Each neuron needs to maintain a careful balance between the changes implicit in experience, and the demands of stability required by its function. This balance tips depending on the neuronal system, but in any role, disease or neural disorders can develop when the regulatory mechanisms involved in neuronal stability fail. The objective of this thesis was to characterize mechanisms underlying neuronal stability and activity maintenance, in the hopes that further understanding of these processes might someday lead to novel interventions for neurological disorders.
The pyloric circuit of decapod crustaceans controls the rhythmic contractions of the foregut musculature, and has long been recognized as an excellent model system in which to study neuronal network stability. Recent experimental evidence has shown that each neuronal cell type of this circuit exhibits a unique set of positive linear correlations between ionic membrane conductances, which suggests that coordinated expression of ion channels plays a role in constraining neuronal electrical activity. In Aim 1, we hypothesized a causal relationship between expressed conductance correlations and features of cellular identity, namely electrical activity type. We partitioned an existing database of conductance-based model neurons based on various measures of intrinsic activity to approximate distinctions between biological cell types. We then tested individual conductance pairs for linear dependence to identify correlations. Similar to experimental results, each activity type investigated had a unique combination of correlated conductances. Furthermore, we found that populations of models that conform to a specific conductance correlation have a higher likelihood of exhibiting a particular feature of electrical activity. We conclude that regulating conductance ratios can support proper electrical activity of a wide range of cell types, particularly when the identity of the cell is well-defined by one or two features of its activity.
The phenomenon of pyloric network recovery after removal of top-down neuromodulatory input--a process termed decentralization--is seen as a classic model of homeostatic change after injury. After decentralization, the pyloric central pattern generator briefly loses its characteristic rhythmic activity, but the same activity profile is recovered 3-5 days later via poorly understood homeostatic changes. This re-emergence of the pyloric rhythm occurs without the full pre-decentralization set of fixed conductance ratios. If conductance ratios stabilize pyloric activity before decentralization as we showed in Aim 1, then other mechanisms must account for the return of the pyloric rhythm after network recovery. Based on vertebrate studies demonstrating a role for the extracellular matrix (ECM) in activity regulation, we hypothesized in Aim 2 that the ECM was participating in activity maintenance in the stomatogastric nervous system. We used the enzyme chondroitinase ABC (chABC) to degrade extracellular chondroitin sulfate (CS) in the stomatogastric ganglion while in organ culture. Our results are the first to demonstrate the presence of CS in the crustacean nervous system via immunochemistry. Furthermore, we show that while ongoing activity is not disrupted by chABC treatment, recovery of pyloric activity after decentralization was significantly delayed without intact extracellular CS. Our results are the first to show that CS has a role in neuronal activity maintenance in crustaceans, and suggest that CS may be involved in initiating or directing activity maintenance needed in times of neuronal stress.
| Identifer | oai:union.ndltd.org:GATECH/oai:smartech.gatech.edu:1853/47654 |
| Date | 08 April 2013 |
| Creators | Hudson, Amber Elise |
| Publisher | Georgia Institute of Technology |
| Source Sets | Georgia Tech Electronic Thesis and Dissertation Archive |
| Detected Language | English |
| Type | Dissertation |
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