Seetha Krishnan1*, Ajay S. Mathuru2*, Caroline Kibat2, Mashiur Rahman3, Charlotte E Lupton2, Jim Stewart3, Adam Claridge-Chang2,3, Shih-Cheng Yen4,5 and Suresh Jesuthasan2,3,6
1 NUS Graduate School for Integrative Sciences and Engineering, National University of Singapore.
2 Institute of Molecular and Cell Biology, Singapore.
3 Duke-NUS Graduate Medical School. Neuroscience and Behavioral Disorders Program.
4 Dept. of Electrical and Computer Engineering, National University of Singapore.
5 Singapore Institute for Neurotechnology, National University of Singapore.
6 Dept. of Physiology, National University of Singapore.
* Co-first author
Published in Current Biology on 22 May2014.
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 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 behavioural 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 four-dimensional maps of odour-evoked activity. Odours activated the habenula in two broad spatio-temporal patterns. Increasing concentrations of a putative social cue (a bile salt) evoked a corresponding increase in neuronal activity in the right dorsal habenula. In behavioural assays, fish were attracted to intermediate but avoided higher concentration of this cue. Increasing cholinergic activity by 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 centre in zebrafish olfaction, and suggest that activity in the right dorsal subdomain gates innate attraction to specific odours.
Figure legend: The head of a zebrafish larva, with the calcium indicator GCaMP3 expressed in the habenula (Hb) and KillerRed in olfactory sensory neurons that project to the olfactory bulb (OB).
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