Pittsburgh Hearing Research Center and Department of Otolaryngology, University of Pittsburgh, Pittsburgh, Pennsylvania 15261 and.
The Third Xiangya Hospital, Central South University, Changsha, China 410013.
J Neurosci. 2019 Jan 30;39(5):854-865. doi: 10.1523/JNEUROSCI.1339-18.2018. Epub 2018 Nov 30.
Neurons in the auditory cortex are tuned to specific ranges of sound frequencies. Although the cellular and network mechanisms underlying neuronal sound frequency selectivity are well studied and reflect the interplay of thalamocortical and intracortical excitatory inputs and further refinement by cortical inhibition, the precise synaptic signaling mechanisms remain less understood. To gain further understanding on these mechanisms and their effects on sound-driven behavior, we used imaging as well as behavioral approaches in awake and behaving female and male mice. We discovered that synaptic zinc, a modulator of neurotransmission and responsiveness to sound, sharpened the sound frequency tuning of principal and parvalbumin-expressing neurons and widened the sound frequency tuning of somatostatin-expressing inhibitory neurons in layer 2/3 of the primary auditory cortex. In the absence of cortical synaptic zinc, mice exhibited reduced acuity for detecting changes in sound frequencies. Together, our results reveal that cell-type-specific effects of zinc contribute to cortical sound frequency tuning and enhance acuity for sound frequency discrimination. Neuronal tuning to specific features of sensory stimuli is a fundamental property of cortical sensory processing that advantageously supports behavior. Despite the established roles of synaptic thalamocortical and intracortical excitation and inhibition in cortical tuning, the precise synaptic signaling mechanisms remain unknown. Here, we investigated these mechanisms in the mouse auditory cortex. We discovered a previously unknown signaling mechanism linking synaptic zinc signaling with cell-specific cortical tuning and enhancement in sound frequency discrimination acuity. Given the abundance of synaptic zinc in all sensory cortices, this newly discovered interaction between synaptic zinc and cortical tuning can provide a general mechanism for modulating neuronal stimulus specificity and sensory-driven behavior.
听觉皮层中的神经元对特定频率范围的声音具有选择性。尽管支持神经元声音频率选择性的细胞和网络机制已经得到了很好的研究，并反映了丘脑皮质和皮质内兴奋性输入的相互作用，以及皮质抑制的进一步细化，但精确的突触信号传递机制仍知之甚少。为了进一步了解这些机制及其对声音驱动行为的影响，我们在清醒和行为的雌性和雄性小鼠中使用了成像和行为方法。我们发现，突触锌（一种神经递质传递和对声音反应性的调节剂）可以锐化主要和表达 parvalbumin 的神经元的声音频率调谐，并拓宽初级听觉皮层 2/3 层中表达 somatostatin 的抑制性神经元的声音频率调谐。在没有皮质突触锌的情况下，小鼠对声音频率变化的检测能力降低。总的来说，我们的结果表明，锌对不同细胞类型的影响有助于皮质声音频率调谐，并提高声音频率辨别能力。神经元对感觉刺激特定特征的调谐是皮质感觉处理的基本特性，有利于行为。尽管已经确定了突触丘脑皮质和皮质内兴奋和抑制在皮质调谐中的作用，但精确的突触信号传递机制仍然未知。在这里，我们在小鼠听觉皮层中研究了这些机制。我们发现了一种以前未知的信号机制，将突触锌信号与细胞特异性皮质调谐以及声音频率辨别锐度的提高联系起来。鉴于突触锌在所有感觉皮层中的丰富存在，这种新发现的突触锌与皮质调谐之间的相互作用可以为调节神经元刺激特异性和感觉驱动行为提供一种通用机制。
