MODULATION OF OLFACTORY CIRCUITS

初级突触回路遍及大多数中枢神经系统，包括 嗅球，使用氨基酸递质，包括谷氨酸，GABA， 还有甘氨酸。尽管在表征这些方面取得了进展 电路，对它们的内源性调制知之甚少 神经活性物质。鉴于氨基酸的公认作用 突触可塑性中的递质及其某些形式的神经病理学 是否有可能通过内源激素调节氨基酸受体 物质会影响这些过程。因此，重要的是要澄清 这种调制背后的机制。 过渡金属锌和铜代表内源性神经活性 球茎中高度集中的物质。因为这些 过渡金属已被证明是由其他神经元释放的。 对于中枢神经系统的区域，有人提出它们的功能是 突触传递过程中的神经调节剂。此外， 锌和/或铜在几种神经病理状态中的意义 (皮克氏病、威尔逊氏病、癫痫和阿尔茨海默病) 表明这些金属可能与异常调制有关 使用氨基酸递质的突触通路。这一假设 进一步得到了实验数据的支持，这些数据展示了氨基的调节 锌和铜的酸性电流。 与锌和铜一样，二肽肌肽也存在于 嗅觉系统。尽管它已被提议作为发射器或 调制器，验证这一假设的尝试产生了模棱两可的结果 结果。然而，研究发现嗅觉感觉神经元含有 锌、肌肽和谷氨酸，暗示着 在神经调节中的作用。我们的飞行员数据显示肌肽 调节锌和铜对氨基酸受体的作用 嗅球神经元也与这种可能性一致。 功能完善的神经回路和丰富的神经活性物质供应 物质使哺乳动物的嗅球成为治疗 研究神经调节。此外，嗅觉障碍是一种 几种相关神经病理状态的早期表现 随着年龄的增长(例如帕金森氏症、阿尔茨海默病) 被认为与氨基酸递质病理有关。 这项提议的目的是探索锌的调节作用， 铜和肌肽对NMDA、GABAA和甘氨酸受体表达的影响 利用电生理学技术原代培养嗅球神经元 专注于它们在突触传递中的作用的技术。

Primary synaptic circuits throughout most of the CNS, including the olfactory bulb, use amino acid transmitters including glutamate, GABA, and glycine. Despite progress in the characterization of these circuits, little is known about their modulation by endogenous neuroactive substances. Given the accepted roles of amino acid transmitters in synaptic plasticity and some forms of neuropathology it is possible that modulation of amino acid receptors by endogenous substances influences these processes. Thus, it is important to clarify mechanisms underlying such modulation. The transition metals, zinc and copper, represent endogenous neuroactive substances which are highly concentrated in the bulb. Because these transition metals have been shown to be released by neurons in other regions of the CNS, it has been proposed that they function as neuromodulators during synaptic transmission. In addition, the implication of zinc and/or copper in several neuropathologic conditions (Pick's disease, Wilson's disease, epilepsy, and Alzheimer's disease) suggests that these metals may be associated with abnormal modulation of synaptic pathways that use amino acid transmitters. This hypothesis is further supported by pilot data demonstrating modulation of amino acid-mediated currents by zinc and copper. Along with zinc and copper, the dipeptide carnosine also is found in the olfactory system. Although it has been proposed as a transmitter or modulator, attempts at verifying this hypothesis have produced equivocal results. However, the finding that olfactory sensory neurons contain zinc, carnosine, and glutamate, suggests the potential for a combined role in neuromodulation. Our pilot data suggesting that carnosine modulates the actions of zinc and copper on amino acid receptors on olfactory bulb neurons also are consistent with this possibility. The well-characterized circuits and rich supply of neuroactive substances make the mammalian olfactory bulb an ideal preparation for studying neuromodulation. Furthermore, olfactory dysfunction is an early manifestation of several neuropathologic conditions associated with aging (e.g. Parkinson's disease, Alzheimer's disease) that are thought to be linked to amino acid transmitter pathology. The goal of this proposal is to explore the modulatory actions of zinc, copper and carnosine on NMDA, GABAA and glycine receptors expressed by olfactory bulb neurons in primary culture, using electrophysiological techniques to focus on their role in synaptic transmission.