Doctor of Philosophy, Tsinghua University (2013)
Master of Science, Beijing Institute Of Technology (2007)
Bachelor of Engineering, Beijing Institute Of Technology (2005)
Mark Schnitzer, Postdoctoral Faculty Sponsor
High-speed recording of neural spikes in awake mice and flies with a fluorescent voltage sensor
2015; 350 (6266): 1361-1366
Genetically encoded voltage indicators (GEVIs) are a promising technology for fluorescence readout of millisecond-scale neuronal dynamics. Prior GEVIs had insufficient signaling speed and dynamic range to resolve action potentials in live animals. We coupled fast voltage-sensing domains from a rhodopsin protein to bright fluorophores via resonance energy transfer. The resulting GEVIs are sufficiently bright and fast to report neuronal action potentials and membrane voltage dynamics in awake mice and flies, resolving fast spike trains with 0.2-millisecond timing precision at spike detection error rates orders of magnitude better than prior GEVIs. In vivo imaging revealed sensory-evoked responses, including somatic spiking, dendritic dynamics, and intracellular voltage propagation. These results empower in vivo optical studies of neuronal electrophysiology and coding and motivate further advancements in high-speed microscopy.
View details for DOI 10.1126/science.aab0810
View details for Web of Science ID 000366162400039
Dexterous robotic manipulation of alert adult Drosophila for high-content experimentation.
2015; 12 (7): 657-660
We present a robot that enables high-content studies of alert adult Drosophila by combining operations including gentle picking; translations and rotations; characterizations of fly phenotypes and behaviors; microdissection; or release. To illustrate, we assessed fly morphology, tracked odor-evoked locomotion, sorted flies by sex, and dissected the cuticle to image neural activity. The robot's tireless capacity for precise manipulations enables a scalable platform for screening flies' complex attributes and behavioral patterns.
View details for DOI 10.1038/nmeth.3410
View details for PubMedID 26005812
The differential requirement of mushroom body ?/? subdivisions in long-term memory retrieval in Drosophila.
Protein & cell
The mushroom body (MB), a bilateral brain structure possessing about 2000-2500 neurons per hemisphere, plays a central role in olfactory learning and memory in Drosophila melanogaster. Extensive studies have demonstrated that three major types of MB neurons (?/?, ?'/?' and ?) exhibit distinct functions in memory processing, including the critical role of approximately 1000 MB ?/? neurons in retrieving long-term memory. Inspired by recent findings that MB ?/? neurons can be further divided into three subdivisions (surface, posterior and core) and wherein the ?/? core neurons play an permissive role in long-term memory consolidation, we examined the functional differences of all the three morphological subdivisions of MB ?/? by temporally precise manipulation of their synaptic outputs during long-term memory retrieval. We found the normal neurotransmission from a combination of MB ?/? surface and posterior neurons is necessary for retrieving both aversive and appetitive long-term memory, whereas output from MB ?/? posterior or core subdivision alone is dispensable. These results imply a specific requirement of about 500 MB ?/? neurons in supporting long-term memory retrieval and a further functional partitioning for memory processing within the MB ?/? region.
View details for PubMedID 23722532
Dissociation of rugose-dependent short-term memory component from memory consolidation in Drosophila.
Genes, brain, and behavior
Extensive investigations show several molecular and neuroanatomical mechanisms underlying short-lived and long-lasting memory in Drosophila. At the molecular level, the genetic pathway of memory formation, which was obtained through mutant research, seems to occur sequentially. So far, studies of Drosophila mutants appear to support the idea that mutants defective in short-term memory (STM) are always associated with long-term memory (LTM) impairment. At the neuroanatomical level, distinct memory traces are partially independently distributed. However, whether memory phase dissociation also exists at the molecular level remains unclear. Here, we report on molecular separation of STM and consolidated memory through genetic dissection of rugose mutants. Mutants in the rugose gene, which encodes an evolutionarily conserved A-kinase anchor protein, show immediate memory defects as assayed through aversive olfactory conditioning. Intriguingly, two well-defined consolidated memory components, anesthesia-resistant memory and protein synthesis-dependent LTM, are both normal in spite of the defective immediate memory after 10-session massed and spaced training. Moreover, rugose genetically interacts with cyclic AMP-protein kinase A signaling during STM formation. Considering our previous study that AKAP Yu specifically participates in LTM formation, these results suggest that there exists a molecular level of memory phase dissociation with distinct AKAPs in Drosophila.
View details for PubMedID 23790035
- Requirement of the combination of mushroom body ? lobe and ?/? lobes for the retrieval of both aversive and appetitive early memories in Drosophila Learning & Memory 2013; 20 (9): 474-481
A Permissive Role of Mushroom Body alpha/beta Core Neurons in Long-Term Memory Consolidation in Drosophila
2012; 22 (21): 1981-1989
Memories are not created equally strong or persistent for different experiences. In Drosophila, induction of long-term memory (LTM) for aversive olfactory conditioning requires ten spaced repetitive training trials, whereas a single trial is sufficient for LTM generation in appetitive olfactory conditioning. Although, with the ease of genetic manipulation, many genes and brain structures have been related to LTM formation, it is still an important task to identify new components and reveal the mechanisms underlying LTM regulation.Here we show that single-trial induction of LTM can also be achieved for aversive olfactory conditioning through inhibition of highwire (hiw)-encoded E3 ubiquitin ligase activity or activation of its targeted proteins in a cluster of neurons, localized within the ?/? core region of the mushroom body. Moreover, the synaptic output of these neurons is critical within a limited posttraining interval for permitting consolidation of both aversive and appetitive LTM.We propose that these ?/? core neurons serve as a "gate" to keep LTM from being formed, whereas any experience capable of "opening" the gate is given permit to be consolidated into LTM.
View details for DOI 10.1016/j.cub.2012.08.048
View details for Web of Science ID 000311060200018
View details for PubMedID 23063437
Involvement of reactive oxygen species and calcium in photo-induced membrane damage in HeLa cells by a bis-methanophosphonate fullerene
JOURNAL OF PHOTOCHEMISTRY AND PHOTOBIOLOGY B-BIOLOGY
2010; 98 (3): 193-198
Photo-excited bioactivities of fullerene derivatives are attracting much attention. In this report, a bis-methanophosphonate fullerene (BMPF) and the other two fullerene derivatives, a bis-malonic acid fullerene (BMAF) and a fullerol were incubated with HeLa cells and irradiated with a green light emitted from a mercury lamp on a fluorescent microscopy. By using DNA fluorescent probe propidium iodide staining method, damage towards cell membrane could be detected when cells were treated by irradiation altogether with BMPF or BMAF at a low concentration (4 microM), and the damage was dose-dependent. The activity of BMPF was much higher than that of BMAF, while fullerol had no effects under the same condition. It was also revealed that different kinds of reactive oxygen species (ROS) correlated to BMPF and BMAF. Additionally, presence of extracellular calcium could promote the activities of both derivatives, while removal of extracellular calcium could not abort their membrane-damaged activities. These results indicated that ROS and calcium were involved in the photosensitization of fullerene derivatives, and BMPF was a superior photosensitizer which would find potential application in biomedical field.
View details for DOI 10.1016/j.jphotobiol.2010.01.001
View details for Web of Science ID 000276116600004
View details for PubMedID 20144875
- Inhibition of DNA restrictive endonucleases by aqueous nanoparticle suspension of methanophosphonate fullerene derivatives and its mechanisms Science in China Series B: Chemistry 2009; 52 (5): 626-631
Photo-induced lipid peroxidation of erythrocyte membranes by a bis-methanophosphonate fullerene
TOXICOLOGY IN VITRO
2007; 21 (8): 1493-1498
Using human erythrocyte membranes (EMs) as a model system, we have examined photo-induced lipid peroxidation by a bis-methanophosphonate fullerene (BMPF) and four other fullerene derivatives including a mono-methanophosphonic acid fullerene (MMPF), a dimalonic acid C(60) (DMA C(60)), a trimalonic acid C(60) (TMA C(60)) and a polyhydroxylated fullerene (fullerol). Lipid peroxidation was assessed as the malondialdehyde (MDA) level measured by the thiobarbituric acid assay. It was observed that BMPF increased the MDA level of EMs after irradiation in both time- and dose-dependent manners. The photo-induced activity became very significant (p<0.01) under the conditions of either the concentration of 10 microM and irradiation time of 30 min or the concentration of 5 microM and irradiation time of 60 min. Involvement of reactive oxygen species (ROS) in the activity was also examined by specific inhibitors of singlet oxygen, superoxide anions and hydroxyl radicals, respectively. While all three kinds were found responsible for the activity, the former two might play more important roles than the last one. Furthermore, the activity of BMPF was the strongest among all tested fullerene derivatives. These results indicated BMPF was a potential photosensitizer that would find application in photodynamic therapy.
View details for DOI 10.1016/j.tiv.2007.06.008
View details for Web of Science ID 000251558100016
View details for PubMedID 17686607