We are excited to welcome Alanna Love and Ze Nan (Tommy) Tang, new MSc students, to the lab.
- (abstract) Natural sensory context drives diverse brain-wide activity during C. elegans mating
Now at Cell… Natural sensory context drives diverse brain-wide activity during C. elegans mating (PDF)
Natural goal-directed behaviors often involve complex sequences of many stimulus-triggered components. Understanding how brain circuits organize such behaviors requires mapping the interactions between an animal, its environment, and its nervous system. Here, we use brain-wide neuronal imaging to study the full performance of mating by the C. elegans male. We show that as mating unfolds in a sequence of component behaviors, the brain operates similarly between instances of each component but distinctly between different components. When the full sensory and behavioral context is taken into account, unique roles emerge for each neuron. Functional correlations between neurons are not fixed but change with behavioral dynamics. From individual neurons to circuits, our study shows how diverse brain-wide dynamics emerge from the integration of sensory perception and motor actions in their natural context.
- Structural Analysis … Ion Beam-Scanning Electron Microscopy
Now published Structural Analysis of the Caenorhabditis elegans Dauer Larval Anterior Sensilla by Focused Ion Beam-Scanning Electron Microscopy at Frontiers in Neuroanatomy! (PDF)
At the end of the first larval stage, the nematode Caenorhabditis elegans developing in harsh environmental conditions is able to choose an alternative developmental path called the dauer diapause. Dauer larvae exhibit different physiology and behaviors from non-dauer larvae. Using focused ion beam-scanning electron microscopy (FIB-SEM), we volumetrically reconstructed the anterior sensory apparatus of C. elegans dauer larvae with unprecedented precision. We provide a detailed description of some neurons, focusing on structural details that were unknown or unresolved by previously published studies. They include the following: (1) dauer-specific branches of the IL2 sensory neurons project into the periphery of anterior sensilla and motor or putative sensory neurons at the sub-lateral cords; (2) ciliated endings of URX sensory neurons are supported by both ILso and AMso socket cells near the amphid openings; (3) variability in amphid sensory dendrites among dauers; and (4) somatic RIP interneurons maintain their projection into the pharyngeal nervous system. Our results support the notion that dauer larvae structurally expand their sensory system to facilitate searching for more favorable environments.
- New 3D models
We’ve been happy to receive so many requests for high resolution 3D renderings of C. elegans neurons (nerve ring) as described in our developmental connectome paper (Witvliet et al. 2021). To help distribute them, we’ve uploaded the 3D models and a blender file containing all the data. Feel free to share this link. Enjoy and have fun playing with them.
- Congratulations, Jun!
Congratulations to Jun Meng, a PhD student in our lab, for her successful final oral exam today for Molecular, cellular and circuit mechanisms that underlie a two-pore potassium channel’s regulation of membrane potential, synaptic activity and locomotion! Jun has been very focused on her completion and we are thrilled with how she defended today.
- Extrasynaptic signaling
See the pre-print of our latest paper
Extrasynaptic signaling enables an asymmetric juvenile motor circuit to produce a symmetric gait
Bilaterians generate motor patterns with symmetries that correspond to their body plans. This is thought to arise from wiring symmetries in their motor circuits. We show that juvenile C. elegans larva has an asymmetrically wired motor circuit, but still generates a bending pattern with dorsal-ventral symmetry. In the juvenile circuit, wiring between excitatory and inhibitory motor neurons coordinates contraction of dorsal muscles with relaxation of ventral muscles, producing dorsal bends. Ventral bending is not driven by analogous wiring. Instead, ventral muscles are excited uniformly by premotor interneurons through extrasynaptic signaling. Ventral bends occur in entrainment to the activity of the same motor neurons that drive dorsal bends. During maturation, the juvenile motor circuit is replaced by two homologous motor circuits that separately drive dorsal and ventral bending. Modeling reveals that the juvenile’s immature motor circuit provides an adequate solution to generate an adult-like gait long before the animal matures (PDF)
- New names
We are thrilled to be back to close to normal in the lab! This means saying hello to new people, including Yi (visiting scholar), Jason (volunteering with the lab), and rotation students (Hetty, Ze Nan, Xenia) from the Dept. of Molecular Genetics. Welcome, everyone!
- Now at Nature
With the Lichtman and Samuel labs, we are happy to announce the official publication of Connectomes across development reveal principles of brain maturation at Nature.
The first wiring map of C. elegans was generated by pioneer Dr. John White and his colleagues at MRC Cambridge more than 30 years ago. It was a composite of partial maps from several different worms due to technical limitations in sample fixation, serial sectioning, and image processing. Inspired by the rigor and vision of the legacy work, we used state-of-the-art electron microscopes to reconstruct the full brain of eight C. elegans individuals to learn how they change with age.
This is the first time that the entire structure of the brain is individually deduced and compared across developmental stages from birth to adulthood. These findings have powerful implications for understanding the fundamental rules that allow the brain’s developmental maturation to take place.
By examining every connection for every neuron, muscle, and glia, we found that the overall geometry, neurite structures, and neurite appositions barely change after birth, but new connections are selectively added as animals grow older. Over the course of development, these additions maintain the brain’s central decision-making circuitry, whereas sensory and motor pathways become substantially remodelled.
By examining the relationship between the structural properties in the newborn’s brain and the adult wiring patterns, we found a few properties and a few “rules” for selective synapse addition, allowing us to correctly predict the wiring patterns of the mature brain.
By analyzing these connections that are like wires in a computational network, we discovered that the new additions follow patterns and their collective changes serve one purpose — enabling effective information processing. Through identifying some key patterns of the brain’s development, we found that substantial connectivity differences make each brain unique.
We are both humbled and honored by this opportunity to continue the C. elegans connectomics work. We thank Dr. Daniel Witvliet, a former PhD student at our lab, for his rigor, talent, generosity, and extraordinary leadership. We thank all the authors, contributors, and collaborators who have made this work wonderful and this experience beautiful. Last and not least, we thank Dr. John White for his warmth, support, encouragement, and vigorous review of our work.
Funding: Canadian Institutes of Health Research (CIHR), the National Institutes of Health (NIH), and Human Frontier, along with support from Sinai Health Foundation and the Radcliffe Institute for Advanced Study at Harvard University.
Dr. Ben Mulcahy (l), Dr. Daniel Witvliet (c), Dr Mei Zhen (r)
Drs. Witvliet and Mulcahy led the study alongside scientists from Harvard’s Brain Institute, including Drs. Aravi Samuel and Jeff Lichtman.
- Christine’s completion
Congratulations to Christine Rehaluk on her recent successful defense of her Masters thesis in physiology!
“Electron Microscopy Analysis of the Gap Junctions of the Adult Caenorhabditis elegans“
Christine studied the bi-directional flow of charged ions and small metabolites through the gap junction pores. From two wildtype adult samples prepared using a Zhen lab protocol (a modified fixation protocol that allows better appearance of gap junctions in the C. elegans brain), Christine completed gap junction annotation, assessing the gap junctions where three innexin proteins that form gap junctions have been removed. Her results show that many gap junctions that reside in the wildtype brains are absent from the triple innexin mutant, validating that the fixation protocol has sufficient specificity for structural mapping of the gap junction connectome. Her comparison between two wildtype gap junction connectomes, as well as with that of the legacy wildtype connectomes, showed that at least some gap junctions are different between four wildtype individuals. The results are consistent with potential wiring differences among an isogenic population, a notion that has been recently validated for the chemical synapse connections.
- Science Robotics Jul 2
We are pleased to announce the publishing of Towards a live soft microrobot: optogenetic locomotion control of Caenorhabditis elegans in Science Robotics (PDF)
- Preprint Britz et al
Congratulations to Susoy et al. for the recent acceptance at Cell of Natural sensory context drives divers brain-wide activity during C. elegans mating (Preprint)
- Witvliet in Nature
Coming soon in Nature: Connectomes across development reveal principles of brain maturation in C. elegans. Congratulations to the authors! (Preprint)
- Science Robotics Jul2021
Coming soon (July 2021) in Science Robotics: Towards a live soft microrobot: optogenetic locomotion control of Caenorhabditis elegans
- Rory Gao
Welcome to Rory Gao, an Engineering Science student at the University of Toronto who is joining us for a summer student!
- Ni Ji – elife
Congratulations to Ni Ji et al. Corollary neuron underlies motor feedback to sustain forward motor state now at eLife (PDF)
- Witvliet in nature
Witvliet et al. Connectomes across development reveal principles of brain maturation in C. elegans was recently accepted in Nature (preprint). Congratulations!
- Real-time volumetric in Nature Methods
Now available in Nature Methods Wang et al. Real-time volumetric reconstruction of biological dynamics with light-field microscopy and deep learning (PDF)
- Welcome Leila Lesanpezeshki
Welcome to Leila Lesanpezeshki – a new postdoctoral fellow who joins us from Texas Tech.
Leila’s PhD focused on developing phenotypic assays to study the neuromuscular function of C. elegans. She developed a 3D burrowing assay using a hydrogel to rapidly assess neuromuscular health in C. elegans disease models. In a NASA funded project, she collaborated on sending worms to space to understand the effect of microgravity on muscle strength during spaceflight using a microfluidic technology developed in her PhD lab. As an engineer at Zhen Lab, she will be leveraging her microfluidic knowledge to develop new assays to understand how neural connectivity affects the behavior and neuromuscular function.
- We are pleased to welcome Jiacheng (Jackie) Chen!
We are pleased to welcome Jiacheng (Jackie) Chen, a new PhD student, to the lab.
- 2020 publications round up
A round-up of publications for 2020, great output with our colleagues:
– Overexpression of an ALS-associated FUS mutation in C. elegans disrupts NMJ morphology and leads to defective neuromuscular transmission. Markert et al. Biology Open (PDF)
– Open syntaxin overcomes synaptic transmission defects in diverse C. elegans exocytosis mutants. Tien et al. Nature Communications (PDF)
– Flexible motor sequence generation during stereotyped escape responses. Yuan et al. eLife (PDF)
– Efficient and cost‐effective 3D cellular imaging by sub‐voxel‐resolving light‐sheet add‐on microscopy. Zhao et al. J. Biophotonics (PDF)
– Optogenetic manipulation of postsynaptic cAMP using a novel transgenic mouse line enables synaptic plasticity and enhanced depolarization in the hippocampal dentate gyrus. Luyben et al. Frontiers in Neural Circuits (PDF)
- Capturing the Continuous Complexity of Behavior in C. elegans
Capturing the Continuous Complexity of Behavior in C. elegans. Congratulations to Tosif Ahamed and Greg J. Stephens on this outstanding work published in Nature Physics! (PDF)
- Welcome to our four Fall20/Winter21 undergrads!
Welcome to our four Fall20/Winter21 undergrads – Samuel Wu, Alice Xu, Mohammad Haddadnia, and Randa Higazy is a 4th year thesis student!
- Welcoming Neeaja Ramakrishnan!
Welcoming Neeaja Ramakrishnan to the PhD program in physiology after her recent reclassification exam. Congratulations!
- Good-bye to Maggie Chang
Good-bye to Maggie Chang, who was with the lab from 2016-2020. We wish her well as she commences a PhD program in biology at McGill.
- Congratulations to Daniel Witvliet!
- Well done on the hard work to Mona Wong!
Well done on the hard work to Mona Wong! She has transferred from the MSc program to a PhD.
- Many congratulations to Daniel Witvliet!
Many congratulations! Daniel Witvliet successfully defended his PhD in June. He’s now a PDF at Harvard.
- Congratulations to Yangning Lu!
Congratulations are in order! Yangning Lu successfully defended his PhD in February and has moved on to a postdoctoral fellowship at MIT.
- 2019 publications round up
A round-up of publications for 2019, great output with our colleagues:
– C. elegans neurons have functional dendritic spines. Cuentas-Condori et al. eLife (PDF)
– A 3D Model of Human Skeletal Muscle Innervated with Stem Cell-derived Motor Neurons Enables Epsilon-subunit Targeted Myasthenic Syndrome Studies. Bakooshli et al. eLife (PDF)
– An Upconversion Nanoparticle Enables Near Infrared-Optogenetic Manipulation of the C. elegans Motor Circuit. Ao et al. ACS Nano (PDF)
– Gain-of-function mutations in the UNC-2/CaV2α channel lead to excitation-dominant synaptic transmission in Caenorhabditis elegans. Huang et al. (PDF)
- Welcome to Hongruo Zhang, William Li, and Julian Moran!
We are excited to welcome three new graduate students: Hongruo Zhang, William Li, and Julian Moran.
- Welcome to Tosif!
Welcome to Tosif Ahamed, our new Postdoctoral Fellow, from Okinawa! He is handling the cold shock alright.
- Congratulations to Daniel and Lisa on becoming parents!
Congratulations to Daniel and Lisa on becoming parents! Welcome, baby Andrew Zhao Witvliet!
- An upconversion nanoparticle enables near infrared-optogenetic stimulation
With Shangbang Gao: An upconversion nanoparticle enables near infrared-optogenetic stimulation, ACS Nano (PDF)
- Welcome to our new graduate student, Mona Wong!
Welcome to our new graduate student, Mona Wong!
- Congratulations to Min for completing his MSc study
Congratulations to Min Wu for completing his MSc study!
- An automated vesicle clustering algorithm
With Christian Stigloher and Philip Kollmannsberger: An automated vesicle clustering algorithm, PLoS One (PDF)
- Congratulations! Ben, Daniel, and our collaborators
Congratulations! Ben, Daniel, and our collaborators. Our EM method paper on the C. elegans connectomics is online. The first paper from this long and hard journey is finally out (PDF)
- A review on the C. elegans motor circuit
With Quan Wen and Shangbang Gao: A review on the C. elegans motor circuit, now published in Royal Philosophical Transactions B. (PDF)
- Congratulations to our collaborator, the Wen lab
Congratulations to our collaborator, the Wen lab. Their study of the forward motor circuit oscillator is accepted for publication by the PNAS. Glad to be part of this nice work
- A rare genetic disorder JBS is likely a glutamate homeostasis metabolic disorder
Congratulations to Jyothsna, Ria, Wesley, Renee, and our collaborators the Calarco and Dennis labs. Our finding that a rare genetic disorder JBS is likely a glutamate homeostasis metabolic disorder, via worm behaviors is accepted for publication at the PLoS Genetics
- Excitatory motor neurons are the C. elegans oscillators
Congratulations to Shangbang, Asuka, Jun, and our collaborators – the Jin, Alkema and Fang-Yen labs – for decoding oscillators of the C. elegans motor circuit
- Welcome, Katarina
Katarina Pankova completed her PhD at the Ludwig Maximilian University of Munich. She will be joining our lab as a postdoctoral fellow
- Welcome, Charline
Charline Roy, a visiting PhD student from the Bessereau Lab joined us this fall. Welcome to Canada!
As of today, the Zhen lab generated 10,000 worm strains! Congratulations to Wesley Hung, who made the ZM10,000
- Funded by CIHR
Our mission, studying the basic biology of the C. elegans neural circuit development and function, has been awarded a CIHR Foundation Grant in the 2016-2017 competition. We are grateful for this opportunity