All ETDs from UAB

Advisory Committee Chair

Guillermo MarquéS

Advisory Committee Members

Elizabeth Sztul

Lucas Pozzo-Miller

Anne Theibert

Brad Yoder

Document Type


Date of Award


Degree Name by School

Doctor of Philosophy (PhD) Heersink School of Medicine


Modification of the actin cytoskeleton is essential for synaptic plasticity, which is believed to underlie the brain's capacity for learning and memory. Regulation of the actin cytoskeleton by LIM Kinases (LIMK1 and LIMK2) and their downstream targets Actin Depolymerization Factor/Cofilin (ADF/Cofilin) in the mouse forebrain modulates dendritic spine morphology, synaptic function, long-term potentiation (LTP), and learning and memory, but appear dispensable for the regulation of most forms of presynaptic plasticity. However, these analyses were performed in mice mutant for single members of these gene families, and thus the interpretation of these results is confounded by potential compensatory activity of homologous genes. The objective of this study is to characterize the role of the single Drosophila homolog of the LIMK family (dLIMK1) and the single neuronally-expressed Drosophila homolog of ADF/Cofilin (Twinstar; Tsr) in morphological and functional plasticity of motoneurons. Additionally, we wish to investigate the actin-based cellular mechanisms that contribute to these forms of synaptic plasticity. We found that dLIMK1 acts via Tsr to restrain synaptic growth in the presynaptic terminal, especially by restraining the formation of immature branching boutons. Functionally, we found that Tsr activity is important for the proper Ca2+-cooperativity of vesicle fusion and normal paired-pulse facilitation (PPF), and that both dLIMK1 and Tsr are required for proper tetanus-induced potentiation (TIP). Furthermore, both dLIMK1 mutants and tsr mutants displayed synaptic depression. These results demonstrate that dLIMK1 and Tsr modulate developmentally-regulated morphological and activity-dependent functional plasticity of Drosophila motoneurons and illustrate the conservation of mechanisms regulating neuronal branching between postsynaptic excitatory neurons in mice and presynaptic motoneurons in Drosophila. These results suggest that the lack of alterations in presynaptic forms of plasticity in mice mutant for LIMK1 or non-muscle cofilin (n-Cof) is a consequence of compensation by LIMK2 and ADF, respectively.



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