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Mismatch negativity (MMN) in freely-moving rats with several experimental controls
Lauren Harms1, W Ross Fulham2, Juanita Todd1
1School 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.
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.
Insights
Researchers developed a rat model for mismatch negativity (MMN), an auditory processing response. This model shows promise for studying schizophrenia and the neurobiology of MMN in humans.
Area of Science:
- Neuroscience
- Auditory Perception
- Animal Models
Background:
- Mismatch negativity (MMN) is a human auditory evoked potential reflecting pattern change detection.
- Reduced MMN amplitude is observed in schizophrenia, necessitating animal models for deeper neurobiological study.
- Validating MMN in rodent models requires controlling for neural adaptation and stimulus-specific responses.
Purpose of the Study:
- To establish a robust and replicable rat model of MMN.
- To investigate the neurobiological underpinnings of MMN.
- To determine if rodent brains can generate human-like MMN independent of adaptation.
Main Methods:
- Surgical implantation of epidural electroencephalographic electrodes in adult rats.
- Recording of electroencephalographic data using wireless telemetry in freely-moving rats.
- Utilizing oddball auditory stimuli with flip-flop, many standards, and cascade control sequences to assess mismatch responses and control for adaptation.
Main Results:
- Both adaptation and adaptation-independent deviance detection were observed for high-frequency (pitch) deviants, but not low-frequency deviants.
- The 'many standards' control method proved optimal for observing adaptation and adaptation-independent mismatch responses in rats.
- The 'cascade' control yielded inconclusive results regarding complex pattern encoding in rats.
Conclusions:
- The rat brain is capable of exhibiting human-like MMN.
- The developed rat model provides a viable platform for further investigation into MMN and its neurobiology.
- This research supports the use of rat models for studying auditory processing deficits relevant to conditions like schizophrenia.
