GABA IN THE OLFACTORY BULB: NEUROCHEMICAL STUDIES

嗅球中的 GABA：神经化学研究

• 批准号: 3398915
• 负责人: MICHAEL R QUINN
• 金额: $ 7.86万
• 依托单位: INSTITUTE FOR BASIC RES IN DEV DISABIL
• 依托单位国家: 美国
• 财政年份: 1982
• 资助国家: 美国
• 起止时间: 1982-02-01 至 1988-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3398915
• 关键词: benzodiazepines; cerebellar Purkinje cell; chemical binding; dendrites; experimental brain lesion; gamma aminobutyrate; glutamates; neural information processing; neurochemistry; neuropharmacology; neurotransmitter metabolism; olfactions; olfactory lobe; radioassay; sensory feedback; stereotaxic techniques; synapses; synaptosomes

Dendrodendritic synapses are the major means of horizontal neuronal connectivity within the olfactory bulb. The specific aims of this proposal are to determine the neurochemical mechanisms utilized by these synapses for processing olfactory sensory information. Accomplishment of the specific aims will help clarify the physiological role of dendrodendritic synapses in olfaction and may be relevant to understanding information processing in other sensory systems. GABA is considered an inhibitory neurotransmitter of granule cells at dendrodendritic synapses with neurochemical evidence provided by the laboratory of the investigator. The proposed experiments will detemrine which additional neurotransmitter systems are involved at these synapses by using high-affinity uptake (presynaptic marker) and receptor binding (postsynaptic) techniques. These biochemical neurotransmitter properties will be characterized kinetically and pharmacologically. The neuronal localization of these synaptic processes will be established by electrolytic lesions of the lateral olfactory tract, by intrabulbar kainic acid induced lesions, and by using the murine neurological mutant, Purkinje cell degeneration. The regulatory influences of dendrodendritic neurotransmitters on the presynaptic release, high-affinity uptake and on the postsynaptic receptor binding of GABA will be determined using dendrodendritic synaptosomes (DDS). Preliminary experiments suggest that the mitral cells use glutamate as an excitatory neurotransmitter and have a clonazepam-sensitive benzodiazepine binding site that is functionally associated with the GABA postsynaptic receptor. Initial studies also suggest that GABA efflux from DDS is stimulated by potassium. GABA and glutamate are considered the major inhibitory and excitatory neurotransmitters of the mammalian central nervous system, respectively. Aberrations in these neurotransmitter systems are implicated in such neurological disorders as Huntington's chorea, epilepsy, olivopontocerebellar atrophy, and Parkinson's disease. Since the olfactory bulb is such a rich source of synapses utilizing both GABA and glutamate, it has the potential of serving as a model for these neurotransmitter systems in general.

树-树突触是神经元水平传递的主要方式 嗅球内的连通性。 本提案的具体目标 是为了确定这些突触的神经化学机制 来处理嗅觉信息。 人文社会科学教育 具体的目标将有助于阐明树突状细胞的生理作用 嗅觉中的突触，可能与理解信息有关 在其他感官系统中进行处理。 GABA被认为是颗粒细胞的抑制性神经递质， 树-树突触与神经化学证据提供的 研究者的实验室。 拟议的实验将确定 哪些额外的神经递质系统参与了这些突触， 使用高亲和力摄取（突触前标记）和受体结合 （突触后）技术。 这些生化神经递质的特性 将在动力学和动力学上表征。 神经元 这些突触过程的定位将通过 外侧嗅束的电解损伤，球内卡因尼克 酸诱导的病变，并通过使用鼠神经突变，浦肯野 细胞退化 树突状细胞的调节作用 神经递质对突触前释放，高亲和力摄取和 GABA的突触后受体结合将使用 树-树突触体（DDS）。 初步实验表明， 二尖瓣细胞使用谷氨酸作为兴奋性神经递质，并具有 氯硝西泮敏感的苯二氮卓类结合位点， 与GABA突触后受体相关。 初步研究还 提示钾刺激GABA从DDS流出。 GABA和谷氨酸被认为是主要的抑制和兴奋 哺乳动物中枢神经系统的神经递质，分别。 这些神经递质系统中的畸变与这种 神经系统疾病如亨廷顿舞蹈病、癫痫、 橄榄体脑桥小脑萎缩和帕金森病。 由于嗅觉 灯泡是利用GABA和谷氨酸的突触的丰富来源， 它有可能作为这些神经递质的模型， 系统一般。