Mechanisms of ionic current changes underlying rhythmic activity recovery after decentralization

Neuronal networks capableof generating rhythmic output in the absence of patterned sensory or central inputs are widely represented in the nervous system where they support a variety of functions, from learning and memory to rhythmic motor activity such as breathing. To perfectly function in a living organism, rhythm-generating networks have to combine the capability of producing a stable output with the plasticity needed to adapt to the changing demands of the organism and environment. This dissertation used the pyloric network of the crab Cancer borealis to identify potential mechanisms that ensure stability and adaptation of rhythm generation by neuronal networks under changing environmental conditions, in particular after the removal of neuromodulatory input to this network (decentralization). For this purpose, changes in ionic currents during the process of network activity recovery after decentralization were studied. The previously unreported phenomenon of coordinated expression of ionic currents within and between network neurons under normal physiological conditions was described. Detailed time course of alterations in current levels and in the coordination of ionic currents during the process of activity recovery after decentralization was determined for pacemaker and follower neurons. During the investigation of the molecular mechanisms underlying the post-decentralization changes, a novel role of central neuromodulators and of the cell-to-cell communication within the network in maintaining ionic current levels and their coordinations was demonstrated. Finally, the involvement of the two mechanisms of network plasticity, namely extrinsic (activity-dependent) and intrinsic (neuromodulator-dependent) regulation, in the recovery process after decentralization was shown. A thorough understanding of the mechanisms that are responsible for the stability and plasticity of neuronal circuits is an important step in learning how to manipulate such networks to cure diseases, enhance performance, build advanced robotic systems, create a functioning computer model of a living organism, etc. The discovery of a novel mechanism of ionic current regulation, i.e. the inter-dependent coordination of different ionic currents, will potentially contribute to this process