Internal physiological states influence behavioral decisions. We have investigated the underlying cellular and molecular mechanisms at the first olfactory synapse for starvation modulation of ...food-search behavior in Drosophila. We found that a local signal by short neuropeptide F (sNPF) and a global metabolic cue by insulin are integrated at specific odorant receptor neurons (ORNs) to modulate olfactory sensitivity. Results from two-photon calcium imaging show that starvation increases presynaptic activity via intraglomerular sNPF signaling. Expression of sNPF and its receptor (sNPFR1) in Or42b neurons is necessary for starvation-induced food-search behavior. Presynaptic facilitation in Or42b neurons is sufficient to mimic starvation-like behavior in fed flies. Furthermore, starvation elevates the transcription level of sNPFR1 but not that of sNPF, and insulin signaling suppresses sNPFR1 expression. Thus, starvation increases expression of sNPFR1 to change the odor map, resulting in more robust food-search behavior.
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► Starvation reshapes olfactory representation in the antennal lobe ► Activation of sNPF receptors upon starvation sensitizes select sensory neurons ► Insulin is a global satiety signal to suppress sNPFR1 expression ► Starvation modulation of Or42b sensory neurons promotes food-search behavior
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Animals are born with a rich repertoire of robust behaviors that are critical for their survival. However, innate behaviors are also highly adaptable to an animal's internal state and external ...environment. Neuromodulators, including biogenic amines, neuropeptides, and hormones, are released to signal changes in animals' circumstances and serve to reconfigure neural circuits. This circuit flexibility allows animals to modify their behavioral responses according to environmental cues, metabolic demands, and physiological states. Aided by powerful genetic tools, researchers have made remarkable progress in
Drosophila melanogaster
to address how a myriad of contextual information influences the input-output relationship of hardwired circuits that support a complex behavioral repertoire. Here we highlight recent advances in understanding neuromodulation of
Drosophila
innate behaviors, with a special focus on feeding, courtship, aggression, and postmating behaviors.
Animals must set behavioural priority in a context-dependent manner and switch from one behaviour to another at the appropriate moment
. Here we probe the molecular and neuronal mechanisms that ...orchestrate the transition from feeding to courtship in Drosophila melanogaster. We find that feeding is prioritized over courtship in starved males, and the consumption of protein-rich food rapidly reverses this order within a few minutes. At the molecular level, a gut-derived, nutrient-specific neuropeptide hormone-Diuretic hormone 31 (Dh31)-propels a switch from feeding to courtship. We further address the underlying kinetics with calcium imaging experiments. Amino acids from food acutely activate Dh31
enteroendocrine cells in the gut, increasing Dh31 levels in the circulation. In addition, three-photon functional imaging of intact flies shows that optogenetic stimulation of Dh31
enteroendocrine cells rapidly excites a subset of brain neurons that express Dh31 receptor (Dh31R). Gut-derived Dh31 excites the brain neurons through the circulatory system within a few minutes, in line with the speed of the feeding-courtship behavioural switch. At the circuit level, there are two distinct populations of Dh31R
neurons in the brain, with one population inhibiting feeding through allatostatin-C and the other promoting courtship through corazonin. Together, our findings illustrate a mechanism by which the consumption of protein-rich food triggers the release of a gut hormone, which in turn prioritizes courtship over feeding through two parallel pathways.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
During the lifespans of most animals, reproductive maturity and mating activity are highly coordinated. In Drosophila melanogaster, for instance, male fertility increases with age, and older males ...are known to have a copulation advantage over young ones. The molecular and neural basis of this age-related disparity in mating behavior is unknown. Here, we show that the Or47b odorant receptor is required for the copulation advantage of older males. Notably, the sensitivity of Or47b neurons to a stimulatory pheromone, palmitoleic acid, is low in young males but high in older ones, which accounts for older males’ higher courtship intensity. Mechanistically, this age-related sensitization of Or47b neurons requires a reproductive hormone, juvenile hormone, as well as its binding protein Methoprene-tolerant in Or47b neurons. Together, our study identifies a direct neural substrate for juvenile hormone that permits coordination of courtship activity with reproductive maturity to maximize male reproductive fitness.
•Or47b odorant receptor is required for the copulation advantage of older males•Older males display a higher Or47b neuronal sensitivity to pheromones•Age-dependent sensitization of the Or47b neurons is controlled by juvenile hormone•Juvenile hormone targets Or47b ORNs to regulate age-dependent male mating drive
In Drosophila melanogaster, older males have a copulation advantage over young adults. Lin and Cao et al. show that the copulation advantage of older males is endowed by a higher sensitivity to stimulatory pheromones. The age-dependent differential sensitivity is regulated by juvenile hormone, which targets sensory neurons in the periphery to coordinate courtship behavior with reproductive maturity.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Not including female rats or mice in neuroscience research has been justified due to the variable nature of female data caused by hormonal fluctuations associated with the female reproductive cycle. ...In this study, we investigated whether female rats are more variable than male rats in scientific reports of neuroscience-related traits.
PubMed and Web of Science were searched for the period from August 1, 2010, to July 31, 2014, for articles that included both male and female rats and that measured diverse aspects of brain function. Only empirical articles using both male and female gonad-intact adult rats, written in English, and including the number of subjects (or a range) were included. This resulted in 311 articles for analysis. Data were extracted from digital images from article PDFs and from manuscript tables and text. The mean and standard deviation (SD) were determined for each data point and their quotient provided a coefficient of variation (CV) as a measure of trait-specific variability for each sex. Additionally, the results were coded for the type of research being measured (behavior, electrophysiology, histology, neurochemistry, and non-brain measures) and for the strain of rat. Over 6000 data points were extracted for both males and females. Subsets of the data were coded for whether male and female mean values differed significantly and whether animals were grouped or individually housed.
Across all traits, there were no sex differences in trait variability, as indicated by the CV, and there were no sex differences in any of the four neuroscience categories, even in instances in which mean values for males and females were significantly different. Female rats were not more variable at any stage of the estrous cycle than male rats. There were no sex differences in the effect of housing conditions on CV. On one of four measures of non-brain function, females were more variable than males.
We conclude that even when female rats are used in neuroscience experiments without regard to the estrous cycle stage, their data are not more variable than those of male rats. This is true for behavioral, electrophysiological, neurochemical, and histological measures. Thus, when designing neuroscience experiments to include both male and female rats, power analyses based on variance in male measures are sufficient to yield accurate numbers for females as well, even when the estrous cycle is not taken into consideration.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
The islet of Langerhans plays a key role in glucose homeostasis through regulated secretion of the hormones insulin and glucagon. Islet research has focused on the insulin‐secreting β‐cells, even ...though aberrant glucagon secretion from α‐cells also contributes to the aetiology of diabetes. Despite its importance, the mechanisms controlling glucagon secretion remain controversial. Proper α‐cell function requires the islet milieu, where β‐ and δ‐cells drive and constrain α‐cell dynamics. The response of glucagon to glucose is similar between isolated islets and that measured in vivo, so it appears that the glucose dependence requires only islet‐intrinsic factors and not input from blood flow or the nervous system. Elevated intracellular free Ca2+ is needed for α‐cell exocytosis, but interpreting Ca2+ data is tricky since it is heterogeneous among α‐cells at all physiological glucose levels. Total Ca2+ activity in α‐cells increases slightly with glucose, so Ca2+may serve a permissive, rather than regulatory, role in glucagon secretion. On the other hand, cAMP is a more promising candidate for controlling glucagon secretion and is itself driven by paracrine signalling from β‐ and δ‐cells. Another pathway, juxtacrine signalling through the α‐cell EphA receptors, stimulated by β‐cell ephrin ligands, leads to a tonic inhibition of glucagon secretion. We discuss potential combinations of Ca2+, cAMP, paracrine and juxtacrine factors in the regulation of glucagon secretion, focusing on recent data in the literature that might unify the field towards a quantitative understanding of α‐cell function.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
Interferon-stimulated genes (ISGs) act in concert to provide a tight barrier against viruses. Recent studies have shed light on the contribution of individual ISG effectors to the antiviral state, ...but most have examined those acting on early, intracellular stages of the viral life cycle. Here, we applied an image-based screen to identify ISGs inhibiting late stages of influenza A virus (IAV) infection. We unraveled a directly antiviral function for the gene SERPINE1, encoding plasminogen activator inhibitor 1 (PAI-1). By targeting extracellular airway proteases, PAI-1 inhibits IAV glycoprotein cleavage, thereby reducing infectivity of progeny viruses. This was biologically relevant for IAV restriction in vivo. Further, partial PAI-1 deficiency, attributable to a polymorphism in human SERPINE1, conferred increased susceptibility to IAV in vitro. Together, our findings reveal that manipulating the extracellular environment to inhibit the last step in a virus life cycle is an important mechanism of the antiviral response.
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•SERPINE1/PAI-1 was identified as an unconventional ISG that acts extracellularly•PAI-1 inhibits influenza A virus (IAV) spread by inhibiting glycoprotein cleavage•Endogenous PAI-1 blocks IAV spread in human and murine cells, ex vivo and in vivo•PAI-1 potentially inhibits other viruses requiring extracellular maturation
Plasminogen activator inhibitor (PAI-1) blocks surface glycoprotein maturation of influenza A virus, thus reducing virus spread in the airways and revealing that the innate immune system, driven by type I IFN, uses modulation of the extracellular environment to inhibit viruses.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Thermosensation is an indispensable sensory modality. Here, we study temperature coding in Drosophila, and show that temperature is represented by a spatial map of activity in the brain. First, we ...identify TRP channels that function in the fly antenna to mediate the detection of cold stimuli. Next, we identify the hot-sensing neurons and show that hot and cold antennal receptors project onto distinct, but adjacent glomeruli in the Proximal-Antennal-Protocerebrum (PAP) forming a thermotopic map in the brain. We use two-photon imaging to reveal the functional segregation of hot and cold responses in the PAP, and show that silencing the hot- or cold-sensing neurons produces animals with distinct and discrete deficits in their behavioral responses to thermal stimuli. Together, these results demonstrate that dedicated populations of cells orchestrate behavioral responses to different temperature stimuli, and reveal a labeled-line logic for the coding of temperature information in the brain.
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► The antenna houses the Drosophila HOT and COLD temperature-sensing neurons ► The hot and cold cells project to separate brain targets in the Protocerebrum (PAP) ► Two-photon calcium imaging reveals a spatial map of temperature in the PAP ► Functional studies show labeled lines for processing thermal signals in the fly brain
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Primary cilia are microtubule-based sensory and signaling organelles on the surfaces of most eukaryotic cells. Despite their early description by microscopy studies, islet cilia had not been examined ...in the functional context until recent decades. In pancreatic islets as in other tissues, primary cilia facilitate crucial developmental and signaling pathways in response to extracellular stimuli. Many human developmental and genetic disorders are associated with ciliary dysfunction, some manifesting as obesity and diabetes. Understanding the basis for metabolic diseases in human ciliopathies has been aided by close examination of cilia action in pancreatic islets at cellular and molecular levels. In this article, we review the evidence for ciliary expression on islet cells, known roles of cilia in pancreas development and islet hormone secretion, and summarize metabolic manifestations of human ciliopathy syndromes. We discuss emerging data on primary cilia regulation of islet cell signaling and the structural basis of cilia-mediated cell crosstalk, and offer our interpretation on the role of cilia in glucose homeostasis and human diseases.
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