Lynn Landmesser, PhD

Professor Emeritus
Department of Neurosciences
School of Medicine

Research Information

Research Projects

We are interested in understanding how genetically encoded molecular signals and the environment interact to form complex neural circuits during embryonic and postnatal development. We focus on the spinal motor circuits that enable normal movement and locomotion and on elucidating mechanisms of motor axon pathfinding; synapse formation; the assembly of locomotor circuits; and the role of electrical activity (environmentally or self-generated) in these processes. We believe that mechanisms used during development to assemble circuits in the brain and spinal cord will be relevant to strategies for restoring neural circuits damaged by disease or injury.

Techniques range from molecular-genetic and cell culture to electrical and optical recording from intact neural circuits and using optogenetics to activate neural circuits in-vivo by light. Although I am no longer taking graduate students, I am actively collaborating with other labs.

Recent research are focused on two projects:

  1. Role of spontaneous electrical activity in neural circuit formation. Rhythmic waves of propagating electrical activity are widespread in developing nervous systems. By altering such activity in intact embryos via the light activated channel, ChR2, we showed that motor axon pathfinding was highly sensitive to the precise frequency of activity and that motoneuron pathfinding errors caused by slowing activity with drugs, could be rescued by driving activity at the normal frequency with light. Thus, modest alterations in activity caused by maternally taken drugs or by various neurological disorders may cause defects in neural circuit formation. We are interested in defining the downstream signaling pathways activated by such activity.
  2. Role of different isoforms of NCAM in formation and maturation of neuromuscular junctions. While NMJs form in NCAM deficient mice, they exhibit multiple structural and functional defects. By dynamically imaging synapse formation in cultures of NCAM deficient motoneurons and myotubes which exogenously express single isoforms of NCAM in motoneurons or myotubes, we found that certain isoforms of NCAM are required either pre- and post-synaptically for stable synapse formation. We are currently studying the cellular and molecular mechanisms by which NCAM enables motor axons to first be attracted to myotubes and to then transform their motile growth cones into stable synapses. Alterations in synapse formation, maturation and stabilization contribute to a number of neurological disorders, including spinal muscular atrophy or SMA.

Awards and Honors

National Academy of Sciences
2001
American Academy of Art and Science
1993

Publications

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Selected Publications 

Landmesser LT (2018) General principles of spinal motor development: early  contributions from research on avian embryos. Int. J. Dev. Biol. Int J Dev Biol 62:235-243.

Hata, K ., Maeno-Hikichi, Y., Yumoto, N., Burden SS, Landmesser, L.T. (2018) Distinct roles of different pre- and post-synaptic NCAM isoforms in early motoneuron-myotube interactions required for functional synapse formation. J. Neurosci. 38:498-510.

Cregg, JM, Jolly RS, Witt W, Chu K, Eastman B,  Alilain WJ, Philippidou P, Landmesser LT, Silver J (2017) A latent propriospinal network can restore diaphragm function after high cervical spinal cord injury. Cell Reports 21:654-665.

Cregg JM, Chu K, Dick TE, Landmesser LT, Silver J (2017) Phasic inhibition  as a mechanism for generation of rapid respiratory rhythms. PNAS 114: 12815-12820.

Kastanenka KV, Landmesser LT (2013) Optogenetic-mediated increases in in vivo spontaneous activity disrupt pool-specific but not dorsal-ventral motoneuron pathfinding. PNAS 110:17528-17533.

Maeno-Hikichi, Y., Polo-Parada, L., Kastanenka, K., Landmesser, L.T. (2011) Frequency dependent modes of synaptic vesicle exocytosis and endocytosis at adult mouse neuromuscular junctions.. J. Neurosci 31: 1093-1105. PMC3642848

Park G-H, Maeno-Hikichi Y, Awano T, Landmesser LT, Monini U (2010) Reduced SMN protein in motor neuronal progenitors functions cell autonomously to cause spinal muscular atrophy in model mice expressing the human centromeric (SMN2) gene. J. Neurosci. 30: 12005-12019. PMCID 2944776

Kastanenka, K.V. and Landmesser, L.T. (2010) In-vivo activation of channelrhodopsin-2 reveals that normal patters of spontaneous activity are required for motoneuron guidance and maintenance of guidance molecules. J. Neurosci. 30:10575-10585.  PMCID  2934783

Kariya S., Park G.H., Maeno-Hikichi Y., Leykekhman O., Lutz C., Arkovitz, M.S., Landmesser, L.T., Monani, U.R. (2008) Reduced SMN protein impairs maturation of the neuromuscular junctions in mouse models of spinal muscular atrophy. Hum. Mol. Genet. 17:2552-2569 PMID 18492800

Hata, K., Polo-Parada , L.. and Landmesser, L.T. (2007) Selective targeting of different neural cell adhesion molecule isoforms during motoneuron-myotube synapse formation in culture and the switch from an immature to mature form of synaptic vesicle cycling. J. Neurosci. 27:14481-14493.

Li, X., Gutierrez, D.V., Hanson, G.M., Han, J., Marl, M.D., Chiel, H., Hegemann, P., Landmesser, L.T. and Herlitze, S. (2005) Fast non-invasive  activation and inhibition of neural and network activity by vertebrate rhodopsin and green algae channelrhodopsin. P.N.A.S. 102:17816-17821.

Hanson M.G., and Landmesser, L. (2004) Normal patterns of spontaneous activity are required for correct  motor axon guidance and the expression of specific guidance molecules. Neuron 43:687-701.

Polo-Parada, L., Plattner, F., Bose, C.M. and Landmesser, L.T. (2005) NCAM acting via  a conserved  C-terminal domain and requiring  MLCK activity is essential for effective  transmission with repetitive stimulation. Neuron 46: 917-931.

Polo-Parada, L., Bose, C.M. and Landmesser, L. (2001) Alterations in Transmission, Vesicle Dynamics, and Transmitter Release Machinery at NCAM-Deficient Neuromuscular Junctions. Neuron 32: 815-828.

Education

Doctor of Philosophy
University of California, Los Angeles
1969
Postdoctoral Fellowship
Neurobiology
University of Utah
1972