GABA IN THE OLFACTORY BULB: NEUROCHEMICAL STUDIES

树突触是水平神经元的主要方式 嗅球内的连通性。这项建议的具体目的 是为了确定这些突触利用的神经化学机制 用来处理嗅觉信息。完成了 特定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 调查员的实验室。拟议中的实验将决定 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。这些生化神经递质特性 将被描述为运动学和药理学的特征。神经细胞 这些突触过程的本地化将通过 球内海人藻氨酸引起的侧嗅束电性损伤 酸诱导的损伤，并通过使用小鼠神经突变体Purkinje 细胞退化。树突状细胞的调节作用 神经递质在突触前释放、高亲和力摄取等方面的作用 GABA的突触后受体结合将用 树突状突触体(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 氯硝西潘敏感的苯二氮卓类功能结合位点 与GABA突触后受体有关。初步研究也包括 提示钾可刺激DDS的GABA外流。 GABA和谷氨酸被认为是主要的抑制性和兴奋性物质 哺乳动物中枢神经系统的神经递质。 这些神经递质系统中的异常与这种 神经疾病如亨廷顿舞蹈症，癫痫， 橄榄桥小脑萎缩和帕金森氏症。因为嗅觉 鳞茎是利用GABA和谷氨酸的丰富突触来源， 它有可能成为这些神经递质的模型 一般情况下，系统。

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.