Neurotransmitter receptors are essential for the function of synapses. The mechanisms by which the type(s), number, and distribution of receptors on a neuron are controlled are likely to play crucial roles in the normal development and the mature function of the central nervous system, and in changes in the nervous system during aging and following injury. This project is designed to reveal fundamental mechanisms by which the number and distribution of receptors are controlled in central nervous system (CNS) neurons. A better understanding of these basic mechanisms would ultimately provide a foundation for understanding, treating, and preventing abnormalities and diseases of the human nervous system. The project will address this goal by examining the developmental regulation of one particular neurotransmitter receptor, that for glycine, on an identified class of rat CNS neurons, spinal motoneurons, in vitro.
The specific aims of the project are to answer the following questions: 1. Is the number of glycine receptors on a motoneuron affected by interactions with other neurons? 2. Is the distribution of glycine receptors on a motoneuron affected by interactions with other neurons? 3. Do rat motoneurons in vitro express both a strychnine-sensitive and a strychnine-insensitive form of glycine receptor, as has been suggested? The experimental paradigm in this research will be to place embryonic rat motoneurons into cell culture, and maintain them either mixed with other neurons or in isolation from other neurons. The glycine receptors on the motoneurons will be characterized as to their number, their distribution on the neuronal surface, and which of two subtypes is present. These properties of the glycine receptors will be compared for motoneurons grown in the presence and in the absence of other neurons. My working hypothesis for these experiments is that the number, the distribution, and the subtype of glycine receptors on a spinal motoneuron can be influenced strongly by other neurons, perhaps through synaptic contacts onto the motoneuron.
| Kumar, David V; Nighorn, Alan; St John, Paul A (2002) Role of Nova-1 in regulating alpha2N, a novel glycine receptor splice variant, in developing spinal cord neurons. J Neurobiol 52:156-65 |
| Withers, M D; St John, P A (1997) Embryonic rat spinal cord neurons change expression of glycine receptor subtypes during development in vitro. J Neurobiol 32:579-92 |
| St John, P A; Ludwig, C P; Lai, J (1997) Substance P receptor expression and cellular responses to substance P in prenatal rat spinal cord cells. J Recept Signal Transduct Res 17:569-83 |
| St John, P A; Stephens, S L (1993) Adult-type glycine receptors form clusters on embryonic rat spinal cord neurons developing in vitro. J Neurosci 13:2749-57 |
