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Dissertation
Mechanisms of rhythmic bursting involving Na⁺ and Ca²⁺ in excitatory networks of brainstem and spinal cord: a modeling study
Doctor of Philosophy (Ph.D.), Drexel University
Dec 2012
DOI:
https://doi.org/10.17918/etd-3978
Abstract
The rhythmic, synchronized bursting of neurons in a network is an important phenomenon that underlies many rhythmic behaviors such as breathing, locomotion, feeding, etc. The basic mechanisms of rhythmic bursting in excitatory networks are currently under debate in some areas of the brainstem and spinal cord, and controversies exist regarding the role of network interactions and cellular properties in their generation. We focus on a specific controversy concerning the role of the membrane currents persistent sodium (INaP) and the calcium-activated nonspecific cation current (ICAN) in network rhythms existing in brainstem slices containing the preBotzinger complex (preBotC), an important preparation relevant for understanding respiratory rhythm generation. We also address another type of rhythm existing in some of these preparations which has been proposed as fictive sighing. Using ideas suggested by and data gathered from experiments in this field, we constructed a mathematical, physiologically realistic model, which includes a description of cellular properties such as INaP, ICAN, Ca²⁺ current (ICa), the Na⁺/K⁺ pump current (IPump), IP3-mediated intracellular Ca²⁺ release, inactivation of INaP and intracellular Ca²⁺ release, and network properties such as synaptic coupling and excitatory drive to the network. Using this model, we investigated how the behavior of an isolated neuron depends on the relative expression of these properties, and how the behavior of a network of coupled neurons depends on the distribution of these properties across the network. We show that the role of a particular current such as INaP or ICAN in a network rhythm may depend on this distribution, and on the conditions of excitatory drive to and the overall strength of synaptic interactions in the network, offering a possible resolution of the controversy regarding the role of these currents in respiratory rhythm generation. We also propose a model of fictive sighing. Although our model was designed to address a specific controversy in a preparation of the brainstem concerned with repiratory rhythmogenesis, we expect that some of our results may be applicable to understanding the basic mechanisms of rhythmic bursting in excitatory networks in other areas of the brainstem and spinal cord.
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Details
- Title
- Mechanisms of rhythmic bursting involving Na⁺ and Ca²⁺ in excitatory networks of brainstem and spinal cord
- Creators
- Patrick E. Jasinski - DU
- Contributors
- Ilya A. Rybak (Advisor) - Drexel University (1970-)
- Awarding Institution
- Drexel University
- Degree Awarded
- Doctor of Philosophy (Ph.D.)
- Publisher
- Drexel University; Philadelphia, Pennsylvania
- Resource Type
- Dissertation
- Language
- English
- Academic Unit
- School of Biomedical Engineering, Science, and Health Systems (1997-2026); Drexel University
- Other Identifier
- 3978; 991014632681504721