Mismatch Responses in the Awake Rat: Evidence from Epidural Recordings of Auditory Cortical Fields

Fabienne Jung,Heike Endepols,Rudolf Graf,Marc Tittgemeyer,Klaas Enno Stephan,Markus Gramer,Heiko Backes,Rosalyn Moran,Tetsuya Kumagai,Manuel S Malmierca

doi:10.1371/journal.pone.0063203

Abstract

Detecting sudden environmental changes is crucial for the survival of humans and animals. In the human auditory system the mismatch negativity (MMN), a component of auditory evoked potentials (AEPs), reflects the violation of predictable stimulus regularities, established by the previous auditory sequence. Given the considerable potentiality of the MMN for clinical applications, establishing valid animal models that allow for detailed investigation of its neurophysiological mechanisms is important. Rodent studies, so far almost exclusively under anesthesia, have not provided decisive evidence whether an MMN analogue exists in rats. This may be due to several factors, including the effect of anesthesia. We therefore used epidural recordings in awake black hooded rats, from two auditory cortical areas in both hemispheres, and with bandpass filtered noise stimuli that were optimized in frequency and duration for eliciting MMN in rats. Using a classical oddball paradigm with frequency deviants, we detected mismatch responses at all four electrodes in primary and secondary auditory cortex, with morphological and functional properties similar to those known in humans, i.e., large amplitude biphasic differences that increased in amplitude with decreasing deviant probability. These mismatch responses significantly diminished in a control condition that removed the predictive context while controlling for presentation rate of the deviants. While our present study does not allow for disambiguating precisely the relative contribution of adaptation and prediction error processing to the observed mismatch responses, it demonstrates that MMN-like potentials can be obtained in awake and unrestrained rats.

Highlights

IntroductionFast and automatic detection of sudden changes is crucial for the survival of any animal
In a volatile environment, fast and automatic detection of sudden changes is crucial for the survival of any animal
The mismatch negativity (MMN) has classically been defined as a component of auditory evoked potentials (AEPs) that is elicited by unexpected stimuli (‘‘oddballs’’ or ‘‘deviants’’) occurring within a stream of homogeneous and predictable sounds (‘‘standards’’) [1]

Summary

Introduction

Fast and automatic detection of sudden changes is crucial for the survival of any animal. This is a predictive coding framework in which the MMN reflects a prediction error dependent updating of a hierarchical model that infers the causes of sensory stimuli and predicts future inputs [12,13] In this theory of MMN generation, model adjustment corresponds to prediction error dependent synaptic plasticity of connections between hierarchically related regions (such as primary and secondary auditory cortex), and adaptation serves to balance the postsynaptic sensitivity to topdown predictions and bottom-up stimulus information, respectively. Adaptation-like mechanisms may act locally in the auditory cortex and modulate how ascending fibers transmit prediction error to higher cortical levels and how descending connections provide contextual guidance to lower levels (i.e., transmit predictions) In this view, the MMN represents a failure to predict bottom-up inputs and suppress prediction error [11,14]

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