GABA AND GLYCINE TRANSMISSION IN OLFACTORY BULB CULTURES

人们普遍认为，哺乳动物大脑中的抑制是由 由GABA提供。而甘氨酸被认为是主要的抑制氨基酸 脑干和脊髓中的酸递质。然而，一个更多的 在过去的几年里，出现了复杂的情况。近期 免疫组织化学和分子生物学研究表明 有多种形式的GABA-A受体具有不同 功能属性。此外，各种证据表明， 甘氨酸可能在大脑的许多区域起抑制递质的作用 在脊髓之外，包括嗅球。 嗅球是研究抑制多样性的理想模型 突触回路。嗅球含有两个初级种群 神经元，一小群二尖瓣/簇状细胞，它们投射到 皮质结构和更大的抑制性群体 中间神经元。因此，嗅球中的绝大多数神经元，如 在其他皮质结构中，有抑制性中间神经元。 免疫组织化学，分子和生理学研究，有 证明在人体内存在许多不同类型的GABA-A受体 嗅球。此外，最近具有挑衅性的证据强烈 这表明甘氨酸也可能对突触抑制起作用。 这项建议的广泛目标是探索功能 GABA-A和甘氨酸受体在嗅球中表达的多样性 神经元，特别关注它们在突触传递中的作用。 实验方法将原代培养和膜片钳技术相结合 记录技术，使我们能够探索 抑制性氨基酸受体在不同物种间的分离分布 鉴定嗅球神经元并确定它们在 突触抑制。这些信息可能会为我们提供更多关于 涉及这些递质的正常和病理过程 系统。

It is widely believed that inhibition in the mammalian brain is mediated by GABA. Whereas glycine is considered to be the dominant inhibitory amino acid transmitter in the brain stem and spinal cord. However, a more complex picture has emerged over the past several years. Recent immunohistochemical and molecular biological studies have demonstrated that there are multiple forms of the GABA-A receptor with different functional properties. Moreover, a variety of evidence suggests that glycine may function as an inhibitory transmitter in many brain regions outside of the spinal cord, including the olfactory bulb. The olfactory bulb is an ideal model to study the diversity of inhibitory synaptic circuits. The olfactory bulb contains two primary populations of neurons, a small population of mitral/tufted cells which project to cortical structures and a much larger population of inhibitory interneurons. Thus, the vast majority of neurons in the olfactory bulb, as in other cortical structures, are inhibitory interneurons. Immunohistochemical, molecular, and physiological studies, have demonstrated that there are many different types of GABA-A receptors in the olfactory bulb. Moreover, provocative recent evidence strongly suggests that glycine also may contribute to synaptic inhibition. The broad objective of this proposal is to explore the functional diversity of the GABA-A and glycine receptors expressed in olfactory bulb neurons with a particular focus on their role in synaptic transmission. The experimental approach will combine primary culture and patch clamp recording techniques to allow us to explore the possibility of a segregated distribution of inhibitory amino acid receptors among identified olfactory bulb neurons and determine their contribution to synaptic inhibition. This information may provide further insight into both normal and pathological processes involving these transmitter systems.