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Inui Tadashi

Faculty of Dental Medicine　Division of Dental Medicine　Department of Functional ScienceAssociate Professor

Researcher basic information

■ Nickname etc.
  • Tadashi Inui
■ Degree
  • 博士（人間科学）, 大阪大学, Feb. 2007
■ URL
researchmap URLホームページURL■ Various IDs
Researcher number
  • 40324735
J-Global ID■ Research Keywords and Fields
Research Keyword
  • 味
  • 味覚
  • 食行動
  • 好き嫌い
  • おいしさ
  • 嗜好
  • 嗜好学習
  • 嫌悪
  • 報酬系
  • 視床下部外側野
  • 分界条床核
  • 扁桃体中心核
  • 扁桃体基底外側核
  • 刺激装置
  • 神経回路
  • 側坐核
  • 情動
  • 味蕾
  • 脳
  • 学習
  • GABA
  • 扁桃体
  • c-fos
  • 味覚嫌悪学習
  • 嗜好性
  • 脳内報酬系
  • 腹側淡蒼球
  • 包括脳ネットワーク
Research Field
  • Humanities & Social Sciences, Family and consumer sciences, and culture and living
  • Life Science, Animal physiological chemistry, physiology and behavioral biology
  • Life Science, Basic brain sciences
  • Humanities & Social Sciences, Experimental psychology
■ Educational Organization

Career

■ Career
Career
  • Feb. 2020 - Present
    Hokkaido University, Graduate School of Dental Medicine, Associate Professor
  • Apr. 2017 - Jan. 2020
    Florida State University, Department of Psychology and Program in Neuroscience, Research Faculty
  • Apr. 2007 - Mar. 2017
    大阪大学 人間科学研究科, 助教
  • 2005 - 2007
    Osaka University, Faculty of Human Sciences, 助手
  • 2002 - 2006
    大阪大学 人間科学研究科, 助手
  • 2001 - 2002
    Osaka University, Faculty of Human Sciences, 助手
  • 2000 - 2001
    大阪大学 人間科学研究科・大学院, 助手
Committee Memberships
  • Apr. 2024 - Present
    日本味と匂学会 運営委員
  • Apr. 2021 - Mar. 2024
    日本味と匂学会 運営委員, Society

Research activity information

■ Awards
  • Oct. 2014, 日本味と匂学会, 論文賞
    乾 賢
  • Oct. 2014, 日本味と匂学会, 研究奨励賞
    乾 賢
  • Aug. 2013, 大阪大学, 大阪大学研究奨励賞
    乾 賢
■ Papers
  • Neural correlates of licking behavior modulated by target position in the striatal matrix compartment
    Taishi Kimoto; Tomohiko Yoshizawa; Yuta Ishimaru; Tadashi Inui; Koichi Nakamura; Yasutaka Yawaka; Makoto Funahashi
    openRxiv, 21 Apr. 2026
    The striatum is a major cortical input site of the basal ganglia and plays a critical role in the control of orofacial movements such as licking. However, how striatal activity relates to the spatial features of licking behavior remains unclear. In this study, we examined whether neural activity in the striatal matrix and striosomal compartments is associated with the spatial position of a licking target during an operant task. Head-fixed mice performed a licking task in which the target positions were varied across three spatial dimensions. Using fiber photometry in Calb1-IRES-Cre and Pdyn-IRES-Cre mice, we recorded calcium signals from matrix and striosomal neurons. Associations between neural activity, target position, and behavioral variables were quantified using linear mixed-effects modeling with cross-validation. Matrix activity prior to licking onset was primarily associated with the dorsal-ventral target position and reaction time. During licking, matrix activity was modulated by anterior-posterior and medial-lateral positions, independent of reaction time and lick count. In contrast, striosomal activity during licking was predominantly associated with the dorsal-ventral position. These findings demonstrate that neural matrix activity is systematically associated with spatial features of licking behavior, with distinct contributions before and during movement. Our results suggest that striatal matrix circuits provide task-relevant spatial signals for the control of orofacial actions.
  • Basolateral amygdala inhibition reduces avoidance in conditioned taste aversion—Transient chemogenetic silencing shifts behavior toward sustained licking
    Tadashi Inui; Emi Kikuchi; Yuto Suzuki; Momoko Hasegawa; Zimo Wei; Helai Huang; Tomohiko Yoshizawa; Makoto Funahashi
    Behavioural Brain Research, 495, 115784, 115784, Elsevier BV, Oct. 2025, [Peer-reviewed], [Lead author, Corresponding author]
    Scientific journal
  • Neural responses prior to licking onset in the striatal matrix compartment in mice
    Yuta Ishimaru; Tomohiko Yoshizawa; Taishi Kimoto; Tadashi Inui; Yasutaka Yawaka; Makoto Funahashi
    Neuroscience, 28 May 2025, [Peer-reviewed]
    Scientific journal
  • Taste preference and conditioned taste aversion of the metallothionein-1/2 null mice
    Nanae Yasuura; Tadashi Inui; Tomohiko Yoshizawa; Norio Sogawa; Yoshiaki Sato; Makoto Funahashi
    Physiology & Behavior, 114757, 114757, Elsevier BV, Nov. 2024, [Peer-reviewed]
    Scientific journal
  • Conditioned nausea induced by cisplatin and emetine identified by a taste reactivity test in rats.
    Shaoyi Su; Zimo Wei; Helai Huang; Tomohiko Yoshizawa; Tadashi Inui; Makoto Funahashi
    Physiology & Behavior, 114278, 114278, Elsevier BV, Jun. 2023, [Peer-reviewed]
    Scientific journal
  • Chemogenetic inhibition of the bed nucleus of the stria terminalis suppresses the intake of a preferable and learned aversive sweet taste solution in male mice.
    Emi Kikuchi; Tadashi Inui; Shaoyi Su; Yoshiaki Sato; Makoto Funahashi
    Behavioural brain research, 439, 114253, 114253, 15 Feb. 2023, [Peer-reviewed], [Corresponding author], [International Magazine]
    English, Scientific journal, Conditioned taste aversion (CTA) is established by pairing a taste solution as a conditioned stimulus (CS) with visceral malaise as an unconditioned stimulus (US). CTA decreases the taste palatability of a CS. The bed nucleus of the stria terminalis (BNST) receives taste inputs from the brainstem. However, the involvement of the BNST in CTA remains unclear. Thus, this study examined the effects of chemogenetic inhibition of the BNST neurons on CS intake after CTA acquisition. An adeno-associated virus was microinjected into the BNST of male C57/BL6 mice to induce the inhibitory designer receptor hM4Di. The mice received a pairing of 0.2% saccharin solution (CS) with 0.3 M lithium chloride (2% BW, intraperitoneal). After conditioning, the administration of clozapine-N-oxide (CNO, 1 mg/kg) significantly enhanced the suppression of CS intake on the retrieval of CTA compared with its intake following saline administration (p < 0.01). We further assessed the effect of BNST neuron inhibition on the intake of water and taste solutions (saccharin, sucralose, sodium chloride, monosodium glutamate, quinine hydrochloride, and citric acid) using naïve (not learned CTA) mice. CNO administration significantly decreased the intake of saccharin and sucralose (p < 0.05). Our results indicate that BNST neurons mediate sweet taste and regulate sweet intake, regardless of whether sweets should be ingested or rejected. BNST neurons may be inhibited in the retrieval of CTA, thereby suppressing CS intake.
  • The Effects of Roux-en-Y Gastric Bypass on Glucose- vs. Fructose-Associated Conditioned Flavor Preference.
    Tadashi Inui; Chizuko Inui-Yamamoto; Fabienne Schmid; Ginger D Blonde; Alan C Spector
    Physiology & behavior, 248, 113730, 113730, 01 May 2022, [International Magazine]
    English, Scientific journal, In rodents, repeated single-bottle exposures to distinctly flavored isocaloric glucose and fructose solutions, two sugars with different metabolic pathways, eventually lead to a preference for the former. Because Roux-en-Y gastric bypass (RYGB) surgery decreases preference for and intake of sugar solutions in rats, we tested whether RYGB would curtail the conditioning of a preference for a glucose-paired vs. fructose-paired flavor. RYGB (♂ n=11; ♀ n=10) and sham-operated (SHAM; ♂ n=9; ♀ n=10) rats were trained with a single bottle (30 min/day) containing 8% glucose solution flavored with either 0.05% grape or cherry Kool-Aid (Glu/CSG) or 8% fructose solution with the alternative Kool-Aid flavor (Fru/CSF) in an alternating fashion for 8 days. To determine baseline preferences, a 4-day 30-min two-bottle test was used to assess preference for Glu/CSG vs. Fru/CSF before training. After training, 2-day 30-min two-bottle tests assessed preference for the a) Glu/CSG (CSG-flavored 8% glucose solution) vs Fru/CSF (CSF-flavored 8% fructose solution), b) CSG- vs. CSF-flavored mixture of 4% glucose & 4% fructose (isocaloric), c) CSG- vs. CSF-flavored 0.2% saccharin ("sweet", no calories), and d) CSG- vs. CSF-flavored water. During training, only male SHAM rats demonstrated progressively increased intake of Glu/CSG over Fru/CSF, and female SHAM rats displayed a trend. RYGB eliminated any difference in single-bottle intake of these solutions during training, regardless of sex. Like their male and female SHAM counterparts, male RYGB rats displayed a conditioned preference for the CSG-associated stimulus in Tests 1-3. Although female RYGB rats displayed acquisition of the conditioned flavor preference in Test 1, unlike the other groups, when the differential sugar cue between the two solutions was removed in Tests 2 and 3, female rats did not display a CSG preference. When the sugar and sweetener cues were both removed on Test 4, all groups displayed some generalization decrement. Thus, RYGB does not compromise the ability of rats to learn and express a glucose- vs. fructose-associated conditioned flavor preference when the exact CS used in training is presented in testing. The mechanistic basis for the sex difference in the effect of RYGB on the generalization decrement observed in this type of flavor preference learning warrants further study.
  • Oromotor and somatic taste reactivity during sucrose meals reveals internal state and stimulus palatability after gastric bypass in rats.
    Ginger D Blonde; Clare M Mathes; Tadashi Inui; Elizabeth A Hamel; Ruth K Price; M Barbara E Livingstone; Carel W Le Roux; Alan C Spector
    American journal of physiology. Regulatory, integrative and comparative physiology, 322, 3, R204-R218, 01 Mar. 2022, [International Magazine]
    English, Scientific journal, After Roux-en-Y gastric bypass (RYGB), rats consume less high-energy foods and fluids, though whether this reflects a concomitant change in palatability remains unclear. By measuring behavior during intraorally delivered liquid meals across days (1 water, 8 sucrose sessions), we showed that RYGB rats (RYGB, n = 8/sex) consumed less 1.0 M sucrose than their sham surgery counterparts (SHAM, n = 8 males, n = 11 females) but displayed similarly high levels of ingestive taste reactivity responses at the start of infusions. Relative to water, both groups increased intake of sucrose, and ingestive responses were dominated by tongue protrusions rather than mouth movements. Thus, RYGB animals still found sucrose palatable despite consuming less than the SHAM group. As the intraoral infusion progressed but before meal termination, aversive behavior remained low and both RYGB and SHAM animals showed fewer ingestive responses, predominantly mouth movements as opposed to tongue protrusions. This shift in responsiveness unrelated to surgical manipulation suggests negative alliesthesia, or a decreased palatability, as rats approach satiation. Notably, only in RYGB rats, across sessions, there was a striking emergence of aversive behavior immediately after the sucrose meal. Thus, although lower intake in RYGB rats seems independent of the hedonic taste properties of sucrose, taste reactivity behavior in these animals immediately after termination of a liquid meal appears to be influenced by postoral events and reflects a state of nimiety or excessive consumption. Measurement of taste reactivity behaviors during an intraorally delivered meal represents a promising way to make inferences about internal state in nonverbal preclinical models.
  • Effects of area postrema lesions and bilateral subdiaphragmatic afferent vagotomy on emetine-induced conditioned taste avoidance in rats.
    Shaoyi Su; Mayu Fujita; Zimo Wei; Heligh Huang; Tomohiko Yoshizawa; Tadashi Inui; Dr Professor Chair Makoto Funahashi
    Physiology & behavior, 113565, 113565, 27 Aug. 2021, [Peer-reviewed], [International Magazine]
    English, Scientific journal, We investigated the effect of area postrema lesions and selective vagotomy of afferent fibers on emetine-induced nausea in rats. We evaluated the acquisition of the conditioned taste avoidance (CTA) to 0.1% saccharin solution after conditioning with emetine dihydrochloride (5.54 mg/kg, i.p., 1% BW). The CTA was measured in three groups of rats: a bilateral subdiaphragmatic afferent vagotomy group, an area postrema lesion group, and a sham lesion group. The bilateral vagotomy and sham groups of rats showed acquisition of CTA within 2 days of the test date. Taste avoidance was never conditioned in the area postrema lesion group. These results indicate that the area postrema plays a crucial role in the induction of emetine-induced nausea.
  • Attenuation of Food Intake by Fragrant Odors: Comparison between Osmanthus fragrans and Grapefruit Odors
    Takashi Yamamoto; Kayoko Ueji; Tadashi Inui; Haruno Mizuta
    Psychology and Patho-physiological Outcomes of Eating [Working Title], IntechOpen, 02 Apr. 2021, [Peer-reviewed], [Invited]
    English, In book, Odors affect various physiological and mental activities. Previous studies in rats have shown that the odors of grapefruit and Osmanthus fragrans (OSM, fragrant tea olive) attenuate food intake, leading to a reduction in body weight gain, but it is not yet clear whether the causative mechanisms underlying these effects are the same for both odors. The first part of the present study revealed that grapefruit odor had no effect on the expression of feeding-related neuropeptides, in contrast to the previous finding that OSM odor suppresses orexigenic and activates anorexigenic neuropeptides in the hypothalamus of the rat. The second part revealed that OSM odor activated the parasympathetic nerve, in contrast to the previous finding demonstrating that grapefruit odor activates sympathetic nerve activity. The third part was performed to confirm the previous findings about the effects of OSM odor on appetitive reactions in humans. In human subjects, we found that continuous exposure to OSM odor attenuated appetite and consumption of snacks (cookies) and improved mood, when evaluated using the POMS (Profile of Mood States) data from university students. In conclusion, OSM odor attenuated appetite and decreased food intake in humans, and the underlying causative mechanisms differed from those mediating the effects of grapefruit odor, specifically in terms of the expression of hypothalamic feeding-related neuropeptides and autonomic nerve activity.
  • Involvement of the area postrema and the nucleus tractus solitarius in the emetogenic action of emetine in rats
    Takanori Sato; Yoshiyuki Hirai; Shaoyi Su; Wei Zimo; Nanae Yasuura; Tadashi Inui; Makoto Funahashi
    Journal of Oral Biosciences, 62, 4, 310, 314, Elsevier BV, Dec. 2020, [Peer-reviewed]
    Scientific journal
  • Neural Isolation of the Olfactory Bulbs Severely Impairs Taste-Guided Behavior to Normally Preferred, But Not Avoided, Stimuli.
    Tadashi Inui
    eNeuro, 7, 2, 01 Mar. 2020, [Peer-reviewed]
    English, Scientific journal, Here we systematically tested the hypothesis that motivated behavioral responsiveness to preferred and avoided taste compounds is relatively independent of the olfactory system in mice whose olfactory bulbs (main and accessory) were surgically disconnected from the rest of the brain [bulbotomy (BULBx)]. BULBx was confirmed histologically as well as functionally with the buried food test. In brief access taste tests, animals received 10-s trials of various concentrations of a taste compound delivered quasirandomly. BULBx C57BL/6 (B6) mice displayed severely blunted concentration-dependent licking for the disaccharide sucrose, the maltodextrin Maltrin, and the fat emulsion Intralipid relative to their sham-operated controls (SHAM B6). Licking for the noncaloric sweetener saccharin was also blunted by bulbotomy, but less so. As expected, mice lacking a functional "sweet" receptor [T1R2+T1R3 knockout (KO)] displayed concentration-dependent responsiveness to Maltrin and severely attenuated licking to sucrose. Like in B6 mice, responsiveness to both stimuli was exceptionally curtailed by bulbotomy. In contrast to these deficits in taste-guided behavior for unconditionally preferred stimuli, BULBx in B6 and KO mice did not alter concentration-dependent decreases for the representative avoided stimuli quinine and citric acid. Nor did it temper the intake of and preference for high concentrations of affectively positive stimuli when presented in long-term (23-h) two-bottle tests, demonstrating that the surgery does not lead to a generalized motivational deficit. Collectively, these behavioral results demonstrate that specific aspects of taste-guided ingestive motivation are profoundly disturbed by eliminating the anatomic connections between the main/accessory olfactory bulbs and the rest of the brain.
  • The Basolateral Nucleus of the Amygdala Executes the Parallel Processes of Avoidance and Palatability in the Retrieval of Conditioned Taste Aversion in Male Rats.
    Tadashi Inui
    eNeuro, 10 Jul. 2019, [Peer-reviewed]
    English, Scientific journal, Conditioned taste aversion (CTA) is an essential behavior for animal survival. Conditioned animals show avoidance and decreased palatability to a conditioned stimulus (CS) on CTA retrieval. In this study, we aimed to determine whether the basolateral nucleus of the amygdala (BLA) is involved in CTA retrieval and whether avoidance and palatability in CTA retrieval are processed in the BLA. We developed an experimental chamber for time-course analysis of the behavior to approach a spout and lick a CS. In this experimental chamber, we analyzed the behavior of male rats following microinjections of GABAA receptor agonist muscimol or saline into the BLA. The rats showed two types of approach behavior: they either (1) approached and licked the spout or (2) approached but did not lick the spout. Muscimol injection into the BLA decreased the frequency of the latter type of approach behavior, indicating that BLA inactivation reduced avoidance to the CS. The muscimol injection into the BLA also significantly increased the consumption of the CS. Lick microstructure analysis demonstrated that intra-BLA muscimol significantly increased licking burst number and size, indicating that BLA inactivation attenuated aversion to the CS as large burst licking is an indicator of high palatability. These results suggest that the increase in CS consumption with intra-BLA muscimol injection was due to alterations in approach and aversive responses to the CS. Therefore, we conclude that the BLA plays an essential role in CTA retrieval by parallel processing of avoidance and palatability.
  • Extracellular glucose-dependent IPSC enhancement by leptin in fast-spiking to pyramidal neuron connections via JAK2-PI3K pathway in the rat insular cortex.
    Tadashi Inui
    Neuropharmacology, 14 Feb. 2019
    Scientific journal, Leptin is produced in the adipocytes and plays a pivotal role in regulation of energy balance by controlling appetite and metabolism. Leptin receptors are widely distributed in the brain, especially in the hypothalamus, hippocampus, and neocortex. The insular cortex (IC) processes gustatory and visceral information, which functionally correlate to feeding behavior. However, it is still an open issue whether and how leptin modulates IC neural activities. Our paired whole-cell patch-clamp recordings using IC slice preparations demonstrated that unitary inhibitory postsynaptic currents (uIPSCs) but not uEPSCs were potentiated by leptin in the connections between pyramidal (PNs) and fast-spiking neurons (FSNs). The leptin-induced increase in uIPSC amplitude was accompanied by a decrease in paired-pulse ratio. Under application of inhibitors of JAK2-PI3K but not MAPK pathway, leptin did not change uIPSC amplitude. Variance-mean analysis revealed that leptin increased the release probability but not the quantal size and the number of release site. These electrophysiological findings suggest that the leptin-induced uIPSC increase is mediated by activation of JAK2-PI3K pathway in presynaptic FSNs. An in vivo optical imaging revealed that leptin application decreased excitatory propagation in IC induced by electrical stimulation of IC. These leptin-induced effects were not observed under the low energy states: low glucose concentration (2.5 mM) in vitro and one-day-fasting condition in vivo. However, leptin enhanced uIPSCs under application of low glucose with an AMPK inhibitor. These results suggest that leptin suppresses IC excitation by facilitating GABA release in FSN→PN connections, which may not occur under a hunger state.
  • Taste preference changes throughout different life stages in male rats
    Chizuko Inui-Yamamoto; Takashi Yamamoto; Katsura Ueda; Michiko Nakatsuka; Shunji Kumabe; Tadashi Inui; Yasutomo Iwai
    PLOS ONE, 12, 7, Jul. 2017, [Peer-reviewed]
    English, Scientific journal
  • Activation of mu-opioid receptors in the ventral pallidum decreases the negative hedonic evaluation of a conditioned aversive taste in rats
    Tadashi Inui; Tsuyoshi Shimura
    BEHAVIOURAL BRAIN RESEARCH, 320, 391, 399, Mar. 2017, [Peer-reviewed]
    English, Scientific journal
  • The role of the rat basolateral amygdala on the retrieval of conditioned taste aversion: microstructural analysis of approach and intake behaviors.
    Tadashi Inui; Tsuyoshi Shimura
    The Japanese journal of taste and smell research, 22, 3, 269, 272, The Japanese Association for the Study of Taste and Smell, Dec. 2015, [Peer-reviewed]
    Japanese, Scientific journal
  • Approach-avoidance conflict during the retrieval of conditioned taste aversion
    Tadashi Inui; Tsuyoshi Shimura
    The Japanese journal of taste and smell research, 21, 3, 269, 272, Dec. 2014, [Peer-reviewed]
    Japanese, Scientific journal
  • Delta-opioid receptor blockade in the ventral pallidum increases perceived palatability and consumption of saccharin solution in rats
    Tadashi Inui; Tsuyoshi Shimura
    BEHAVIOURAL BRAIN RESEARCH, 269, 20, 27, Aug. 2014, [Peer-reviewed]
    English, Scientific journal
  • Neural substrates for the retrieval of conditioned taste aversion revealed by manganese-enhanced MRI
    Tadashi Inui; Tsuyoshi Shimura; Chizuko Inui-Yamamoto; Yoshichika Yoshioka; Izumi Ohzawa
    2014 WORLD AUTOMATION CONGRESS (WAC): EMERGING TECHNOLOGIES FOR A NEW PARADIGM IN SYSTEM OF SYSTEMS ENGINEERING, 2014, [Peer-reviewed]
    English, International conference proceedings
  • Activation of efferents from the basolateral amygdala during the retrieval of conditioned taste aversion
    Tadashi Inui; Chizuko Inui-Yamamoto; Yoshichika Yoshioka; Izumi Ohzawa; Tsuyoshi Shimura
    NEUROBIOLOGY OF LEARNING AND MEMORY, 106, 210, 220, Nov. 2013, [Peer-reviewed]
    English, Scientific journal
  • The odor of Osmanthus fragrans attenuates food intake
    Takashi Yamamoto; Tadashi Inui; Tadataka Tsuji
    SCIENTIFIC REPORTS, 3, Mar. 2013, [Peer-reviewed]
    English, Scientific journal
  • Effects of microinjections of delta-opioid receptors antagonist into the ventral pallidum on consumption and palatability of sweet taste solution in rats
    Tadashi Inui; Tsuyoshi Shimura
    The Japanese Journal of Taste and Smell Research, Dec. 2012, [Peer-reviewed]
    Japanese, Scientific journal
  • Activation of output neurons in the basolateral nucleus of the amygdala by a learned aversive taste: a manganese-enhanced MRI study.
    Tadashi Inui; Chizuko Inui-Yamamoto; Izumi Ohzawa; Yoshichika Yoshioka; Tsuyoshi Shimura
    The Japanese Journal of Taste and Smell Research, Dec. 2011, [Peer-reviewed]
    Japanese, Scientific journal
  • ACTIVATION OF PROJECTIVE NEURONS FROM THE NUCLEUS ACCUMBENS TO VENTRAL PALLIDUM BY A LEARNED AVERSIVE TASTE STIMULUS IN RATS: A MANGANESE-ENHANCED MAGNETIC RESONANCE IMAGING STUDY
    T. Inui; C. Inui-Yamamoto; Y. Yoshioka; I. Ohzawa; T. Shimura
    NEUROSCIENCE, 177, 66, 73, Mar. 2011, [Peer-reviewed]
    English, Scientific journal
  • Activation of efferent connections of the basolateral nucleus of amygdala on the retrieval of conditioned taste aversion memory: manganese-enhanced MRI study
    Inui-Yamamoto C; Inui T; Ohzawa I; Ueda K; Iwai Y; Shimura T; Yoshioka Y
    The Japanese journal of taste and smell research, 17, 3, 305, 308, The Japanese Association for the Study of Taste and Smell, Dec. 2010, [Peer-reviewed]
    Japanese, Scientific journal
  • The brain mechanisms of taste reactivity responses by microinjection of GABAA receptors agonist into the ventral pallidum in rats
    Inui T; Shimura T
    The Japanese journal of taste and smell research, 17, 3, 263, 266, The Japanese Association for the Study of Taste and Smell, Dec. 2010, [Peer-reviewed]
    Japanese, Scientific journal
  • Involvement of GABA receptors in the basolateral amygdala on the retrieval of conditioned taste aversion in rats
    Kajikawa F; Inui T; Yasoshima Y; Shimura T
    The Japanese journal of taste and smell research, 17, 3, 259, 262, The Japanese Association for the Study of Taste and Smell, Dec. 2010, [Peer-reviewed]
    Japanese, Scientific journal
  • THE BRAIN MAPPING OF THE RETRIEVAL OF CONDITIONED TASTE AVERSION MEMORY USING MANGANESE-ENHANCED MAGNETIC RESONANCE IMAGING IN RATS
    C. Inui-Yamamoto; Y. Yoshioka; T. Inui; K. S. Sasaki; Y. Ooi; K. Ueda; A. Seiyama; I. Ohzawa
    NEUROSCIENCE, 167, 2, 199, 204, May 2010, [Peer-reviewed]
    English, Scientific journal
  • The visualization of the efferent neuronal projection in the nucleus accumbens on the retrieval of conditioned taste aversion memory using manganese-enhanced MRI in rats
    INUI YAMAMOTO Chizuko; INUI Tadashi; YOSHIOKA Yoshichika; SHIMURA Tsuyoshi; OHZAWA Izumi
    The Japanese journal of taste and smell research, 16, 3, 355, 358, The Japanese Association for the Study of Taste and Smell, Dec. 2009, [Peer-reviewed]
    Japanese, Scientific journal
  • The neural mechanisms of aversive taste reactivity by stimulation of GABA_A receptors in the ventral pallidum in rats
    INUI Tadashi; SHIMURA Tsuyoshi
    The Japanese journal of taste and smell research, 16, 3, 339, 342, The Japanese Association for the Study of Taste and Smell, Dec. 2009, [Peer-reviewed]
    Japanese, Scientific journal
  • Cannabinoid in the nucleus accumbens enhances the intake of palatable solution
    Yuhei Shinohara; Tadashi Inui; Takashi Yamamoto; Tsuyoshi Shimura
    NEUROREPORT, 20, 15, 1382, 1385, Oct. 2009, [Peer-reviewed]
    English, Scientific journal
  • Cannabinoid in the nucleus accumbens enhances the intake of palatable solution.
    Tadashi Inui
    Neuroreport, 01 Oct. 2009, [Peer-reviewed]
    Scientific journal, It has been suggested that the activation of cannabinoid receptors in the nucleus accumbens shell facilitates feeding behavior. However, it remains unclear whether cannabinoid ligands enhance the palatability of food to facilitate feeding. In this study, we examined whether microinjecting an endogenous cannabinoid agonist, anandamide into the nucleus accumbens shell would affect the intake of water, sweet or bitter solutions. Microinjections of anandamide into the nucleus accumbens shell selectively increased the intake of saccharin (sweet) solution, but had no effect on the intake of water nor quinine (bitter) solution. These results suggest that activation of the cannabinoid receptors in the nucleus accumbens shell selectively facilitates the intake of palatable foods and solutions.
  • Spatial differences in molecular characteristics of the pontine parabrachial nucleus
    Naohiro Maeda; Mayuko Onimura; Makoto Ohmoto; Tadashi Inui; Takashi Yamamoto; Ichiro Matsumoto; Keiko Abe
    BRAIN RESEARCH, 1296, 24, 34, Oct. 2009, [Peer-reviewed]
    English, Scientific journal
  • Cannabinoid in the nucleus accumbens enhances the intake of palatable solution
    Yuhei Shinohara; Tadashi Inui; Takashi Yamamoto; Tsuyoshi Shimura
    NeuroReport, 20, 15, 1382, 1385, Oct. 2009, [Peer-reviewed]
    English, Scientific journal
  • 味覚嫌悪学習における脳内報酬系の役割
    乾 賢; 山本 隆; 志村 剛
    日本味と匂学会誌, Aug. 2009, [Peer-reviewed]
    Japanese
  • GABAergic transmission in the rat ventral pallidum mediates a saccharin palatability shift in conditioned taste aversion
    Tadashi Inui; Takashi Yamamoto; Tsuyoshi Shimura
    EUROPEAN JOURNAL OF NEUROSCIENCE, 30, 1, 110, 115, Jul. 2009, [Peer-reviewed]
    English, Scientific journal
  • GABAergic transmission in the rat ventral pallidum mediates a saccharin palatability shift in conditioned taste aversion
    Tadashi Inui; Takashi Yamamoto; Tsuyoshi Shimura
    EUROPEAN JOURNAL OF NEUROSCIENCE, 30, 1, 110, 115, Jul. 2009, [Peer-reviewed]
    English, Scientific journal
  • Functional Organization of the Rodent Parabrachial Nucleus
    Takashi Yamamoto; Motohide Takemura; Tadashi Inui; Kunio Torii; Naohiro Maeda; Makoto Ohmoto; Ichiro Matsumoto; Keiko Abe
    INTERNATIONAL SYMPOSIUM ON OLFACTION AND TASTE, 1170, 378, 382, 2009, [Peer-reviewed]
    English, Scientific journal
  • 味覚嫌悪学習獲得による嗜好性変化における腹側淡蒼球μオピオイド受容体の役割
    乾 賢; 山本 隆; 志村 剛
    日本味と匂学会誌, Dec. 2008, [Peer-reviewed]
    Japanese, Scientific journal
  • Effects of inactivation of the central nucleus of the amygdala on palatability-induced ingestion
    SHINOHARA Yuhei; YASOSHIMA Yasunobu; INUI Tadashi; SHIMURA Tsuyoshi
    The Japanese journal of taste and smell research, 15, 3, 303, 306, The Japanese Association for the Study of Taste and Smell, Dec. 2008, [Peer-reviewed]
    Japanese, Scientific journal
  • The role of the ventral pallidum GABAergic system in conditioned taste aversion: Effects of microinjections of a GABA(A) receptor antagonist on taste palatability of a conditioned stimulus
    Tadashi Inui; Tsuyoshi Shimura; Takashi Yamamoto
    BRAIN RESEARCH, 1164, 117, 124, Aug. 2007, [Peer-reviewed]
    English, Scientific journal
  • The role of the ventral pallidum GABAergic system in conditioned taste aversion: Effects of microinjections of a GABA(A) receptor antagonist on taste palatability of a conditioned stimulus
    Tadashi Inui; Tsuyoshi Shimura; Takashi Yamamoto
    BRAIN RESEARCH, 1164, 117, 124, Aug. 2007, [Peer-reviewed]
    English, Scientific journal
  • The role of the ventral pallidum GABAergic system in conditioned taste aversion: effects of microinjections of a GABAA receptor antagonist on taste palatability of a conditioned stimulus.
    Tadashi Inui
    Brain research, Elsevier, 27 Jun. 2007, [Peer-reviewed]
    English, Scientific journal, When subjects receive a taste stimulus (conditioned stimulus, CS) that is paired with malaise, they acquire conditioned taste aversion (CTA). It is thought that the taste CS changes from appetitive to aversive after acquisition of CTA. Previous studies have suggested that the ventral pallidum (VP) is involved in the hedonics of taste stimuli, therefore the present study investigated whether the VP is a neural substrate for the shift in preference of the CS after CTA acquisition. In the first experiment, CTA-learned rats received microinjections of the GABAA receptor antagonist bicuculline into the VP just before presentation of the CS (saccharin or quinine) in a single-bottle test. The bicuculline-injected rats showed higher intake of the saccharin CS than the vehicle-injected rats. To test whether these results were due to a change in taste preference for the CS, in the second experiment, we examined the effects of bicuculline on the affective aspects of the saccharin CS using a taste reactivity test, which is a useful tool for evaluating taste palatability. The bicuculline-injected rats showed higher appetitive and lower aversive responses to the saccharin CS than the vehicle-inj
  • The involvement of GABAergic system of the ventral pallidum in the retrieval of conditioned taste aversion in rats
    Tadashi Inui; Tsuyoshi Shimura; Takashi Yamamoto
    日本味と匂学会誌, Dec. 2006, [Peer-reviewed]
    Japanese, Scientific journal
  • Effects of brain lesions on taste-potentiated odor aversion in rats
    Tadashi Inui; Tsuyoshi Shimura; Takashi Yamamoto
    Behavioral Neuroscience, 120, 3, 590, 599, 3, Jun. 2006, [Peer-reviewed], [International Magazine]
    English, Scientific journal
  • Effects of Brain Lesions on Taste-Potentiated Odor Aversion in Rats.
    Tadashi Inui; Tsuyoshi Shimura; Takashi Yamamoto
    Behavioral Neuroscience, 120, 3, 590, 9, Jun. 2006, [Peer-reviewed], [International Magazine]
    English, Scientific journal, Rats failed to acquire aversions to odor stimulus, which was followed 30 min later by an unconditioned stimulus (US). However, when the odor stimulus was accompanied by a taste stimulus, they acquired odor aversions as well as taste aversions. In this phenomenon, referred to as a taste-potentiated odor aversion, lesions of the amygdala disrupted both taste and odor aversions, whereas lesions of the parvicellular part of ventroposteromedial thalamic nucleus (VPMpc) or insular cortex (IC) disrupted taste aversion but attenuated only odor aversion. These results suggest that both taste and odor stimuli are associated with US in the amygdala and that taste inputs delivered to the amygdala through the IC and/or VPMpc play an important role in potentiation of odor aversion.
  • Effects of brain lesions on taste-potentiated odor aversion in rats
    Tadashi Inui; Tsuyoshi Shimura; Takashi Yamamoto
    BEHAVIORAL NEUROSCIENCE, 120, 3, 590, 599, Jun. 2006, [Peer-reviewed]
    English, Scientific journal
  • The microinfusions of GABAA receptors antagonist into the ventral pallidum disrupt the retrieval of conditioned taste aversion in rats
    Tadashi Inui; Tsuyoshi Shimura; Takashi Yamamoto
    日本味と匂学会誌, Dec. 2005, [Peer-reviewed]
    Japanese, Scientific journal
  • Expression of c-fos mRNA on the acquisition and retrieval of conditioned taste aversion in rats.
    Tadashi Inui; Takashi Yamamoto
    The Japanese journal of taste and smell research, 9, 3, 687, 690, The Japanese Association for the Study of Taste and Smell, Dec. 2002, [Peer-reviewed]
    Japanese, Scientific journal
  • Some analyses of drinking behavior in rats with a system monitoring fluid intake
    Tadashi Inui; Miki Watanabe; Takashi Yamamoto
    The Japanese journal of taste and smell research, 8, 3, 515, 518, The Japanese Association for the Study of Taste and Smell, Dec. 2001
    Japanese, Scientific journal
  • The behavioral experiments on taste in rats.
    Tadashi Inui
    日本味と匂学会誌, 8, 209-214, 8, 2, 209, 214, Aug. 2001, [Peer-reviewed]
    Japanese
  • Corticofugal Influence on Taste Responses in the Parabrachial Nucleus of the Rat.
    Zoltan Karadi; Ken'ichi Tokita; Tadashi Inui; Tsuyoshi Shimura; Takashi Yamamoto
    The Japanese journal of taste and smell research, 7, 3, 579, 580, The Japanese Association for the Study of Taste and Smell, Dec. 2000, [Peer-reviewed]
    Japanese, Scientific journal
  • Development of drinking behavior monitoring system for the rat.
    Tadashi Inui; Takashi Yamamoto
    日本味と匂学会誌, 7, 659-662, 7, 3, 659, 662, Dec. 2000, [Peer-reviewed]
    Japanese, Scientific journal
  • Olfactory learnings and brain mechanisms
    Tadashi Inui; Takashi Yamamoto
    AROMA RESEARCH, 1, 8-15, 1, 2, 8, 15, フレグランスジャーナル社, May 2000, [Peer-reviewed]
    Japanese
  • Brain regions involved in conditioned odor aversion in rats.
    Tadashi Inui; Takashi Yamamoto
    The Japanese journal of taste and smell research, 6, 3, 371, 374, The Japanese Association for the Study of Taste and Smell, Dec. 1999, [Peer-reviewed]
    Japanese, Scientific journal
  • The odor aversion learning in rats.
    Tadashi Inui; Takashi Yamamoto
    The Japanese journal of taste and smell research, 5, 3, 273, 276, The Japanese Association for the Study of Taste and Smell, Dec. 1998, [Peer-reviewed]
    Japanese, Scientific journal
■ Other Activities and Achievements
■ Books and other publications
  • おいしさの科学とビジネス展開の最前線
    乾 賢, 第15章 味覚の中枢機序
    シーエムシー出版, Jul. 2017, [Joint work]
■ Lectures, oral presentations, etc.
  • Roles of glutamatergic and GABAergic neurons in the lateral hypothalamus on the expression of conditioned taste aversion
    Tadashi Inui
    The 21th International Symposium on Molecular and Neural Mechanisms of Taste and Olfactory Perception, 02 Mar. 2025, English, Nominated symposium
    [Invited]
  • Role of the central nucleus of the amygdala in behavioral expression on retrieval of conditioned taste aversion memory
    Tadashi Inui
    The 20th International Symposium on Molecular and Neural Mechanisms of Taste and Olfactory Perception, 26 Nov. 2023, English, Invited oral presentation
    25 Nov. 2023 - 26 Nov. 2023, [Invited]
  • The GABAergic System in the Ventral Pallidum Is Involved in the Retrieval of Conditioned Taste Aversion in Rats.
    INUI Tadashi
    The 17th Annual Meeting of the European Chemoreception Research Organization (ECRO), 2006, English, Nominated symposium
    [International presentation]
■ Syllabus
  • 口腔生物学と医学, 2024年, 博士後期課程, 歯学院
  • 咬合咀嚼生理学研究, 2024年, 博士後期課程, 歯学院
  • 摂食行動制御学研究, 2024年, 博士後期課程, 歯学院
  • 発表・論文執筆法演習Ⅰ, 2024年, 博士後期課程, 歯学院
  • 発表・論文執筆法演習Ⅱ, 2024年, 博士後期課程, 歯学院
  • 発表・論文執筆法演習Ⅲ, 2024年, 博士後期課程, 歯学院
  • 頭顎口定位制御学, 2024年, 博士後期課程, 歯学院
  • 頭顎口定位制御学, 2024年, 博士後期課程, 歯学院
  • 頭顎口定位制御学研究, 2024年, 博士後期課程, 歯学院
  • 生理学的解析技法, 2024年, 博士後期課程, 歯学院
  • 関連臨床医学, 2024年, 学士課程, 歯学部
  • アクティブラーニング科目Ⅰ, 2024年, 学士課程, 歯学部
  • 生理学・口腔生理学Ⅰ, 2024年, 学士課程, 歯学部
  • 生理学・口腔生理学Ⅱ, 2024年, 学士課程, 歯学部
  • 生理学・口腔生理学実習, 2024年, 学士課程, 歯学部
  • 健康と社会, 2024年, 学士課程, 全学教育
■ Affiliated academic society
  • Society for Neuroscience
  • 歯科基礎医学会
  • 日本神経科学会
  • 日本生理学会
  • 日本味と匂学会
■ Research Themes
  • Elucidation of the mechanism of updating the conditioned memory acquired by nausea and vomiting and development of a novel nausea suppression method.
    Grants-in-Aid for Scientific Research
    01 Apr. 2025 - 31 Mar. 2028
    舩橋 誠; 乾 賢; 吉澤 知彦
    Japan Society for the Promotion of Science, Grant-in-Aid for Scientific Research (C), Hokkaido University, 25K12947
  • 塩味嗜好における性差の解明
    ソルト・サイエンス研究財団研究助成
    Apr. 2025 - Mar. 2026
    ソルト・サイエンス研究財団
  • うま味の嗜好に基づく摂取行動における視床下部外側野の役割
    第30回うま味研究会研究助成
    Jan. 2024 - Dec. 2025
    うま味研究会
  • Neurophysiological study for the elucidation of the difference of the central mechanism of nausea and vomiting and the development of the nausea suppression therapy.
    Grants-in-Aid for Scientific Research Grant-in-Aid for Scientific Research (C)
    01 Apr. 2022 - 31 Mar. 2025
    舩橋 誠; 乾 賢; 吉澤 知彦
    Japan Society for the Promotion of Science, Grant-in-Aid for Scientific Research (C), Hokkaido University, 22K09900
  • The role of the lateral hypothalamus in conditioned taste aversion
    Grants-in-Aid for Scientific Research Grant-in-Aid for Scientific Research (C)
    01 Apr. 2022 - 31 Mar. 2025
    乾 賢
    Japan Society for the Promotion of Science, Grant-in-Aid for Scientific Research (C), Hokkaido University, 22K09912
  • 塩味嗜好学習の表出に関わる神経回路の機能解明
    ソルト・サイエンス研究財団研究助成
    Apr. 2024 - Mar. 2025
    ソルト・サイエンス研究財団
  • 塩味嗜好学習に関わる神経回路の同定
    ソルト・サイエンス研究財団研究助成
    Apr. 2023 - Mar. 2024
    ソルト・サイエンス研究財団
  • 神経性食欲不振症の中枢神経機序の解明
    武田科学振興財団医学研究助成
    Apr. 2020 - Mar. 2023
    武田科学振興財団
  • The role of the central nucleus of the amygdala in conditioned taste aversion
    Grants-in-Aid for Scientific Research Grant-in-Aid for Research Activity Start-up
    11 Sep. 2020 - 31 Mar. 2022
    Inui Tadashi
    To reveal the neural mechanisms underlying conditioned taste aversion (CTA), this project aimed to investigate the role of the central nucleus of the amygdala (CeA) in the retrieval of CTA. We developed a microstructural behavioral analysis system and examined the effect of manipulation of the neuronal activities in the CeA on ingestive behavior. Mice induced with inhibitory designer receptors in the CeA neurons were conditioned aversion to a sweet taste solution. The mice were injected with a designer ligands (Experimental group) or vehicle (Control group), and then exposed to the sweet taste solution. The Experimental group drank larger volume of the solution than the Control group. The behavioral analysis showed that the increased intake was caused by attenuation of disgust and anxiety to the solution. Therefore, it is suggested that the CeA neurons mediate disgust and anxiety during the retrieval of CTA.
    Japan Society for the Promotion of Science, Grant-in-Aid for Research Activity Start-up, Hokkaido University, 20K23041
  • The mechanisms of palatability of foods: Effects of rarity
    Grants-in-Aid for Scientific Research Grant-in-Aid for Challenging Exploratory Research
    01 Apr. 2015 - 31 Mar. 2017
    Inui Tadashi
    Palatability of foods, which has reward value, easily induce overeating in humans. It is assumed that there are central nervous systems involved in the palatability of foods. The present study aimed to establish a behavioral experimental paradigm and elucidate the neural mechanisms of the palatability of foods. Juvenile Wistar rats were presented wth sunflower seeds for 10 min. The consumed volume (g) and eating duration (sec) showed daily increase, indicating the palatability of the sunflower seeds gradually elevated. We also evaluated the opening of the eyes during the feeding and found that the rats tend to close their eyes during eating the sunflower seeds, but not normal chow, with time- and day-dependent changes. These results suggest that the volume and duration of eating the sunflower seeds are negatively correlated with the opening of the rat's eyes. Therefore, the present study revealed that using a sunflower seed and measuring eye opening are useful experimental paradigms.
    Japan Society for the Promotion of Science, Grant-in-Aid for Challenging Exploratory Research, Osaka University, 15K12353
  • A study of neuronal mechanisms underlying overconsumption of highly preferred taste stimuli under chronic mild stress
    Grants-in-Aid for Scientific Research Grant-in-Aid for Scientific Research (C)
    01 Apr. 2014 - 31 Mar. 2017
    SHIMURA Tsuyoshi; YASOSHIMA Yasunobu; INUI Tadashi
    Systemic injections of yohimbine, an α-adrenoceptor antagonist, selectively increase the consumption of a highly preferred sweet liquid food but not the normal chow in rats. Temporary inactivation of the basolateral nucleus of the amygdala by a pharmacological treatment abolished the facilitatory intake of a preferred food by yohimbine. Since yohimbine is known to evoke a mild stress, it is suggested that neural circuits including the basolateral nucleus of the amygdala have a pivotal role for overconsumption of highly preferred food under a weak stress condition in general.
    Japan Society for the Promotion of Science, Grant-in-Aid for Scientific Research (C), Osaka University, 26350146
  • Mechanisms of anorectic hormone-induced gustatory regulation in the cerebral cortex
    Grants-in-Aid for Scientific Research Grant-in-Aid for Scientific Research (B)
    01 Apr. 2013 - 31 Mar. 2016
    KOBAYASHI Masayuki; CUI Yelong; INUI Tadashi; MIZOGUCHI Naoko; YAMAMOTO Kiyofumi
    Leptin plays a pivotal role in regulation of energy balance by controlling appetite and metabolism. The insular cortex (IC) processes gustatory and visceral information, which functionally correlate to feeding behavior. However, it is still an open issue how leptin modulates synaptic transmission in the IC and other cortical areas. We recorded excitatory propagation by an optical imaging technique using in vivo preparations. Leptin effectively suppressed the amplitude and area of excitatory propagation in the IC. Paired whole-cell patch-clamp recordings from pyramidal and fast-spiking cells were performed using rat IC slice preparations to explore the mechanisms of leptin-induced suppression of excitatory propagation. Leptin reciprocally modulated uEPSCs and uIPSCs via presynaptic mechanisms, and as a whole, leptin suppresses neural excitability in the IC. Leptin-induced suppression of excitation may contribute the refinement of cortico-cortical information processing of gustation.
    Japan Society for the Promotion of Science, Grant-in-Aid for Scientific Research (B), Nihon University, 25293379
  • Study for the brain mechanisms of ingestive behavior -interaction between palatability and memory-
    Grants-in-Aid for Scientific Research Grant-in-Aid for Scientific Research (C)
    01 Apr. 2012 - 31 Mar. 2015
    INUI Tadashi
    To reveal the ingestive behavior regulated by palatability and memory, we aimed to assess the brain mechanisms of memory establishment and palatability shift in conditioned taste aversion (CTA) in rats. Initially, we developed an experimental chamber for detecting the rat's approaches to a drinking spout, and counting their licks to the spout. We found that the rats show increased "conflict" (rats approach, but not lick, the spout) and decreased "burst" (high-frequency of licks) after conditioning. We defined that conflict indicates memory establishment, and burst indicates palatability shift. Based on these ideas, in behavioral pharmacology experiments, we examined the effects of temporal inactivation of the basolateral amygdala (BLA) on conflict and burst. We demonstrated that BLA inactivation significantly decreases conflict and increases burst. These results suggest that the BLA is a key brain region for both of memory establishment and palatability shift in CTA.
    Japan Society for the Promotion of Science, Grant-in-Aid for Scientific Research (C), Osaka University, 24500973
  • 摂取行動を制御する大脳基底核オピオイド性神経伝達メカニズムの解明
    三島海雲記念財団研究助成金
    Apr. 2011 - Mar. 2012
    三島海雲記念財団
  • The role of the brain network involved in feeding behavior
    Grants-in-Aid for Scientific Research Grant-in-Aid for Young Scientists (B)
    2010 - 2011
    INUI Tadashi; INUI Chizuko; SHIMURA Tsuyoshi
    We examined the signal transduction pathways in the brain involved in the recall of food memory. When human and animals eat some foods followed by malaise or nausea, they learn the taste of the foods as the signal of danger and became to dislike the foods. This phenomenon is referred to as conditioned taste aversion(CTA). In this study, we found the changes in the activities of the signal transduction pathways in the brain after CTA, suggesting that the plastic changes in the brain network are involved in the shift in feeding behavior(from like to dislike).
    Japan Society for the Promotion of Science, Grant-in-Aid for Young Scientists (B), Osaka University, 22700748
  • 味覚嗜好性に基づく摂取行動における脳内報酬系の役割に関する研究
    すかいらーくフードサイエンス研究所学術研究助成金
    Apr. 2007 - Mar. 2008
    すかいらーくフードサイエンス研究所
  • 味覚嫌悪学習における脳内報酬系の役割の解明
    ネスレ栄養科学会議研究助成金
    Apr. 2007 - Mar. 2008
    ネスレ栄養科学会議
  • Research on the central taste information processing related to food reward
    Grants-in-Aid for Scientific Research Grant-in-Aid for Scientific Research (C)
    2007 - 2008
    SHIMURA Tsuyoshi; INUI Tadashi; SHINOHARA Yuhei
    本研究は、飲食物の摂取に重要な味覚嗜好性がどのような神経回路の働きで生じるのかを明らかにするために、味覚情報が脳内報酬系にアクセスする過程を検索することを目的としている。本年度は行動薬理学的実験および免疫組織化学的実験により次の成果を得た。
    1.脳内報酬系の枢軸である側坐核は、飲食物摂取行動にも重要な役割を果たしている。ラットの側坐核に脳内大麻様物質(カンナビノイド)であるアナンダマイドを微量注入したところ、本来嗜好性の高い甘味溶液に限ってその摂取量が増加することが確認された。従来から麻薬様物質(オピオイド)注入でも高嗜好性の飲食物摂取が増加することが報告されているので、側坐核ではカンナビノイドとオピオイドの相互作用が生じていることが示唆された。
    2.側坐核からの出力を受ける腹側淡蒼球も嗜好性味刺激の摂取に深く関わっている。味刺激摂取後に内臓不快感を経験させて味覚嫌悪学習を獲得したラットの腹側淡蒼
    Japan Society for the Promotion of Science, Grant-in-Aid for Scientific Research (C), Osaka University, Competitive research funding, 19530657
  • 味覚嫌悪学習における脳内報酬系の役割を解明する
    科学研究費補助金(若手研究(B))
    2005 - 2007
    乾 賢
    飲食物の摂取後に下痢や嘔吐を経験すると、その飲食物の味を嫌うようになる。これを味覚嫌悪学習(conditioned taste aversion, CTA)という。この学習は味刺激を条件刺激(conditioned stimulus, CS)、内臓不快感を無条件刺激(unconditioned stimulus,US)とする連合学習である。CTAの脳内メカニズムは十分に解明されていない。近年、脳内報酬系といわれる神経系が味覚嗜好性(味のおいしさ・まずさ)に関与することが明らかになりつつある。そこで本研究では脳内報酬系の一部位である腹側淡蒼球のCTAにおける役割について検討した。平成18年度までに、サッカリン溶液(甘味)に対するCTAを獲得させたラットの腹側淡蒼球にGABAA受容体阻害薬であるbicucullineを局所注入すると、CSに対する嗜好性が嫌悪性から嗜好性へと変化し(味覚反応性テスト)、CSの摂取量が増加する(一ビン法)ことを明らかにした。そこで今年度は、動物が生得的に嫌う苦味(キニーネ溶液)をCSとして同様の手続きで実験を行った。その結果、腹側淡
    文部科学省, 若手研究(B), 大阪大学, Competitive research funding, 17730431
  • Neuroscientific studies on brain mechanisms controlling ingestive behavior on the basis of cognitive and affective aspects of taste.
    Grants-in-Aid for Scientific Research Grant-in-Aid for Scientific Research (B)
    2005 - 2006
    YAMAMOTO Takashi; SHIMURA Tsuyoshi; INUI Tadashi; WAKISAKA Satoshi; INOUE Tomio
    The purpose of the present research project was to elucidate brain mechanisms controlling ingestive behavior on the basis of cognitive and affective aspects of taste. The following results were obtained:
    1) Conditioned taste aversion
    With the c-fos immunohistochemical method, we have suggested that the enhanced taste sensitivity to facilitate detection of the conditioned stimulus originates in the central nucleus of the amygdala and the hedonic shift, from positive to negative, originates in the basolateral nucleus of the amygdala.
    2) Brain substance
    Injection of cannabinoid agonists into the nucleus accumbens enhanced the ingestion of saccharin, but not quinine, indicating that the cannabinoid receptors in the nucleus accumbens play an important role in eliciting palatability.
    3) Reward system
    Microinjections of an opioid agonist, DAMGO, or an GABA antagonist, bicuculline, into the ventral pallidum attenuated the expression of conditioned taste aversion, indicating that the reward system is concerned with the taste aversion learning.
    4) Brain imaging
    Magnetic responses recorded from the human cortex suggest that the sourness component of citric acid is greatly diminished at the level of subcortical relays, and mostly sweetness information reaches the cortical primary taste area.
    Japan Society for the Promotion of Science, Grant-in-Aid for Scientific Research (B), Osaka University, 17390494
  • 味覚情報の神経伝達に関与する機能性分子の探索とその役割の解明
    科学研究費助成事業
    2004 - 2005
    山本 隆; 志村 剛; 乾 賢; 姜 英男
    味覚の重要な機能として5基本味をはじめとする味の質の識別と快・不快の判断があるが、そのメカニズムには不明な点が多い。本研究では、1)末梢神経系では、約10日でターンオーバーを繰り返す味細胞とシナプス結合をする味覚神経線維が常に一定の特徴ある味応答特性を維持するメカニズムと、2)中枢神経系では、味の質的な情報と必ず連動する快・不快の情報の発現メカニズムの解明である。本年度は主として2)の項目について研究を行った。
    末梢神経レベルでの機能性分子の探索は技術的に極めて困難であることがわかったので、発想の転換を計って、ラットなどげっ歯類の第2次味覚中継核である橋の結合腕傍核(PBN)に着目し、神経細胞の特性を明らかにすることを目標とした。PBNは先行研究により、味質や嗜好性に応じて局在的な細胞の分布を示すことが知られているからである。アプローチとして、DNAマイクロアレイを用いた遺伝子発現解析を選択した。PBNでの遺伝子発現は内側部と外側部で前方部と後方部、また三叉神経主知覚各や青斑核、三叉神経中脳路核との間でいくつかの特定の遺伝子において発現様式が異なることが明らかとなった。PBNの尾側部では、CGRP、ニューロテンシンなどの発現が顕著であった。一方、味の種類によって応答に違いがみられるかを検証するため、蔗糖と食塩の混合液(好ましい味)とデナトニウムと塩酸の混合液(まずい味)をそれぞれラットの口に入れたときの遺伝子発現の違いを調べたが、現在のところ明確な違いが認められていない。今後さらに検討を加える予定である。
    日本学術振興会, 萌芽研究, 大阪大学, 16659510
  • Neuroscientific studies on brain mechanisms of affective behavior, learning and memory of taste.
    Grants-in-Aid for Scientific Research
    2002 - 2004
    YAMAMOTO Takashi; SHIMURA Tsuyoshi; INUI Tadashi; MURAKAMI Hideaki; INOUE Tomio
    The purpose of the present research project was to reveal brain substances activated by taste stimuli and to show plastic changes of responsiveness of neurons by those substances in rats. The experiments on humans aims to disclose brain functions about taste quality processing and hedonic evaluation of taste with the use of non-invasive brain imaging techniques. The following results were obtained :
    1)Brain mechanisms of taste preference learning : Injections of a dopamine D1 receptor antagonist or a glutamine receptor antagonist into the ventral pallidum decreased saccharin intake, while a opioid receptor antagonist increased saccharin intake.
    2)Microdialysis study : Brain histamine release was increased by quinine, but no release by sucrose or saccharin, indicating that histamine release was related aversive taste.
    3)Brain mechanisms of taste aversion learning : Injections of bicuculline, GABA receptor antagonist, into the ventral pallidum in the rat trained to reject saccharin attenuated aversions to saccharin.
    4)Non-invasive brain imaging study : Magnetic response of the brain was greater to simultaneous simulation of odor and visual image when delivered matched than mismatched.
    Japan Society for the Promotion of Science, Grant-in-Aid for Scientific Research (B), Osaka University, 14370593
  • 味覚嫌悪学習と嗅覚嫌悪学習の脳機序、特に扁桃体の役割についての研究
    科学研究費補助金(奨励研究(A), 若手研究(B))
    2001 - 2002
    乾 賢
    味覚嫌悪学習の獲得および想起過程における扁桃体の機能を,c-fos mRNAの発現を指標として調べた.c-fosは他の遺伝子の発現を調節する転写調節因子の一つである.また神経細胞が興奮した直後に発現する遺伝子である最初期遺伝子の一つである.従って,学習・記憶によって活動する脳部位を同定し,その機能を調べることができる.先行研究により,味覚嫌悪学習には扁桃体,結合腕傍核,孤束核などが関与することが知られている.しかし,学習の獲得過程や想起過程においてこれらの部位の活動が経時的にどのように変化するかはわかっていなかった.そこで発現・分解のtime courseが短いmRNAをターゲットとして,in situ hybridization法とRT-PCR法を用いて,c-fos mRNAの発現部位と発現量の変化について検討した.
    獲得過程
    in situ hybridization法の結果,条件づけの30分後から60分後にかけて扁桃体(中心核),結合腕傍核,孤束核のいづれの部位においてもc-fos mRNAの発現量が有意に増加し,240分後までには消失した.RT-PCR法
    文部科学省, 若手研究(B), 大阪大学, Competitive research funding, 13710035
  • Development of a computor-controlled gustatory stimulator for magnetoencephalography
    Grants-in-Aid for Scientific Research
    1999 - 2001
    YAMAMOTO Takashi; INUI Tadashi; YAMAGUCHI Masahiko; TONOIEKE Mitsuo
    The magnetoencephalography (MEG) is one of the non-invasive functional brain imaging techniques. MEG has good temporal resolution in comparison to functional magnetic resonance imaging (fMRI) or positron emission tomography (PET), and can give a good estimation of the localization of the activity much more precisely than electroencephalography. The purpose of the present study is to construct a convenient equipment controlled by a computer system to deliver taste solutions to the subject's tongue with accurate onset times.
    A newly manufactured computer-controlled stimulus delivery system was constructed to apply taste solution and rinsing water through a Teflon tube to a flow chamber covering the anterior part of the subject's tongue. A small babble was inserted between the rinse and taste solution to prevent diffusion of fluids. The flow rate the water and stimuli was 200 ml/min. The outlet from the chamber was led to outside of the shielded room and the taste solutions and rinsing water were discarded. Taste solutions were colored red to allow their detection by an optical sensor, but water was not colored. The sensor was positioned just before the entry to the mouthpiece. This onset of taste stimulation provided a trigger signal for MEG averaging.
    Japan Society for the Promotion of Science, Grant-in-Aid for Scientific Research (B), Osaka University, 11557135
  • 味の嗜好性(おいしさ)嫌悪性(まずさ)発現に関与する脳内生理活性物質の探索
    科学研究費助成事業
    1999 - 2000
    山本 隆; 乾 賢; 硲 哲崇
    我々の開発した味覚刺激装置は、味溶液、洗浄水、空気をそれぞれ独立して制御できる電磁弁を介してテフロンチューブにより被験者の口腔内へ流すことができるような仕組みとなっている。チューブ内では微小の空気によって洗浄水と味溶液は隔絶するように電磁弁がコンピュータ制御されている。舌刺激部分は、円筒形のチューブで被験者がこれに舌先端部分を挿入することによって広範囲に刺激できる仕組みとなっている。味溶液は着色されており、これを色検知センサーで検出することにより味刺激のオンセットを計測している。センサーと舌との間隔は25mmで、その遅れは125msであり、データ解析の際に差し引かれている。味溶液と蒸留水は、室温に保たれている。舌刺激部位における水圧変動を解消するために、溶液をポンプで吸引することにより刺激時の流速を一定に保った(約20cm/sec)。
    これまでの装置では、味刺激は単一のものしか与えることができなかったので、今年度は、例えば、クエン酸とショ糖など異なる2種の味刺激を交互あるいはランダムに刺激する装置を開発し、感覚強度の減弱が少なく、脳磁界計測において精度の高い味応答が得られることを確認した。
    溶液刺激は味覚応答を得る上で必要不可欠であるが、より簡便に脳磁界応答を記録することを目的に、電気味覚計を応用した刺激装置の開発にも取りかかった。来年度中には電気味覚刺激装置を完成させる予定である。
    日本学術振興会, 萌芽的研究, 大阪大学, 11877322
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