Intellectual Merit. How different are neurons of the same class across animals, or within a given animal? How precisely must neurons constrain the values of their many membrane conductances for them to function correctly in the networks in which they are found? Theoretical work using computer models has argued that similar activity patterns, both at the single neuron level and at the network level, can arise from different combinations of correlated and compensating membrane and synaptic currents. Recent work has added biological evidence for this novel idea: levels of both membrane conductance and the expression of genes responsible for the proteins which allow current to flow across the cell membrane (ion channels) vary considerably in the same cell in different animals. These results suggest that different solutions exist to carry out the same function in neurons from different animals. The first goal of this proposal is to investigate the functional relationships between different ion channel proteins that lead to these various solutions. This will be accomplished by studying the expression of multiple ion channel genes simultaneously in single identified neurons in the stomatogastric ganglion of the crab, Cancer borealis. A detailed analysis of these expression patterns will determine relationships of channel expression and membrane currents in single cells. The ability of these conductances to balance and compensate for one another then will be tested using a combination of computational (theoretical) and biological experiments that alter endogenous membrane conductances and look for compensation by other currents. The second goal of this proposal is to understand the mechanisms of how consistent network output is maintained in the face of radically altered inputs. The rhythmic activity of the stomatogastric ganglion is dependent on descending input from other centers of the nervous system. The activity of the stomatogastric ganglion activity stops completely soon after these inputs are removed, but if one waits 2-3 days the rhythm recovers. This recovery may at least in part be the result of changes in the expression of ion channels that re-tune these networks to regain functional output. Experiments will be performed to investigate the underlying changes in neuronal properties that lead to this recovery of rhythm.
Broader Implications. Previous work suggests that individual neurons use a combination of tuning rules to find combinations of conductance densities that allow them adequate performance in the networks in which they are found. Such homeostatic plasticity recently has become an area of increased attention because it has implications for the function of neural networks at all levels of the nervous system. Incorporation of undergraduate students into the conceptual and experimental activities has been and will continue to be an integral part of Dr. Schulz' professional efforts.
