The primary goal of this research is to understand the operation of the spinal networks responsible for generating locomotor activity in the mouse. In the past year, we have been developing mice that express light-activated channels that can hyperpolarize and depolarize neurons. We hope to use these mice to test the role of specific spinal neuron types in the genesis of locomotor activity. We are also continuing our imaging studies and have published work in the spinal cord of the chick embryo showing that motoneurons, the output elements of the spinal cord, seem to be critical in activating the spinal network during each cycle of spontaneous rhythmic activity. ? In a collaborative project with Dr. Aharon Lev-Tov (Hebrew University, Israel) we have been investigating how locomotor activity in the lumbar cord can be triggered by stimulating sensory nerves that innervate the tail. We have identified a class of interneurons whose axons travel in the ventral part of the spinal cord that appear to mediate this effect. We are currently establishing if these neurons, or a subset of them, project to the cerebellum. We have also been developing a preparation of the spinal cord that will allow studies of locomotor activity in the adult spinal cord. Currently our work is restricted to the neonate because its isolated spinal cord can be maintained alive in vitro whereas the adult cord cannot. ? Finally, we have begun a new project working with the very simple organism - C.Elegans - to use optical methods to analyze its locomotor circuitry. This model system should allow us to rapidly evaluate the utility of specific calcium and voltage sensitive proteins as reporters of neural activity and generate hypotheses about the operation of motor circuits that can be tested in the more complex nervous system of the mouse.

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Intramural Research (Z01)
Project #
1Z01NS003022-01
Application #
7594713
Study Section
Project Start
Project End
Budget Start
Budget End
Support Year
1
Fiscal Year
2007
Total Cost
$945,506
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
O'Donovan, Michael J; Bonnot, Agnes; Mentis, George Z et al. (2008) Imaging the spatiotemporal organization of neural activity in the developing spinal cord. Dev Neurobiol 68:788-803
Arai, Yoshiyasu; Mentis, George Z; Wu, Jiang-Young et al. (2007) Ventrolateral origin of each cycle of rhythmic activity generated by the spinal cord of the chick embryo. PLoS One 2:e417
Blivis, D; Mentis, G Z; O'donovan, M J et al. (2007) Differential effects of opioids on sacrocaudal afferent pathways and central pattern generators in the neonatal rat spinal cord. J Neurophysiol 97:2875-86
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