Network Function in the Developing Spinal Cord of the Chick Embryo

O'Donovan, Michael J.

Abstract

The primary objective of this work is to elucidate the cellular and synaptic mechanisms responsible for the genesis of spontaneous rhythmic activity in the developing spinal cord. Experiments are performed on isolated preparations of the chick and mouse spinal cords maintained in vitro. We use electrophysiological, optical and anatomical methods to analyze the function and properties of the developing networks. Recently we formulated a quantitative and qualitative model to account for the genesis of rhythmic activity by developing spinal networks. Crucial to this model are our recent observations that network activity and synaptic transmission are depressed after a spontaneous episode. This depression arises in part because of a decrease in the responsiveness of postsynaptic glutamate and GABA receptors. We have also been investigating the spontaneous activity generated by the lumbosacral cord of the fetal mouse. We have found that activity comprises large recurrent depolarizations that can be recorded from the ventral roots. In neonatal cords (P3) it has been possible to activate another network that may be the precursor of the adult locomotor network. Once active, this network drives contralateral motoneurons to discharge in an alternating manner. Imaging studies are currently in progress to identify the interneurons responsible for this pattern of activity.

Funding Agency

• Agency: National Institute of Health (NIH)
• Institute: National Institute of Neurological Disorders and Stroke (NINDS)
• Type: Intramural Research (Z01)
• Project #: 1Z01NS002787-10
• Application #: 6111867
• Study Section: Special Emphasis Panel (LNLC)
• Support Year: 10
• Fiscal Year: 1998

Institution

• Name: National Institute of Neurological Disorders and Stroke
• Country: United States

Publications

Bonnot, Agnes; Chub, Nikolai; Pujala, Avinash et al. (2009) Excitatory actions of ventral root stimulation during network activity generated by the disinhibited neonatal mouse spinal cord. J Neurophysiol 101:2995-3011

Jean-Xavier, Celine; Mentis, George Z; O'Donovan, Michael J et al. (2007) Dual personality of GABA/glycine-mediated depolarizations in immature spinal cord. Proc Natl Acad Sci U S A 104:11477-82

Oz, Murat; Yang, Keun-Hang; Shippenberg, Toni S et al. (2007) Cholecystokinin B-type receptors mediate a G-protein-dependent depolarizing action of sulphated cholecystokinin ocatapeptide (CCK-8s) on rodent neonatal spinal ventral horn neurons. J Neurophysiol 98:1108-14

Personius, Kirkwood E; Chang, Qiang; Mentis, George Z et al. (2007) Reduced gap junctional coupling leads to uncorrelated motor neuron firing and precocious neuromuscular synapse elimination. Proc Natl Acad Sci U S A 104:11808-13

Mentis, George Z; Siembab, Valerie C; Zerda, Ricardo et al. (2006) Primary afferent synapses on developing and adult Renshaw cells. J Neurosci 26:13297-310

Tabak, Joel; O'Donovan, Michael J; Rinzel, John (2006) Differential control of active and silent phases in relaxation models of neuronal rhythms. J Comput Neurosci 21:307-28

Mentis, George Z; Gravell, Maneth; Hamilton, Rebecca et al. (2006) Transduction of motor neurons and muscle fibers by intramuscular injection of HIV-1-based vectors pseudotyped with select rabies virus glycoproteins. J Neurosci Methods 157:208-17

Chub, Nikolai; Mentis, George Z; O'donovan, Michael J (2006) Chloride-sensitive MEQ fluorescence in chick embryo motoneurons following manipulations of chloride and during spontaneous network activity. J Neurophysiol 95:323-30

O'Donovan, Michael J; Bonnot, Agnes; Wenner, Peter et al. (2005) Calcium imaging of network function in the developing spinal cord. Cell Calcium 37:443-50

Mentis, George Z; Alvarez, Francisco J; Bonnot, Agnes et al. (2005) Noncholinergic excitatory actions of motoneurons in the neonatal mammalian spinal cord. Proc Natl Acad Sci U S A 102:7344-9