Two major goals in neuroscience are to define neural circuits which select and modulate behavior and to identify genes which contribute to the development of these circuits. Invertebrate species have yielded key insights into behavioral genetics because the nervous system is relatively simple and because their behaviors are stereotyped and genetically specified.
Zebrafish larvae have identifiable neurons and a repertoire of genetically determined behaviors. We exploit these advantages of the zebrafish to understand at the cellular and molecular level how neural circuits modulate behavior.
Our studies are directed at revealing brainstem circuits that represent the core of the extrapyramidal system which is the fundamental basis of movement in higher vertebrates. A better understanding of how these circuits work will generate new insights into the pathology of neurological disorders.
The two major behavioral paradigms we use to investigate these questions are modulation of the acoustic startle response by prepulse inhibition, and modulation of the locomotor repertoire during a phototaxis based navigational task.
The Burgess Lab is part of the National Institute of Child Health and Human Development (NICHD), located on the NIH campus in Bethesda, just outside of Washington DC.
As in mammals, the acoustic startle responses in zebrafish larvae is inhibited when the startle stimulus is preceded by a weak auditory prepulse. Using a variety of genetic and cellular approaches, we are identifying genes and neurons mediating this mode of startle modulation. In humans, reductions in prepulse inhibition of startle occurs have been demonstrated in several neurological conditions, including schizophrenia. Thus, our work in zebrafish aims to provide insights into fundamental processes required for normal brain function.
Zebrafish larvae show robust phototaxis toward a target light source. Phototaxis is a relatively complex navigational task involving modulation of several elements in the larval movement repertoire. Larvae first trigger turning movements to steer them toward the target, then adjust their rate of forward movement according to how well oriented they actually are. This paradigm represents an opportunity to trace the flow of sensory information from the retina, through central processing mechanisms determining behavioral choice, to motor output.
Acoustic stimuli elicit two main types of response. 'SLC' responses are short latency, high performance maneuvers that rapidly displace the larvae from its original position. These responses are initiated within 8-15 ms of the stimulus (depending on temperature) and consistent of an initial C-bend to one side, following by a large C-bend to the other side, then a bout of burst swimming. These movements are so explosive that larvae frequently roll sideways as in the example on the right. SLC responses are highly stereotyped 'all-or-nothing' events produced by the firing of the Mauthner cell. Thus although the probability of triggering an SLC increases with more intense stimuli, the magnitude and speed of the response does not change.
For video of various maneuvers, go to the Maneuvers page of the Burgess Lab site.
The software evaluates high speed video recordings of larval locomotion, automatically identifying the position and curvature of larvae in each frame. This enables locomotor events to be recognized and classified for subsequent statistical analyses. For examples of motor events that Flote automatically identifies, see the 'Motor' page of this website.
For examples of analysis using Flote, see these papers:
Flote is freely available for research purposes and runs under the IDL VM platform. To request a copy, please write to Harold Burgess at email@example.com
Burgess HA, Schoch H and Granato M. (2010) Distinct Retinal Pathways Drive Spatial Orientation Behaviors in Zebrafish Navigation. Current Biology doi:10.1016/j.cub.2010.01.022
Burgess HA, Johnson SL and Granato M. (2009) Unidirectional startle responses and disrupted left-right coordination of motor behaviors in robo3 mutant zebrafish. Genes, Brain and Behavior 8:500-11.
Burgess, H.A. and Granato, M. "Sensorimotor gating in larval zebrafish", J. Neuroscience 27(18):4984-94 (2007)
Burgess, H.A. and Granato, M. "Modulation of locomotor activity in larval zebrafish during light adaptation." J Exp Biol. 210:2526-39. (2007)
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