Specialized neurons in the right habenula mediate response to aversive olfactory cues

Abstract

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 2a (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.

Diversification of habenular organization and asymmetries in teleosts: Insights from the Atlantic salmon and European eel

“…In this species, asymmetries are restricted to the dorsal habenula (dHb) and consist of different relative proportions between two nuclei, an early-born lateral one (dHbl) and a late-born medial one (dHbm), which prevail respectively on the left and the right side ( Gamse et al, 2005 ; Aizawa et al, 2007 ; deCarvalho et al, 2014 ). Asymmetries in dHb result in differential processing of sensory signals between the left and the right habenula sides ( Dreosti et al, 2014 ) and their abolition affects behavioral and emotional responses to environmental cues, including fear responses, food seeking, and light preference ( Facchin et al, 2015 ; Duboué et al, 2017 ; Zhang et al, 2017 ; Chen et al, 2019 ; Choi et al, 2021 ).…”

A scalable assay for chemical preference of small freshwater fish

“…In many previous experimental studies exploiting direct chemical place preference (Braubach et al, 2009; Koide et al, 2009; Hussain et al, 2013; Krishnan et al, 2014; Wakisaka et al, 2017; Lucon-Xiccato et al, 2020; Choi et al, 2021) the tested compound was not marked, inserted locally with a brief shot and was assumed to remain localized while the animal could freely explore the test chamber. Hence there have been large uncertainties over when the animal was actually in contact with the compound and at what concentration, which restricted the behavioral analyses to basic measurements over short runs.…”

“…Representative trajectories of a fish in contact with CA are shown in figure 4A: it homogeneously occupies all available space during control or below a concentration threshold, but when CA above the concentration threshold is infused the fish globally avoids this side of the setup, though some short incursions are still performed from time to time. To quantify this behavior we computed the time-based preference index ( PI t ), a quantity that has been widely used in the literature (Koide et al, 2009; Mann et al, 2003; Wakisaka et al, 2017; Lucon-Xiccato et al, 2020; Choi et al, 2021; Herrera et al, 2021) and defined as:…”

Habenula bibliometrics: Thematic development and research fronts of a resurgent field

“…Using in vivo Ca 2+ imaging, several studies have demonstrated that the sensory responses of dHb neurons are asymmetric and subpopulation-specific. The left and right dHb neurons preferentially responded to visual and olfactory cues, respectively ( Jetti et al, 2014 ; Zhang et al, 2017 ; Chen et al, 2019 ; Choi et al, 2021 ). New imaging approaches ( Ahrens et al, 2013 ; Voleti et al, 2019 ; Zhang Z. et al, 2021 ) as well as novel biosensors ( Patriarchi et al, 2018 ; Mohr et al, 2020 ; Sha et al, 2020 ) may facilitate studies on the larger scale neural basis of habenula-related behaviors.…”