학술논문
Multimodal interactions in taste decoding / 미각 상호작용의 분자 기전
Document Type
Dissertation/ Thesis
Author
Source
Subject
Language
English
Abstract
섭식행동을 결정하기 위해서 신경계는 다양한 감각정보를 수집하고 통합한다. 맛감각이 섭식행동 결정에 있어서 강한 효과를 보이기 때문에 많은 연구들은 각각의 맛감각이 어떻게 신호 변환 및 전달되고 섭식행동에 영향을 끼치는지 집중해왔다. 하지만 대부분의 연구들은 음식이 순수화합물로 이루어진 것이 아니라 여러 가지 맛 물질이 혼재된 혼합물의 형태라는 사실과 맛감각과 더불어 다른 여러 종류의 감각정보를 동시에 제공한다는 사실을 간과하고 있다. 본 연구는 음식으로부터 유래하는 다양한 감각정보 사이의 상호작용을 규명함에 그 목적을 둔다.첫 번째 파트에서는 쓴맛물질에 의한 단맛인지억제의 분자적 기전을 다룬다. 좋아하거나 싫어하는 맛 물질이 섞여있는 경우, 동물은 음식을 섭취할 것인지에 대한 결정을 해야만 한다. 설탕에 쓴맛물질을 첨가하면 섭식행동을 억제하고 이 억제는 후각결합단백의 일종인 OBP49a에 의존한다. 정상 초파리에서 설탕에 의해 유도되는 활동전위가 쓴맛물질에 의해 억제되는데 Obp49a 결핍 돌연변이에서 이러한 현상의 장애를 발견하였다. 하지만 OBP49a의 결손은 단맛 혹은 쓴맛물질이 단독으로 주어진 경우, 각각의 맛 물질에 대한 반응 자체에는 어떠한 영향도 끼치지 않았다. 보조세포에서 발현되는 OBP49a는 설탕과 쓴맛물질이 혼합될 때 단맛신경세포의 신경활성을 억제한다. 이러한 발견은 후각단백결합의 기대치 않았던 미각에 대한 역할을 증명하고, 서로 반대되는 좋아하고 싫어하는 정보의 통합에 관여하는 분자적 요소로서 작용한다는 것을 확인하였다.두 번째 파트에서는 촉각이 섭식행동을 조절하는 기전을 다룬다. 맛감각은 음식의 접촉을 동반하므로 촉각/기계적 감각과 항상 결부될 수밖에 없다. 이러한 관계를 다루는 몇몇 심리학적 시도는 존재했지만 이 현상의 기전을 다루는 연구는 없었다. 본 연구는 촉각이 맛감각의 인지에 영향을 미친다는 것을 보인다. 음식의 굳기가 증가할수록 정상 초파리는 이분적 섭식선택실험과 PER 실험에서 점진적인 회피도를 보인다. Nanchung 결핍 돌연변이는 음식의 굳기에 대한 회피도 형성에 장애를 보인다. Labellum의 기계적 수용신경세포의 억제는 nan 돌연변이와 같은 행동결핍을 보인다. 기계적 수용신경세포의 인위적인 활성을 부여하면 PER반응을 억제한다. 기계적 수용신경세포에 의한 섭식행동억제는 단맛신경세포에 대한 직접적인 GABA성 시냅스를 통해 매개된다. 결론적으로, 단맛세포의 활성은 두 가지 다른 경로를 통해 조절될 수 있다. 먼저 쓴맛 물질은 설탕수용체의 일부인 GR64a에 대한 OBP49a의 길항작용을 통해 단맛세포의 활성을 억제한다. 둘째로, 음식의 굳기는 labellum의 기계적 수용세포에 의해 감지되고 GABA성 시냅스를 통해 단맛신경세포의 축삭 말단의 활성도를 억제한다. 이러한 두 가지 예는 맛인지에 있어서 다감각적 통합의 간단한 모델을 제시한다.
The nervous system receives and integrates multimodal sensory information to make a decision for feeding behaviors. As taste has strong effects on feeding behavior, many researches have focused on how each taste modality can be transduced and influences feeding behavior. Most of them ignored that food is made up of multiple tastants, not pure tastant, and provides multiple sensory information simultaneously, not only gustatory information. The aim of this study is to reveal the interactions between different sensory information derived from food.In first part, molecular mechanism of suppression of sweet taste by bitter chemicals was revealed. Animals are often confronted with the decision as to consume a diet that contains competing attractive and aversive compounds. Addition of bitter compounds to sucrose suppressed feeding behavior, and this inhibition depended on the odorant binding protein, OBP49a. In wild-type flies, bitter compounds suppressed sucrose-induced action potentials, and the inhibition was impaired in Obp49a mutants. However, loss of OBP49a did not affect action potentials in sugar- or bitter-activated gustatory receptor neurons (GRNs) when the GRNs were presented with just one type of tastant. OBP49a was expressed in accessory cells, and acted non-cell autonomously to attenuate nerve firings in sugar-activated GRNs when bitter compounds were combined with sucrose. These findings demonstrate an unexpected role for an OBP in taste, and identify a molecular player involved in the integration of opposing attractive and aversive gustatory inputs.In second part, I revealed how tactile sensation could modulate feeding behavior. As taste sensation must accompany contact with food, the sense of taste always accompanies with touch/mechanosesation which may affect feeding behavior. Even though several studies using psychological approaches have shown this interaction, but no one has suggested mechanistic insight of it. In this study, it is showed that tactile sense can affect the perception of taste. As the food hardness increases, wild-type flies displayed avoidance gradually in both two-way choice and proboscis extension reflex (PER) assay. But nanchung (nan) mutants showed impaired avoidance for food hardness. Inhibition of the mechanosensory neurons in the labellum recapitulated the impaired choice behavior of nan mutants. Activation of the mechanosensory neurons in labellum inhibited PER. The inhibition of feeding by mechanosensory neurons was mediated by GABAergic synapse. In conclusion, the activity of sweet neurons can be regulated by two distinct pathways. First, bitter chemicals can suppress sweet neurons’ activity with antagonistic effect of OBP49a on GR64a. Second, food hardness is detected by mechanosensory neurons in labellum, which can suppress the activity of sweet neuronal axon terminals via GABAergic synapse. These two examples represent simple models of multisensory integration in taste sensation.
The nervous system receives and integrates multimodal sensory information to make a decision for feeding behaviors. As taste has strong effects on feeding behavior, many researches have focused on how each taste modality can be transduced and influences feeding behavior. Most of them ignored that food is made up of multiple tastants, not pure tastant, and provides multiple sensory information simultaneously, not only gustatory information. The aim of this study is to reveal the interactions between different sensory information derived from food.In first part, molecular mechanism of suppression of sweet taste by bitter chemicals was revealed. Animals are often confronted with the decision as to consume a diet that contains competing attractive and aversive compounds. Addition of bitter compounds to sucrose suppressed feeding behavior, and this inhibition depended on the odorant binding protein, OBP49a. In wild-type flies, bitter compounds suppressed sucrose-induced action potentials, and the inhibition was impaired in Obp49a mutants. However, loss of OBP49a did not affect action potentials in sugar- or bitter-activated gustatory receptor neurons (GRNs) when the GRNs were presented with just one type of tastant. OBP49a was expressed in accessory cells, and acted non-cell autonomously to attenuate nerve firings in sugar-activated GRNs when bitter compounds were combined with sucrose. These findings demonstrate an unexpected role for an OBP in taste, and identify a molecular player involved in the integration of opposing attractive and aversive gustatory inputs.In second part, I revealed how tactile sensation could modulate feeding behavior. As taste sensation must accompany contact with food, the sense of taste always accompanies with touch/mechanosesation which may affect feeding behavior. Even though several studies using psychological approaches have shown this interaction, but no one has suggested mechanistic insight of it. In this study, it is showed that tactile sense can affect the perception of taste. As the food hardness increases, wild-type flies displayed avoidance gradually in both two-way choice and proboscis extension reflex (PER) assay. But nanchung (nan) mutants showed impaired avoidance for food hardness. Inhibition of the mechanosensory neurons in the labellum recapitulated the impaired choice behavior of nan mutants. Activation of the mechanosensory neurons in labellum inhibited PER. The inhibition of feeding by mechanosensory neurons was mediated by GABAergic synapse. In conclusion, the activity of sweet neurons can be regulated by two distinct pathways. First, bitter chemicals can suppress sweet neurons’ activity with antagonistic effect of OBP49a on GR64a. Second, food hardness is detected by mechanosensory neurons in labellum, which can suppress the activity of sweet neuronal axon terminals via GABAergic synapse. These two examples represent simple models of multisensory integration in taste sensation.