Cannabinoid overrides triggers of GABAergic plasticity in vestibular circuits and distorts the development of navigation
Summary: Early life exposure to cannabis can result in long-lasting deficits in spatial navigation. We ask if the development of this behavior is subject to early life activity of type I cannabinoid receptor (CB1R) in the vestibular nucleus. In rodents, we found that local exposure to CB1R agonist w...
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| Language: | English |
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Elsevier
2025-06-01
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| Series: | iScience |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2589004225008272 |
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| author | Wei Shi Kenneth Lap-Kei Wu Mengliu Yang Francisco Paulo De Nogueira Botelho Oscar Wing-Ho Chua Hui-Jing Hu Ka-Pak Ng Ulysses Tsz-Fung Lam Kin-Wai Tam Chun-Wai Ma Daisy Kwok-Yan Shum Ying-Shing Chan |
| author_facet | Wei Shi Kenneth Lap-Kei Wu Mengliu Yang Francisco Paulo De Nogueira Botelho Oscar Wing-Ho Chua Hui-Jing Hu Ka-Pak Ng Ulysses Tsz-Fung Lam Kin-Wai Tam Chun-Wai Ma Daisy Kwok-Yan Shum Ying-Shing Chan |
| author_sort | Wei Shi |
| collection | DOAJ |
| description | Summary: Early life exposure to cannabis can result in long-lasting deficits in spatial navigation. We ask if the development of this behavior is subject to early life activity of type I cannabinoid receptor (CB1R) in the vestibular nucleus. In rodents, we found that local exposure to CB1R agonist within the first postnatal week, but not thereafter, led to a decline in the induction efficacy of long-term depression at GABAergic synapses (LTDGABA), a key step in the hard-wiring of vestibular circuits. Within this critical period, endocannabinoid-mediated LTDGABA at inhibitory neurons was selectively triggered by cholecystokinin, whereas that at excitatory neurons was by serotonin. Neonatal exposure to cannabinoids extended the phase of high GABAergic synaptic plasticity and overrode the synapse-specific, modulatory mechanism for plasticity. Such treatment delayed the postnatal emergence of vestibular-dependent reflexes and deranged adult navigational behavior. Deficits in higher functions are thus attributable to the maldevelopment of sensory processing circuits resulting from early cannabis exposure. |
| format | Article |
| id | doaj-art-ab2cb3d89424492fb876c205b5996fda |
| institution | Kabale University |
| issn | 2589-0042 |
| language | English |
| publishDate | 2025-06-01 |
| publisher | Elsevier |
| record_format | Article |
| series | iScience |
| spelling | doaj-art-ab2cb3d89424492fb876c205b5996fda2025-08-20T03:53:47ZengElsevieriScience2589-00422025-06-0128611256610.1016/j.isci.2025.112566Cannabinoid overrides triggers of GABAergic plasticity in vestibular circuits and distorts the development of navigationWei Shi0Kenneth Lap-Kei Wu1Mengliu Yang2Francisco Paulo De Nogueira Botelho3Oscar Wing-Ho Chua4Hui-Jing Hu5Ka-Pak Ng6Ulysses Tsz-Fung Lam7Kin-Wai Tam8Chun-Wai Ma9Daisy Kwok-Yan Shum10Ying-Shing Chan11School of Biomedical Sciences, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Pokfulam, Hong Kong SAR, P.R. China; Beijing Advanced Innovation Center for Big Data-based Precision Medicine, School of Engineering and Medicine, Beihang University, Beijing, P.R. ChinaSchool of Biomedical Sciences, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Pokfulam, Hong Kong SAR, P.R. China; Neuroscience Research Centre, The University of Hong Kong, Pokfulam, Hong Kong SAR, P.R. ChinaBeijing Advanced Innovation Center for Big Data-based Precision Medicine, School of Engineering and Medicine, Beihang University, Beijing, P.R. ChinaSchool of Biomedical Sciences, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Pokfulam, Hong Kong SAR, P.R. ChinaSchool of Biomedical Sciences, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Pokfulam, Hong Kong SAR, P.R. ChinaSchool of Biomedical Sciences, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Pokfulam, Hong Kong SAR, P.R. ChinaSchool of Biomedical Sciences, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Pokfulam, Hong Kong SAR, P.R. ChinaSchool of Biomedical Sciences, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Pokfulam, Hong Kong SAR, P.R. ChinaSchool of Biomedical Sciences, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Pokfulam, Hong Kong SAR, P.R. China; Neuroscience Research Centre, The University of Hong Kong, Pokfulam, Hong Kong SAR, P.R. ChinaSchool of Biomedical Sciences, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Pokfulam, Hong Kong SAR, P.R. ChinaSchool of Biomedical Sciences, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Pokfulam, Hong Kong SAR, P.R. China; State Key Laboratory of Brain and Cognitive Sciences, The University of Hong Kong, Pokfulam, Hong Kong SAR, P.R. China; Neuroscience Research Centre, The University of Hong Kong, Pokfulam, Hong Kong SAR, P.R. China; Corresponding authorSchool of Biomedical Sciences, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Pokfulam, Hong Kong SAR, P.R. China; State Key Laboratory of Brain and Cognitive Sciences, The University of Hong Kong, Pokfulam, Hong Kong SAR, P.R. China; Neuroscience Research Centre, The University of Hong Kong, Pokfulam, Hong Kong SAR, P.R. China; Corresponding authorSummary: Early life exposure to cannabis can result in long-lasting deficits in spatial navigation. We ask if the development of this behavior is subject to early life activity of type I cannabinoid receptor (CB1R) in the vestibular nucleus. In rodents, we found that local exposure to CB1R agonist within the first postnatal week, but not thereafter, led to a decline in the induction efficacy of long-term depression at GABAergic synapses (LTDGABA), a key step in the hard-wiring of vestibular circuits. Within this critical period, endocannabinoid-mediated LTDGABA at inhibitory neurons was selectively triggered by cholecystokinin, whereas that at excitatory neurons was by serotonin. Neonatal exposure to cannabinoids extended the phase of high GABAergic synaptic plasticity and overrode the synapse-specific, modulatory mechanism for plasticity. Such treatment delayed the postnatal emergence of vestibular-dependent reflexes and deranged adult navigational behavior. Deficits in higher functions are thus attributable to the maldevelopment of sensory processing circuits resulting from early cannabis exposure.http://www.sciencedirect.com/science/article/pii/S2589004225008272Natural sciencesBiological sciencesNeuroscience |
| spellingShingle | Wei Shi Kenneth Lap-Kei Wu Mengliu Yang Francisco Paulo De Nogueira Botelho Oscar Wing-Ho Chua Hui-Jing Hu Ka-Pak Ng Ulysses Tsz-Fung Lam Kin-Wai Tam Chun-Wai Ma Daisy Kwok-Yan Shum Ying-Shing Chan Cannabinoid overrides triggers of GABAergic plasticity in vestibular circuits and distorts the development of navigation iScience Natural sciences Biological sciences Neuroscience |
| title | Cannabinoid overrides triggers of GABAergic plasticity in vestibular circuits and distorts the development of navigation |
| title_full | Cannabinoid overrides triggers of GABAergic plasticity in vestibular circuits and distorts the development of navigation |
| title_fullStr | Cannabinoid overrides triggers of GABAergic plasticity in vestibular circuits and distorts the development of navigation |
| title_full_unstemmed | Cannabinoid overrides triggers of GABAergic plasticity in vestibular circuits and distorts the development of navigation |
| title_short | Cannabinoid overrides triggers of GABAergic plasticity in vestibular circuits and distorts the development of navigation |
| title_sort | cannabinoid overrides triggers of gabaergic plasticity in vestibular circuits and distorts the development of navigation |
| topic | Natural sciences Biological sciences Neuroscience |
| url | http://www.sciencedirect.com/science/article/pii/S2589004225008272 |
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