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.

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Method to Extend Research in Time (MERIT) Award (R37)
Project #
5R37NS017323-31
Application #
8206574
Study Section
Sensorimotor Integration Study Section (SMI)
Program Officer
Chen, Daofen
Project Start
1981-04-01
Project End
2013-03-31
Budget Start
2012-01-01
Budget End
2013-03-31
Support Year
31
Fiscal Year
2012
Total Cost
$406,182
Indirect Cost
$141,704
Name
Cornell University
Department
Other Basic Sciences
Type
Schools of Arts and Sciences
DUNS #
872612445
City
Ithaca
State
NY
Country
United States
Zip Code
14850
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
Hu, Emilie; Demmou, Lynda; Cauli, Bruno et al. (2011) VIP, CRF, and PACAP act at distinct receptors to elicit different cAMP/PKA dynamics in the neocortex. Cereb Cortex 21:708-18
Johnson, Bruce R; Brown, Jessica M; Kvarta, Mark D et al. (2011) Differential modulation of synaptic strength and timing regulate synaptic efficacy in a motor network. J Neurophysiol 105:293-304
Harris-Warrick, Ronald M; Johnson, Bruce R (2010) Checks and balances in neuromodulation. Front Behav Neurosci 4:
Ouyang, Q; Patel, V; Vanderburgh, J et al. (2010) Cloning and distribution of Ca2+-activated K+ channels in lobster Panulirus interruptus. Neuroscience 170:692-702
Zhong, Guisheng; Droho, Steven; Crone, Steven A et al. (2010) Electrophysiological characterization of V2a interneurons and their locomotor-related activity in the neonatal mouse spinal cord. J Neurosci 30:170-82
Harris-Warrick, Ronald M (2010) General principles of rhythmogenesis in central pattern generator networks. Prog Brain Res 187:213-22
Peck, Jack H; Gaier, Eric; Stevens, Erin et al. (2006) Amine modulation of Ih in a small neural network. J Neurophysiol 96:2931-40