A neuron model with unbalanced synaptic weights explains the asymmetric effects of anaesthesia on the auditory cortex

PLoS Biol. 2023 Feb 21;21(2):e3002013. doi: 10.1371/journal.pbio.3002013. eCollection 2023 Feb.

Abstract

Substantial progress in the field of neuroscience has been made from anaesthetized preparations. Ketamine is one of the most used drugs in electrophysiology studies, but how ketamine affects neuronal responses is poorly understood. Here, we used in vivo electrophysiology and computational modelling to study how the auditory cortex of bats responds to vocalisations under anaesthesia and in wakefulness. In wakefulness, acoustic context increases neuronal discrimination of natural sounds. Neuron models predicted that ketamine affects the contextual discrimination of sounds regardless of the type of context heard by the animals (echolocation or communication sounds). However, empirical evidence showed that the predicted effect of ketamine occurs only if the acoustic context consists of low-pitched sounds (e.g., communication calls in bats). Using the empirical data, we updated the naïve models to show that differential effects of ketamine on cortical responses can be mediated by unbalanced changes in the firing rate of feedforward inputs to cortex, and changes in the depression of thalamo-cortical synaptic receptors. Combined, our findings obtained in vivo and in silico reveal the effects and mechanisms by which ketamine affects cortical responses to vocalisations.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acoustic Stimulation
  • Anesthesia*
  • Animals
  • Auditory Cortex* / physiology
  • Auditory Perception / physiology
  • Chiroptera* / physiology
  • Ketamine* / pharmacology
  • Neurons / physiology

Substances

  • Ketamine

Grants and funding

This work was supported by Deutsche Forschungsgemeinschaft (DFG) - Project number 428645493 to JCH. https://gepris.dfg.de/gepris/projekt/428645493 The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript