Auditory Information Processing in the Amygdala

杏仁核的听觉信息处理

• 批准号: 10186458
• 负责人: Alexander Galazyuk
• 金额: $ 59.03万
• 依托单位: NORTHEAST OHIO MEDICAL UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1990
• 资助国家: 美国
• 起止时间: 1990-12-01 至 2023-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10186458
• 关键词: AMPA Receptors; Acoustics; Affect; Agonist; Amygdaloid structure; Animal Model; Auditory; Auditory area; Behavior; Behavioral; Brain region; Cholinergic Receptors; Communication; Data; Disease; Disease model; Elements; Emotional; Functional disorder; GABA Receptor; Glutamate Receptor; Glutamates; Goals; Hearing; Medial geniculate body; Mediating; Methods; Mood Disorders; Mouse Strains; Muscarinic Acetylcholine Receptor; N-Methyl-D-Aspartate Receptors; Neuromodulator; Neurons; Neurotransmitters; Pathway interactions; Pattern; Pharmaceutical Preparations; Physiological; Play; Positive Valence; Post-Traumatic Stress Disorders; Process; Resistance; Role; Schizophrenia; Shapes; Signal Transduction; Speech; Speech Sound; Stimulus; Structure; Synapses; System; Testing; Thalamic structure; Therapeutic; Tinnitus; Ultrasonics; Work; auditory processing; auditory thalamus; autism spectrum disorder; basal forebrain; base; cholinergic; experimental study; improved; information processing; neuromechanism; neuroregulation; normal hearing; optogenetics; postsynaptic; receptor; response; showing emotion; social; sound; transmission process; vocalization

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.

项目摘要 这项工作的长期目标是提高对声学基础的神经机制的理解 沟通。我们的前提是，杏仁核是与情感表达相关的大脑区域 在此过程中的关键作用。杏仁核“决定”声信号是显着还是显着，并且 它的价是基于声音序列的上下文信息为正还是负面的，其他 感觉，听众的内部状态。 Amygdala策划了适当的情感反应 对于收到的声音交流信号及其上下文。此外，杏仁核调节 通过其直接和间接项目对听觉皮层和其他听觉的直接和间接项目的响应能力 结构。换句话说，杏仁核很可能会影响我们听到和回应社会发声的方式。 我们的中心假设是基底外侧杏仁核（BLA）接收有关所有类型社会的信息 发声以及BLA中的机制提供了一定时刻的评估 这些基于周围环境的社会信号。该评估由高度选择性表示 大多数BLA神经元对上下文厌恶的人声刺激的反应以及与上下文相关的临时性 响应模式。我们假设该评估取决于兴奋性听觉输入的整合 具有GABA能抑制和神经调节输入。我们将检查基础的选择性，临时性 响应模式以及四个特定目的的上下文调制。首先，我们将使用细胞内记录 检查BLA中对声乐刺激的子阈值和上端的反应。第二，我们将检查 使用光遗传学的听觉皮质和丘脑输入对杏仁核神经元反应的贡献 分别灭活这些输入的方法。在最后两个目标中，我们将结合本地应用 具有单神经元记录的药物，以检查介导谷氨酸能的受体的贡献 兴奋和GABA能抑制，以及可能传达的胆碱能调节的接收器 与收到的社会发声相关的上下文信息。我们将使用普通的听力鼠标 菌株，CBA/CAJ，具有充分理解的声学通信系统。 这些具体目标提供了一种相互联系的方法来了解在内部作用的机制 基底外侧杏仁核有助于分析社会发声中的意义。这些机制是 在声学交流中很重要，因为杏仁核与导致改变的疾病有关 对言语的情感反应，例如精神分裂症，自闭症和某些形式的创伤后压力 紊乱。此外，这些研究将评估与影响治疗药物有关的机制 杏仁核中的谷氨酸能，GABA能和胆碱能传播。