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.

项目概要 这项工作的长期目标是提高对声学基础神经机制的理解 我们的前提是杏仁核（与情绪表达相关的大脑区域）发挥作用。 杏仁核在这个过程中发挥着关键作用，它“决定”声音信号是否重要或显着。 根据声音序列的上下文信息，其价是正还是负，其他 感官和听者的内部状态会协调适当的情绪反应。 此外，杏仁核还对接收到的声音通信信号及其上下文进行调节。 通过直接和间接投射到听觉皮层和其他听觉区域对声音信号的反应 换句话说，杏仁核可能会影响我们听到和回应社交发声的方式。 我们的中心假设是基底外侧杏仁核（BLA）接收有关所有社会类型的信息 发声，并且 BLA 内的机制提供对发声含义的即时评估 这些基于周围环境的社会信号是通过高度选择性来表达的。 大多数 BLA 神经元对情境厌恶的声音刺激和情境依赖的时间反应 我们着迷的是，这种评估取决于兴奋性听觉输入的整合。 通过 GABA 能抑制和神经调节输入，我们将检查选择性、时间性的基础。 反应模式和四个具体目标中的上下文调制首先，我们将使用细胞内记录。 检查 BLA 中对声音刺激的阈下和阈上反应。 使用光遗传学研究听觉皮层和丘脑输入对杏仁核神经元反应的贡献 分别停用每个输入的方法在最后两个目标中，我们将结合本地应用程序。 单神经元记录药物来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受体 与接收到的社交发声相关的上下文信息我们将使用正常听力的鼠标。 菌株，CBA/CaJ，具有众所周知的声学通信系统。 这些具体目标提供了一种相互关联的方法来理解在 基底外侧杏仁核有助于分析社会发声的意义。 在声音交流中很重要，因为杏仁核参与导致声音交流的疾病 对言语的情绪反应，例如精神分裂症、自闭症和某些形式的创伤后应激障碍 此外，这些研究将评估与治疗药物影响相关的机制 杏仁核中的谷氨酸能、GABA能和胆碱能传递。