Synaptic Organization of the Auditory System

听觉系统的突触组织

• 批准号: 7879989
• 负责人: DOUGLAS L OLIVER
• 金额: $ 44.4万
• 依托单位: UNIVERSITY OF CONNECTICUT SCH OF MED/DNT
• 依托单位国家: 美国
• 财政年份: 1982
• 资助国家: 美国
• 起止时间: 1982-04-01 至 2014-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7879989
• 关键词: Auditory; Auditory Physiology; Auditory area; Auditory system; Axon; Axonal Transport; Axosomatic Synapse; Bilateral; Brain; Brain Stem; Brain region; Cell Nucleus; Cerebral cortex; Cochlear nucleus; Complex; Dendrites; Ear; Excision; Excitatory Synapse; Gap Junctions; Glutamates; Goals; Grant; Green Fluorescent Proteins; Hearing; Implant; In Situ Hybridization; Inferior Colliculus; Lateral lemniscus; Maps; Medial geniculate body; Membrane; Microanatomy; Midbrain structure; Morphology; Mus; Nerve; Neurons; Oryctolagus cuniculus; Output; Pathology; Pathway interactions; Patients; Pattern; Preparation; Process; Progress Reports; Property; Site; Slice; Source; Stroke; Structure; Synapses; Synaptic Vesicles; Testing; Thalamic structure; Transgenic Mice; Travel; audiogenic seizure; auditory pathway; base; computerized data processing; deafness; excitatory neuron; hearing impairment; neuronal cell body; relating to nervous system; research study; response; segregation; sound; synaptic function; tumor

DESCRIPTION (provided by applicant): The general goal of this project is to understand how information about sound is processed by the brain. The inferior colliculus (IC) is the main auditory structure in the midbrain. All information about sound must pass through the IC as it travels from the ear to the cerebral cortex. This project continues our effort to understand the cellular basis for function of the IC. Despite numerous studies, far too little is known about how microanatomy, neuronal specializations, and synaptic organization underlie auditory processing in the IC. There are two very different types of excitatory input on neurons in the IC. We have discovered that specialized "calyx-like" axosomatic synapses occur on the large GABAergic neurons in IC. These synapses contain VGLUT2, a molecule that loads the transmitter glutamate into synaptic vesicles. These excitatory synapses are absent on excitatory neurons or smaller GABAergic neurons where dendritic excitatory synapses predominate. Two basic circuits in the IC are proposed. In one, large GABAergic IC neurons receive a dense, excitatory synaptic input on the cell body and proximal dendrites. The other circuit has smaller glutamatergic and GABAergic IC neurons with glutamatergic inputs only on dendrites. GABAergic neurons in IC are studied in two experiments. We will show: (1) the large GABAergic neurons project exclusively to the thalamus; (2) the GABAergic neurons with and without calyx-like inputs will differ in their firing patterns and intrinsic membrane properties. Excitatory inputs to IC are studied in experiments to reveal the structure and function of the VGLUT2 calyx-like input to the large GABAergic IC neurons (circuit 1). We will show: (3) segregated auditory brainstem neurons expressing VGLUT1 or VGLUT2 that project to IC; (4) VGLUT2 axosomatic synapse originates from a single source in the auditory brainstem, and that this specialized synapse comes from a single axon; and (5) the VGLUT2 axosomatic synapses on GABAergic neurons differ from other glutamate synapses in IC. Brain circuitry in the IC is notable because the IC receives both inhibitory and excitatory inputs from the lower auditory brainstem. The excitatory inputs to the IC are segregated into functional zones, but it is not clear if inhibitory inputs also follow the same pattern. Here, in experiment 6, we will use auditory physiology with an unanesthetized rabbit preparation to relate the patterns of inhibitory input to neural responses in the IC. We will specifically test the hypothesis that the ICc domains have different patterns of inhibitory inputs. The inferior colliculus is important for normal hearing since it is a major part of the central auditory pathway and neurons from the auditory cortex to the cochlear nucleus send direct connections to the inferior colliculus. Pathology such as stroke or tumor in the inferior colliculus may contribute to deafness, hearing loss, or audiogenic seizures. The inferior colliculus is now the site of auditory midbrain implants to electrically stimulate the central auditory pathway in patients after surgical removal of the eighth nerve.

描述（由申请人提供）：该项目的一般目标是了解大脑如何处理有关声音的信息。下丘（IC）是中脑的主要听觉结构。有关声音的所有信息都必须通过IC从耳朵到大脑皮层时通过IC。该项目继续我们努力了解IC功能的细胞基础。尽管进行了许多研究，但对微观解剖学，神经元专业和突触组织的了解得多的知之甚少。 IC中神经元的两种截然不同的兴奋性输入类型。我们发现，在IC中的大型GABA能神经元上出现了专门的“花萼状”轴突突触。这些突触含有VGLUT2，这是一种将发射机谷氨酸加载到突触囊泡中的分子。这些兴奋性突触不存在于兴奋性神经元或较小的GABA能神经元中，而树突状兴奋性突触占主导地位。提出了IC中的两个基本电路。一方面，大的GABA能神经元在细胞体和近端树突上获得致密的兴奋性突触输入。另一个电路具有较小的谷氨酸能和GABA能IC神经元，仅在树突上输入谷氨酸能。在两个实验中研究了IC中的GABA能神经元。我们将显示：（1）专门针对丘脑的大型GABA能神经元项目； （2）具有和没有花萼样输入的GABA能神经元在发射模式和内在膜特性上会有所不同。在实验中研究了对IC的兴奋性输入，以揭示vglut2花萼状输入对大型GABA能IC神经元的结构和功能（电路1）。我们将显示：（3）隔离听觉的脑干神经元，表达vglut1或vglut2将其投影到IC； （4）VGLUT2轴突突触源自听觉脑干中的单个来源，并且该专门的突触来自单个轴突； （5）GABA能神经元上的VGLUT2轴突突触与IC中其他谷氨酸突触不同。 IC中的脑电路是值得注意的，因为IC从低听觉脑干中同时接收抑制性和兴奋性输入。将IC的兴奋性输入隔离为功能区域，但尚不清楚抑制输入是否也遵循相同的模式。在这里，在实验6中，我们将使用带有未经麻醉的兔子准备的听觉生理学，以将抑制性输入的模式与IC中的神经反应相关联。我们将特别检验以下假设：ICC域具有不同的抑制输入模式。下丘对于正常听力很重要，因为它是中央听觉途径的主要部分，而从听觉皮层到耳蜗核的神经元的神经元则直接连接到下丘。诸如下丘中的中风或肿瘤之类的病理可能导致耳聋，听力丧失或听力性癫痫发作。现在，下丘丘是听觉中脑植入物的部位，可在手术去除第八神经后电气刺激患者的中央听觉途径。