Spontaneous Activity Governs Olfactory Representations in Spatially Organized Habenular Microcircuits

Abstract

The medial habenula relays information from the sensory areas via the interpeduncular nucleus to the periaqueductal gray that regulates animal behavior under stress conditions. Ablation of the dorsal habenula (dHb) in zebrafish, which is equivalent to the mammalian medial habenula, was shown to perturb experience-dependent fear. Therefore, understanding dHb function is important for understanding the neural basis of fear. In zebrafish, the dHb receives inputs from the mitral cells (MCs) of the olfactory bulb (OB), and odors can trigger distinct behaviors (e.g., feeding, courtship, alarm). However, it is unclear how the dHb processes olfactory information and how these computations relate to behavior. In this study, we demonstrate that the odor responses in the dHb are asymmetric and spatially organized despite the unorganized OB inputs. Moreover, we show that the spontaneous dHb activity is not random but structured into functionally and spatially organized clusters of neurons, which reflects the favored states of the dHb network. These dHb clusters are also preserved during odor stimulation and govern olfactory responses. Finally, we show that functional dHb clusters overlap with genetically defined dHb neurons, which regulate experience-dependent fear. Thus, we propose that the dHb is composed of functionally, spatially, and genetically distinct microcircuits that regulate different behavioral programs.

The ancestral role of nodal signalling in breaking L/R symmetry in the vertebrate forebrain

“…Understanding whether, as in zebrafish 7,8 , habenular asymmetries controlled by this ancestral heritable mechanism may influence the processing and integration of sensory information in cyclostomes and chondrichthyans could reveal ancient adaptive mechanisms responsible for the fixation of this trait in the last common ancestor of vertebrates.…”

“…A remarkable property of habenulae is that they exhibit marked left-right asymmetries in size, gene expression and neuronal organization in a number of species belonging to all major vertebrate taxa [3][4][5] , albeit with a high degree of variability in asymmetry magnitude and laterality 4,6 . In the zebrafish, these neuroanatomical asymmetries correlate with markedly different habenulae responses to sensory stimuli 7,8 . Habenular asymmetry thus provides a model system to (i) decipher the mechanisms underlying L/R asymmetry diversification in vertebrates and (ii) study the relationship between behavioural and morphological adaptations related to forebrain asymmetries throughout vertebrate evolution.…”

Effects of lorazepam and WAY-200070 in larval zebrafish light/dark choice test

“…Habenula is an ancient dorsal thalamic structure conserved in vertebrates (Sutherland, 1982). Neurons in habenula are tuned to visual, olfactory, and nociceptive pain inputs (Dreosti et al, 2014;Gao et al, 1996;Jetti et al, 2014). Importantly, habenula is a hub connecting the forebrain limbic system to the brain stem monoaminergic neurons (Hikosaka, 2010).…”

The utility of zebrafish as a model for behavioural genetics

“…Experimental manipulation of the Wnt signalling pathway (by subjecting tailbud-stage embryos to a short cold pulse or by using the pharmacological inhibitor IWR-1) [20] can force the Hb into a double-right or double-left configuration and trigger loss of brain responsiveness to one of these stimuli [19 ]. Intriguingly, odour presentation appears to activate distinct ensembles of Hb neurons that combine with spontaneous neural activity to switch between different types of behavioural output [21 ]. In summary, a combination of mutant analysis and cutting-edge tools has begun to unravel the genetic and neural basis of lateralised behaviours, demonstrating a link between asymmetry at the level of brain anatomy and behaviour.…”