S-Space College of Medicine/School of Medicine (의과대학/대학원) Dept. of Biomedical Sciences (대학원 의과학과) Theses (Ph.D. / Sc.D._의과학과)
Noradrenergic Regulation of Neuroglia Interaction is Essential for Proper Cerebellar Output and Cerebellum-Dependent Motor Coordination
소뇌 출력과 운동협응에 있어서 노르아드레날린에 의한 신경-아교세포 상호작용조절의 중요성에 대한 연구
- 의과대학 의과학과
- Issue Date
- 서울대학교 대학원
- Norepinephrine; Locus Coeruleus; Calcium; Bergmann Glia; Purkinje Cell; Neuroglia interaction; Motor coordination; Dystonia
- 학위논문 (박사)-- 서울대학교 대학원 : 의과학과, 2015. 2. 김상정.
- BACKGROUND: Locus coeruleus (LC)-norepinephrine (NE) system exerts prominent effects on neurons and astrocytes in many brain regions, including the cerebellum, thereby contributing to arousal. However, the possible NE-driven interaction between neurons and glia in the cerebellum and its physiological role during arousal remains to be understood.
MATERIALS AND METHODS: To visualize the Ca2+ activity of Purkinje cell (PC), molecular layer interneuron (MLI) and Bergmann glia (BG) in intact cerebellar cortex lobule V/VI, two-photon calcium imaging using a calcium dye OGB-1 and genetically encoded calcium indicator GCaMP6f (viral expression) was performed in anesthetized and awake head-fixed mice. Noxious electrical stimuli was delivered to anesthetized mice and startle stimuli to resting awake mice during two-photon imaging to induce arousal-like state and arousal behavior, respectively.
RESULTS: 1) Noxious electrical stimulation in anesthetized mice or startle stimulation in awake mice results in NE release and subsequent BG Ca2+ response in the cerebellum. 2) The BG Ca2+ response coincides with phasic suppression of PC dendritic calcium spike activity during electrical stimulation in anesthetized mice and during arousal behavior in awake mice. 3) Cerebellum specific blockades of both alpha1-adrenergic receptor (AR) and glial GABA channel, Best1, result in abnormally elevated network synchrony and increased Ca2+ transients in PC dendrites during resting and arousal state: aberrantly increased PC output. 4) alpha1-AR and Best1 blockade induce locomotion disability and dystonic behavior which was coincided with PC burst activity.
CONCLUSION: Taken together, it is suggested that NE-driven inhibitory gliotransmission mediates suppression of PC dendritic Ca2+ activity and it supports proper PC output and cerebellum-dependent motor coordination, otherwise inducing dystonic behavior.