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Melina E Hale, PhD

My research integrates biomechanics and neurobiology to study how axial movements are generated and coordinated to respond to the physical properties of an organism's environment. Of particular interest to me are the startle response and rhythmic swimming behaviors of fishes. These behaviors provide excellent model systems for examining motor control and the mechanics of axial movement. Because the startle response involves a discrete behavior, large neurons and simple neural circuits, it has been important in studies of motor control. Because it is critical for survival and involves maximal performance, it has been important for work on muscle physiology and performance. Rhythmic axial and fin swimming has long been studied in lampreys and tadpoles to examine central pattern generation in spinal circuits and in a wide diversity fishes to understand the relationship between morphology and movement.



The scope of questions I am asking can be divided into three interconnected research initiatives. The first explores the broad question: How do morphology, physiology and the physics of the aquatic environment interact to produce swimming movement? To address this question, I examine the scaling of locomotor performance through development with changes in the physics of movement such as the Reynolds number, a ratio of inertial to viscous forces. The second area examines the generation of swimming movements. Questions I am addressing include: How do reticulospinal and spinal neurons and circuits generate startle behavior? And, how are gate transitions due to the physics of movement mediated neurally? To address these questions I examine reticulospinal and spinal interneuron morphology and function in zebrafish and examine comparatively species that differ in components of their startle neural circuits. A third area of research examines the evolution of neural circuits and behaviors. Through this work I am addressing the general question: How are neural circuits and behaviors modified evolutionarily? I examine the startle neural circuit in fishes comparatively within a phylogenetic context. In addition, mutant and transgenic zebrafish are providing new ways of addressing evolutionary questions such as this.



My approaches to these questions include using zebrafish as a model as well as comparative work on actinopterygian fishes. Larval zebrafish, in addition to being an excellent genetic system, are transparent which makes optical imaging of neuron morphology and activity as well as targeted neuron ablations possible in whole, in vivo preparations. With these techniques, we are able to combine functional imaging studies of neurons with behavior. In order to look simultaneously at neuron activity and fish movement, we label cells with calcium sensitive dyes and simultaneously image neurons firing with confocal microscopy and axial movements with high-speed video. With a complementary set of techniques, we kill neurons with cell targeted laser ablations and can compare behavior before and after the cells are removed. Because with such ablations we are able to very specifically remove cells without collateral damage, these techniques allow fine manipulation of the system.