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Sub-Anesthetic Ketamine Administration Decreases Deviance Detection Responses at the Cellular, Population- and
Maria Isabel Carreño-Muñoz1,2, Alessandra Ciancone Chama1,2, Pegah Chehrazi1,2
1Department of Neurosciences, Université de Montréal, Montreal, Canada.
The European Journal of Neuroscience
|April 1, 2026
Summary
Novelty detection in the auditory cortex involves NMDA receptor signaling. Ketamine, an NMDA receptor antagonist, disrupts neuronal responses to deviant sounds and impairs communication between auditory and parietal cortices.
Area of Science:
- Neuroscience
- Auditory Processing
- Sensory Perception
Background:
- Neuronal processing of sensory events is influenced by predictability, with habituation to repetitive stimuli and enhanced responses to novel, deviant stimuli.
- Mismatch negativity (MMN) is an electroencephalographic marker for auditory deviant detection, known to depend on NMDA receptor signaling.
- The precise neuronal and mesoscale mechanisms of NMDA receptor-dependent novelty processing remain incompletely understood.
Purpose of the Study:
- To investigate the role of NMDA receptor signaling in auditory novelty detection at the neuronal and mesoscale levels.
- To identify specific neuronal responses in the auditory cortex to deviant auditory stimuli.
- To examine the impact of NMDA receptor blockade on inter-cortical communication during novelty detection.
Main Methods:
- Multi-electrode array recordings in awake mice to capture neuronal activity in the primary auditory cortex (A1).
- Administration of ketamine, an NMDA receptor antagonist, to assess its effects on neuronal responses and inter-cortical connectivity.
- Weighted phase lag index (wPLI) analysis to evaluate functional connectivity between A1 and the posterior parietal cortex (PPC).
Main Results:
- A subpopulation of A1 neurons exhibited a biphasic spiking response to deviant sounds, with the second peak abolished by ketamine.
- The PPC responded to deviant, but not repetitive, sounds, a response dependent on NMDA receptor signaling.
- Functional connectivity between A1 and PPC following deviant detection was observed, but impaired by ketamine.
Conclusions:
- NMDA receptor signaling is crucial for processing auditory novelty, influencing both specific neuronal responses in A1 and inter-cortical communication.
- Ketamine administration disrupts these NMDA receptor-dependent mechanisms, highlighting the role of NMDA receptors in auditory deviance detection and information flow.
- Findings provide insights into the neural basis of novelty processing and the mechanisms underlying NMDA receptor function in sensory cortices.
