Tissue-type plasminogen activator induces conditioned receptive field plasticity in the mouse auditory cortex

Tissue-type plasminogen activator (tPA) is a serine protease that is expressed in various compartments in the brain. It is involved in neuronal plasticity, learning and memory, and addiction. We evaluated whether tPA, exogenously applied, could influence neuroplasticity within the mouse auditory cortex. We used a frequency-pairing paradigm to determine whether neuronal best frequencies shift following the pairing protocol. tPA administration significantly affected the best frequency after pairing, whereby this depended on the pairing frequency relative to the best frequency. When the pairing frequency was above the best frequency, tPA caused a best frequency shift away from the conditioned frequency. tPA significantly widened auditory tuning curves. Our data indicate that regional changes in proteolytic activity within the auditory cortex modulate the fine-tuning of auditory neurons, supporting the function of tPA as a modulator of neuronal plasticity.