集齐这七位国内科学家的报告，就可以...

Zhian Hu, Ph.D. , M.D.

Professor, Chongqing Collaborative Center for Brain Science, China

Zhian Hu’s lab is interested in the dissecting neural circuits underlying the wake-sleep behavior. Multiple brain regions play roles in the sleep-wake cycle. However, the exact underlying mechanism is not entirely clear. We demonstrated that the paraventricular thalamus (PVT) is a key wakefulness-controlling nucleus in the thalamus (Science, 2018). While the arousal-promoting systems innervate the consciousness-related brain areas to maintain awakening, arousal is also well-known to be the basis of the memory. Thus, another direction of the lab is to explore how the arousal systems regulate the spatial episodic memory. We found that hypocretin neurons in hypothalamus directly innervate prefrontal cortex and facilitate the encoding of episodic memory via increasing neural excitability. (J. Neurosci. Res., 2005; Cerebral cortex, 2010). Moreover, we identified a new functional pathway of the hypothalamic histaminergic arousal system-entorhinal cortex, and revealed how this pathway regulates episodic learning and memory at the molecular, cellular and network levels (Cerebral Cortex 2016, 2018). These findings provide new insights into how the arousal state modulates episodic memory.

Abstract

Entorhinal cortex (EC), as the gateway of the hippocampus, is regarded as a part of “GPS” system in our brain. We have found that hypocretins functioned at the glutamatergic terminals and recruited the local GABAergic neurons via stimulating local glutamate release in the entorhinal cortex. The activation of the GABAergic neurons by hypocretins drove the gamma oscillations and contributed to the spatial memory. Recent studies of the hypocretinergic modulation of entorhinal cortex will be presented.

Rongqing Chen, Ph.D.

Professor, Southern Medical University, Guangzhou, China

Chen’s lab is interested in the mechanism of epileptic seizure pathogenesis and the therapy strategies. Also cellular and molecular mechanism of neuronal plasticity are his lab’s research direction.

Abstract

Loss of balance between neural excitation and inhibition toward overexcitation may lead to many neurological disorders such as migraine, epilepsy and autism. At the synaptic level, glutamatergic and GABAergic synaptic transmissions dominate the excitation and inhibition of postsynaptic neurons, respectively. While at the cellular level, numerous ions and their channels participate in the tuning of intrinsic neuronal excitability. However, it is unclear whether and how excessive neuronal hyperexcitation might call up a neuronal intrinsic plasticity of inhibition to return neuronal stability under physiological or pathophysiological conditions. Here, we report that a seizure-like strong depolarization could induce a short-term neuronal inhibition at mouse hippocampal CA3 region via a mechanism of membrane shunting. This depolarization-induced shunting inhibition (DShI) is non-synaptic, but neuronal intrinsic short-term plasticity that is able to diminish inotropic receptors’ responses to their ligands and action potential firing. We demonstrate that DShI is mediated by K2P type potassium channels, of which migraine-associated TRESK channel at least partially makes contribution. Genetic knockout of TRESK channel exacerbates the sensitivity and severity of epileptic seizures of mice challenged with convulsant stimulation. Thus our work uncovers a novel type of neuronal intrinsic plasticity and the underlying mechanism. TRESK channel might be a therapeutic target for epileptic seizures.

Yulong Li, Ph.D.

Principal Investigator, Peking University, China

The biggest challenge to study brain is its complexity. Li lab's research centers on "synapse", the fundamental unit for the communication between brain cells, called neurons. They carry two layers of research: first, we develop cutting edge research tools, namely advanced imaging probes, to untangle the complexity of nervous system in space and in time; second, capitalizing on the advancement of research toolkits, Li lab studies the regulation of synaptic transmission, focusing on the modulation of presynaptic transmitter release in health (e.g. sleep) and in disease conditions (e.g. neurodegenerative disease). Specifically, for tool development. 

Abstract

Purinergic transmitters, e.g. adenosine (Ado), ADP and ATP, are playing important roles in a plethora of physiological processes, including sleep-wake control, learning and memory, and immune response. Malfunction of the purinergic signaling is implicated in diseases such as sleep disorders, epileptic seizures, migraine and pain. A major obstacle to decipher the function of purinergic transmission is the lack of direct, sensitive, and non-invasive method to monitor structurally similar purinergic transmitters, ideally with high spatial and temporal resolution in vivo. Here by tapping into human P1 (Ado) and P2Y receptor family, we developed a toolbox of genetically-encoded GPCR-activation based (GRAB) green fluorescent sensors, with unique molecular specificity for Ado, ADP, ATP and UTP. Purinergic GRAB sensors exhibit robust fluorescence increases upon cognate ligand binding - they inherit their parental purinergic receptors’ binding specificity and affinity. Using GRABAdo, we successfully monitored electrical stimulation and high-K+ application evoked elevation of extracellular Ado levels in cultured neurons. Aided by fiber photometry, we also successfully detected rapid changes of Ado levels during chemical induced seizures as well as during sleep-wake cycles in mice in vivo. Similarly, using GRABATP, we successfully observed mechanical-stimulation evoked ATP waves in cultured astrocytes & neurons with single cell resolution. Finally, we further expanded the repertoire of GRAB sensors for detecting dopamine, norepinephrine, 5-HT and octopamine. In sum, the newly developed purinergic and monoaminergic GRAB sensors provide powerful tools for understanding the regulation and malfunction of purinergic and monoaminergic systems in physiological and pathological processes.

Qian Yang, Ph.D.

Professor, Tangdu Hospital, Xi’an, China

Dr. Yang’s research interest are regulation of neuronal homeostasis in stress and the pathogenesis of neurodegenerative disease caused by the homeostasis disturbance.

Abstract

Neurons are highly sensitive to changes in their environment, and have developed dynamic adaptive processes to sense and copy with stress caused by such changes.  MiRNAs (microRNAs) are a recently discovered class of non-coding small RNAs that are involved in regulating many cellular processes including stress.  Dysfunction of miRNAs has been implicated in many pathological processes including both Alzheimer's and Parkinson's diseases.  On the one hand, miRNAs modulate pathways and genes relevant to both genetic and sporadic forms of AD and PD.  On the other hand, many of these miRNAs are themselves altered in these diseases.  MiRNA biogenesis is controlled by several tightly coupled sequential steps governed by multiple protein complexes and subjected to intricate regulation.  The entire process is initiated in the nucleus by the conversion of the long primary miRNA transcripts to the hairpin structured precursor miRNA (pre-miRNAs) by the RNase III enzyme Drosha.  The pre-miRNA is transported to the cytoplasm where it is cleaved by RNase III enzyme Dicer to generate matural miRNA. Inhibiting miRNA biogenesis by conditionally knocking out Dicer in neurons, which blocks miRNA biogenesis at a step downstream of Drosha, causes mice to develop progressive neurodegeneration and AD-like tau hyperphosphorylation.  Studies of postmortem human brain show that the proteostasis of Drosha appears to be dysregulated in AD. These findings offer perhaps the strongest evidence for a potential link between miRNA biogenesis and AD and highlight the need to further explore the role of dysregulation of miRNA biogenesis  and the pathogenic process of neurodegeration.

Xiaoqun Wang, Ph.D.

Principal Investigator, vice Director of State Key Laboratory of Brain & Cognitive Sciences, Institute of Biophysics, Chinese Academy of Sciences.

My lab is interested in the function and regulation of neural stem cells in the mammalian brains. More specifically we are working on 1) Neural stem cell subtypes; 2) Niches and neural differentiation of neural stem cell; 3) Modeling human brain developmental diseases with pluripotent stem cells and in animal models; 4) Cellular mechanism regulating neuronal stem cell fate and circuits formation during the development of cerebral cortex; 5) Molecular regulations of nervous system diseases, including lisencephaly, microcephaly, autism, depression and neurodegenerative diseases.

Abstract

The human brain contains billions of neurons that were originally generated from neuroepithelial cells. The cerebral cortex can be divided into the following lobes: the frontal lobe (FL), parietal lobe (PL), occipital lobe (OL) and temporal lobe (TL), with each showing specialized functions in sensory and motor control and having specific projections to different targets of the nervous system. Our previous study revealed the developmental process of the human prefrontal cortex, which is the most uniquely expanded region of the human nervous system5. However, spatial and temporal regulation of different brain region at single-cell resolution at a serial of embryonic time points has not yet been performed systemically. We identified 29 cell sub-clusters, which showed different proportions in each region and the pons showed especially high percentage of astrocytes. Embryonic neurons were not as diverse as adult neurons, although they possessed important features of their destinies in adults. Neuron development was unsynchronized in the cerebral cortex, as dorsal regions appeared to be more mature than ventral regions at this stage. Region-specific genes were comprehensively identified in each neuronal sub-cluster, and a large proportion of these genes were neural disease related. Our results present a systematic landscape of the regionalized gene expression and neuron maturation of the human cerebral cortex.

Shengtao Hou, Ph.D.

Brain Research Center & Department of Biology, Southern University of Science and Technology (SUSTech); Department of Biochemistry, Microbiology and Immunology, University of Ottawa, Canada

Dr. Shengtao Hou is a Professor of Neurobiology.  He is the Founding Director for SUSTech Brain Research Center and the Executive Director for SUSTech Institute of Neuroscience. He is also the Associate Chair for the Department of Biology and the Founding Director for SUSTech Global Engagement Office. He received his doctoral degree from the Faculty of Medicine, University of Glasgow in 1991. After completing his postdoctoral trainings at King’s College London (1991-1993) and the Department of Biochemistry, University of Bristol (1993-1996), Dr. Hou was recruited by the National Research Council of Canada as an Assistant Research Officer in May 1996. Since then, Dr Hou has risen to the ranks of Group leader and tenured Senior Research Officer (since 2005). He is also an Adjunct full Professor at the Department of Biochemistry, Immunology and Microbiology of the University of Ottawa (since 2002).  Professor Hou’s research is focused on identifying novel molecular targets in the complex cascade of post stroke brain and developing novel experimental strategies and drugs relevant to clinical therapeutics.

Abstract

Both stroke and Parkinson’s disease are leading causes of death and disability in the world. However, drug therapeutics are limited. My laboratory has been developing electrical deep brain stimulation and LED light therapy to treat Parkinson’s and stroke, respectively, with remarkable results. I will share some of the exciting results. Further development of these tools will be of significant therapeutic value for clinical use.   

Chao Ma, M.D.

Professor, Institute of Basic Medical Sciences & Neuroscience Center, Chinese Academy of Medical Sciences, China

Dr. Chao Ma graduated from Peking Union Medical College and obtained his MD degree in 1999. After one year of surgical residency in the Peking Union Medical College Hospital, he went to Yale University School of Medicine as a Postdoctoral Associate in 2000, and was promoted to Assistant Professor in 2008. In December 2011, Dr. Ma returned to Peking Union Medical College and served as Professor and Chair of Human Anatomy, Histology and Embryology in the Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences since then. He founded the Human Brain Bank in Chinese Academy of Medical Sciences in 2012, initiated the “China Human Brain Banking Consortium” in 2014 and established the “Standard Operational Protocol of Human Brain Banking in China” in 2016. Research interests include: 1. Neural mechanisms of pain and pruritus; and 2. Human brain banking, brain aging and dementia.

Abstract

We investigated the proteomic profiles of amyloid plaques (APs) in Alzheimer’s disease (AD) and age-matched non-AD brains from the postmortem human brain bank at Chinese Academy of Medical Sciences/Peking Union Medical College, and compared the results with the APs from APP/PS1 transgenic model mice. APs and adjacent control regions were collected from fresh-frozen brain sections using laser capture dissection. Proteins were quantitated using tag-labelling coupled high-throughput mass spectra. Over 4000 proteins were accurately quantified, and more than 40 were identified as highly enriched in both AD and non-AD APs, including APOE, midkine, VGFR1 and complement C4. Intriguingly, proteins including synaptic structural proteins and complement C1r, C5 and C9 were found to be upregulated in AD APs but not non-AD APs. Moreover, the proteomic pattern of AD APs was distinct from APP/PS1 APs, and exhibited some correlation with aging hippocampus. This study demonstrated unexpected differences between AD, non-AD APs and APP/PS1 mouse APs, which may relate to different pathological processes. Our results provide new insight into amyloid plaque composition and potentially novel bio-targets for the diagnosis and treatment of AD.