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

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

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acoustic Stimulation
  • Animals
  • Auditory Cortex / physiology*
  • Electroencephalography
  • Evoked Potentials, Auditory / physiology*
  • Frontal Lobe / physiology*
  • Humans
  • Models, Animal
  • Rats
  • Skull / physiology

Grant support

This project was funded by a National Health and Medical Research Council of Australia Project Grant, ID 1026070. The contents of this article are solely the responsibility of the authors and do not reflect the views of the NHMRC (http://nhmrc.gov.au). Support was received from the University of Newcastle Near Miss grant, CAPEX funding and travel fellowship schemes (http://www.newcastle.edu.au). Further support was provided by the Hunter Medical Research Institute (http://www.hmri.com.au) and the Schizophrenia Research Institute (http://www.schizophreniaresearch.org.au), which are supported by infrastructure funding from NSW Health. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.