Hometown: Evansville, IN
BS Biological Sciences
West Lafayette, IN
In the Miller Lab...
The nervous system is dynamically remodeled during development by processes that require transcriptional control and neural activity. Neuronal plasticity has been observed in a wide array of organisms, suggesting that the underlying mechanisms are likely conserved. Therefore, in the MIller Lab, we can use the simple model organism, C. elegans, to investigate genes that modulate synaptic assembly and maintenance.
The C. elegans motor circuit is reorganized during larval development to accommodate the birth of new motor neurons. One of the most striking changes involves the embryonic DD GABAergic motor neurons which execute a genetic program to reverse their synaptic polarity (DD polarity reversal) (White et al., 1978). The net effect of this developmentally regulated remodeling event is to switch DD output from the ventral nerve cord (embryonic) to the dorsal nerve cord (larval). This polarity reversal in DD motor neurons coincides with the birth of GABAergic VD motor neurons which innervate ventral body muscles. Thus, DD remodeling insures that both ventral and dorsal muscles receive GABAergic inputs. This arrangement is readily visualized with the synaptic marker, SNB-1::GFP, which produces discrete GFP puncta distributed along both the dorsal (DD) and ventral (VD) sides of the adult animal (see below).
The transcription factor UNC-55 prevents the execution of this genetic program in VD motor neurons which nornally do not remodel during development; in unc-55 mutants, VD motor neurons adopt the dorsal polarity of DD motor neurons (Walthall and Plunkett, 1995) (Shan et al, 2005). Thus, genes that UNC-55 represses are likely to drive the synaptic remodeling program. We have identified the Deg/ENaC ion channel UNC-8 as a target of UNC-55 and regulator of remodeling. My studies have uncovered that UNC-8 is required for disassembly of the ventral DD synapses (and ventral VD synapses in unc-55 mutants). Additionally, we see that UNC-8 functions in an activity-dependent pathway to regulate the removal of ventral synaptic proteins.
- Miller-Fleming TYNE, Petersen SARAH. Manning L, Matthewman C, Gornet M, Beers A, Hori S, Mitani S, Bianchi L, Richmond J, Miller DAVID. The DEG/ENaC channel protein UNC-8 drives activity-dependent synapse removal in remodeling GABAergic neurons. ELife. 2016 Jul 12;5. e14599. Online article PMID: 27403890 [PubMed]. PMCID: PMC4980115 .