Emre Yaksi

The Fungal Aroma Gene ATF1 Promotes Dispersal of Yeast Cells through Insect Vectors

Yeast cells produce various volatile metabolites that are key contributors to the pleasing fruity and flowery aroma of fermented beverages. Several of these fruity metabolites, including isoamyl acetate and ethyl acetate, are produced by a dedicated enzyme, the alcohol acetyl transferase Atf1. However, despite much research, the physiological role of acetate ester formation in yeast remains unknown. Using a combination of molecular biology, neurobiology, and behavioral tests, we demonstrate that deletion of ATF1 alters the olfactory response in the antennal lobe of fruit flies that feed on yeast cells. The flies are much less attracted to the mutant yeast cells, and this in turn results in reduced dispersal of the mutant yeast cells by the flies. Together, our results uncover the molecular details of an intriguing aroma-based communication and mutualism between microbes and their insect vectors. Similar mechanisms may exist in other microbes, including microbes on flowering plants and pathogens.

Left-Right Asymmetry Is Required for the Habenulae to Respond to Both Visual and Olfactory Stimuli

Summary Left-right asymmetries are most likely a universal feature of bilaterian nervous systems and may serve to increase neural capacity by specializing equivalent structures on left and right sides for distinct roles [1]. However, little is known about how asymmetries are encoded within vertebrate neural circuits and how lateralization influences processing of information in the brain. Consequently, it remains unclear the extent to which lateralization of the nervous system is important for normal cognitive and other brain functions and whether defects in lateralization contribute to neurological deficits [2]. Here we show that sensory responses to light and odor are lateralized in larval zebrafish habenulae and that loss of brain asymmetry leads to concomitant loss of responsiveness to either visual or olfactory stimuli. We find that in wild-type zebrafish, most habenular neurons responding to light are present on the left, whereas neurons responding to odor are more frequent on the right. Manipulations that reverse the direction of brain asymmetry reverse the functional properties of habenular neurons, whereas manipulations that generate either double-left- or double-right-sided brains lead to loss of habenular responsiveness to either odor or light, respectively. Our results indicate that loss of brain lateralization has significant consequences upon sensory processing and circuit function.

Spontaneous Activity Governs Olfactory Representations in Spatially Organized Habenular Microcircuits

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.

Neural circuits mediating olfactory-driven behavior in fish

The fish olfactory system processes odor signals and mediates behaviors that are crucial for survival such as foraging, courtship, and alarm response. Although the upstream olfactory brain areas (olfactory epithelium and olfactory bulb) are well-studied, less is known about their target brain areas and the role they play in generating odor-driven behaviors. Here we review a broad range of literature on the anatomy, physiology, and behavioral output of the olfactory system and its target areas in a wide range of teleost fish. Additionally, we discuss how applying recent technological advancements to the zebrafish (Danio rerio) could help in understanding the function of these target areas. We hope to provide a framework for elucidating the neural circuit computations underlying the odor-driven behaviors in this small, transparent, and genetically amenable vertebrate.

Gustatory-mediated avoidance of bacterial lipopolysaccharides via TRPA1 activation in Drosophila

Detecting pathogens and mounting immune responses upon infection is crucial for animal health. However, these responses come at a high metabolic price (McKean and Lazzaro, 2011, Kominsky et al., 2010), and avoiding pathogens before infection may be advantageous. The bacterial endotoxins lipopolysaccharides (LPS) are important immune system infection cues (Abbas et al., 2014), but it remains unknown whether animals possess sensory mechanisms to detect them prior to infection. Here we show that Drosophila melanogaster display strong aversive responses to LPS and that gustatory neurons expressing Gr66a bitter receptors mediate avoidance of LPS in feeding and egg laying assays. We found the expression of the chemosensory cation channel dTRPA1 in these cells to be necessary and sufficient for LPS avoidance. Furthermore, LPS stimulates Drosophila neurons in a TRPA1-dependent manner and activates exogenous dTRPA1 channels in human cells. Our findings demonstrate that flies detect bacterial endotoxins via a gustatory pathway through TRPA1 activation as conserved molecular mechanism. DOI: http://dx.doi.org/10.7554/eLife.13133.001

Methods for studying the zebrafish brain: past, present and future.

The zebrafish (Danio rerio) is one of the most promising new model organisms. The increasing popularity of this amazing small vertebrate is evident from the exponentially growing numbers of research articles, funded projects and new discoveries associated with the use of zebrafish for studying development, brain function, human diseases and screening for new drugs. Thanks to the development of novel technologies, the range of zebrafish research is constantly expanding with new tools synergistically enhancing traditional techniques. In this review we will highlight the past and present techniques which have made, and continue to make, zebrafish an attractive model organism for various fields of biology, with a specific focus on neuroscience.

Tcf7l2 Is Required for Left-Right Asymmetric Differentiation of Habenular Neurons

Summary Background Although left-right asymmetries are common features of nervous systems, their developmental bases are largely unknown. In the zebrafish epithalamus, dorsal habenular neurons adopt medial (dHbm) and lateral (dHbl) subnuclear character at very different frequencies on the left and right sides. The left-sided parapineal promotes the elaboration of dHbl character in the left habenula, albeit by an unknown mechanism. Likewise, the genetic pathways acting within habenular neurons to control their asymmetric differentiated character are unknown. Results In a forward genetic screen for mutations that result in loss of habenular asymmetry, we identified two mutant alleles of tcf7l2, a gene that encodes a transcriptional regulator of Wnt signaling. In tcf7l2 mutants, most neurons on both sides differentiate with dHbl identity. Consequently, the habenulae develop symmetrically, with both sides adopting a pronounced leftward character. Tcf7l2 acts cell automously in nascent equipotential neurons, and on the right side, it promotes dHbm and suppresses dHbl differentiation. On the left, the parapineal prevents this Tcf7l2-dependent process, thereby promoting dHbl differentiation. Conclusions Tcf7l2 is essential for lateralized fate selection by habenular neurons that can differentiate along two alternative pathways, thereby leading to major neural circuit asymmetries.

Rer1p maintains ciliary length and signaling by regulating γ-secretase activity and Foxj1a levels.

Rer1p is an ER/cis-Golgi membrane protein that maintains ciliary length and function by reducing γ-secretase complex assembly and activity (thereby balancing Notch signaling) and increasing Foxj1a expression.

Reduced Lateral Inhibition Impairs Olfactory Computations and Behaviors in a Drosophila Model of Fragile X Syndrome

Summary Fragile X syndrome (FXS) patients present neuronal alterations that lead to severe intellectual disability, but the underlying neuronal circuit mechanisms are poorly understood. An emerging hypothesis postulates that reduced GABAergic inhibition of excitatory neurons is a key component in the pathophysiology of FXS. Here, we directly test this idea in a FXS Drosophila model. We show that FXS flies exhibit strongly impaired olfactory behaviors. In line with this, olfactory representations are less odor specific due to broader response tuning of excitatory projection neurons. We find that impaired inhibitory interactions underlie reduced specificity in olfactory computations. Finally, we show that defective lateral inhibition across projection neurons is caused by weaker inhibition from GABAergic interneurons. We provide direct evidence that deficient inhibition impairs sensory computations and behavior in an in vivo model of FXS. Together with evidence of impaired inhibition in autism and Rett syndrome, these findings suggest a potentially general mechanism for intellectual disability.

Motile-Cilia-Mediated Flow Improves Sensitivity and Temporal Resolution of Olfactory Computations

Motile cilia are actively beating hair-like structures that cover the surface of multiple epithelia. The flow that ciliary beating generates is utilized for diverse functions and depends on the spatial location and biophysical properties of cilia. Here we show that the motile cilia in the nose of aquatic vertebrates are spatially organized and stably beat with an asymmetric pattern, resulting in a robust and stereotypical flow around the nose. Our results demonstrate that these flow fields attract odors to the nose pit and facilitate detection of odors by the olfactory system in stagnant environments. Moreover, we show that ciliary beating quickly exchanges the content of the nose, thereby improving the temporal resolution of the olfactory system for detecting dynamic changes of odor plumes in turbulent environments. Altogether, our work unravels a central function of ciliary beating for generating flow fields that increase the sensitivity and the temporal resolution of olfactory computations in the vertebrate brain.