Lynn Landmesser, Ph.D.

Lynn Landmesser, Ph.D.
Arline J. & Curtis F. Garvin Professor of Medicine Emerita
Professor Emerita of Neurosciences
Distinguished University Professor
Department of Neurosciences
Case Western Reserve University


School of Medicine, Room E643
10900 Euclid Ave
Cleveland OH, 44106-4975

Phone : (216) 368-3996
Fax : (216) 368-4650
Email : lynn.landmesser@case.edu
 
 

RESEARCH INTERESTS

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 in birds and mammals 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. Current efforts are focused on two projects:

1) Role of spontaneous electrical activity in neural circuit formation. Rhythmic waves of propagating electrical activity are widespread in the developing nervous systems of birds and mammals. By altering such activity in intact chick 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, including transients of cAMP, using a light activated adenylyl cyclase BPAC.

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 firdt 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.

SELECTED PUBLICATIONS

  1. Maeno-Hikichi Y., Herlitze S., Landmesser L.T. (2014)
    Roles of spontaneous cAMP transients in spinal motor circuit development probed with the light activated adenylyl-cyclase BPAC. (in preparation).
  2. Hata K., Maeno-Hikichi, Y., Herlitze S., and Landmesser L.T. (2014)
    Distinct roles of different pre- and post-synaptic NCAM isoforms in early motoneuron-myotube interactions required for functional synapse formation (in preparation).
  3. Kastanenka K.V., Landmesser L.T. (2013)
    Optogenetic-mediated increases in in vivo spontaneous activity disrupt pool-specific but not dorsal-ventral motoneuron pathfinding. PNAS. 110:17528-17533.
  4. 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.
  5. 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.
  6. Kastanenka K.V. and Landmesser L.T. (2010)
    In-vivo activation of channelrhodopsin-2 reveals that normal patterns of spontaneous activity are required for motoneuron guidance and maintenance of guidance molecules. J. Neurosci. 30:10575-10585..
  7. Wang, S., Polo-Parada L. and Landmesser L.T. (2009)
    Characterization of rhythmic Ca2+ transients in early embryonic chick motoneurons: Ca2+ sources and effects of altered activation of transmitter receptors. J. Neurosci. 29:15232-15244..
  8. Hanson MG, Milner LD, Landmesser LT. (2008)
    Spontaneous rhythmic activity in early chick spinal cord influences distinct motor axon pathfinding decision. Brain Research Reviews. 57:77-85.
  9. 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.
  10. Hanson MG, Landmesser LT. (2006)
    Increasing the frequency of spontaneous rhythmic activity disrupts pool-specific axon fasciculation and pathfinding of embryonic spinal motoneurons. J. Neurosci. 2006 Dec 6; 26(49):12769-80.
  11. Li X, Gutierrez DV, Hanson MG, Han J, Mark MD, Chiel H, Hegemann P, Landmesser LT, Herlitze S. (2005)
    Fast noninvasive activation and inhibition of neural and network activity by vertebrate rhodopsin and green algae channelrhodopsin. Proc Natl Acad Sci U S A. 2005 Dec; 6(102(49)):17816-17821. Epub 2005 Nov 23.
  12. Polo-Parada L, Plattner F, Bose C, Landmesser LT. (2005)
    NCAM 180 acting via a conserved C-terminal domain and MLCK is essential for effective transmission with repetitive stimulation. Neuron. 2005 Jun 16; 46(6):917-931.
  13. Chan SA, Polo-Parada L, Landmesser LT, Smith C. (2005)
    Adrenal chromaffin cells exhibit impaired granule trafficking in NCAM knockout mice. J Neurophysiol. 2005 Aug; 94(2):1037-1047. 2005/03/30 [aheadofprint].
  14. Hanson MG, Landmesser LT. (2004)
    Normal patterns of spontaneous activity are required for correct motor axon guidance and the expression of specific guidance molecules. Neuron. 2004 Sep 2; 43(5):687-701.
  15. Polo-Parada L, Bose CM, Plattner F, Landmesser LT. (2004)
    Distinct roles of different neural cell adhesion molecule (NCAM) isoforms in synaptic maturation revealed by analysis of NCAM 180 kDa isoform-deficient mice. J Neurosci. 2004 Feb 25; 24(8):1852-1864.
  16. Hanson MG, Landmesser LT. (2003)
    Characterization of the circuits that generate spontaneous episodes of activity in the early embryonic mouse spinal cord. J Neurosci. 2003 Jan 15; 23(2):587-600.
  17. Polo-Parada L, Bose CM, Landmesser LT. (2001)
    Alterations in transmission, vesicle dynamics, and transmitter release machinery at NCAM-deficient neuromuscular junctions. Neuron. 2001 Dec 6; 32(5):815-828.
  18. Landmesser LT. (2001)
    The acquisition of motoneuron subtype identity and motor circuit formation. Int J Dev Neurosci. 2001 Apr; 19(2):175-182.
  19. Rafuse VF, Polo-Parada L, Landmesser LT. (2000)
    Structural and functional alterations of neuromuscular junctions in NCAM-deficient mice. J Neurosci. 2000 Sep 1; 20(17):6529-6539.
 
faculty/landmesser/index.txt · Last modified: 2014/11/13 00:17 (external edit)
 
Content © 1995-2007 by the Department of Neurosciences
in the School of Medicine at Case Western Reserve University.
All rights reserved.
Legal Notice

Web Design: rafael.salazar@case.edu
Recent changes RSS feed Powered by PHP Valid XHTML 1.0 Valid CSS Driven by DokuWiki