A neuron model with unbalanced synaptic weights explains asymmetric effects of ketamine in auditory cortex

Ketamine anesthesia does not uniformly suppress auditory cortex responses to all sounds. In bats, multifunctional neurons that process both echolocation and communication sounds are affected asymmetrically: under anesthesia, communication contexts cause global suppression of responses to lagging sounds, while echolocation contexts do not. This asymmetry depends on the frequency composition of sounds, not their temporal patterns. A computational model shows that anesthesia modulates spiking activity in a channel-specific way, decreasing responses to high-frequency sounds and increasing adaptation in corresponding cortical synapses. These findings indicate that ketamine anesthesia unbalances cortical inputs, altering how neurons respond to natural vocalizations in ways not predictable from known anesthetic effects.

Study at a glance

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.