Abstract
Efficient sensory processing requires that the brain maximize its response to unexpected stimuli, while suppressing responsivity to expected events. Mismatch negativity (MMN) is an auditory event-related potential that occurs when a regular pattern is interrupted by an event that violates the expected properties of the pattern. According to the predictive coding framework there are two mechanisms underlying the MMN: repetition suppression and prediction error. MMN has been found to be reduced in individuals with schizophrenia, an effect believed to be underpinned by glutamate N-methyl-d-aspartate receptor (NMDA-R) dysfunction. In the current study, we aimed to test how the NMDA-R antagonist, MK-801 in the anaesthetized rat, affected repetition suppression and prediction error processes along the auditory thalamocortical pathway. We found that low-dose systemic administration of MK-801 differentially affect thalamocortical responses, namely, increasing thalamic repetition suppression and cortical prediction error. Results demonstrate an enhancement of neuronal mismatch, also confirmed by large scale-responses. Furthermore, MK-801 produces faster and stronger dynamics of adaptation along the thalamocortical hierarchy. Clearly more research is required to understand how NMDA-R antagonism and dosage affects processes contributing to MMN. Nonetheless, because a low dose of an NMDA-R antagonist increased neuronal mismatch, the outcome has implications for schizophrenia treatment.
Highlights
Recordings were performed in the medial geniculate body (MGB) and in the auditory cortex (AC) while playing oddball and control sequences in anesthetized rats
Since we found no statistically significant differences when we compare mean baseline-corrected spike counts between the use of the cascade and many-standards sequences for the control group and MK-801 group, except for the MGBNL from the MK-801 group (Table 1: Cascade vs. many-standard controls analysis, p > 0.05 within all fields and groups, except for the M GBNL from the MK-801 group where p = 0.0286), the CAS sequence was chosen to control for repetition effects
We demonstrate that the neuronal index of mismatch, derived from single-cell recordings, is profoundly affected along the auditory thalamocortical system in rats treated acutely with N-methyl-d-aspartate receptor (NMDA-R) antagonist, MK-801
Summary
The predictive coding framework has emerged as an appealing model of M MN3 and of how sensory information is processed. MMN could reflect a process of prediction error, where the sensory memory of regular stimuli that establishes a predictive model is violated upon the presentation of an unexpected DEV stimulus. This violation results in an enhanced neural response, allowing detection of the environmental change and an update of the predictive model. There is evidence in both humans and rodents that MMN receives contributions from both prediction error and repetition suppression at various levels of the auditory s ystem[11, 12].
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