An important problem in the development of the nervous system is how the electrophysiological phenotype of a neuron is matched to the signal processing requirements of the neural circuit in which it is found. It is proposed to work on a simple mammalian model system in which it can be determined how adult electrophysiological properties and potassium channel gene expression are established and maintained in sympathetic neurons that have different processing functions. In the peripheral sympathetic nervous system, neurons in paravertebral ganglia have different firing properties compared with those in prevertebral ganglia and this is due in large part to differential expression of voltage-activated potassium channels. Electrophysiological phenotype appears to be determined by target of innervation. The main hypothesis tested is that the sympathetic neurons that project to the gut receive a second differentiation signal that can induce changes in the firing properties and potassium channel expression of these neurons.
Specific Aims 1 and 2 are directed toward determining whether the intestinal wall can determine the electrophysiological phenotype of innervating sympathetic neurons.
Specific Aim 3 will test the effects of one potential target-derived trophic molecule on the differentiation of firing properties in sympathetic neurons. The purpose of these studies is to develop an experimental framework in which it will be possible to study the molecular mechanisms by which electrophysiological firing properties are controlled.
| Shi, W; Wymore, R S; Wang, H S et al. (1997) Identification of two nervous system-specific members of the erg potassium channel gene family. J Neurosci 17:9423-32 |
