报告1
【主题】 Cortico-basal Ganglia Loop and Pathophysiology of Movement Disorders
【时间】2017年11月1日（周三），13:00-14:30
【地点】北京大学王克桢楼1113会议室
【报告人】Atsushi Nambu
Division of System Neurophysiology, National Institute for Physiological Sciences, Okazaki, Japan
Department of Physiological Sciences, SOKENDAI, Okazaki, Japan
【邀请人】Yuji Naya 研究员
Abstract
The basal ganglia (BG) govern cortical activity through the thalamus and control voluntary movements. The striatum and subthalamic nucleus (STN) are the input structures of the BG, while the internal segment of the globus pallidus (GPi) and substantia nigra pars reticulata (SNr) are the output nuclei. There are three major pathways that connect the input and output stations of the BG to modulate GPi/SNr activity: the cortico-STN-GPi/SNr hyperdirect, cortico-striato-GPi/SNr direct, and cortico-striato-external pallido (GPe)-STN-GPi/SNr indirect pathways. A signal through the direct pathway inhibits a specific population of GPi/SNr neurons, resulting in disinhibition of the thalamus and cortex and a release of only a selected motor program at a selected timing. On the other hand, signals through the hyperdirect and indirect pathways excite the surrounding wide areas of the GPi/SNr, resulting in inhibition of the thalamus and cortex and suppression of other competing motor programs.
Malfunctions of the BG cause severe disturbances in the execution of voluntary movements. In Parkinson’s disease, the hyperdirect and indirect pathways dominate over the direct pathway in both spatial and temporal domains, and thus, intended motor programs cannot be released, causing akinesia. On the other hand, in dystonia, the direct pathway dominates over the other pathways spatiotemporally, and thus, unintended movements are randomly released, causing involuntary movements.
Such symptoms of movement disorders can be ameliorated by stereotactic surgery by making a small lesion or applying high-frequency electrical stimulation (deep brain stimulation, DBS) in the BG. Our study showed that GPi-DBS inhibits cortically induced responses and spontaneous discharges in the GPi by strong GABAergic inhibition, suggesting that GPi-DBS blocks information flow through the GPi. Thus, both DBS and lesions seem to block abnormal information flow from the BG to the thalamus and cortex and suppress the expression of motor symptoms of movement disorders.
报告2
【主题】Electrical synapses and their interactions with chemical synapses
【时间】2017年11月2日（周四），15:00-16:30
【地点】金光101报告厅
【报告人】Alberto E. Pereda, M.D., Ph.D
Professor，Dominick P. Purpura Department of Neuroscience
Albert Einstein College of Medicine
【邀请人】Dr. Yulong Li
Information of the Speaker
Dr. Pereda’s lab is interested in investigating the properties and dynamics of gap junction-mediated electrical synapses in the vertebrate brain, in particular their interactions with chemical synapses, focusing on understanding the plastic properties of electrical synapses at mixed (electrical and chemical) auditory contacts on the teleost Mauthner cells. They found that the strength of these electrical synapses is highly regulated by a variety of mechanisms, including the activation of nearby glutamate receptors by synaptic activity, endocannabinoids and dopamine.
报告3
【主题】Clinical, genetic, and biochemical characterization of human circadian regulation
【时间】2017年11月6日（周三），13:00-15:00
【地点】北京大学王克桢楼1113会议室
【报告人】Prof. Louis J. Ptáček, MD
Investigator, Howard Hughes Medical Institute
John C. Coleman Distinguished Professor of Neurology
University of California, San Francisco
【邀请人】Prof.Yi Rao
Abstract
Sleep regulation is a very mysterious phenomenon. Despite the fact that sleep is an essential component of the human experience occupying ~1/3 of our lives, little is known about what sleep is and what purposes it serves. It is clear that chronic disruption of sleep leads to increased risks of not only motor vehicle accidents, but also many diseases like cancer, obesity and diabetes, autoimmune disorders, neurodegeneration, and psychiatric diseases. We’ve reported genes and mutations that cause people to be extreme morning larks (lifelong tendency to go to sleep and to wake up very early). We and our collaborators have also reported the first families and gene/mutation causing people to be natural short sleepers, with a life-long requirement of only 4-6 hours of sleep/night to feel good and perform at a high level. We’ve used human genetics in combination with detailed biochemical analysis and circadian phosphoproteomics to help reveal basic mechanistic insights underlying the mysteries of human sleep behavior. Our vision for this work is to ultimately improve human safety and health. Insights into the details of sleep mechanisms will ultimately lead to better sleep medicines for travelers and shift workers. In addition to decreasing disease risks, such medications will also be used in conjunction with other medications to align drug administration with the best circadian time-of-day to optimize the benefit while minimizing side-effects.
报告4
【主题】The chemical characterization of the brain:from new measurement tools to new neurochemical insights
【时间】2017年11月7日（周三），13:00-15:00
【地点】北京大学王克桢楼1113会议室
【报告人】Prof.Jonathan V. Sweedler
Center for Advanced Study Professor
Director of the School of Chemical Sciences
University of Illinois at Urbana-Champaign,
Urbana IL 61801 USA
【邀请人】Dr. Yulong Li
Abstract
In the postgenomic era, one expects the suite of chemical players in a brain region to be known and their functions uncovered. However, many cell-to-cell signaling molecules remain poorly characterized and for those that are known, their localization and dynamics are oftentimes unknown. A suite of small-scale measurement approaches are described that allow the investigation of individual neurons and small brain regions; these approaches include capillary scale separations, direct mass spectrometric-based profiling and mass spectrometry imaging. Several applications of single cell microanalysis are highlighted including the discovery of unusual metabolites to characterizing the neuropeptides in single cells. Single cell assays allow differences in the metabolome and peptidome from supposedly homogeneous populations of cells to be explored. As a further example, a unique matrix assisted laser desorption / ionization time of flight mass spectrometry approach is described that probes thousands of cells for their small molecule content. Current technology efforts involve extending the depth of metabolome coverage and adapting our approaches to high throughput single cell assays. By obtaining information from thousands of individual cells, rare cells are found and subtle differences in cell populations are measured. Imaging mass spectrometry and dynamic sampling of the extracellular environment also provide a functional context for the discovery of novel cell to cell signaling molecules. Our overarching goal is to uncover the complex chemical mosaic of the brain and pinpoint key cellular players in a range of physiological and pathological processes.
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