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PLoS One. 2014 Oct 21;9(10):e110892. doi: 10.1371/journal.pone.0110892. eCollection 2014.

Mismatch negativity (MMN) in freely-moving rats with several experimental controls.

Author information

1
School of Psychology, University of Newcastle, Callaghan, NSW, Australia; Priority Centre for Translational Neuroscience and Mental Health Research, University of Newcastle, Newcastle, NSW, Australia; Schizophrenia Research Institute, Darlinghurst, NSW, Australia; Hunter Medical Research Institute, Newcastle, NSW, Australia.
2
Priority Centre for Translational Neuroscience and Mental Health Research, University of Newcastle, Newcastle, NSW, Australia; Schizophrenia Research Institute, Darlinghurst, NSW, Australia; Hunter Medical Research Institute, Newcastle, NSW, Australia; School of Medicine and Public Health, University of Newcastle, Callaghan, NSW, Australia.
3
School of Psychology, University of Newcastle, Callaghan, NSW, Australia; Priority Centre for Translational Neuroscience and Mental Health Research, University of Newcastle, Newcastle, NSW, Australia; Hunter Medical Research Institute, Newcastle, NSW, Australia.
4
School of Psychology, University of Newcastle, Callaghan, NSW, Australia; Priority Centre for Translational Neuroscience and Mental Health Research, University of Newcastle, Newcastle, NSW, Australia; Schizophrenia Research Institute, Darlinghurst, NSW, Australia.
5
Department of Psychology, University of Jyvaskyla, Jyvaskyla, Finland.
6
School of Psychiatry, Faculty of Medicine, University of New South Wales, Sydney, NSW, Australia; Neuroscience Research Australia, Randwick, NSW, Australia.

Abstract

Mismatch negativity (MMN) is a scalp-recorded electrical potential that occurs in humans in response to an auditory stimulus that defies previously established patterns of regularity. MMN amplitude is reduced in people with schizophrenia. In this study, we aimed to develop a robust and replicable rat model of MMN, as a platform for a more thorough understanding of the neurobiology underlying MMN. One of the major concerns for animal models of MMN is whether the rodent brain is capable of producing a human-like MMN, which is not a consequence of neural adaptation to repetitive stimuli. We therefore tested several methods that have been used to control for adaptation and differential exogenous responses to stimuli within the oddball paradigm. Epidural electroencephalographic electrodes were surgically implanted over different cortical locations in adult rats. Encephalographic data were recorded using wireless telemetry while the freely-moving rats were presented with auditory oddball stimuli to assess mismatch responses. Three control sequences were utilized: the flip-flop control was used to control for differential responses to the physical characteristics of standards and deviants; the many standards control was used to control for differential adaptation, as was the cascade control. Both adaptation and adaptation-independent deviance detection were observed for high frequency (pitch), but not low frequency deviants. In addition, the many standards control method was found to be the optimal method for observing both adaptation effects and adaptation-independent mismatch responses in rats. Inconclusive results arose from the cascade control design as it is not yet clear whether rats can encode the complex pattern present in the control sequence. These data contribute to a growing body of evidence supporting the hypothesis that rat brain is indeed capable of exhibiting human-like MMN, and that the rat model is a viable platform for the further investigation of the MMN and its associated neurobiology.

PMID:
25333698
PMCID:
PMC4205004
DOI:
10.1371/journal.pone.0110892
[Indexed for MEDLINE]
Free PMC Article

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