Neuronal ensembles during development of tonotopic maps in the auditory systems

梯形体内侧核（medial nucleus of The梯形体，MNTB）通过向哺乳动物脑干中的听觉神经元传递快速而精确的突触抑制，在声音定位中起着关键作用。先前的研究表明，活动依赖机制参与了早期发育过程中听觉通路的完善。然而，一个仍然令人困惑的基本问题涉及到活动的性质，因为细化在听力开始之前就开始了。我们已经确定，在听力发作之前，自发性突发放电是自发性脑电活动的主要形式。本提案的主要目标是使用创新的电生理和成像技术来确定MNTB体内活动依赖性发育的细胞和突触机制。在第一个目标中，我们将研究爆发活动背后的机制。使用电生理技术，我们将测试不同类型的突触在爆发活动中的作用。例如，我们预测突触传递拮抗剂将在出生后早期发育期间阻断破裂活动。在进一步的电生理和免疫染色实验中，我们将研究电压激活电导Ih的发育特性和作用，这可能涉及到MNTB细胞电特性的微调及其对突触刺激的反应。在第二个目标中，我们将使用双光子钙成像来测量听力前大鼠MNTB中细胞群的活性。我们将通过电生理学实验验证这一方法，并描述自发性集合活动的空间和时间特性，以及这些模式在出生后发育过程中如何变化。最后，在第三个目标中，与dr。Peqa， Tchernikovsky和Smotherman我们将使用第一个和第二个目标中描述的类似方法，结合声音刺激来确定MNTB合奏对简单和复杂声音的响应。通过控制声音刺激的频谱内容，我们将研究哺乳动物脑干短期适应的能力和局限性。

DESCRIPTION (provided by applicant): PROJECT SUMMARY The medial nucleus of the trapezoid body (MNTB) plays a key role in sound localization by delivering fast and precise synaptic inhibition to auditory neurons in the mammalian brainstem. Previous studies indicate that activity-dependent mechanisms are involved in the refinement of this auditory pathway during early development. However, a fundamental issue that remains puzzling concerns the nature of the activity, since the refinement begins before the onset of hearing. We have identified spontaneous burst firing as the major form of spontaneous electrical activity before hearing onset. The major goal of this proposal is to use innovative electrophysiological and imaging techniques to determine the cellular and synaptic mechanisms of activity-dependent development in the MNTB in vivo. In the first aim, we will study the mechanisms that underlie bursting activity. Using electrophysiological techniques we will test the role of different types of synapses in bursting activity. For example, we predict that antagonists of synaptic transmission will block bursting activity during early postnatal development. In additional electrophysiological and immunostaining experiments we will study the developmental properties and roles of the voltage-activated conductance Ih, which could be involved in the fine tuning of electrical properties of MNTB cells and their responses to synaptic stimulation. In the second aim we will use two-photon calcium imaging to measure the activity of cellular ensembles in the MNTB of prehearing rats. We will validate this approach with electrophysiology experiments and will describe the spatial and temporal properties of the spontaneous ensemble activity, and how these patterns change during postnatal development. Finally, in the third aim, and in collaboration with Drs. Peqa, Tchernikovsky and Smotherman we will use similar methods described in the first and second aims in combination with sound stimulation to determine the responses of MNTB ensembles to simple and complex sounds. By manipulating the spectral content of sound stimuli we will study the capacity and limitations for short-term adaptation in the mammalian brainstem.