Smart Caitlin, Mitchell Anna, McCutcheon Fiona, Medcalf Robert L, Thiele Alexander
Molecular Neurotrauma and Haemostasis, Australian Centre for Blood Diseases, Central Clinical School, Monash University, Melbourne, VIC 3004, Australia.
Biosciences Institute, Newcastle University, Newcastle upon Tyne NE1 7RU, UK.
iScience. 2023 Jan 7;26(2):105947. doi: 10.1016/j.isci.2023.105947. eCollection 2023 Feb 17.
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.
组织型纤溶酶原激活剂（tPA）是一种丝氨酸蛋白酶，在大脑的各个区域均有表达。它参与神经元可塑性、学习与记忆以及成瘾过程。我们评估了外源性应用的tPA是否会影响小鼠听觉皮层内的神经可塑性。我们采用频率配对范式来确定在配对方案后神经元的最佳频率是否发生偏移。给予tPA显著影响了配对后的最佳频率，这取决于配对频率相对于最佳频率的情况。当配对频率高于最佳频率时，tPA导致最佳频率向远离条件频率的方向偏移。tPA显著拓宽了听觉调谐曲线。我们的数据表明，听觉皮层内蛋白水解活性的区域变化调节了听觉神经元的精细调谐，支持tPA作为神经元可塑性调节剂的功能。
