Cholinergic modulation incorporated with a tone presentation induces frequency-specific threshold decreases in the auditory cortex of the mouse.

Learning-induced or experience-dependent auditory cortical plasticity has often been characterized by frequency-specificity. Studies have revealed the critical role of the cholinergic basal forebrain and acoustic guidance. Cholinergic facilitation of specific thalamocortical inputs potentially determines such frequency-specificity but this issue requires further clarification. To examine the cholinergic effects on thalamocortical circuitry of specific frequency channels, we recorded the responses of cortical neurons while pairing basal forebrain activation or acetylcholine (ACh) microiontophoresis with tone presentations at 10 dB below the neuronal response threshold. We found that both basal forebrain activation and acetylcholine microiontophoresis paired with a tone induced a significant decrease in response threshold of the recorded cortical neurons to the frequency of the paired tone, and that this threshold decrease could be eliminated by atropine microiontophoresis. Our data suggest that cortical acetylcholine specifically facilitates thalamocortical circuitry tuned to the frequency of a presented tone; it is the first, fundamental step towards frequency-specific cortical plasticity evoked by auditory learning and experience.