Journal of Neuroscience Methods | 2019
Double-epoch subtraction reveals long-latency mismatch response in urethane-anaesthetized mice
Abstract
BACKGROUND\nAnaesthetized rodents are examined for their capacity to model human mismatch negativity (MMN). In the present study, oddball and deviant-alone control paradigms, with stimuli varying in frequency (ascending and descending) and intensity (louder and quieter), were presented to anaesthetized mice to determine whether they elicit a translational mismatch response (MMR).\n\n\nNEW METHOD\nResulting waveforms displayed long-latency (>200\u2009ms post-stimulus) components, only made fully visible from oddball paradigm data by applying a double-epoch subtraction. In this approach, an extended epoch containing two consecutive standard evoked responses was subtracted from the response to an oddball followed by a standard (i.e. oddball:standard - standard:standard).\n\n\nRESULTS\nThe trailing standard responses effectively cancelled each other out, revealing biphasic long-latency components. These MMR waveforms correlated strongly with deviant-alone paradigm evoked potentials >200\u2009ms post-stimulus, potentially indicative of shared underlying mechanisms. Interestingly, these components were absent from the quieter oddball MMR.\n\n\nCOMPARISON WITH EXISTING METHOD(S)\nClassical mismatch negativity computation is incapable of fully characterizing the long-latency biphasic response observed from this study, due to the inbuilt constraint of a single stimulus epoch. These results also suggest that the deviant-alone paradigm may be considered akin to a positive control for sensory-memory disruption, widely thought to be at the root of MMN generation in humans.\n\n\nCONCLUSIONS\nLong-latency auditory evoked potential components are observed from anaesthetized mice in response to frequency and increasing intensity oddball stimuli. These display some congruencies with human MMN.