The long-term objective of this project is to determine how glial cells effect changes in synaptic connections. In parasympathetic ganglia, synapses cluster near the nucleus of glia called satellite cells. This relationship is retained as both synapses and satellite cells undergo. rearrangements over time, suggesting that these glia have a role in the maintenance of synapses and that they may participate in synaptic remodeling. The research described here examines this relationship with 3 objectives. The first objective is to determine how satellite cells are added postnatally to neurons. The addition of glia will be measured using quantitative light microscopy. Bromodeoxyuridine immunohistochemistry will be used to explore whether mitosis accounts the addition of glia. To determine if they arise from cells associated with neurons, the fate of individual satellite cells labeled with intracellular dextran-- rhodamine will be monitored by repeated examination with in vivo video microscopy. The second objective is to establish the function of platelet-growth factor (PDGF) in regulating the proliferation of satellite cells after axotomy of their associated neurons. PDGF is present in many neurons and mitogenic to glia. Following axotomy of the superior cervical ganglion, changes of gene expression for PDGF and its receptor will be monitored using the polymerase chain reaction. It will then be determined whether the proliferative response is blocked with antibodies against PDGF and its receptor. The third objective links satellite cell proliferation to synaptic remodeling. It will be determined by direct observation with in vivo microscopy whether synaptic remodeling continues in older mice when satellite cell number no longer increases, and whether synaptic remodeling is induced when satellite cells are stimulated to divide. These experiments are designed to explore how glial cells elicit changes in synaptic connections. They will provide insights as to how the nervous system responds to injury. Furthermore, the understanding of how glial cells bring about synaptic change is directly relevant to the normal development of the nervous system and to disorders arising from abnormal development.
| Kim, J Y; Sutton, M E; Lu, D J et al. (1999) Activation of neurotrophin-3 receptor TrkC induces apoptosis in medulloblastomas. Cancer Res 59:711-9 |
| Kwon, Y K; Bhattacharyya, A; Alberta, J A et al. (1997) Activation of ErbB2 during wallerian degeneration of sciatic nerve. J Neurosci 17:8293-9 |
| Bhattacharyya, A; Watson, F L; Bradlee, T A et al. (1997) Trk receptors function as rapid retrograde signal carriers in the adult nervous system. J Neurosci 17:7007-16 |
| Pomeroy, S L; Zurakowski, D; Khoxayo, S et al. (1996) Postnatal addition of satellite cells to parasympathetic neurons. J Comp Neurol 375:518-25 |
| Segal, R A; Pomeroy, S L; Stiles, C D (1995) Axonal growth and fasciculation linked to differential expression of BDNF and NT3 receptors in developing cerebellar granule cells. J Neurosci 15:4970-81 |
| Segal, R A; Goumnerova, L C; Kwon, Y K et al. (1994) Expression of the neurotrophin receptor TrkC is linked to a favorable outcome in medulloblastoma. Proc Natl Acad Sci U S A 91:12867-71 |
