The classic guidance molecules, Netrin and its receptor Frazzled (Fra), dictate the strength of
synaptic connections in the giant fiber system (GFS) of Drosophila melanogaster by regulating
gap junction localization in the pre-synaptic terminal. In Netrin mutant animals the synaptic
coupling between a giant interneuron and the jump motor neuron was weakened. Dye-coupling
between these two neurons was severely compromised or absent. These mutants exhibited
anatomically and physiologically defective synapses between the giant fiber (GF) and
tergotrochanteral motor neuron (TTMn). In cases where Netrin mutants displayed apparently
normal synaptic anatomy, half of the specimens exhibited physiologically defective synapses.
Dye-coupling between the giant fiber and the motor neuron was reduced or eliminated,
suggesting that gap junctions were disrupted in the Netrin mutants. When we examined the gap
junctions with antibodies to Shaking-B Innexin (ShakB), they were significantly decreased or
absent in the pre-synaptic terminal of the mutant GF. This data is the first to show that Netrin and
Frazzled regulate placement of gap junctions pre-synaptically at a central synapse. In the Drosophila Giant Fiber System, we demonstrate a mechanism that ensures the monoinnervation of two homologous motor neurons by two homologous interneurons. In a scenario where both interneurons could synapse with both motor neuron targets, each interneuron exclusively synapsed with only one target and the circuit functions at normal physiological levels. This innervation pattern depended on the ratio of netrin-to-frazzled expression. When Netrin was over expressed in the system, shifting the ratio in favor of Netrin,
both interneurons synapsed with both target motor neurons and physiological function was reduced. This resulted in the polyinnervationof a single target. In contrast, when Frazzled was over expressed in the system, one interneuron innervated both targets and excluded the remaining interneuron from making any synaptic contact. This resulted in a single interneuron mono-innervating both motor neurons and physiological function was mutant. The orphaned interneuron made no synaptic contact with either motor neuron target. Physiological function was only normal when the Netrin-Frazzled ratio was at endogenous levels and each GF monoinnervated one motor neuron. When we examined the gap junctions at this synapse in experimental animals, there was a significant reduction of gap junction hemichannels in the presynaptic terminal of axons that deviated from normal innervation patterns. While the synapse dyecoupled, the reduction in gap junction hemichannels reduced function in the circuit. / Includes bibliography. / Dissertation (Ph.D.)--Florida Atlantic University, 2013.
| Identifer | oai:union.ndltd.org:fau.edu/oai:fau.digital.flvc.org:fau_13085 |
| Contributors | Orr, Brian (author), Murphey, Rodney K. (Thesis advisor), Charles E. Schmidt College of Science (Degree grantor), Department of Biological Sciences |
| Publisher | Florida Atlantic University |
| Source Sets | Florida Atlantic University |
| Language | English |
| Detected Language | English |
| Type | Electronic Thesis or Dissertation, Text |
| Format | 109 p., Online Resource |
| Rights | All rights reserved by the source institution, http://rightsstatements.org/vocab/InC/1.0/ |
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