Abstract

: This proposal will explore the late developmental events that sculpt connectivity in the spinal cord as a function of synaptic activity. Previous work has shown that the postnatal development of molecular composition and dendritic architecture in spinal motor neurons depends upon glutamatergic synaptic activity in early postnatal life. The glutamate receptors expressed by developing motor neurons are qualitatively and quantitatively different from those expressed by adult motor neurons. Do these distinct neonatal glutamate receptors play a special role in promoting the activity-dependent development of motor neurons? This hypothesis will be tested by using herpes-simplex based viral vectors to infect spinal neurons in vivo in order to increase the expression of AMPA (specific aim 1) and NMDA (specific aim 2) receptor subunits that undergo the most marked developmental change in expression.
Specific aim 3 will test the hypothesis that glutamate receptor stimulation is mediated by activation of neuronal or endothelial forms of NOS during early postnatal life by using acute application of NOS antagonists or examining dendritic development in NOS knock-out mice.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Research Project (R01)
Project #
3R01NS029837-07S1
Application #
6321330
Study Section
Neurology B Subcommittee 2 (NEUB)
Program Officer
Nichols, Paul L
Project Start
1993-02-01
Project End
2000-08-31
Budget Start
1999-09-01
Budget End
2000-08-31
Support Year
7
Fiscal Year
2000
Total Cost
$25,000
Indirect Cost

  Institution

Name
Yale University
Department
Neurology
Type
Schools of Medicine
DUNS #
082359691
City
New Haven
State
CT
Country
United States
Zip Code
06520

  Publications

Zhang, L; Hsu, F-C; Mojsilovic-Petrovic, J et al. (2015) Structure-function analysis of SAP97, a modular scaffolding protein that drives dendrite growth. Mol Cell Neurosci 65:31-44
Kalb, Robert G; Zhou, Weiguo; Zhang, Lei (2013) The molecular basis of experience-dependent motor system development. Adv Exp Med Biol 782:23-38
Jeong, Goo-Bo; Mojsilovic-Petrovic, Jelena; Boccitto, Marco et al. (2011) Signaling events in axons and/or dendrites render motor neurons vulnerable to mutant superoxide dismutase toxicity. J Neurosci 31:295-9
Zhou, Weiguo; Zhang, Lei; Guoxiang, Xiong et al. (2008) GluR1 controls dendrite growth through its binding partner, SAP97. J Neurosci 28:10220-33
Zhang, Lei; Schessl, Joachim; Werner, Markus et al. (2008) Role of GluR1 in activity-dependent motor system development. J Neurosci 28:9953-68
Xiong, Guoxiang; Mojsilovic-Petrovic, Jelena; Perez, Cristian A et al. (2007) Embryonic motor neuron dendrite growth is stunted by inhibition of nitric oxide-dependent activation of soluble guanylyl cyclase and protein kinase G. Eur J Neurosci 25:1987-97
Kalb, Robert; Solomon, David (2007) Space exploration, Mars, and the nervous system. Arch Neurol 64:485-90
Mojsilovic-Petrovic, Jelena; Jeong, Goo-Bo; Crocker, Amanda et al. (2006) Protecting motor neurons from toxic insult by antagonism of adenosine A2a and Trk receptors. J Neurosci 26:9250-63
Jeong, Goo-Bo; Werner, Markus; Gazula, Valeswara-Rao et al. (2006) Bi-directional control of motor neuron dendrite remodeling by the calcium permeability of AMPA receptors. Mol Cell Neurosci 32:299-314
David, Samuel; Stegenga, Susan L; Hu, Peter et al. (2005) Expression of serum- and glucocorticoid-inducible kinase is regulated in an experience-dependent manner and can cause dendrite growth. J Neurosci 25:7048-53

Showing the most recent 10 out of 35 publications