Sub-Anesthetic Ketamine Administration Decreases Deviance Detection Responses at the Cellular, Population- and Mesoscale Levels.
Maria Isabel Carreño-muñoz, Alessandra Ciancone Chama, Pegah Chehrazi, Bidisha Chattopadhyaya, Graziella Di Cristo
European Journal of Neuroscience April 1, 2026 DOI: 10.1111/ejn.70471 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Experimental study Peer reviewed |
|---|---|
| Population | Awake mice |
| Intervention | Ketamine |
| Dose | acute sub-anesthetic injection |
| Topics | Ketamine Esketamine |
| Keywords | Auditory Deviance detection Mismatch negativity Posterior parietal cortex Wpli |
| Key findings | A biphasic spiking response in A1 neurons and PPC responses to deviant sounds depend on intact NMDA receptor signaling, and ketamine impairs A1-PPC functional connectivity during deviance detection. |
Abstract
In the neocortex, neuronal processing of sensory events is significantly influenced by their predictability. A common example is the suppression of responses to repetitive stimuli in sensory cortices, a phenomenon known as habituation. Within a sensory information stream, whenever a novel stimulus deviates from expectations, enhanced brain responses are observed. Mismatch negativity (MMN), the electroencephalographic waveform reflecting rule violations, is a well-established biomarker for auditory deviant detection. MMN has been shown to depend on intact NMDA receptor signaling across species; nevertheless, the underlying mechanisms at the neuronal and mesoscale levels are still not fully understood. Using multi-electrode array recordings in awake mice, we identified a specific biphasic spiking response in a subpopulation of primary auditory cortex (A1) neurons elicited by deviant, but not standard, sounds, wherein the second peak is abolished by acute sub-anesthetic injection of ketamine, a partial non-competitive NMDA receptor antagonist. We further showed that the posterior parietal cortex (PPC), a critical hub for multisensory integration and sensorimotor coordination, responds to deviant, but not repetitive, sounds, and this response is dependent upon intact NMDA receptor-mediated signaling. Finally, to explore the effects of ketamine on inter-cortical communication following deviance detection, we performed weighted phase lag index (wPLI) analyses during the presentation of deviant and standard sounds. This analysis showed a functional connectivity between A1 and PPC following deviant detection, which is impaired by ketamine administration. Altogether, our findings provide novel insights into the NMDA receptor-dependent mechanisms underlying the processing of novelty in auditory stimuli.
Comparable studies
Other preclinical and animal studies on ketamine, most cited first.
| Study | Year | Design | Participants |
|---|---|---|---|
| mTOR-Dependent Synapse Formation Underlies the Rapid Antidepressant Effects of NMDA Antagonists Rats | 2010 | Observational study | |
| Activation of Glutamatergic Neurotransmission by Ketamine: A Novel Step in the Pathway from NMDA Receptor Blockade to Dopaminergic and Cognitive Disruptions Associated with the Prefrontal Cortex Conscious rats | 1997 | Dose-response study with microdialysis and behavioral testing | |
| NMDAR inhibition-independent antidepressant actions of ketamine metabolites Mice | 2016 | Preclinical study | |
| The dissociative anaesthetics, ketamine and phencyclidine, selectively reduce excitation of central mammalian neurones by N‐methyl‐aspartate Spinal neurons in decerebrate or pentobarbitone-anaesthetized cats and rats | 1983 | Experimental study | |
| R-ketamine: a rapid-onset and sustained antidepressant without psychotomimetic side effects Mice | 2015 | Experimental study |
Citations in the library
Cites 5
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- Evidence that Subanesthetic Doses of Ketamine Cause Sustained Disruptions of NMDA and AMPA-Mediated Frontoparietal Connectivity in Humans Journal of Neuroscience August 19, 2015
- Decreased directed functional connectivity in the psychedelic state. Neuroimage December 17, 2019
- N-methyl-D-aspartate receptor antagonism impairs sensory gating in the auditory cortex in response to speech stimuli. Psychopharmacology July 2022
- A comprehensive analysis of auditory event-related potentials and network oscillations in an NMDA receptor antagonist mouse model using a novel wireless recording technology. Physiological reports August 2018