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Zhen, Mei

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Zhen, Mei

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2015 - 20202

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Author's Publications: search.filters.isAuthorOfPublication.62dac1cb-33d4-4622-83ae-2ecac802f657

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    Connectomes across development reveal principles of brain maturation
    (Cold Spring Harbor Laboratory, 2020-04-30) Witvliet, Daniel; Mulcahy, Ben; Mitchell, James; Meirovitch, Yaron; Berger, Daniel; Wu, Yuelong; Liu, Yufang; Koh, Wan Xian; Parvathala, Rajeev; Holmyard, Douglas; Schalek, Richard; Shavit, Nir; Chisholm, Andrew; Lichtman, Jeff; Samuel, Aravi; Zhen, Mei
    From birth to adulthood, an animal’s nervous system changes as its body grows and its behaviours mature. The form and extent of circuit remodelling across the connectome is unknown. We used serial-section electron microscopy to reconstruct the full brain of eight isogenic C. elegans individuals across postnatal stages to learn how it changes with age. The overall geometry of the nervous system is preserved from birth to adulthood. Upon this constant scaffold, substantial changes in chemical synaptic connectivity emerge. Comparing connectomes among individuals reveals substantial connectivity differences that make each brain partly unique. Comparing connectomes across maturation reveals consistent wiring changes between different neurons. These changes alter the strength of existing connections and create new connections. Collective changes in the network alter information processing. Over development, the central decision-making circuitry is maintained whereas sensory and motor pathways substantially remodel. With age, the brain progressively becomes more feedforward and discernibly modular. Developmental connectomics reveals principles that underlie brain maturation.
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    Pan-neuronal imaging in roaming Caenorhabditis elegans
    (Proceedings of the National Academy of Sciences, 2015) Venkatachalam, Vivek; Ji, Ni; Wang, Xian-Ling; Clark, Christopher; Mitchell, James; Klein, Mason; Tabone, Christopher; Florman, Jeremy; Ji, Hongfei; Greenwood, Joel S.f.; Chisholm, Andrew; Srinivasan, Jagan; Alkema, Mark; Zhen, Mei; Samuel, Aravi
    We present an imaging system for pan-neuronal recording in crawling Caenorhabditis elegans. A spinning disk confocal microscope, modified for automated tracking of the C. elegans head ganglia, simultaneously records the activity and position of ∼80 neurons that coexpress cytoplasmic calcium indicator GCaMP6s and nuclear localized red fluorescent protein at 10 volumes per second. We developed a behavioral analysis algorithm that maps the movements of the head ganglia to the animal’s posture and locomotion. Image registration and analysis software automatically assigns an index to each nucleus and calculates the corresponding calcium signal. Neurons with highly stereotyped positions can be associated with unique indexes and subsequently identified using an atlas of the worm nervous system. To test our system, we analyzed the brainwide activity patterns of moving worms subjected to thermosensory inputs. We demonstrate that our setup is able to uncover representations of sensory input and motor output of individual neurons from brainwide dynamics. Our imaging setup and analysis pipeline should facilitate mapping circuits for sensory to motor transformation in transparent behaving animals such as C. elegans and Drosophila larva.