Grant: Discovery Grants Program - Individual

The vertebrate nervous system contains an amazing diversity of different types of nerve cells. Each type of nerve cell can be characterized by its morphology, the chemicals that it releases, the chemicals it responds to, and the pattern of electrical activity that it displays. This last property can be termed the electrical phenotype. There are broad categories of electrical activity, for example nerve cells that cannot fire action potentials, those that only show voltage oscillations in their membrane, and those that fire in bursts. Mature nerve cells develop from stem cells that are inexcitable, in other words they cannot generate voltage changes in their membranes. Therefore, during development, they must synthesize specialized proteins, the voltage-sensitive ion channels, to give them electrical excitability. Also, because there are differences in excitability from type to type they incorporate both different types of channels (depending on which ions pass through) and different numbers of channels. Very little is known about the mechanisms that regulate this process, though it seems that there is feedback between electrical activity and the synthesis of new channels through the levels of calcium in the cell. We will use stem cells from the most ancient group of multi-celled animals, the jellyfish, to examine how the earliest animals alter the excitability of nerve cells during development. It is important to determine if there are some ancient "rules" about the order of channel addition to prevent nerve cells from passing through intermediate excitability states that are non-adaptive or even fatal to the cell. These studies are important for understanding how implanted progenitor nerve cells, used for therapy of diseases such as Parkinson's, can be persuaded to differentiate the correct electrical phenotype.