We demonstrate that Caenorhabditis elegans is able to form an association between the presence of the odorant benzaldehyde and the food content of its environment. When exposed to 100% benzaldehyde for 1 h in the absence of food the naive attractive response is reduced, and we have found that this olfactory adaptation is attenuated by the presence of food. Contrary to nonassociative (single stimulus) learning theory, this response is not a function of the total time of exposure to benzaldehyde but rather an associative function of the ability of benzaldehyde to predict a nutrient-deficient environment. Genetic and pharmacological evidence revealed that the effects of food in this learning paradigm are mediated by serotonergic signaling. Food is a powerful motivator for animals, and many behaviors depend on food availability and recent nutritional history. For the nematode Caenorhabditis elegans, the presence of Escherichia coli, the standard laboratory food source, modulates multiple behaviors including locomotion, egg laying, and pharyngeal pumping (1, 2). In addition to these acute modulatory effects, food deprivation has been shown to alter more complex behavioral phenomena such as thermotaxis (3) and chemotaxis (CTX; ref. 4), and prolonged starvation can lead to the expression of an alternative developmental pathway leading to a period of relative metabolic stasis, the dauer larva stage (5). Food also has been used as an unconditioned stimulus (US) in associativelearning paradigms. Differential pairing of food with watersoluble chemoattractants (e.g., Na ϩ or Cl Ϫ ) leads to associative conditioning such that ions recently paired with food (CS ϩ ion) are preferred to ions that have not been paired recently with food (CS Ϫ ion; ref. 6).Food is clearly a salient environmental cue for C. elegans, and it is likely that nematodes use odor cues to locate food and avoid detrimental environments. C. elegans utilizes six primary sensory neurons to respond to more than 40 different volatile attractants and repellents (7). Prolonged exposure to some odorants leads to a decrease in the level of attraction to that specific odorant because of a phenomenon called olfactory adaptation (8). For example, exposure to benzaldehyde for 1 h causes a significant decrease in subsequent chemotactic scores. Adaptation in this context is used to refer to a behavioral response rather than its mechanisms. Previous investigations into this behavioral response have demonstrated that the reduction of CTX is susceptible to dishabituation, confirming that it is not the result of fatigue in sensory or motor systems but rather the result of a learning process (9). Indeed, prolonged exposure to a high concentration of benzaldehyde leads to the development of an aversive response to the odorant such that the animals will actively avoid a point source of benzaldehyde. This behavioral switch is produced by the dynamic interaction of two separate (attractive and aversive) benzaldehyde-responsive motivational systems (9).We investigated the relation...

Axons are guided to their targets by molecular cues expressed in their environment. How is the presence of these cues regulated? Although some evidence indicates that morphogens establish guidance cue expression as part of their role in patterning tissues, an important question is whether morphogens are then required to maintain guidance signals. We found that fibroblast growth factor (FGF) signaling sustains the expression of two guidance cues, semaphorin3A (xsema3A) and slit1 (xslit1), throughout the period of Xenopus optic tract development. With FGF receptor inhibition, xsema3A and xslit1 levels were rapidly diminished, and retinal ganglion cell axons arrested in the mid-diencephalon, before reaching their target. Importantly, direct downregulation of XSema3A and XSlit1 mostly phenocopied this axon guidance defect. Thus, FGFs promote continued presence of specific guidance cues critical for normal optic tract development, suggesting a second later role for morphogens, independent of tissue patterning, in maintaining select cues by acting to regulate their transcription.

The role of extrinsic cues in guiding developing axons is well established; however, the means by which the activity of these extrinsic cues is regulated is poorly understood. A disintegrin and metalloproteinase (ADAM) enzymes are Zn-dependent proteinases that can cleave guidance cues or their receptors in vitro. Here, we identify the first example of a metalloproteinase that functions in vertebrate axon guidance in vivo. Specifically, ADAM10 is required for formation of the optic projection by Xenopus retinal ganglion cell (RGC) axons. Xadam10 mRNA is expressed in the dorsal neuroepithelium through which RGC axons extend. Pharmacological or molecular inhibition of ADAM10 within the brain each resulted in a failure of RGC axons to recognize their target. In contrast, molecular inhibition of ADAM10 within the RGC axons themselves had no effect. These data argue strongly that in the dorsal brain ADAM10 acts cell non-autonomously to regulate the guidance of RGC axons.

Camouflage is driven by light perceived from the surrounding environment. During evolution, skin patterns and colours as well as behavioural responses were selected as strategies by prey and predators to avoid being detected (crypsis). Cryptic strategies that include masquerade, disruptive and distractive coloration, surface disruption, and countershading generally occur concomitantly with a degree of surface colour matching (Cuthill et al., 2017;Skelhorn & Rowe, 2016). This mimicking of background colour can be

Lower vertebrates use rapid light-regulated changes in skin colour for camouflage (background adaptation) or during circadian variation in irradiance levels. Two neuroendocrine systems, the eye/alpha-melanocyte-stimulating hormone (α-MSH) and the pineal complex/melatonin circuits, regulate the process through their respective dispersion and aggregation of pigment granules (melanosomes) in skin melanophores. During development, Xenopus laevis tadpoles raised on a black background or in the dark perceive less light sensed by the eye and darken in response to increased α-MSH secretion. As embryogenesis proceeds, the pineal complex/melatonin circuit becomes the dominant regulator in the dark and induces lightening of the skin of larvae. The eye/α-MSH circuit continues to mediate darkening of embryos on a black background, but we propose the circuit is shut down in complete darkness in part by melatonin acting on receptors expressed by pituitary cells to inhibit the expression of pomc, the precursor of α-MSH.