EXCITATORY SYNAPTIC TRANSMISSION IN NEOSTRIATUM

拟议研究的目的是加深我们对这种方式的理解 其中谷氨酸和多巴胺能突触传递有助于 新纹状体的功能。之前的实验已经证明 离子亲和性谷氨酸受体和代谢性谷氨酸受体在脑内的作用 皮质纹状体突触传递。此外，两种形式的突触 在这些突触上观察到了抑郁(STD和LTD)。实验 旨在确定：1)所涉及的突触改变的轨迹 纹状体LTD；2)皮质纹状体和黑质纹状体传入的作用 在引发纹状体有限公司方面的投入；3)涉及的机制 代谢型谷氨酸受体对信息传递的突触前调控。 谷氨酸或相关氨基酸是主要的兴奋性神经递质。 在哺乳动物的中枢神经系统中。在尾状核和壳核内，谷氨酸- 含有来自大脑皮层和丘脑的纤维形成突触 神经元，最显著的是中等刺状神经元。激活这些 突触使纹状体神经元去极化，从而直接激活神经元 或增加它们被其他输入激活的可能性。一个 对丹参生理学和药理性质的进一步认识 这些突触对功能性新纹状体的欣赏至关重要。 电路。多巴胺能黑质纹状体通路也起着显著的作用 在纹状体功能调节中的作用，并关键地参与了 帕金森病和其他神经性疾病的神经病理学 牵涉到基底节。然而，人们对此知之甚少。 在细胞水平上激活该通路的后果 生理学和突触传递。我们的假设是 谷氨酸能皮质区纹状体传递及其作用的研究进展 纹状体功能中的多巴胺能黑质纹状体传递将有助于 涉及损害的障碍治疗方法的发展 纹状体功能。

The aim of the proposed research is to further our understanding of the way in which glutamatergic and dopaminergic synaptic transmission contribute to the function of the neostriatum. Previous experiments have demonstrated roles for both ionotropic and metabotropic glutamate receptors in corticostriatal synaptic transmission. In addition, two forms of synaptic depression (STD and LTD) have been observed at these synapses. Experiments are designed to determine: 1) The synaptic locus of alterations involved in striatal LTD; 2) The role of corticostriatal and nigrostriatal afferent inputs in eliciting striatal LTD; 3) The mechanisms involved in presynaptic modulation of transmission by metabotropic glutamate receptors. Glutamate or a related amino acid is the major excitatory neurotransmitter in the mammalian CNS. Within the caudate nucleus and putamen, glutamate- containing fibers from the cortex and possibly thalamus form synapses with neurons, most notably the medium spiny neurons. Activation of these synapses depolarizes striatal neurons which activates the neurons directly or increases the likelihood of their being activated by other inputs. A further understanding of the physiologic and pharmacologic properties of these synapses is critical to the appreciation of functional neostriatal circuitry. The dopaminergic nigrostriatal pathway also plays a prominent role in regulation of striatal function, and is critically involved in the neuropathology of Parkinson's disease and other neurological disorders involving the basal ganglia. However, relatively little is known about the consequences of activation of this pathway at the level of cellular physiology and synaptic transmission. It is our hypothesis that elucidation of the role of glutamatergic corticostriatal transmission and dopaminergic nigrostriatal transmission in striatal function will aid in the development of therapeutic approaches to disorders involving impairment of striatal function.