ACTIVITY DEPENDENT DEVELOPMENT OF SPINAL MOTOR NEURONS

Yale University, New Haven CT

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Abstract

DESCRIPTION (Adapted from applicant's 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.