TY - JOUR TI - Specialized neurons in the right habenula mediate response to aversive olfactory cues AU - Choi, Jung-Hwa AU - Duboue, Erik R AU - Macurak, Michelle AU - Chanchu, Jean-Michel AU - Halpern, Marnie E A2 - Wyart, Claire A2 - Bronner, Marianne E A2 - Wee, Caroline Lei A2 - Mameli, Manuel VL - 10 PY - 2021 DA - 2021/12/08 SP - e72345 C1 - eLife 2021;10:e72345 DO - 10.7554/eLife.72345 UR - https://doi.org/10.7554/eLife.72345 AB - Hemispheric specializations are well studied at the functional level but less is known about the underlying neural mechanisms. We identified a small cluster of cholinergic neurons in the dorsal habenula (dHb) of zebrafish, defined by their expression of the lecithin retinol acyltransferase domain containing 2 a (lratd2a) gene and their efferent connections with a subregion of the ventral interpeduncular nucleus (vIPN). The lratd2a-expressing neurons in the right dHb are innervated by a subset of mitral cells from both the left and right olfactory bulb and are activated upon exposure to the odorant cadaverine that is repellent to adult zebrafish. Using an intersectional strategy to drive expression of the botulinum neurotoxin specifically in these neurons, we find that adults no longer show aversion to cadaverine. Mutants with left-isomerized dHb that lack these neurons are also less repelled by cadaverine and their behavioral response to alarm substance, a potent aversive cue, is diminished. However, mutants in which both dHb have right identity appear more reactive to alarm substance. The results implicate an asymmetric dHb-vIPN neural circuit in the processing of repulsive olfactory cues and in modulating the resultant behavioral response. KW - left-right asymmetry KW - zebrafish KW - lateralization KW - interpeduncular nucleus KW - cadaverine JF - eLife SN - 2050-084X PB - eLife Sciences Publications, Ltd ER -