Estrogens are well-known to regulate development of sexual dimorphism of the brain; however, their role in embryonic brain development prior to sex-differentiation is unclear. Using estrogen biosensor zebrafish models, we found that estrogen activity in the embryonic brain occurs from early neurogenesis specifically in a type of glia in the olfactory bulb (OB), which we name estrogen-responsive olfactory bulb (EROB) cells. In response to estrogen, EROB cells overlay the outermost layer of the OB and interact tightly with olfactory sensory neurons at the olfactory glomeruli. Inhibiting estrogen activity using an estrogen receptor antagonist, ICI182,780 (ICI), and/or EROB cell ablation impedes olfactory glomerular development, including the topological organisation of olfactory glomeruli and inhibitory synaptogenesis in the OB. Furthermore, activation of estrogen signalling inhibits both intrinsic and olfaction-dependent neuronal activity in the OB, whereas ICI or EROB cell ablation results in the opposite effect on neuronal excitability. Altering the estrogen signalling disrupts olfaction-mediated behaviour in later larval stage. We propose that estrogens act on glia to regulate development of OB circuits, thereby modulating the local excitability in the OB and olfaction-mediated behaviour.

Chemically mediated interaction through so-called infochemicals (Hay, 2009;, often also referred to as semiochemicals, is arguably the oldest and most widespread form of communication (Wyatt, 2003). Infochemicals provide the basis for the vast majority of ecological processes across the tree of life in both terrestrial and aquatic ecosystems (Brönmark & Hansson, 2012;Wyatt, 2014), serving as cues or signals released into the surroundings or present on the surface of organisms (Wyatt, 2014). They cover a broad range of functions, mediating

With carbon dioxide (CO2) levels rising dramatically, climate change threatens marine environments. Due to increasing CO2 concentrations in the ocean, pH levels are expected to drop by 0.4 units by the end of the century. There is an urgent need to understand the impact of ocean acidification on chemical-ecological processes. To date, the extent and mechanisms by which the decreasing ocean pH influences chemical communication are unclear. Combining behaviour assays with computational chemistry, we explore the function of the predator related cue 2-phenylethylamine (PEA) for hermit crabs (Pagurus bernhardus) in current and end-of-the-century oceanic pH. Living in intertidal environments, hermit crabs face large pH fluctuations in their current habitat in addition to climate-change related ocean acidification. We demonstrate that the dietary predator cue PEA for mammals and sea lampreys is an attractant for hermit crabs, with the potency of the cue increasing with decreasing pH levels. In order to explain this increased potency, we assess changes to PEA’s conformational and charge-related properties as one potential mechanistic pathway. Using quantum chemical calculations validated by NMR spectroscopy, we characterise the different protonation states of PEA in water. We show how protonation of PEA could affect receptor-ligand binding, using a possible model receptor for PEA (human TAAR1). Investigating potential mechanisms of pH-dependent effects on olfactory perception of PEA and the respective behavioural response, our study advances the understanding of how ocean acidification interferes with the sense of smell and thereby might impact essential ecological interactions in marine ecosystems.

With carbon dioxide (CO2) levels rising dramatically, climate change threatens marine environments. Due to increasing CO2 concentrations in the ocean, pH levels are expected to drop by 0.4 units by the end of the century. There is an urgent need to understand the impact of ocean acidification on chemical-ecological processes. To date, the extent and mechanisms by which the decreasing ocean pH influences chemical communication are unclear. Combining behaviour assays with computational chemistry, we explore the function of the predator related cue 2-phenylethylamine (PEA) for hermit crabs (Pagurus bernhardus) in current and end-of-the-century oceanic pH. We demonstrate that this dietary predator cue for mammals and sea lampreys is an attractant for hermit crabs. Furthermore, we show that the potency of the cue increases at pH levels expected for the year 2100. In order to explain this increased potency, we assess changes to PEA’s conformational and charge-related properties as one potential mechanistic pathway. Using quantum chemical calculations validated by NMR spectroscopy, we characterise the different protonation states of PEA in water. We show how protonation of PEA could affect receptor-ligand binding, using a possible model receptor for PEA (human TAAR1). Investigating potential mechanisms of pH dependent effects on olfactory perception of PEA and the respective behavioural response, our study advances the understanding of how ocean acidification interferes with the sense of smell and thereby might impact essential ecological interactions in marine ecosystems.

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Estrogen is well-known to regulate development of sexual dimorphisms of the brain, however its role in the brain during early embryonic development prior to sex-differentiation is unclear. Using estrogen biosensor zebrafish models, we found that estrogen activity in the embryonic brain occurs specifically in a type of glia located within the OB, which we name estrogen-responsive olfactory bulb/EROB cells. With estrogen activity, EROB cells extend their ramified projections that overlay the OB outermost layer and tightly interact with olfactory sensory neurons (OSNs) at the olfactory glomeruli. Pharmacologically inhibiting estrogen activity and/or EROB cell ablation impedes olfactory glomerular development, including OSN pathfinding, topological organisation of olfactory glomeruli and inhibitory neurogenesis in the OB. Furthermore, activation of this estrogen/EROB-dependent mechanism decreases the intrinsic neuronal activity primarily in the OB, and this alteration of estrogen signalling disrupts olfaction-mediated behaviour. We propose that estrogen acts on glia to regulate development of functional OB circuits, thereby modulating the local intrinsic excitability in the OB and olfaction-mediated behaviour. Our data also suggest a possibility that the estrogen/EROB cascade may be an important site of action for environmental estrogens causative of neurodevelopmental impairments in animals and humans.

The reproduction of many brachyuran crustaceans involves the formation of mating pairs often around the time of the female moult with attraction of a sexual partner and mating behaviour controlled by sex pheromones. In shore crabs, Carcinus maenas, females produce sex pheromones that are released in the urine. High Performance Liquid Chromatography analysis (HPLC) of female urine shows that the pheromone, identified as the nucleotide uridine diphosphate (UDP), elutes as an unresolved peak with structurally related nucleotides. We examined female urine samples over the moult cycle and detected UDP as well as uridine triphosphate (UTP). Bioassays were conducted to establish the possibility of a blend of nucleotides forming a sex pheromone bouquet in C. maenas. Whilst UDP induced the male mate guarding behaviour (cradling), a mixture of the two nucleotides at a ratio of 4:1 UDP:UTP elicited an even stronger mating response than either UDP or UTP individually. The urine concentration and composition of these nucleotides changes over the moult period pre and post ecdysis, providing evidence that a pheromone bouquet composition is not always constant. The change of the bouquet is related to the physiological state of the sender, here the moult cycle. Our study unravels the functionality of reaction-specific molecules in a pheromone bouquet. Whilst UDP is the mating signal, UTP acts as an attractant and combined they maximise the reproductive response. The use of bouquets provides species-specificity, potentially enabling reproductive isolation of sympatric species, and contains valuable information on the physiological state of the sender.

No abstract