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

Abstract

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. r 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. r This cortical response is driven by gain enhancement of thalamocortical input processing selectively within granular layers due to an increased recurrent excitation. r Time-frequency analysis indicates a higher broadband magnitude response and prolonged phase coherence in granular layers, possibly pointing to disinhibition of this recurrent excitation. r 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.

The extracellular matrix regulates cortical layer dynamics and cross-columnar frequency integration in the auditory cortex

“…Those short-latent sinks reflect the synaptic afferent input from the lemniscal auditory part of the thalamus, the ventral medial geniculate body (vMGB), with main projections to granular layers and collaterals within layer Vb [26][27][28] . This has been revealed by earlier studies showing persistent thalamocortical inputs in corresponding layers after intracortical silencing with the GABA A -agonist muscimol 22,23,29 in accordance with reports by others 28,30 . Early sinks were followed by synaptic activation of supragranular (I/II) and deep infragranular (VI) layers ( Fig.…”

“…In this study, we investigated the effects of ECM removal acutely and under ketamine-xylazine anesthesia. We have recently shown that, in addition to generally very similar spatiotemporal activity patterns, anesthesia mainly influences gain enhancement in layer III/IV at best frequency stimulation 29 . Particularly, ketamine-xylazine had only minor effects on the spectral beta range and off-BF-evoked activity, which showed strongest effects after HYase treatment.…”

“…These changes in the spatiotemporal synaptic pattern were accompanied by an increase of lateral corticocortical input revealed by CSD residual analysis 22 . Utilizing a multitaper spectral analysis of tone-evoked oscillatory circuit responses 24 , we revealed a layer specific change of the oscillatory power in the beta band (25)(26)(27)(28)(29)(30)(31)(32)(33)(34)(35)(36) within infragranular layers Vb. To investigate how these synaptic spatiotemporal changes are mediated by the translaminar dynamics of cortical network activity, we implemented time-domain Granger causality (GC) measures mapping the directional causal relationship between activity across cortical layers.…”

Removal of the extracellular matrix biases auditory cortical layer dynamics towards supragranular frequency integration

“…In this study, we investigated the effects of ECM removal acutely and under ketamine-xylazine anaestesia. We have recently shown that, in addition to generally very similar spatiotemporal activity patterns, anesthesia mainly influences gain enhancement in layer III/IV at best frequency stimulation (Deane et al, 2020). Particularly, ketamine-xylazine had only minor effects on the spectral beta range and off-BF-evoked activity, which showed strongest effects after HYase treatment.…”

“…The location of the field AI in primary ACx was identified by vasculature landmarks and physiological parameters (Happel et al, 2010). In this study, we analyzed only data from recordings which exceed 90 minutes after implantation of the electrode–a state where the cortical responses under anesthesia have been largely stabilized as reported recently (Deane et al, 2020).…”