NIH Research Festival
Motivated states allow plasticity of an animal’s behavior, facilitating adaptive responses to fluctuating internal homeostatic states and external challenges. A nearly universal motivated drive exists for finding resources; whether food, shelter, or mates. These goals are achieved by active modulation of sensory responsiveness and locomotor patterns. However, in most environments, navigatable cues are not immediately available. This challenge is overcome using sophisticated and conserved behavioral patterns broadly observed across species. Despite the importance of these goal-directed behaviors for survival, the underlying neural mechanisms are poorly understood, mostly due to a lack of vertebrate genetic models. Light is a potent behavioral driver for zebrafish, as well as for many organisms. We first identified a previously uncharacterized light-search state in larval zebrafish, performed in the absence of salient navigation cues. Using spatial analysis we found that after loss of illumination, larvae first show movement patterns consistent with a local search behavior that gradually transitions to an outward roaming phase. Each phase of the search process exhibited distinct patterns of sensory responsiveness and movement trajectories that allowed efficient identification and navigation to local or remote sources of illumination respectively. We identified that the initiation of the local search pattern, yet not the roaming search required retinal input. Conversely, zebrafish otpa mutants, null for the transcription factor orthopediaA, failed to transition out of the local-search response. OrthopediaA is required for mid-brain dopaminergic (DA) neurons, thyrotropin (trh) and somatatostatin (sst) neurosecretory neurons, as well as melanopsin (opn4a) expressing deep-brain photoreceptors in the anterior hypothalamus. Using CRISPR generated mutants we found that the otpa phenotype was not due to DA or trh neuron loss. However, loss of opn4a deep-brain photoreceptors and sst signaling recapitulated the transition defect observed in otpa. Thus, in response to loss of illumination, zebrafish perform classic search strategies observed in numerous species including C. elegans, Drosphilia, and mammals – including humans. These results demonstrate dynamic regulation of search state transition. By using this novel model we can dissect the circuitry of goal-mediated behavior and explore the mechanisms for how organisms respond to complex and challenging environments.
Scientific Focus Area: Neuroscience
This page was last updated on Friday, March 26, 2021