The establishment of neuronal polarity constitutes a central phase in neuronal development and synaptogenesis. In my thesis, I study factors that regulate the development of neuronal polarity and its relationship with neurotransmitter receptor expression. For my experiments, I have investigated the development of sensory neurons from neonatal rat nodose ganglia in culture. Sensory neurons have a pseudo-unipolar morphology, do not extend dendrites, and are devoid of synaptic connections on their somata. However, nodose neurons form synapses de novo in cultures, and I show that the neurons have retained the ability to extend dendrites. Extrinsic factors control dendrite extension by these neurons: the ganglionic satellite cells inhibit the growth of dendrites and induce the neurons to develop a unipolar morphology. In the absence of satellite cells, nodose neurons establish a new multipolar morphology and, in response to nerve growth factor (NGF), extend several dendrites. However, brain-derived neurotrophic factor (BDNF) and neurotrophin-3 (NT-3) do not induce the neurons to extend dendrites, but promote the expression of properties typical of nodose neurons in vivo. / As nodose neurons acquire a new dendrite-axonal polarity in the presence of NGF, they increase the density of functional neuronal nicotinic acetylcholine receptors (nAChRs) on their somato-dendritic domains. To learn more about the relationship between dendrites extension and nAChR gene expression, I have examined the changes in transcript levels of nAChR subunits in neonatal rat sympathetic neurons developing in culture. I show that the developmental pattern of nAChR subunit expression in the cultured neurons follows closely that of sympathetic neurons developing in vivo, with the exception of one specific subunit $ alpha sb7$. I show that the increase in $ alpha sb3$ mRNA levels correlates well with an increase in the density of functional nAChRs on the neurons. In addition, my results suggest that these increases are regulated by mechanisms intrinsic to neonatal sympathetic neurons. On the other hand, the changes in $ alpha sb7$ gene expression, which correlate with changes in $ alpha$-bungarotoxin binding, are activity-dependent and regulated by a calcium/calmodulin-dependent protein kinase pathway. The results presented in this thesis provide insights on how neurons are influenced in their extension of dendrites and how this extension affects neurotransmitter receptor expression.
| Identifer | oai:union.ndltd.org:LACETR/oai:collectionscanada.gc.ca:QMM.29006 |
| Date | January 1995 |
| Creators | De Koninck, Paul |
| Contributors | Cooper, Ellis (advisor), Carbonetto, Salvatore (advisor) |
| Publisher | McGill University |
| Source Sets | Library and Archives Canada ETDs Repository / Centre d'archives des thèses électroniques de Bibliothèque et Archives Canada |
| Language | English |
| Detected Language | English |
| Type | Electronic Thesis or Dissertation |
| Format | application/pdf |
| Coverage | Doctor of Philosophy (Department of Biology.) |
| Rights | All items in eScholarship@McGill are protected by copyright with all rights reserved unless otherwise indicated. |
| Relation | alephsysno: 001474592, proquestno: NN08091, Theses scanned by UMI/ProQuest. |
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