Umeå universitets logga

umu.sePublikationer
Ändra sökning
RefereraExporteraLänk till posten
Permanent länk

Direktlänk
Referera
Referensformat
  • apa
  • ieee
  • vancouver
  • Annat format
Fler format
Språk
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Annat språk
Fler språk
Utmatningsformat
  • html
  • text
  • asciidoc
  • rtf
Cortico-cortical connectivity behind acoustic information transfer to mouse orbitofrontal cortex is sensitive to neuromodulation and displays local sensory gating: relevance in disorders with auditory hallucinations?
Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB).
Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB).
Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB).
2021 (Engelska)Ingår i: Journal of Psychiatry & Neuroscience, ISSN 1180-4882, E-ISSN 1488-2434, Vol. 46, nr 3, s. E371-E387Artikel i tidskrift (Refereegranskat) Published
Abstract [en]

Background: Auditory hallucinations (which occur when the distinction between thoughts and perceptions is blurred) are common in psychotic disorders. The orbitofrontal cortex (OFC) may be implicated, because it receives multiple inputs, including sound and affective value via the amygdala, orchestrating complex emotional responses. We aimed to elucidate the circuit and neuromodulatory mechanisms that underlie the processing of emotionally salient auditory stimuli in the OFC — mechanisms that may be involved in auditory hallucinations. Methods: We identified the cortico-cortical connectivity conveying auditory information to the mouse OFC; its sensitivity to neuromodulators involved in psychosis and postpartum depression, such as dopamine and neurosteroids; and its sensitivity to sensory gating (defective in dysexecutive syndromes). Results: Retrograde tracers in OFC revealed input cells in all auditory cortices. Acoustic responses were abolished by pharmacological and chemogenetic inactivation of the above-identified pathway. Acoustic responses in the OFC were reduced by local dopaminergic agonists and neurosteroids. Noticeably, apomorphine action lasted longer in the OFC than in auditory areas, and its effect was modality-specific (augmentation for visual responses), whereas neurosteroid action was sex-specific. Finally, acoustic responses in the OFC reverberated to the auditory association cortex via feedback connections and displayed sensory gating, a phenomenon of local origin, given that it was not detectable in input auditory cortices. Limitations: Although our findings were for mice, connectivity and sensitivity to neuromodulation are conserved across mammals. Conclusion: The corticocortical loop from the auditory association cortex to the OFC is dramatically sensitive to dopamine and neurosteroids. This suggests a clinically testable circuit behind auditory hallucinations. The function of OFC input–output circuits can be studied in mice with targeted and clinically relevant mutations related to their response to emotionally salient sounds.

Ort, förlag, år, upplaga, sidor
Canadian Medical Association (CMA) , 2021. Vol. 46, nr 3, s. E371-E387
Nationell ämneskategori
Neurovetenskaper Neurologi
Identifikatorer
URN: urn:nbn:se:umu:diva-184452DOI: 10.1503/jpn.200131ISI: 000743686000007Scopus ID: 2-s2.0-85107241570OAI: oai:DiVA.org:umu-184452DiVA, id: diva2:1567990
Tillgänglig från: 2021-06-17 Skapad: 2021-06-17 Senast uppdaterad: 2023-09-05Bibliografiskt granskad

Open Access i DiVA

Fulltext saknas i DiVA

Övriga länkar

Förlagets fulltextScopus

Person

Tripathi, AnushreeSulis Sato, SebastianMedini, Paolo

Sök vidare i DiVA

Av författaren/redaktören
Tripathi, AnushreeSulis Sato, SebastianMedini, Paolo
Av organisationen
Institutionen för integrativ medicinsk biologi (IMB)
I samma tidskrift
Journal of Psychiatry & Neuroscience
NeurovetenskaperNeurologi

Sök vidare utanför DiVA

GoogleGoogle Scholar

doi
urn-nbn

Altmetricpoäng

doi
urn-nbn
Totalt: 485 träffar
RefereraExporteraLänk till posten
Permanent länk

Direktlänk
Referera
Referensformat
  • apa
  • ieee
  • vancouver
  • Annat format
Fler format
Språk
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Annat språk
Fler språk
Utmatningsformat
  • html
  • text
  • asciidoc
  • rtf