Circuiterie à l'échelle du cerveau sous-tendant une habituation auditive altérée dans des modèles de poisson-zèbre de l'autisme

Titre original en anglais : Brain-Wide Circuitry Underlying Altered Auditory Habituation in Zebrafish Models of Autism

Cette publication est incluse dans le projet « Contributions académiques de personnes autistes sur l’autisme ». un auteur·ice de cette publication est identifié·e comme autiste dans le projet.

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Wilde, M., Ghanbari, A., Mancienne, T., Moran, A., Poulsen, R. E., Constantin, L., Lee, C., Scholz, L. A., Arnold, J., Qin, W., Karle, T. J., Petrou, S., Favre-Bulle, I., Hoffman, E. J., & Scott, E. K. (2026). Brain-Wide Circuitry Underlying Altered Auditory Habituation in Zebrafish Models of Autism. Journal of Neuroscience, 46(35), e0364262026. https://doi.org/10.1523/jneurosci.0364-26.2026

Date de publication: 30/07/2026 Ajout dans AutiHub: 30/09/2026 Type: Article Langue de l’article: Anglais
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Auteurs

Auteur·ices des publications
15
Auteur·ices de la publication identifié·es comme autistes
1 / 15 (6,7 %)
  1. Maya Wilde
  2. Anahita Ghanbari
  3. Tessa Mancienne
  4. Ailís Moran
  5. Rebecca E. Poulsen *
  1. Lena Constantin
  2. Conrad Lee
  3. Leandro Aluisio Scholz
  4. Joshua Arnold
  5. Wei Qin
  1. Timothy J. Karle
  2. Steven Petrou
  3. Itia Favre-Bulle
  4. Ellen J. Hoffman
  5. Ethan K. Scott

Résumé

Il est largement admis que le traitement auditif se déroule différemment dans l'autisme, bien que les schémas d'activité cérébrale sous-jacents à ces différences soient mal compris. La diversité de l'autisme signifie également que les réseaux à l'échelle du cerveau peuvent changer de diverses manières pour produire des résultats comportementaux similaires. Nous avons utilisé des larves de poisson-zèbre pour étudier l'habituation auditive dans trois lignées génétiques pertinentes pour l'autisme : fmr1, mecp2 et cntnap2. Dans des tests comportementaux en nage libre, nous avons constaté que chaque lignée présentait un profil unique d'hyperréactivité auditive et/ou d'habituation réduite par rapport aux types sauvages. En combinant la transparence optique des larves de poisson-zèbre avec des indicateurs calciques génétiquement encodés et la microscopie à feuille de lumière, nous avons ensuite observé l'activité à l'échelle du cerveau avec une résolution cellulaire lors de stimuli sonores répétés. Chaque lignée a montré des altérations uniques de l'activité spontanée à l'échelle du cerveau, du traitement auditif et de l'adaptation en réponse à des stimuli acoustiques répétitifs. Nous avons également observé des points communs dans l'activité entre nos lignées génétiques, indiquant des modifications de circuits partagées sous-tendant certains aspects de leurs phénotypes comportementaux. Ceux-ci se situaient principalement dans des régions impliquées dans l'intégration sensorielle et le filtrage sensorimoteur plutôt que dans les aires auditives primaires. Les phénotypes qui se chevauchent comprennent des différences dans l'activité et la connectivité fonctionnelle du télencéphale, des régions dopaminergiques et du locus ceruleus. Les phénotypes uniques comprennent une activité accrue dans les régions auditives et un déséquilibre excitation/inhibition dans le cervelet chez fmr1, ainsi que des différences de l'activité des réseaux au fil du temps chez mecp2 et cntnap2. La comparaison de ces réseaux auditifs distincts mais se chevauchant à l'échelle du cerveau suggère que divers facteurs génétiques peuvent contribuer à des effets comportementaux similaires par le biais d'une gamme de mécanismes à l'échelle des circuits et des réseaux.

Auditory processing is widely understood to occur differently in autism, though the patterns of brain activity underlying these differences are not well understood. The diversity of autism also means brain-wide networks may change in various ways to produce similar behavioral outputs. We used larval zebrafish to investigate auditory habituation in three genetic lines relevant to autism: fmr1, mecp2, and cntnap2. In free-swimming behavioral tests, we found each line had a unique profile of auditory hyperresponsiveness and/or reduced habituation compared with wild types. Combining the optical transparency of larval zebrafish with genetically encoded calcium indicators and light-sheet microscopy, we then observed brain-wide activity at cellular resolution during repeated sound stimuli. Each line showed unique alterations in brain-wide spontaneous activity, auditory processing, and adaptation in response to repetitive acoustic stimuli. We also observed commonalities in activity across our genetic lines that indicate shared circuit changes underlying certain aspects of their behavioral phenotypes. These were predominantly in regions involved in sensory integration and sensorimotor gating rather than primary auditory areas. Overlapping phenotypes include differences in the activity and functional connectivity of the telencephalon, dopaminergic regions, and the locus ceruleus. Unique phenotypes include increased activity in auditory regions and excitatory/inhibitory imbalance in the cerebellum in fmr1 and differences in network activity over time in mecp2 and cntnap2. Comparing these distinct but overlapping brain-wide auditory networks suggests that diverse genetic factors may contribute to similar behavioral effects through a range of circuit- and network-scale mechanisms.

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Références citées
88
Avec un DOI
88
Sans DOI, à partir du texte brut de la bibliographie
0
5 / 88 (5,7 %) références citées comprennent au moins une personne identifiée comme autiste.
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0 / 88 (0,0 %)
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Sans titre structuré
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Sans identifiant stable
0
Références avec noms bruts d’auteurices restant à vérifier
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565
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565
À partir du texte brut validé de la bibliographie
0
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87 / 565 (15,4 %) noms sont associés à un·e auteurice déjà présent·e dans AutiHub. 478 / 565 (84,6 %) noms ne sont pas encore associés.
Noms associés à une personne identifiée comme autiste
7 / 565 (1,2 %)
Calculé sur l’ensemble des noms d’auteurices détectés dans la bibliographie citée. Parmi les noms associés à un·e auteurice déjà présent·e dans AutiHub : 7 / 87 (8,0 %). Personnes distinctes identifiées comme autistes : 3 / 485 (0,6 %).
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