Auditory Information Processing in the Amygdala

项目摘要 这项工作的长期目标是提高对声学基础神经机制的理解 通信我们的前提是，杏仁核，一个与情绪表达有关的大脑区域， 在这一过程中发挥着关键作用。杏仁核“决定”一个声音信号是否重要或突出， 基于来自声音序列的上下文信息，其效价是正的还是负的， 感觉，以及听者的内心状态。杏仁核协调适当的情绪反应 用于所接收的语音通信信号及其上下文。此外，杏仁核调节 通过直接和间接投射到听觉皮层和其他听觉器官， 结构.换句话说，杏仁核可能会影响我们如何听到和回应社交声音。 我们的中心假设是，基底外侧杏仁核（BLA）接收有关所有类型的社会信息。 发声，BLA内的机制提供了对发声的意义的每时每刻的评估， 这些社会信号基于周围的环境。这种评价是由高度选择性的 大多数BLA神经元对背景厌恶性声音刺激的反应和背景依赖性时间刺激的反应 回应的模式。我们假设这种评估依赖于兴奋性听觉输入的整合 GABA能抑制和神经调节输入。我们将研究选择性的基础，时间 反应模式，和上下文调制的四个具体目标。首先，我们将使用细胞内记录 目的：研究声刺激对BLA阈下和阈上反应的影响。第二，我们将研究 应用光遗传学方法研究听皮层和丘脑输入对杏仁核神经元反应的影响 方法来分别对这些输入中的每一个进行排序。在最后两个目标中，我们将结合联合收割机的本地应用 单神经元记录的药物，以检查受体介导的多巴胺能神经递质的贡献， 兴奋和GABA能抑制，以及胆碱能调节受体，可能传达 与所接收的社交发声相关联的上下文信息。我们将使用一只听力正常的老鼠 应变，CBA/CaJ，有一个很好的理解声学通信系统。 这些具体目标提供了一种相互关联的方法来理解内部的作用机制 基底外侧杏仁核，有助于分析社会发声的意义。这些机制是 杏仁核在声音交流中很重要，因为杏仁核与导致改变的 对言语的情绪反应，如精神分裂症、自闭症和某些形式的创伤后应激 disorder.此外，这些研究将评估与治疗药物影响 杏仁核中的谷氨酸能、GABA能和胆碱能传递。

Project Summary The long-term goal of this work is to improve the understanding of neural mechanisms that underlie acoustic communication. Our premise is that the amygdala, a brain region associated with emotional expression, plays a critical role in this process. The amygdala “decides” whether a vocal signal is significant, or salient, and whether its valence is positive or negative based on contextual information from the vocal sequence, other senses, and the listener's internal state. The amygdala orchestrates emotional responses that are appropriate for the received vocal communication signals and their context. Further, the amygdala modulates responsiveness to vocal signals through its direct and indirect projections to auditory cortex and other auditory structures. In other words, the amygdala is likely to influence how we hear and respond to social vocalizations. Our central hypothesis is that the basolateral amygdala (BLA) receives information about all types of social vocalizations, and that mechanisms within the BLA provide moment-by-moment assessment of the meaning of these social signals based on the surrounding context. This assessment is expressed by highly selective responses of most BLA neurons for contextually aversive vocal stimuli and by context-dependent temporal patterns of response. We hypothesize that this assessment depends on integration of excitatory auditory inputs with GABAergic inhibition and neuromodulatory inputs. We will examine bases for selectivity, temporal response patterns, and contextual modulation in four Specific Aims. First, we will use intracellular recording to examine subthreshold and suprathreshold responses to vocal stimuli in BLA. Second, we will examine the contributions of auditory cortical and thalamic inputs to the responses of amygdalar neurons, using optogenetic methods to separately inactivate each of these inputs. In the final two Aims, we will combine local application of drugs with single neuron recordings to examine the contributions of receptors mediating glutamatergic excitation and GABAergic inhibition, as well as receptors for cholinergic modulation that are likely to convey contextual information associated with the received social vocalizations. We will use a normal hearing mouse strain, CBA/CaJ, that has a well understood acoustic communication system. These Specific Aims provide an interconnected approach to understand the mechanisms acting within the basolateral amygdala that contribute to the analysis of meaning in social vocalizations. These mechanisms are important in acoustic communication because the amygdala is involved in disorders that result in an altered emotional response to speech, such as schizophrenia, autism, and some forms of post-traumatic stress disorder. Furthermore, these studies will assess mechanisms related to therapeutic drugs affecting glutamatergic, GABAergic, and cholinergic transmission in the amygdala.