Homeostatic regulation mechanism of spontaneous firing determines glutamate responsiveness in the midbrain dopamine neurons |
| |
Authors: | Shin Hye Kim Jin Young Jang Miae Jang Ki Bum Um Sungkwon Chung Hyun Jin Kim Myoung Kyu Park |
| |
Affiliation: | 1. Department of Physiology, Sungkyunkwan University School of Medicine, 300 Chunchun-dong, Jangan-ku, Suwon 440-746, Republic of Korea;2. Center For Molecular Medicine, Samsung Biomedical Research Institute, 300 Chunchun-dong, Jangan-ku, Suwon 440-746, Republic of Korea |
| |
Abstract: | Autonomous tonic firing of the midbrain dopamine neuron is essential for maintenance of ambient dopamine level in the brain, in which intracellular Ca2+ concentration ([Ca2+]c) plays a complex but pivotal role. However, little is known about Ca2+ signals by which dopamine neurons maintain an optimum spontaneous firing rate. In the midbrain dopamine neurons, we here show that spontaneous firing evoked [Ca2+]c changes in a phasic manner in the dendritic region but a tonic manner in the soma. Tonic levels of somatic [Ca2+]c strictly tallied with spontaneous firing rates. However, manipulatory raising or lowering of [Ca2+]c with caged compounds from the resting firing state proportionally suppressed or raised spontaneous firing rate, respectively, suggesting presence of the homeostatic regulation mechanism for spontaneous firing rate via tonic [Ca2+]c changes of the soma. More importantly, abolition of this homeostatic regulation mechanism significantly exaggerated the responses of tonic firings and high-frequency phasic discharges to glutamate. Therefore, we conclude that this Ca2+-dependent homeostatic regulation mechanism is responsible for not only maintaining optimum rate of spontaneous firing, but also proper responses to glutamate. Perturbation of this mechanism could cause dopamine neurons to be more vulnerable to glutamate and Ca2+ toxicities. |
| |
Keywords: | Dopamine neurons Ca2+ signaling Ca2+-mediated feedback regulation Spontaneous firing Substantia nigra Ca2+ caging and uncaging |
本文献已被 ScienceDirect 等数据库收录! |
|