka, Japan
Prediction and avoidance of future aversive events are vital abilities for survival in animals. The midbrain dopamine plays an important role in aversive learnings such as fear conditioning. Previous studies found that striatal dopamine release is inhibited in response to aversive predictive cues and aversive stimuli themselves; however, little is known about how cortical and subcortical dopamine release dynamics change during learning of associations between cues and aversive events. To address this question, we conducted multi-site recording of dopamine release in the frontal cortex, the nucleus accumbens and the amygdala in mice during differential auditory fear conditioning. In the present study, we trained mice in an auditory fear conditioning paradigm where one auditory stimulus (CS+) is followed by a mild electrical shock (US) and another is not (CS-). As a result, we found learning dependent changes of dopamine release during CS+. In the nucleus accumbens, dopamine levels were significantly decreased during the CS+ following conditioning. On the other hand, dopamine releases in the frontal cortex and amygdala were increased during CS+ especially after several days of conditioning. These results suggest the possibility that experience-dependent changes in both cortical and subcortical dopamine releases are important for adaptive fear learning and prediction in mice. | | 7月7日（金） 10:40-12:40 Room F
2SY⑤-4
Whole-brain mapping of locus coeruleus noradrenergic projections in mice
勢力 薫1, 笠井 淳史1, 橋本 均1,2,3,4,5
1. 大阪大学 大学院薬学研究科, 2. 大阪大学 先導的学際研究機構, 3. 大阪大学 連合小児発達学研究科, 4. 大阪大学 データビリティフロンティア機構, 5. 大阪大学 医学系研究科 分子医薬
Kaoru Seiriki1, Kasai Atsushi1, Hitoshi Hashimoto1,2,3,4,5
1. Grad. Sch. of Pharmaceitical Sci., Osaka Univ., Osaka, Japan, 2. Inst. for Open and Transdisciplinary Res. Initiatives, Osaka Univ., Osaka, Japan, 3. Mol. Res. Center for Children's Mental Development, Osaka Univ. Osaka, Japan, 4. Inst. for Datability Sci., Osaka Univ., 5. Dept. Mol. Pharmaceutical Sci., Grad. Sch. Med., Osaka Univ., Osaka, Japan
The locus coeruleus noradrenergic (LC-NA) system is considered to play crucial roles in multiple brain functions including arousal, emotional and stress responses. Recent studies have shown the functional and anatomical heterogeneity of LC-NA neurons in a projection target-specific manner. LC-NA neurons have broad axonal projection throughout the whole brain, but recent technological advances have revealed that individual neurons or neuronal subpopulations send distinct efferent projections to specific brain regions. However, it is still controversial whether LC-NA neurons have mutually exclusive or some overlapped projection patterns. Furthermore, it remains elusive whether projection-defined LC-NA subsets have different reactivity to external stimuli such as stress. We are currently investigating axonal projection patterns of LC-NA neurons and functions of projection-defined subpopulations underlying stress-induced behavioral alterations using the whole-brain imaging system, FAST (block-FAce Serial microscopy Tomography) and cell-type-selective AAV vectors. | |
|
|
