A neuron model with unbalanced synaptic weights explains asymmetric effects of ketamine in auditory cortex
bioRxiv Preprint Server – June 12, 2022
Source: bioRxiv
Summary
Anesthetics, vital for surgery, surprisingly alter how the brain processes sound. Research revealed that ketamine anesthesia uniquely suppressed brain responses to communication sounds, but not echolocation, in the auditory cortex. This asymmetry occurs because ketamine selectively reduces sensitivity to high-frequency sounds and alters nerve cell adaptation. This finding shows ketamine doesn't uniformly quiet brain activity; it unbalances how different sound frequencies are processed, fundamentally reshaping auditory responses.
Abstract
Although new advances in neuroscience allow the study of vocal communication in awake animals, substantial progress in the processing of vocalizations has been made from brains of anaesthetized preparations. Thus, understanding how anaesthetics affect neuronal responses is of paramount importance. Here, we used electrophysiological recordings and computational modelling to study how the auditory cortex of bats responds to vocalizations under anaesthesia and in wakefulness. We found that multifunctional neurons that process echolocation and communication sounds were affected by ketamine anaesthesia in a manner that could not be predicted by known anaesthetic effects. In wakefulness, acoustic contexts (preceding echolocation or communication sequences) led to stimulus-specific suppression of lagging sounds, accentuating neuronal responses to sound transitions. However, under anaesthesia, communication contexts (but not echolocation) led to a global suppression of responses to lagging sounds. Such asymmetric effect was dependent on the frequency composition of the contexts and not on their temporal patterns. We constructed a neuron model that could replicate the data obtained in vivo. In the model, anaesthesia modulates spiking activity in a channel-specific manner, decreasing responses of cortical inputs tuned to high-frequency sounds and increasing adaptation in the respective cortical synapses. Combined, our findings obtained in vivo and in silico reveal that ketamine anaesthesia does not reduce uniformly the neurons’ responsiveness to low and high frequency sounds. This effect depends on combined mechanisms that unbalance cortical inputs and ultimately affect how auditory cortex neurons respond to natural sounds in anaesthetized preparations.