We are interested in the neuronal mechanisms by which the nervous system generates and coordinates rhythmic movements. Rhythmically active neural networks - central pattern generators (CPGs) -program the underlying motor pattern for these movements. In invertebrates - where the restricted number, large size, and identifiability of neurons offer technical advantages - progress in understanding CPGs and their adaptive modulation has been rapid. The study of these networks contributes not only to our understanding of motor systems but to our general understanding of the dynamics of neuronal ensembles. We analyze at the cellular and network level the heartbeat CPG in the leech This CPG comprises a network of oscillatory heart interneurons that interact synaptically among themselves and with segmental heart motor neurons. We use models that incorporate biophysical detail about intrinsic currents and synapses as tools to generate experimentally testable hypotheses and to extract principles of organization that can be transferred to other networks. Our immediate goal is complete models of the heartbeat CPG and of its interaction with segmental heart motor neurons to produce the heartbeat motor pattern. Our proposal is a step-by-step process for achieving this goal. 1a. To determine the strength and dynamics of the inhibitory synapses from two newly discovered premotor heart interneuron pairs onto rear heart motor neurons, and their activity pattern. 1b. To determine the intrinsic properties of the heart motor neurons and the properties of their intrasegmental electrical coupling and to analyze how heart motor neurons respond to inhibitory input and electrical coupling using dynamic clamp. 2. To determine the strength and dynamics of inhibitory connections and electrical coupling among heart interneurons. 3a. To construct a model of the heart motor neuron ensemble. 3a. To construct a canonical model of the heartbeat CPG. The models of this proposal cannot be separated from the experiments;the models are partially constructed, and through their deficiencies and successes they have generated and will continue to generate testable hypotheses and suggested new measurements to constrain parameters. Through the close interaction of modeling and experiments, we will refine the models and identify mechanisms by which oscillatory premotor networks attain functional phase relations and how they interact with motor neurons to produce coordinated behavior. This process will provide insights generally applicable to the normal functioning of CPGs and their coordination of motor neurons that will be useful in understanding the reaction of these networks to injury and disease. PUBLIC HEALTH RELEVACE Rhythmically active neural networks - central pattern generators (CPGs) - program rhythmic movements such as breathing and locomotion. In invertebrates - where the restricted number, large size, and identifiability of neurons offer technical advantages - progress in understanding CPGs has been rapid. The study of these networks will provide insights generally applicable to the normal functioning of CPGs that will be useful in understanding the reaction of CPG networks in vertebrates to spinal cord injury and disease and contribute to our general understanding of the dynamics of neuronal ensembles.

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Research Project (R01)
Project #
5R01NS024072-27
Application #
8044861
Study Section
Sensorimotor Integration Study Section (SMI)
Program Officer
Chen, Daofen
Project Start
1984-07-01
Project End
2013-03-31
Budget Start
2011-04-01
Budget End
2013-03-31
Support Year
27
Fiscal Year
2011
Total Cost
$332,281
Indirect Cost
Name
Emory University
Department
Biology
Type
Schools of Arts and Sciences
DUNS #
066469933
City
Atlanta
State
GA
Country
United States
Zip Code
30322
Marin, Boris; Barnett, William H; Doloc-Mihu, Anca et al. (2013) High prevalence of multistability of rest states and bursting in a database of a model neuron. PLoS Comput Biol 9:e1002930
Lamb, Damon G; Calabrese, Ronald L (2013) Correlated conductance parameters in leech heart motor neurons contribute to motor pattern formation. PLoS One 8:e79267
Lamb, Damon G; Calabrese, Ronald L (2012) Small is beautiful: models of small neuronal networks. Curr Opin Neurobiol 22:670-5
Roffman, Rebecca C; Norris, Brian J; Calabrese, Ronald L (2012) Animal-to-animal variability of connection strength in the leech heartbeat central pattern generator. J Neurophysiol 107:1681-93
Wright Jr, Terrence Michael; Calabrese, Ronald L (2011) Patterns of presynaptic activity and synaptic strength interact to produce motor output. J Neurosci 31:17555-71
Wright Jr, Terrence M; Calabrese, Ronald L (2011) Contribution of motoneuron intrinsic properties to fictive motor pattern generation. J Neurophysiol 106:538-53
Calabrese, Ronald L; Norris, Brian J; Wenning, Angela et al. (2011) Coping with variability in small neuronal networks. Integr Comp Biol 51:845-55
Wenning, Angela; Norris, Brian J; Doloc-Mihu, Anca et al. (2011) Bringing up the rear: new premotor interneurons add regional complexity to a segmentally distributed motor pattern. J Neurophysiol 106:2201-15
Norris, Brian J; Wenning, Angela; Wright, Terrence Michael et al. (2011) Constancy and variability in the output of a central pattern generator. J Neurosci 31:4663-74
Weaver, Adam L; Roffman, Rebecca C; Norris, Brian J et al. (2010) A role for compromise: synaptic inhibition and electrical coupling interact to control phasing in the leech heartbeat CpG. Front Behav Neurosci 4:

Showing the most recent 10 out of 69 publications