学習・長期記憶1
Learning and Long-term Memory 1
O2-8-4-1
線虫の味覚神経においてホスホリパーゼC-εは経験に依存した塩走性を制御する
Phospholipase C-ε regulates memory-dependent salt chemotaxis in a single gustatory neuron in C. elegans

○國友博文1, 岩田遼1, 佐藤博文1, 飯野雄一1
○Hirofumi Kunitomo1, Ryo Iwata1, Hirofumi Sato1, Yuichi Iino1
東京大学大学院 理学系研究科 生物化学専攻1
Department of Biophysics and Biochemistry, Graduate School of Science, University of Tokyo, Tokyo, Japan1

It is poorly understood how a neural circuit memorizes the intensity of sensory stimuli and regulates navigation behaviors based on the memory. The soil nematode C. elegans migrates up and down salt gradient toward the salt concentration range to which it has previously been exposed with food. This behavioral preference is plastic and learning a novel concentration takes a few hours. Therefore, C. elegans memorizes the environmental salt concentration during cultivation and orient themselves to proper directions by comparing the salt concentration of current environment to the memorized one.
Sensory input to the ASER gustatory neuron, which is located at the head of the animal, is required and sufficient for the behavior. Calcium imaging experiments revealed that ASER is always stimulated by decreases in salt concentration and the magnitude of the response is graded according to cultivation concentrations. These results suggest that the memory of salt concentration is at least in part represented by the responsivity of the ASER sensory neuron. However, the mechanisms as to how the activity of ASER generates navigation to opposite directions remain to be elucidated.
Here we report that plc-1, which encodes the phospholipase C-ε, acts in ASER to regulate experience-dependent chemotaxis. A missense mutation of the gene pe1237 confers preference for higher concentrations compared to wild type, whereas a deletion mutation pe1238 confers preference for lower concentrations. Chemotaxis defects of pe1238 animals were rescued by expressing plc-1(+) in ASER. The property of ASER responses in plc-1 mutants was comparable to that of wild type. On the other hand, the responses of a postsynaptic interneuron AIB to salt stimuli were potentiated in pe1237, but rather depressed in pe1238. These results indicate that plc-1 modulate salt chemotaxis in ASER by regulating synaptic mechanisms downstream of sensory inputs.
O2-8-4-2
線虫C. elegansの温度受容細胞における温度記憶の解析
Dissecting thermal memory in a thermosensory neuron of C. elegans

○小林曉吾1, 森郁恵1
○Kyogo Kobayashi1, Ikue Mori1
名古屋大院・ 理・ 生命理学1
Div. Biol. Sci., Nagoya Univ., Nagoya1

Many organisms including human are able to choose an appropriate behavioral strategy based on the past experience. Unveiling the mechanisms underlying a memory-based behavior is a fundamental question in neuroscience. The soil nematode Caenorhabditis elegans shows thermal memory-based behavior called thermotaxis: the animals migrate to the cultivation temperature on a temperature gradient after cultivated at a certain temperature with food (Hedgecock and Russell 1975). Previous studies have revealed a neural circuit that regulates thermotaxis in which the thermosensory neuron AFD plays a prominent role (Kimata et al., 2012). In vivo calcium imaging showed that the AFD neuron increases intracellular calcium concentration by responding to warming only around the cultivation temperature. This suggests that the AFD neuron itself remembered cultivation temperature and implicates a possibility that AFD neuron functions as not only a thermosensory neuron but also a thermal memory cell (Kimura et al., 2004). To investigate whether AFD neuron memorizes temperature without any other neurons, we established in vitro calcium imaging system for primary cultured C. elegans neurons, aiming to analyze the AFD neurons in an isolated state from the neural circuit. Using this system, we found that cultured AFD neuron responded to temperature stimuli in a culture-temperature depending manner: a response temperature was lower when cultured at lower temperature and higher when cultured at higher temperature. This result suggests that AFD neuron can form and maintain the temperature memory by itself.
O2-8-4-3
ドーパミントランスポーターによるドーパミンシグナルの制御
Regulation of dopamine signaling by dopamine transporter in fly brain

○上野太郎1, 粂和彦1
○Taro Ueno1, Kazuhiko Kume1
熊本大学 発生医学研究所 多能性幹細胞分野1
Stem Cell Biol, IMEG, Kumamoto University1

Dopamine mediates diverse functions such as motivation, reward, attention, learning/memory and sleep/arousal. For these functions, precise location and timing of dopamine signaling are required. Recent studies with model organisms including fly elucidated specific neural circuits for each functions of dopamine. However, understanding the mechanism by which dopamine participates these activities requires comprehension of the dynamics of dopamine signaling. Dopamine transporter (DAT) reuptake released dopamine from synaptic cleft and has a key role in limiting dopamine signaling. This role is evident when DAT is inhibited by therapeutic agents such as Ritalin (methylphenidate) or psychostimulant drugs of abuse such as amphetamine and cocaine. In addition to the role for regulating amplitude of dopamine signaling, DAT is considered to participate for gating spillover of dopamine.
Flies with the Drosophila dopamine transporter (dDAT) mutation show enhancement of dopamine signaling, which results in short sleep and memory impairment. Here we report the effect of dDAT expression in vivo. We show that dDAT expression not only in dopamine neurons but also in other cells such as glial cells can rescue the short sleep phenotype of dDAT mutant. Consistent with the sleep phenotype, dDAT expression which results in the normal sleep also rescued the down-regulation of D1-like receptor dDA1 in dDAT mutant. Extrasynaptic dDAT expression also rescued memory impairment in dDAT mutant. On the other hand, strong dDAT expression in mushroom body which is the target of the memory forming dopamine neurons abolished olfactory aversive memory formation. These results provide insight into regulatory systems that modulate dopamine system function.
O2-8-4-4
The dorsomedial telencephalon is essential for active avoidance response in zebrafish
○Pradeep Lal1,2, Mari Hiratani1, Maximiliano L Suster1,3, Koichi Kawakami1,2
National Institute of Genetics, Japan1, The Graduate University for Advanced Studies (SOKENDAI), Japan2

Forebrain structures have been shown to be involved in learning and memory in mammals. However, neural circuits involved in these processes are still largely unexplored. Zebrafish presents tremendous potential in identifying such functional neural circuits common to vertebrate. In this study, we regionalize the adult zebrafish brain and selectively manipulate specific neuronal populations to understand their roles in active avoidance response. First, using the Tol2 transposon-mediated gene trap and enhancer trap methods, we created transgenic fish lines that expressed the Gal4 transactivator in specific tissues. In these lines, Gal4 is visualized with UAS:GFP. We analyzed 349 Gal4 transgenic lines and collected 77 lines that showed strong GFP expression in specific regions of the adult brain. Next, we developed an active avoidance response assay system in which adult zebrafish showed robust learning in associating visual stimuli to electric shock. Finally, to inhibit the function of the Gal4 expressing neurons, we crossed the Gal4 lines with effector fish that carried botulinum neurotoxin gene downstream of UAS. Using the active avoidance response assay, we analyzed 29 double transgenic fish lines and found that 17 lines exhibited abnormalities in avoidance response. From these 17 lines, two transgenic lines had Gal4 expression specific to a subpopulation of neurons in the dorsomedial telencephalon. In mammals, active avoidance response is mediated by amygdala. From this study and previous anatomical studies, we think that dorsomedial telencephalon in zebrafish may be the functional equivalent of amygdala in mammals. Further, we found that the Gal4 expressing neurons in the two lines project their axons to entopeduncular nucleus and hypothalamus in the forebrain. Our present study revealed functional neural circuits involved in active avoidance response in zebrafish and will shed light on understanding of common neuronal basis of fear memories in vertebrate.
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