Circuiterie à l’échelle du cerveau sous-jacente à 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

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Wilde, M., Ghanbari, A., Mancienne, T., Moran, A., Poulsen, R., Constantin, L., Lee, C. C., Scholz, L. A., Arnold, J., Qin, W., Karle, T. J., Petrou, S., Favre‐Bulle, I. A., Hoffman, E. J., & Scott, E. K. (2024). Brain-wide circuitry underlying altered auditory habituation in zebrafish models of autism [Preprint]. openRxiv. https://doi.org/10.1101/2024.09.04.611137

Date de publication: 05/09/2024 Ajout dans AutiHub: 05/07/2026 Type: Prépublication 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 Poulsen *
  1. Lena Constantin
  2. Conrad C.Y. Lee
  3. Leandro A. Scholz
  4. Joshua Arnold
  5. Wei Qin
  1. T. J. Karle
  2. Steven Petrou
  3. Itia A. Favre‐Bulle
  4. Ellen J. Hoffman
  5. Ethan K. Scott

Résumé

Résumé Le traitement auditif est largement reconnu comme se produisant 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 se modifier de diverses manières pour produire des résultats comportementaux similaires. Nous avons utilisé des larves de poisson-zèbre pour étudier l’habituation auditive dans quatre lignées génétiques pertinentes pour l’autisme : fmr1, mecp2, scn1lab et cntnap2. Lors de tests comportementaux en nage libre, nous avons constaté que chaque lignée présentait un profil unique d’hypersensibilité auditive et/ou d’habituation retardée. En combinant la transparence optique des larves de poisson-zèbre avec des indicateurs calciques génétiquement encodés et la microscopie par feuille de lumière, nous avons ensuite observé l’activité à l’échelle du cerveau avec une résolution cellulaire pendant l’habituation auditive. Comme pour le comportement, 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 similitudes d’activité entre nos lignées génétiques indiquant des modifications de circuits partagées sous-jacentes à certains aspects de leurs phénotypes comportementaux. Celles-ci se situaient principalement dans des régions impliquées dans l’intégration sensorielle et le filtrage sensorimoteur plutôt que dans les zones auditives primaires. Les phénotypes qui se chevauchent comprennent des différences dans l’activité et la connectivité fonctionnelle du télencéphale, du thalamus, des régions dopaminergiques et du locus coeruleus, ainsi qu’un déséquilibre excitation/inhibition dans le cervelet. Les phénotypes uniques comprennent une perte d’activité dans l’habenula chez scn1lab, une activité accrue dans les régions auditives chez fmr1, et des différences d’activité des réseaux au cours du temps chez mecp2 et cntnap2. La comparaison de ces réseaux auditifs distincts mais se chevauchant à l’échelle du cerveau améliore notre compréhension de la manière dont divers facteurs génétiques peuvent produire des effets comportementaux similaires par le biais d’un éventail de mécanismes à l’échelle des circuits et des réseaux.

Abstract 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 four genetic lines relevant to autism: fmr1, mecp2, scn1lab and cntnap2. In free-swimming behavioral tests, we found each line had a unique profile of auditory hypersensitivity and/or delayed habituation. 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 auditory habituation. As with behavior, 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, thalamus, dopaminergic regions, and the locus coeruleus, and excitatory/inhibitory imbalance in the cerebellum. Unique phenotypes include loss of activity in the habenula in scn1lab, increased activity in auditory regions in fmr1, and differences in network activity over time in mecp2 and cntnap2. Comparing these distinct but overlapping brain-wide auditory networks furthers our understanding of how diverse genetic factors can produce similar behavioral effects through a range of circuit- and network-scale mechanisms.

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Ces indicateurs décrivent la bibliographie citée importée pour cette publication. Les métriques de références citées utilisent le total des références citées comme dénominateur. Les métriques d’auteurices cité·es indiquent si elles utilisent toutes les occurrences d’auteurices cité·es ou seulement les occurrences rattachées à des auteurices déjà intégré·es à la base de données AutiHub. Ils utilisent les rattachements mis en cache entre les auteurices cité·es et les auteurices intégré·es à la base de données AutiHub. Dernier calcul : 16/08/2026 11:30.

Références citées
83
Nombre total de références citées intégrées pour cette publication.
Références citées avec un·e auteur·ice identifié·e comme autiste
4 / 83 (4,8 %)
Occurrences d’auteur·ices cité·es identifié·es comme autistes
4 / 532 (0,8 %)
Parmi les occurrences rattachées à des auteurices intégré·es à la base de données AutiHub : 4 / 69 (5,8 %). Auteurices cité·es distinct·es identifié·es comme autistes : 1 / 460 (0,2 %).
Occurrences citées rattachées à la base AutiHub
69 / 532 (13,0 %)
Auteurices cité·es distinct·es rattaché·es : 27 / 460 (5,9 %)
Occurrences rattachées, non identifiées comme autistes
65 / 69 (94,2 %)
Parmi les seules occurrences rattachées. Sur l’ensemble des occurrences d’auteurices cité·es : 65 / 532 (12,2 %). Auteurices cité·es distinct·es rattaché·es, non identifié·es comme autistes : 26 / 27 (96,3 %).
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