Seetha Krishnan1, Ajay S Mathuru2, Caroline Kibat2, Mashiur Rahman3, Charlotte E Lupton2, Jim Stewart3, Adam Claridge-Chang4, Shih-Cheng Yen5, Suresh Jesuthasan6. 1. NUS Graduate School for Integrative Sciences and Engineering, National University of Singapore, Singapore 117456, Singapore. 2. Institute of Molecular and Cell Biology, Singapore 138673, Singapore. 3. Neuroscience and Behavioral Disorders Program, Duke-NUS Graduate Medical School, Singapore 169857, Singapore. 4. Institute of Molecular and Cell Biology, Singapore 138673, Singapore; Neuroscience and Behavioral Disorders Program, Duke-NUS Graduate Medical School, Singapore 169857, Singapore. 5. Department of Electrical and Computer Engineering, National University of Singapore, Singapore 117583, Singapore; Singapore Institute for Neurotechnology, National University of Singapore, Singapore 117456, Singapore. 6. Institute of Molecular and Cell Biology, Singapore 138673, Singapore; Neuroscience and Behavioral Disorders Program, Duke-NUS Graduate Medical School, Singapore 169857, Singapore; Department of Physiology, National University of Singapore, Singapore 117597, Singapore. Electronic address: sureshjj@imcb.a-star.edu.sg.
Abstract
BACKGROUND: The habenula consists of an evolutionarily conserved set of nuclei that control neuromodulator release. In lower vertebrates, the dorsal habenula receives innervation from sensory regions, but the significance of this is unclear. Here, we address the role of the habenula in olfaction by imaging neural activity in larval zebrafish expressing GCaMP3 throughout the habenula and by carrying out behavioral assays. RESULTS: Activity in several hundred neurons throughout the habenula was recorded using wide-field fluorescence microscopy, fast focusing, and deconvolution. This enabled the creation of 4D maps of odor-evoked activity. Odors activated the habenula in two broad spatiotemporal patterns. Increasing concentrations of a putative social cue (a bile salt) evoked a corresponding increase in neuronal activity in the right dorsal habenula. In behavioral assays, fish were attracted to intermediate concentration of this cue but avoided higher concentration. Increasing cholinergic activity through nicotine exposure rendered the intermediate concentration aversive in a habenula-dependent manner. Pharmacologically blocking nicotinic receptors or lesioning the right dorsal habenula attenuated avoidance. CONCLUSIONS: These data provide physiological and functional evidence that the habenula functions as a higher center in zebrafish olfaction and suggest that activity in the right dorsal subdomain gates innate attraction to specific odors.
BACKGROUND: The habenula consists of an evolutionarily conserved set of nuclei that control neuromodulator release. In lower vertebrates, the dorsal habenula receives innervation from sensory regions, but the significance of this is unclear. Here, we address the role of the habenula in olfaction by imaging neural activity in larval zebrafish expressing GCaMP3 throughout the habenula and by carrying out behavioral assays. RESULTS: Activity in several hundred neurons throughout the habenula was recorded using wide-field fluorescence microscopy, fast focusing, and deconvolution. This enabled the creation of 4D maps of odor-evoked activity. Odors activated the habenula in two broad spatiotemporal patterns. Increasing concentrations of a putative social cue (a bile salt) evoked a corresponding increase in neuronal activity in the right dorsal habenula. In behavioral assays, fish were attracted to intermediate concentration of this cue but avoided higher concentration. Increasing cholinergic activity through nicotine exposure rendered the intermediate concentration aversive in a habenula-dependent manner. Pharmacologically blocking nicotinic receptors or lesioning the right dorsal habenula attenuated avoidance. CONCLUSIONS: These data provide physiological and functional evidence that the habenula functions as a higher center in zebrafish olfaction and suggest that activity in the right dorsal subdomain gates innate attraction to specific odors.
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