Animals can selectively respond to a target sound despite simultaneous distractors, just as humans can respond to one voice at a crowded cocktail party. To investigate the underlying neural mechanisms, we recorded single-unit activity in primary auditory cortex (A1) and medial prefrontal cortex (mPFC) of rats selectively responding to a target sound from a mixture. We found that prestimulus activity in mPFC encoded the selection rule-which sound from the mixture the rat should select. Moreover, electrically disrupting mPFC significantly impaired performance. Surprisingly, prestimulus activity in A1 also encoded selection rule, a cognitive variable typically considered the domain of prefrontal regions. Prestimulus changes correlated with stimulus-evoked changes, but stimulus tuning was not strongly affected. We suggest a model in which anticipatory activation of a specific network of neurons underlies the selection of a sound from a mixture, giving rise to robust and widespread rule encoding in both brain regions.
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