My main interests are focused upon how neurons within the vertebrate nervous system develop and how that development is governed by neural activity. The model system that I have chosen to pursue these interests in is the zebrafish, Danio rario. There are several advantages for utilizing zebrafish as a model system for studying the development of neural circuits: (1) Compared to mammals, zebrafish have relatively simple nervous systems with far fewer neurons. (2)With respect to motor behaviors, teleost fish, including zebrafish, are able to swim, and this swimming behavior is subject to modulation by a variety of stimuli. Furthermore, the cellular network that produces swimming known as the central pattern generator (CPG), has been well characterized in both Xenopus embryos and lampreys. It has been hypothesized that the CPG for swimming in teleost fish is similar to those that have been described for the lamprey and Xenopus embryos. Since the zebrafish is capable of producing a well characterized motor behavior that is generated by a simple neural network, it is an ideal system to study how either intrinsic (genetic lesion) or extrinsic (chemical perturbation) factors modulate neural development. (3) Recently, a large scale mutagenisis screen in zebrafish, culminating with simple behavioral assays, isolated over 150 motility mutants. Roughly one third of these mutants have abnormalities in skeletal muscle while the remaining two thirds are defective in locomotion even though their muscle development appears normal.
Previously, I studied the macho (mao) zebrafish mutant which does not respond to touch. However, embryos with this mutation can spontaneously swim. Dr. Angeles B. Ribera at the University of Colorado Health Sciences Center has shown that these touch-insensitive mutants have deficient sodium currents in a class of spinal sensory cells known as Rohon-Beard neurons. In my studies, I investigated the resulting developmental consequences that arose due to loss of neural activity in Rohon-Beard neurons of mao mutants.
Recently, I have turned my attention towards understanding how neuronal nicotinic acetylcholine receptor (nAChR) activation regulates neuronal development. A significant number of women smoke during pregnancy. Moreover, exposure of the developing fetus to nicotine from the maternal serum has been linked to a number of developmental abnormalities including: spontaneous abortions, low birth weight, sudden infant death and significant cognitive, intellectual and behavioral impairments in off-spring. Exposure to nicotine has also been purported to have many effects on the developing nervous system. This lab utilizes embryonic zebrafish as a model system to gain insight into how (nAChR) activation via nicotine alters organism as well as neuronal development. Ultimately, we would like to know the cellular mechanisms that underlie nicotine’s action.
Nicotinic receptors mediate changes in spinal motoneuron development and axonal pathfinding in embryonic zebrafish exposed to nicotine. K.R. Svoboda, Vijayaraghavan, S. and Tanguay, R.L. Journal of Neuroscience (In Press)
Activity regulates programmed cell death of zebrafish Rohon-Beard neurons. Svoboda, K.R., Linares, A.E. and Ribera, A.B. Development, 2001,Vol. 128(18):3511-20.
Interactions between the neural networks for escape and swimming in goldfish. Svoboda, K.R. and Fetcho, J.R. Journal of Neuroscience, 1996, Vol. 16(2):843-852.