科学研究

学术报告

Susan Jones: 中脑多巴胺能神经元中突触和突触外NMDA谷氨酸受体活性的调控

    |    分享:
2019-12-04

Chinese Institute for Brain Research, Beijing Seminar

 

SEMINAR TYPE

B-Type

 

PREFERRED LOCATION

Third Floor Lecture Hall, Jianzan Building (Phase I)

Chinese Institute for Brain Research, Beijing

 

TIME

10:00-10:30  Monday,October 28th, 2019

 

SPEAKER

Susan Jones,博士

剑桥大学

生理、发育与神经科学系

 

HOST

Dr. Magdalena J Koziol

 

TOPIC

中脑多巴胺能神经元中突触和突触外NMDA谷氨酸受体活性的调控

 

ABSTRACT

哺乳动物大脑中大多数兴奋性突触传递是由突触后离子型谷氨酸受体介导的。 N-甲基-D-天冬氨酸受体(NMDARs)是Ca2+通透的谷氨酸受体,其在神经发育,突触可塑性和细胞存活中起着重要作用。在神经元功能障碍时, NMDA受体的过度兴奋被认为可导致细胞死亡,进而可引发神经退行性疾病(例如阿尔茨海默氏病和帕金森氏病),缺血性中风和癫痫。有趣的是,NMDA受体可以通过称为“电流迫降”的过程自动调节其自身的活性和表面密度。在黑质致密区(SNc)多巴胺能(DA)神经元中,我们观察到NMDA受体介导的电流下降,这是由细胞内Ca2+缓冲作用的增加,Ca 2+流入的减少和抑制半胱氨酸蛋白酶活性——钙蛋白酶而引起的。钙蛋白酶可通过限制经过NMDA受体的Ca2 +流入来维持多巴胺神经元的细胞内Ca2 +稳态;这对神经元的存活非常重要。帕金森患者的SNc-DA神经元具有明显的病理学特性,并且在帕金森患者中通常能检测到SNc的谷氨酸能刺激的高频发放。因此,我们探讨了SNc-DA神经元中兴奋性突触中高频刺激的影响。我们观察到强且持久的NMDAR-EPSCs(NMDA受体介导的兴奋性突触后电流),并且谷氨酸转运阻断剂(TBOA)可以在幅度和持续时间上增加NMDAR-EPSCs,这表明突触外的谷氨酸的“溢出”可能受谷氨酸转运蛋白的调节,因此限制了突触外NMDA受体的激活。我们还观察到TBOA引发的强直NMDA受体介导的电流增加,这表明谷氨酸转运蛋白最小化了由周围谷氨酸引起的NMDA受体介导的强直活性。总之,SNc-DA神经元的NMDA受体的活性调节机制的缺陷可能对神经元存活产生不利影响,并且可能会导致神经退行性疾病。

 

SPEAKER BIOGRAPHY

Dr Sue Jones is a Senior Lecturer and Principal Investigator at the University of Cambridge, where her lab studies the properties and regulation of NMDA glutamate receptors in dopamine neurons; these are the cells primarily affected in Parkinson’s disease. Sue obtained her PhD in Neuropharmacology at University College London, working with Professor David Brown on the modulation of voltage-dependent potassium ion channels. She then moved to the USA to carry out postdoctoral research with Dr Jerry Yakel at NIH, working on nicotinic acetylcholine and serotonin receptor ion channels, and with Dr Julie Kauer at Duke University and Brown University, studying the effects of drugs of abuse on glutamatergic synaptic plasticity in midbrain dopamine neurons.  She moved to the University of Cambridge to start her own lab in 2002, where she is currently a Senior Lecturer in the Department of Physiology, Development & Neuroscience. Her lab studies glutamatergic synapses in the mammalian brain and has a general interest in normal synaptic function and dysfunction in brain disorders, with a particular focus on NMDA receptors in midbrain dopamine neurons. She also teaches undergraduate medical and science students in Neuroscience, Physiology and Anatomy, serves on the Departmental Management Committee and is the Chair of the PDN Communications Committee.