Neural networks that organize rhythmic behaviors, such as locomotion or respiration, face two competing challenges. On the one hand, the behavior must be flexible, to suit the changing demands on the animal. To achieve this flexibility, the neural network is modulated to alter its cellular and synaptic properties in order to generate variants of the basic behavior. On the other hand, the behavior must be stable, and operate within the range that is useful for the animal. To achieve this stability, the neural network contains homepstatic mechanisms that maintain the properties of its neurons and synapses within a set range of parameter space. How these mechanisms work is poorly understood. We will study the mechanisms of modulation and homeostasis in a small model network, the 14-neuron pyloric network in the stomatogastric ganglion of the spiny lobster. We focus on how ionic currents shape network firing properties, are modulated to generate new behaviors, and are regulated to maintain homeostasis. We will first analyze how three ionic currents help to shape oscillatory bursting activity in neurons, and how three monoamines, dopamine, serotonin and octopamine, modify those currents and the resulting network motor pattern. Second, we will continue to , clone genes for ionic currents, and to manipulate their expression in single neurons to study their specific roles in shaping the pyloric motor pattern. Third, we have recently discovered a novel activity-independent form of homeostatic regulation of ionic currents, and will study the molecular mechanisms by which up- regulation of a potassium current leads to a compensatory up-regulation of a slow inward current. Finally, we will continue to study the dynamics of synaptic transmission and the ionic mechanisms by which synapses are modulated by monoamines to functionally """"""""rewire"""""""" the network. The goal of this work is to understand the biological basis for behavioral flexibility and stability in simple behaviors. The crustacean stomatogastric system allows a unique opportunity to study the control of network output at the level of single identified neurons and synapses. By studying the detailed molecular and biophysical mechanisms of modulation and homeostasis in this simple invertebrate network, we hope to derive general principles for how complex behaviors are generated, such as gait shifts during locomotion, and how critical behaviors, such as respiration, are constrained to operate within a set range that keeps us alive.

National Institute of Health (NIH)
National Institute of Neurological Disorders and Stroke (NINDS)
Method to Extend Research in Time (MERIT) Award (R37)
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Sensorimotor Integration Study Section (SMI)
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Chen, Daofen
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Cornell University
Other Basic Sciences
Schools of Arts and Sciences
United States
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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
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
Goeritz, Marie L; Ouyang, Qing; Harris-Warrick, Ronald M (2011) Localization and function of Ih channels in a small neural network. J Neurophysiol 106:44-58
Zhong, Guisheng; Sharma, Kamal; Harris-Warrick, Ronald M (2011) Frequency-dependent recruitment of V2a interneurons during fictive locomotion in the mouse spinal cord. Nat Commun 2:274
Harris-Warrick, Ronald M (2011) Neuromodulation and flexibility in Central Pattern Generator networks. Curr Opin Neurobiol 21:685-92

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