Research Topics
Genomes and GenesSpecies | Jeff W LichtmanSummaryAffiliation: Harvard University Country: USA Publications
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Publications
In vivo imaging of axonal degeneration and regeneration in the injured spinal cordMartin Kerschensteiner
Department of Molecular and Cellular Biology, Harvard University, 7 Divinity Avenue, Cambridge, Massachusetts 02138, USA
Nat Med 11:572-7. 2005..These results suggest that time-lapse imaging of spinal cord injury may provide a powerful analytical tool for assessing the pathogenesis of spinal cord injury and for evaluating therapies that enhance regeneration...
Effects of neurotoxic and neuroprotective agents on peripheral nerve regeneration assayed by time-lapse imaging in vivoY Albert Pan
Department of Anatomy and Neurobiology, Washington University Medical School, St. Louis, Missouri 63110, USA
J Neurosci 23:11479-88. 2003..Because neuropathy is the major dose-limiting side effect of vincristine, we propose that its efficacy could be enhanced by coadministration of FK506 analogs that are neuroactive but not immunosuppressive...
Ome sweet ome: what can the genome tell us about the connectome?Jeff W Lichtman
Department of Molecular and Cellular Biology and Center for Brain Science, Harvard University, Cambridge, MA 02138, USA
Curr Opin Neurobiol 18:346-53. 2008..Remarkably similar objections were voiced when the Human Genome Project, now widely viewed as a success, was first proposed. We revisit that controversy to ask if it holds any lessons for proposals to map the connectome...
Fluorescence microscopyJeff W Lichtman
Department of Molecular and Cell Biology, Harvard University, 7 Divinity Avenue, Cambridge, Massachusetts 02138, USA
Nat Methods 2:910-9. 2005..This review attempts to provide a framework for understanding excitation of and emission by fluorophores, the way fluorescence microscopes work, and some of the ways fluorescence can be optimized...
The big and the small: challenges of imaging the brain's circuitsJeff W Lichtman
Molecular and Cellular Biology and Center for Brain Science, Harvard University, Cambridge, MA 02138, USA
Science 334:618-23. 2011..These difficulties also explain the thrust behind the enormous amount of innovation centered on microscopy in neuroscience. We highlight some recent progress and the challenges that remain...
Translational neuroscience during the Second World WarJeff W Lichtman
Harvard University, USA
J Exp Biol 209:3485-7. 2006
Imaging the neuromuscular junction over the past centuriesJu Lu
Department of Molecular and Cellular Biology, Harvard University, Cambridge, MA 02138, USA
Sheng Li Xue Bao 59:683-96. 2007..In this paper we review the historical development of research on some key aspects of the NMJ, including its structure, nicotinic acetylcholine receptor distribution, the process of synaptic vesicle release, and its development...
A technicolour approach to the connectomeJeff W Lichtman
Department of Molecular and Cellular Biology and Center for Brain Science, Harvard University, Cambridge, Massachusetts 02138, USA
Nat Rev Neurosci 9:417-22. 2008..Here we review recent advances in this area, along with some of the opportunities that these advances present and the obstacles that remain...
Pervasive synaptic branch removal in the mammalian neuromuscular system at birthJuan C Tapia
Department of Molecular and Cellular Biology, Harvard University, Cambridge, MA 02138, USA
Neuron 74:816-29. 2012..Analogous changes in connectivity may occur in the CNS. VIDEO ABSTRACT:..
Attenuation of age-related changes in mouse neuromuscular synapses by caloric restriction and exerciseGregorio Valdez
Department of Molecular and Cellular Biology and Center for Brain Science, Harvard University, Cambridge, MA 02138, USA
Proc Natl Acad Sci U S A 107:14863-8. 2010..These results demonstrate a critical effect of aging on synaptic structure and provide evidence that interventions capable of extending health span and lifespan can partially reverse these age-related synaptic changes...
Lysosomal activity associated with developmental axon pruningJae W Song
Department of Molecular and Cellular Biology, Harvard University, Cambridge, Massachusetts 02138, USA
J Neurosci 28:8993-9001. 2008..We propose that lysosomal activity is a central feature of synapse elimination. Moreover, staining for lysosomal activity may serve as a marker for regions of the developing nervous system undergoing axon pruning...
Chapter 11: Imaging fluorescent mice in vivo using confocal microscopyStephen G Turney
Department of Molecular and Cellular Biology, Center for Brain Science, Harvard University, Cambridge, Massachusetts 02138, USA
Methods Cell Biol 89:309-27. 2008....
Transgenic strategies for combinatorial expression of fluorescent proteins in the nervous systemJean Livet
Department of Molecular and Cellular Biology and Center for Brain Science, Harvard University, Cambridge, Massachusetts 02138, USA
Nature 450:56-62. 2007..The ability of the Brainbow system to label uniquely many individual cells within a population may facilitate the analysis of neuronal circuitry on a large scale...
Shared resistance to aging and ALS in neuromuscular junctions of specific musclesGregorio Valdez
Department of Molecular and Cellular Biology and Center for Brain Science, Harvard University, Cambridge, Massachusetts, United States of America
PLoS ONE 7:e34640. 2012..Together, these results reveal novel structural, regional and molecular parallels between aging and ALS...
Rapid and modifiable neurotransmitter receptor dynamics at a neuronal synapse in vivoCorey M McCann
Department of Molecular and Cellular Biology, Harvard University, 7 Divinity Ave, Cambridge, Massachusetts 02138, USA
Nat Neurosci 11:807-15. 2008..Therefore, neurotransmitter receptor dynamism associated with rapid changes in synaptic efficacy precedes long-lasting structural changes in synaptic connectivity...
The interscutularis muscle connectomeJu Lu
Department of Molecular and Cellular Biology, Harvard University, Cambridge, Massachusetts, USA
PLoS Biol 7:e32. 2009..This variability may arise from the dominant role of synaptic competition in establishing the final circuit...
Seeing circuits assembleJeff W Lichtman
Department of Molecular and Cellular Biology, Center for Brain Science, Harvard University, Cambridge, MA 02138, USA
Neuron 60:441-8. 2008..e., neurons, glia, and progenitors) that inhabit brains. New tools will certainly be needed if we wish to monitor the myriad cooperative and competitive interactions at play in the cellular society that builds brains...
Imaging axonal transport of mitochondria in vivoThomas Misgeld
Department of Molecular and Cellular Biology, Harvard University, 7 Divinity Avenue, Cambridge, Massachusetts 02138, USA
Nat Methods 4:559-61. 2007..We show that axon damage and recovery lead to early and sustained changes in anterograde and retrograde transport. In vivo imaging of mitochondria will be a useful tool to analyze this essential organelle...
Reversing the outcome of synapse elimination at developing neuromuscular junctions in vivo: evidence for synaptic competition and its mechanismStephen G Turney
Center for Brain Science and Department of Molecular and Cellular Biology, Harvard University, Cambridge, Massachusetts, United States of America
PLoS Biol 10:e1001352. 2012..These results demonstrate competition at the synaptic level and enable us to provide a conceptual framework for understanding this form of synaptic plasticity...
In vivo imaging of presynaptic terminals and postsynaptic sites in the mouse submandibular ganglionCorey M McCann
Department of Molecular and Cellular Biology, Harvard University, Cambridge, Massachusetts 02138, USA
Dev Neurobiol 68:760-70. 2008..The submandibular ganglion is an ideal site to study the formation, elimination, and maintenance of synaptic connections between neurons in vivo...
Semi-automated reconstruction of neural processes from large numbers of fluorescence imagesJu Lu
Department of Molecular and Cellular Biology, Harvard University, Cambridge, Massachusetts, United States of America
PLoS ONE 4:e5655. 2009..5 mm per hour. We found an error rate in the automatic tracing mode of approximately 1 error per 250 um of axonal length. We demonstrated the capacity of the program by reconstructing the connectome of motor axons in a small mouse muscle...
Agrin promotes synaptic differentiation by counteracting an inhibitory effect of neurotransmitterThomas Misgeld
Department of Molecular and Cellular Biology, Harvard University, Cambridge, MA 02138, USA
Proc Natl Acad Sci U S A 102:11088-93. 2005..Similar interactions between neurotransmitters and synaptic organizing molecules may operate at synapses in the central nervous system...
Rapid synapse elimination after postsynaptic protein synthesis inhibition in vivoCorey M McCann
Department of Molecular and Cellular Biology, Harvard University, Cambridge, Massachusetts 02138, USA
J Neurosci 27:6064-7. 2007....
Controlling the orientation and synaptic differentiation of myotubes with micropatterned substratesJacinthe Gingras
Department of Molecular and Cellular Biology, Harvard University, Cambridge, Massachusetts, USA
Biophys J 97:2771-9. 2009..Our results represent what we believe is a new approach for musculoskeletal tissue engineering, and our model sheds light on mechanisms of myotube alignment in vivo...
High-contrast en bloc staining of neuronal tissue for field emission scanning electron microscopyJuan Carlos Tapia
Department of Molecular and Cellular Biology, Harvard University, Cambridge, Massachusetts, USA
Nat Protoc 7:193-206. 2012..This protocol takes 7-15 d to prepare resin-embedded tissue, cut sections and produce serial section images...
Agrin and synaptic laminin are required to maintain adult neuromuscular junctionsMelanie A Samuel
Department of Molecular and Cellular Biology and Center for Brain Science, Harvard University, Cambridge, Massachusetts, United States of America
PLoS ONE 7:e46663. 2012..Together, these results demonstrate that pre- and post-synaptic organizers actively function to maintain the structure and function of adult NMJs...
It's lonely at the top: winning climbing fibers ascend dendrites soloRyan W Draft
Department of Molecular and Cellular Biology, Center for Brain Science, Harvard University, Cambridge, MA 02138, USA
Neuron 63:6-8. 2009..In this issue of Neuron, Hashimoto et al. show that, by the time climbing fibers ascend the dendrites, the winner and losers are already decided...
Super-resolution laser scanning microscopy through spatiotemporal modulationJu Lu
Department of Molecular and Cellular Biology, Center for Brain Science, Department of Chemistry and Chemical Biology, Harvard University, USA
Nano Lett 9:3883-9. 2009..When combined with multiphoton excitation, both schemes can image thick samples with three-dimensional optical sectioning and much improved resolution...
Developmental bias in cleavage-stage mouse blastomeresInna Tabansky
The Howard Hughes Medical Institute, Harvard University, Cambridge, MA 02138, USA Harvard Stem Cell Institute, Harvard University, Cambridge, MA 02138, USA Department of Stem Cell and Regenerative Biology, Harvard University, Cambridge, MA 02138, USA Department of Molecular and Cellular Biology, Harvard University, Cambridge, MA 02138, USA
Curr Biol 23:21-31. 2013..To determine whether blastomere allocation to the two earliest lineages is random, we developed and utilized a recombination-mediated, noninvasive combinatorial fluorescent labeling method for embryonic lineage tracing...
Mouse transgenic lines that selectively label type I, type IIa, and types IIX+B skeletal muscle fibersJoe V Chakkalakal
Department of Molecular and Cellular Biology, Center for Brain Science, Harvard University, 52 Oxford Street, Cambridge, Massachusetts
Genesis 50:50-8. 2012..We demonstrate their use for motor unit reconstruction and live imaging of nerve-dependent alterations in fiber type. genesis 50:50-58, 2012. © 2011 Wiley Periodicals, Inc...
Peptide tags for labeling membrane proteins in live cells with multiple fluorophoresCorey M McCann
Harvard University, Cambridge, MA, USA
Biotechniques 38:945-52. 2005....
Functional muscle regeneration with combined delivery of angiogenesis and myogenesis factorsCristina Borselli
Wyss Institute, Harvard University, Cambridge, MA 02138, USA
Proc Natl Acad Sci U S A 107:3287-92. 2010..These results support the utility of simultaneously targeting distinct aspects of the regenerative process...
Axon branch removal at developing synapses by axosome sheddingDerron L Bishop
Department of Molecular and Cellular and Biology, Harvard University, Cambridge, MA 02138, USA
Neuron 44:651-61. 2004..After this engulfment, the axosome's contents mix with the cytoplasm of the glial cell. Axosome shedding might underlie other forms of axon loss and may provide a pathway for interactions between axons and glia...
Repulsive force based snake model to segment and track neuronal axons in 3D microscopy image stacksHongmin Cai
Center for Bioinformatics, Harvard Center for Neurodegeneration and Repair, and Department of Radiology, Brigham and Women's Hospital, Boston, MA 02114, USA
Neuroimage 32:1608-20. 2006..Individual axons can then be extracted based on the segmentation results. The utility and performance of the method are demonstrated using 3D axonal images obtained from transgenic mice that express fluorescent protein...
Genetic evidence that relative synaptic efficacy biases the outcome of synaptic competitionMario Buffelli
Department of Anatomy and Neurobiology, Washington University School of Medicine, 660 South Euclid, St Louis, Missouri 63110, USA
Nature 424:430-4. 2003..Here we use a genetic method to selectively inhibit neurotransmission from one of two inputs to a single target cell. We show that more powerful inputs are strongly favoured competitors during synapse elimination...
Pre-existing pathways promote precise projection patternsQuyen T Nguyen
Department of Anatomy and Neurobiology, Washington University School of Medicine, St. Louis, MO 63110, USA
Nat Neurosci 5:861-7. 2002..These results suggest that nonspecific guidance cues can be sufficient to generate specific synaptic circuitry...
Roles of neurotransmitter in synapse formation: development of neuromuscular junctions lacking choline acetyltransferaseThomas Misgeld
Department of Anatomy and Neurobiology, Washington University School of Medicine, St Louis, MO 63110, USA
Neuron 36:635-48. 2002..At subsequent stages, neurotransmission delays some steps in synaptic maturation but accelerates others. Thus, neurotransmission affects synaptogenesis from early stages and coordinates rather than drives synaptic maturation...
Tyrosine-phosphorylated and nonphosphorylated isoforms of alpha-dystrobrevin: roles in skeletal muscle and its neuromuscular and myotendinous junctionsR Mark Grady
Dept of Pediatrics, Washington University School of Medicine, Pediatric Research Bldg, St Louis, MO 63110, USA
J Cell Biol 160:741-52. 2003..More generally, alphaDB may play multiple roles in muscle by means of differential distribution of isoforms with distinct signaling or structural properties...
In vivo time-lapse imaging of synaptic takeover associated with naturally occurring synapse eliminationMark K Walsh
Department of Anatomy and Neurobiology, Washington University School of Medicine, Saint Louis, MO 63110, USA
Neuron 37:67-73. 2003..These results show synaptic competition is not always monotonic and that one axon's contraction in synaptic area is associated with another axon's expansion...
The role of neuronal identity in synaptic competitionNarayanan Kasthuri
Department of Anatomy and Neurobiology, Washington University School of Medicine, St Louis, Missouri 63110, USA
Nature 424:426-30. 2003..An accompanying paper tests the idea that the amount of neurotransmitter released is this global resource...
Synaptic dynamism measured over minutes to months: age-dependent decline in an autonomic ganglionWen-Biao Gan
Department of Anatomy and Neurobiology, Washington University School of Medicine, 660 South Euclid, Box 8108, St. Louis, Missouri 63110, USA
Nat Neurosci 6:956-60. 2003..The long-term stability of synaptic patterns could provide a structural basis for the persistence of memory in the adult nervous system...
Watching the neuromuscular junctionJeff W Lichtman
Department of Anatomy and Neurobiology, Washington University Medical School, St Louis, MO 63110, USA
J Neurocytol 32:767-75. 2003..The development, maturation, stability, remodeling and regeneration of neuromuscular junctions and motor units can then be assessed over intervals ranging from seconds to months...
Nerve-independent formation of a topologically complex postsynaptic apparatusTerrance T Kummer
Dept. of Anatomy and Neurobiology, Washington University School of Medicine, 660 South Euclid Ave, St. Louis, MO 63110, USA
J Cell Biol 164:1077-87. 2004..These results reveal the sequence of steps by which a topologically complex domain forms on a cell and suggest an unexpected nerve-independent role for the postsynaptic cell in generating this topological complexity...
Age-associated synapse elimination in mouse parasympathetic gangliaJay S Coggan
Neurobiology Section, Division of Biology, University of California, San Diego, La Jolla, California 92093, USA
J Neurobiol 60:214-26. 2004..These results demonstrate primary, age-associated synapse elimination with functional consequences that cannot be explained by pre- or postsynaptic cell death...
Neurotransmitter receptor dynamics studied in vivo by reversible photo-unbinding of fluorescent ligandsMohammed Akaaboune
Department of Anatomy and Neurobiology, Washington University School of Medicine, 660 South Euclid Avenue, St. Louis, MO 63110, USA
Neuron 34:865-76. 2002..These results demonstrate remarkable molecular dynamism underlying macroscopic stability of the postsynaptic membrane, and establish alpha-dystrobrevin as a key control point for regulation of mobility and turnover...
A compensatory subpopulation of motor neurons in a mouse model of amyotrophic lateral sclerosisAnneliese M Schaefer
Department of Anatomy and Neurobiology, Washington University School of Medicine, Saint Louis, MO 63110, USA
J Comp Neurol 490:209-19. 2005..Identification of factors that protect "compensatory" motor neurons from degenerative changes may provide new targets for therapeutic intervention...
The rise of the 'projectome'Narayanan Kasthuri
Nat Methods 4:307-8. 2007
Development of presynaptic inhibition onto retinal bipolar cell axon terminals is subclass-specificTimm Schubert
Department of Biological Structure, University of Washington, Seattle, Washington 98195 7420, USA
J Neurophysiol 100:304-16. 2008..Our data suggest that presynaptic modulation of glutamate transmission from bipolar cells matures rapidly and is differentially coordinated for GABAergic and glycinergic synapses onto distinct bipolar cell subclasses...
Research Grants
- Confocal/Multiphoton MicroscopeJeff Lichtman; Fiscal Year: 2004..It will be available to other members of the Neuroscience community at Washington University, particularly for exploring and developing new optical imaging tools. ..
- COMPETITION BETWEEN AXONS AT THE NEUROMUSCULAR JUNCTIONJeff Lichtman; Fiscal Year: 2006..It is hoped that these experiments will provide essential and fundamental insights into the cell biological phenomena that regulate synapse number and distribution in the nervous system. ..
- COMPETITION BETWEEN AXONS AT THE NEUROMUSCULAR JUNCTIONJeff Lichtman; Fiscal Year: 2007....
- COMPETITION BETWEEN AXONS AT THE NEUROMUSCULAR JUNCTIONJeff Lichtman; Fiscal Year: 2007..abstract_text> ..
- COMPETITION BETWEEN AXONS AT THE NEUROMUSCULAR JUNCTIONJeff W Lichtman; Fiscal Year: 2010..abstract_text> ..
- COMPETITION BETWEEN AXONS AT THE NEUROMUSCULAR JUNCTIONJeff Lichtman; Fiscal Year: 2001..Because learning disorders and memory impairments are common but at present almost entirely without rational treatment, the kind of basic information this proposal aims to provide concerning how synapses change is likely to be useful. ..
- COMPETITION BETWEEN AXONS AT THE NEUROMUSCULAR JUNCTIONJeff Lichtman; Fiscal Year: 1993..As such, understanding the biological basis of this phenomenon is fundamental to an understanding of brain maturation and function...
- Cellular and Molecular Analysis of Defects at Aging Neuromuscular SynapsesJoshua R Sanes; Fiscal Year: 2010..Together, these studies will provide insights into age-related neural defects that may not only provide ways to ameliorate sarcopenia but also be generally applicable to the nervous system. ..
