JP279705.pdf 4,84MB
1000 Titel
  • Ketamine anaesthesia induces gain enhancement via recurrent excitation in granular input layers of the auditory cortex
1000 Autor/in
  1. Deane, Katrina E |
  2. Brunk, Michael |
  3. Curran, Andrew William |
  4. Zempeltzi, Maria-Marina |
  5. Ma, Jing |
  6. Lin, Xiao |
  7. Abela, Francesca |
  8. Aksit, Sümeyra |
  9. Deliano, Matthias |
  10. Ohl, Frank W. |
  11. Happel, Max |
1000 LeibnizOpen
1000 Publikationstyp
  1. Artikel |
1000 Online veröffentlicht
  • 2020-06-30
1000 Erschienen in
1000 Quellenangabe
  • 598(13):2741-2755
1000 FRL-Sammlung
1000 Copyrightjahr
  • 2020
1000 Lizenz
1000 Verlagsversion
  • |
1000 Ergänzendes Material
  • |
1000 Publikationsstatus
1000 Begutachtungsstatus
1000 Sprache der Publikation
1000 Abstract/Summary
  • KEY POINTS: Ketamine is a common anaesthetic agent used in research and more recently as medication in treatment of depression. It has known effects on inhibition of interneurons and cortical stimulus-locked responses, but the underlying functional network mechanisms are still elusive. Analysing population activity across all layers within the auditory cortex, we found that doses of this anaesthetic induce a stronger activation and stimulus-locked response to pure-tone stimuli. This cortical response is driven by gain enhancement of thalamocortical input processing selectively within granular layers due to an increased recurrent excitation. Time-frequency analysis indicates a higher broadband magnitude response and prolonged phase coherence in granular layers, possibly pointing to disinhibition of this recurrent excitation. These results further the understanding of ketamine's functional mechanisms, which will improve the ability to interpret physiological studies moving from anaesthetized to awake paradigms and may lead to the development of better ketamine-based depression treatments with lower side effects. ABSTRACT: Ketamine is commonly used as an anaesthetic agent and has more recently gained attention as an antidepressant. It has been linked to increased stimulus-locked excitability, inhibition of interneurons and modulation of intrinsic neuronal oscillations. However, the functional network mechanisms are still elusive. A better understanding of these anaesthetic network effects may improve upon previous interpretations of seminal studies conducted under anaesthesia and have widespread relevance for neuroscience with awake and anaesthetized subjects as well as in medicine. Here, we investigated the effects of anaesthetic doses of ketamine (15 mg kg-1 h-1 i.p.) on the network activity after pure-tone stimulation within the auditory cortex of male Mongolian gerbils (Meriones unguiculatus). We used laminar current source density (CSD) analysis and subsequent layer-specific continuous wavelet analysis to investigate spatiotemporal response dynamics on cortical columnar processing in awake and ketamine-anaesthetized animals. We found thalamocortical input processing within granular layers III/IV to be significantly increased under ketamine. This layer-dependent gain enhancement under ketamine was not due to changes in cross-trial phase coherence but was rather attributed to a broadband increase in magnitude reflecting an increase in recurrent excitation. A time-frequency analysis was indicative of a prolonged period of stimulus-induced excitation possibly due to a reduced coupling of excitation and inhibition in granular input circuits - in line with the common hypothesis of cortical disinhibition via suppression of GABAergic interneurons.
1000 Sacherschließung
lokal mesoscopic
lokal continuous wavelet analysis
lokal auditory cortex
lokal ketamine anaesthesia
lokal microcircuitry
lokal current source density
lokal population dynamics
lokal laminar recording
1000 Fächerklassifikation (DDC)
1000 Liste der Beteiligten
1000 Label
1000 Förderer
  1. Deutsche Forschungsgemeinschaft |
  2. Leibniz-Gemeinschaft |
  3. China Scholarship Council |
1000 Fördernummer
  1. DFG SFB 779
  2. -
  3. 201506290028; 201408430074
1000 Förderprogramm
  1. -
  2. -
  3. -
1000 Dateien
1000 Förderung
  1. 1000 joinedFunding-child
    1000 Förderer Deutsche Forschungsgemeinschaft |
    1000 Förderprogramm -
    1000 Fördernummer DFG SFB 779
  2. 1000 joinedFunding-child
    1000 Förderer Leibniz-Gemeinschaft |
    1000 Förderprogramm -
    1000 Fördernummer -
  3. 1000 joinedFunding-child
    1000 Förderer China Scholarship Council |
    1000 Förderprogramm -
    1000 Fördernummer 201506290028; 201408430074
1000 Objektart article
1000 Beschrieben durch
1000 @id frl:6423612.rdf
1000 Erstellt am 2020-10-16T11:07:27.556+0200
1000 Erstellt von 242
1000 beschreibt frl:6423612
1000 Bearbeitet von 25
1000 Zuletzt bearbeitet Thu Feb 25 10:11:07 CET 2021
1000 Objekt bearb. Thu Feb 25 10:11:07 CET 2021
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