The primary purpose of this work is to elucidate the cellular and synaptic mechanisms responsible for the genesis of rhythmic activity by the vertebrate spinal cord. Experiments are performed on isolated preparations of the chick and mouse spinal cords maintained in vitro. Most of our effort is focused on understanding the mechanisms responsible for locomotor activity by the mouse spinal cord. We have discovered that electrical activation of motoneurons ? generally considered the output elements of the spinal cord ? can trigger locomotor-like activity. This suggests the existence of unexpected connections between motoneurons and the spinal circuitry responsible for generating locomotion. We are investigating these connections using optical and electrophysiological methods.? ? We have also developed a new method based on electroporation to load calcium-sensitive dyes into neurons. We are applying this technique to the mouse spinal cord in combination with 2-photon microscopy to identify neurons activated by motoneuron stimulation. We have found evidence that ventral root stimulation results in an unexpected monosynaptic glutamatergic response in Renshaw cells and possibly other motoneurons. We are now investigating these connections to understand their role in locomotion.

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Intramural Research (Z01)
Project #
1Z01NS002787-18
Application #
7323208
Study Section
(LNLC)
Project Start
Project End
Budget Start
Budget End
Support Year
18
Fiscal Year
2006
Total Cost
Indirect Cost
City
State
Country
United States
Zip Code
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
Oz, Murat; Yang, Keun-Hang; O'donovan, Michael J et al. (2005) Presynaptic angiotensin II AT1 receptors enhance inhibitory and excitatory synaptic neurotransmission to motoneurons and other ventral horn neurons in neonatal rat spinal cord. J Neurophysiol 94:1405-12
O'Donovan, Michael J (2005) Serotonergic neurones drive spontaneous activity in the developing mouse hindbrain. J Physiol 566:643

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