The general goal of this proposal is to study the role of neuromodulators in the generation and modification of behavior. Simple behaviors are generated within the central nervous system by limited circuits of neurons called Central Pattern Generators (CPGs). CPGs can produce stereotyped motor patterns in isolation, but they depend on extensive modulatory input to produce the normal variety of related behaviors. The cellular mechanisms involved in this modulation have not been studied. I propose that modulatory inputs change the active components of the CPG by adding and subtracting cells from the circuit, changing firing characteristics of neurons, and changing synaptic efficacy within the circuit. To test this hypothesis, I will analyze the cellular and ionic mechanisms whereby serotonin, octopamine and dopamine modulate the well-characterized 14-neuron CPG for the pyloric rhythm in the stomatogastric ganglion of the lobster. Using electrophysiological and pharmacological techniques, I will answer several questions: 1) How many of the 14 identified neurons are directly excited or inhibited by an amine? 2) Are synaptic connections in the circuit modified by amines? 3) What are the ionic mechanisms for amine excitation and inhibition of each target neuron? This work will describe how generalized CPGs are sculpted by modulatory inputs to produce specific functional circuits generating a wide spectrum of behaviors.

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Research Project (R01)
Project #
5R01NS017323-05
Application #
3397488
Study Section
Neurology B Subcommittee 1 (NEUB)
Project Start
1981-04-01
Project End
1987-11-30
Budget Start
1985-12-01
Budget End
1986-11-30
Support Year
5
Fiscal Year
1986
Total Cost
Indirect Cost
Name
Cornell University
Department
Type
Schools of Arts and Sciences
DUNS #
City
Ithaca
State
NY
Country
United States
Zip Code
14850
Garcia, Virginia B; Abbinanti, Matthew D; Harris-Warrick, Ronald M et al. (2018) Effects of Chronic Spinal Cord Injury on Relationships among Ion Channel and Receptor mRNAs in Mouse Lumbar Spinal Cord. Neuroscience 393:42-60
Bos, Rémi; Harris-Warrick, Ronald M; Brocard, Cécile et al. (2018) Kv1.2 Channels Promote Nonlinear Spiking Motoneurons for Powering Up Locomotion. Cell Rep 22:3315-3327
Husch, Andreas; Dietz, Shelby B; Hong, Diana N et al. (2015) Adult spinal V2a interneurons show increased excitability and serotonin-dependent bistability. J Neurophysiol 113:1124-34
Masino, Mark A; Abbinanti, Matthew D; Eian, John et al. (2012) TTX-resistant NMDA receptor-mediated membrane potential oscillations in neonatal mouse Hb9 interneurons. PLoS One 7:e47940
Husch, Andreas; Van Patten, Gabrielle N; Hong, Diana N et al. (2012) Spinal cord injury induces serotonin supersensitivity without increasing intrinsic excitability of mouse V2a interneurons. J Neurosci 32:13145-54
Kvarta, Mark D; Harris-Warrick, Ronald M; Johnson, Bruce R (2012) Neuromodulator-evoked synaptic metaplasticity within a central pattern generator network. J Neurophysiol 108:2846-56
Zhong, Guisheng; Shevtsova, Natalia A; Rybak, Ilya A et al. (2012) Neuronal activity in the isolated mouse spinal cord during spontaneous deletions in fictive locomotion: insights into locomotor central pattern generator organization. J Physiol 590:4735-59
Abbinanti, Matthew D; Harris-Warrick, Ronald M (2012) Serotonin modulates multiple calcium current subtypes in commissural interneurons of the neonatal mouse. J Neurophysiol 107:2212-9
Abbinanti, Matthew D; Zhong, Guisheng; Harris-Warrick, Ronald M (2012) Postnatal emergence of serotonin-induced plateau potentials in commissural interneurons of the mouse spinal cord. J Neurophysiol 108:2191-202
Kadiri, Lolahon R; Kwan, Alex C; Webb, Watt W et al. (2011) Dopamine-induced oscillations of the pyloric pacemaker neuron rely on release of calcium from intracellular stores. J Neurophysiol 106:1288-98

Showing the most recent 10 out of 20 publications