Resubmission of Functional approach to communication sound processing in mouse auditory cortex

项目摘要 声音交流对于包括人类在内的许多物种的正常社会互动至关重要，然而- 沟通功能和功能障碍的社会方面往往被忽视，在研究大脑如何重新 能够感知和学习交流的声音。一个关键的大脑机制涉及大脑中的神经可塑性， 听觉皮层支持学习新的交流声音的社会意义。然而，我们的电路和 细胞水平上对这种可塑性的理解更多的是基于对声音的显著性的研究 通过非社会强化程序，而不是通过奖励社会互动。因此有 我们对沟通、声音处理和可塑性的神经原理的认识存在差距， 现实社会听觉学习我们的长期目标是了解电路和细胞机制下- 说谎的听觉系统的编码的社会学习的声音类别，因此，导致潜在的缺陷， 可以推断通信处理。我们的目标是揭示社会学习一个声音 类别改变高阶听觉皮层场的神经元调谐和对声学变化的耐受性， 类别的声音特征。我们的中心假设是，核心听觉皮层和次级听觉皮层- 音频场A2本质上被调谐到描述声音的复频率轨迹的参数， 在这些参数中表现出更大容差的次级场中的电子。学习a的社会意义 然后，特定的声音类别使神经元沿着通过Core和A2的前馈通路偏置， 与所学类别的可能参数相协调。我们调查这一假设，利用产妇 幼鼠和成年雌性之间的超声波交流的小鼠模型。当小狗的叫声变成了行为- 与母亲相关的是，听觉皮层中的神经元以意想不到的方式改变了它们的反应方式。 从非社会性听觉学习范式。该建议解决了两个潜在的神经机制 明确的目标。首先，使用细胞外电生理学，我们将确定如何从神经转化 核心到A2改变神经元调谐和容忍的声学特征的幼崽呼叫类别。二是利用 一种新的社会强化听觉训练范式，我们将确定如何校准，明确的社会经验， 新的声音类别修改了Core到A2的神经转换。本研究的意义在于 其独特的能力，以弥合科学之间的差距感官和社会/行为神经科学的动物 一个模型，在该模型中，可以从系统向下进行高级听觉功能（交流）的研究 到分子水平。

PROJECT SUMMARY Acoustic communication is critical for normal social interactions in many species, including humans, yet so- cial aspects of communication functions and dysfunctions are often overlooked in studies of how the brain re- sponds to and learns communication sounds. One key brain mechanism concerns the neural plasticity within the auditory cortex to support learning the social meaning of new communication sounds. However, our circuit and cellular level understanding of such plasticity is more often based on studies where a sound's salience is acquired through nonsocial reinforcement procedures, rather than from rewarding social interactions. Hence, there is a gap in our knowledge of the neural principles for communication sound processing and plasticity during more realistic social auditory learning. Our long-term goal is to understand the circuit and cellular mechanisms under- lying the auditory system's encoding of socially-learned sound categories, so that causes underlying deficits in communication processing can be inferred. Our objective here is to uncover whether socially learning a sound category alters higher-order auditory cortical fields' neuronal tuning and tolerance for acoustic variability in that category's sound features. Our central hypothesis is that both Core auditory cortex and secondary auditory cor- tical field A2 are intrinsically tuned to parameters describing complex frequency trajectories of sounds, with neu- rons in a secondary field exhibiting greater tolerance in these parameters. Learning the social meaning of a specific sound category then biases neurons along a feedforward pathway through Core and A2 to become more attuned to the likely parameters of the learned category. We investigate this hypothesis by exploiting a maternal mouse model of ultrasonic communication between pups and adult females. When pup calls become behavior- ally relevant to mothers, neurons in the auditory cortex changes how they respond in ways that were not expected from nonsocial auditory learning paradigms. This proposal addresses the underlying neural mechanisms in two specific aims. First, using extracellular electrophysiology, we will determine how the neural transformation from Core to A2 alters neuronal tuning and tolerance for the acoustic features of the pup call category. Second, using a new socially-reinforced auditory training paradigm, we will determine how calibrated, explicit social experience with a novel sound category modifies the Core to A2 neural transformation. This research's significance lies in its unique ability to bridge the scientific gap between sensory and social/behavioral neuroscience in an animal model in which studies of a high level auditory function (communication) can be conducted from a systems down to a molecular level.