## Ketamine anaesthesia induces gain enhancement via recurrent excitation in granular input layers of the auditory cortex

Please always quote using this URN: urn:nbn:de:bvb:20-opus-216123
• 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 asKetamine 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.

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Author: Katrina E. Deane, Michael G. K. Brunk, Andrew W. Curran, Marina M. Zempeltzi, Jing Ma, Xiao Lin, Francesca Abela, Sümeyra Aksit, Matthias Deliano, Frank W. Ohl, Max F. K. Happel urn:nbn:de:bvb:20-opus-216123 Journal article Graduate Schools / Graduate School of Life Sciences English The Journal of Physiology 2020 598 13 2741 2755 The Journal of Physiology 2020, 598(13):2741–2755. DOI: 10.1113/JP279705 https://doi.org/10.1113/JP279705 6 Technik, Medizin, angewandte Wissenschaften / 61 Medizin und Gesundheit / 610 Medizin und Gesundheit auditory cortex; continuous wavelet analysis; current source density; ketamine anaesthesia; laminar recording; mesoscopic; microcircuitry; population dynamics 2021/07/02 CC BY: Creative-Commons-Lizenz: Namensnennung 4.0 International