On the origin of appetite: GLWamide in jellyfish represents an ancestral satiety neuropeptide.

Food intake is regulated by internal state. This function is mediated by hormones and neuropeptides, which are best characterized in popular model species. However, the evolutionary origins of such feeding-regulating neuropeptides are poorly understood. We used the jellyfish Cladonema to address this question. Our combined transcriptomic, behavioral, and anatomical approaches identified GLWamide as a feeding-suppressing peptide that selectively inhibits tentacle contraction in this jellyfish. In the fruit fly Drosophila, myoinhibitory peptide (MIP) is a related satiety peptide. Surprisingly, we found that GLWamide and MIP were fully interchangeable in these evolutionarily distant species for feeding suppression. Our results suggest that the satiety signaling systems of diverse animals share an ancient origin.

Suppression of Dopamine Neurons Mediates Reward.

Massive activation of dopamine neurons is critical for natural reward and drug abuse. In contrast, the significance of their spontaneous activity remains elusive. In Drosophila melanogaster, depolarization of the protocerebral anterior medial (PAM) cluster dopamine neurons en masse signals reward to the mushroom body (MB) and drives appetitive memory. Focusing on the functional heterogeneity of PAM cluster neurons, we identified that a single class of PAM neurons, PAM-γ3, mediates sugar reward by suppressing their own activity. PAM-γ3 is selectively required for appetitive olfactory learning, while activation of these neurons in turn induces aversive memory. Ongoing activity of PAM-γ3 gets suppressed upon sugar ingestion. Strikingly, transient inactivation of basal PAM-γ3 activity can substitute for reward and induces appetitive memory. Furthermore, we identified the satiety-signaling neuropeptide Allatostatin A (AstA) as a key mediator that conveys inhibitory input onto PAM-γ3. Our results suggest the significance of basal dopamine release in reward signaling and reveal a circuit mechanism for negative regulation.

Mushroom body output differentiates memory processes and distinct memory-guided behaviors.

The mushroom body (MB) of Drosophila melanogaster has multiple functions in controlling memory and behavior.1-9 However, circuit mechanisms that generate this functional diversity are largely unclear. Here, we systematically probed the behavioral contribution of each type of MB output neuron (MBON) by blocking during acquisition, retention, or retrieval of reward or punishment memories. We evaluated the contribution using two conditioned responses: memory-guided odor choice and odor source attraction. Quantitative analysis revealed that these conditioned odor responses are controlled by different sets of MBONs. We found that the valence of memory, rather than the transition of memory steps, has a larger impact on the patterns of required MBONs. Moreover, we found that the glutamatergic MBONs forming recurrent circuits commonly contribute to appetitive memory acquisition, suggesting a pivotal role of this circuit motif for reward processing. Our results provide principles how the MB output circuit processes associative memories of different valence and controls distinct memory-guided behaviors.

Neurochemical Organization of the Drosophila Brain Visualized by Endogenously Tagged Neurotransmitter Receptors.

Neurotransmitters often have multiple receptors that induce distinct responses in receiving cells. Expression and localization of neurotransmitter receptors in individual neurons are therefore critical for understanding the operation of neural circuits. Here we describe a comprehensive library of reporter strains in which a convertible T2A-GAL4 cassette is inserted into endogenous neurotransmitter receptor genes of Drosophila. Using this library, we profile the expression of 75 neurotransmitter receptors in the brain. Cluster analysis reveals neurochemical segmentation of the brain, distinguishing higher brain centers from the rest. By recombinase-mediated cassette exchange, we convert T2A-GAL4 into split-GFP and Tango to visualize subcellular localization and activation of dopamine receptors in specific cell types. This reveals striking differences in their subcellular localization, which may underlie the distinct cellular responses to dopamine in different behavioral contexts. Our resources thus provide a versatile toolkit for dissecting the cellular organization and function of neurotransmitter systems in the fly brain.

Serotonin syndrome triggered by postoperative administration of serotonin noradrenaline reuptake inhibitor (SNRI).

BACKGROUND: Serotonin syndrome is a rare but potentially severe disease, which is caused by hyperstimulation of serotonin receptors in the central nervous system. Several antidepressants exert their effect by modulating intrasynaptic serotonin concentration and anesthetics may affect the metabolism of serotonin, implicating to induce serotonin syndrome in patients taking those antidepressants. We present a case which provoked serotonin syndrome immediately after taking serotonin noradrenaline reuptake inhibitor (SNRI) in the postoperative period. CASE PRESENTATION: A 31-year-old female underwent laparoscopic ovarian cystectomy under general anesthesia with propofol, fentanyl, and remifentanil. She has been taking duloxetine, a SNRI for depression. She developed myoclonus seizure with an increase of blood pressure and heart rate after taking duloxetine on the day after the surgery, which was subsided by a non-selective serotonin receptor antagonist. CONCLUSIONS: Anesthesiologists should be aware of the risk of perioperative serotonin syndrome in patients taking antidepressants affecting serotonin metabolism.

Functional dissociation in sweet taste receptor neurons between and within taste organs of Drosophila.

Finding food sources is essential for survival. Insects detect nutrients with external taste receptor neurons. Drosophila possesses multiple taste organs that are distributed throughout its body. However, the role of different taste organs in feeding remains poorly understood. By blocking subsets of sweet taste receptor neurons, we show that receptor neurons in the legs are required for immediate sugar choice. Furthermore, we identify two anatomically distinct classes of sweet taste receptor neurons in the leg. The axonal projections of one class terminate in the thoracic ganglia, whereas the other projects directly to the brain. These two classes are functionally distinct: the brain-projecting neurons are involved in feeding initiation, whereas the thoracic ganglia-projecting neurons play a role in sugar-dependent suppression of locomotion. Distinct receptor neurons for the same taste quality may coordinate early appetitive responses, taking advantage of the legs as the first appendages to contact food.

Reward signal in a recurrent circuit drives appetitive long-term memory formation.

Dopamine signals reward in animal brains. A single presentation of a sugar reward to Drosophila activates distinct subsets of dopamine neurons that independently induce short- and long-term olfactory memories (STM and LTM, respectively). In this study, we show that a recurrent reward circuit underlies the formation and consolidation of LTM. This feedback circuit is composed of a single class of reward-signaling dopamine neurons (PAM-α1) projecting to a restricted region of the mushroom body (MB), and a specific MB output cell type, MBON-α1, whose dendrites arborize that same MB compartment. Both MBON-α1 and PAM-α1 neurons are required during the acquisition and consolidation of appetitive LTM. MBON-α1 additionally mediates the retrieval of LTM, which is dependent on the dopamine receptor signaling in the MB α/ß neurons. Our results suggest that a reward signal transforms a nascent memory trace into a stable LTM using a feedback circuit at the cost of memory specificity.

Histological differences of skin among three body regions in male and female Hokkaido sika deer (Cervus nippon yesoensis).

The Hokkaido sika deer (Cervus Nippon yesoensis), the largest and most abundant of the sika deer subspecies in Japan, has recently attracted new attention as a target for leather production, in addition to its meat value. To provide fundamental data for facilitating the effective use of skin for leather, the histological properties of skin at the shoulder, back and abdominal regions of male and female deer were compared. The results showed that the thickness of the outer skin layer was not significantly different across all regions irrespective of sex. Regarding collagen composition, we found that large-diameter collagen fibrils were heavily distributed in the shoulder of male deer, whereas small-diameter collagen fibrils were largely confined to the abdomen of female deer. We hope this regional histological data will lead to more efficient processing of Hokkaido sika deer skin for leather production.

Concise synthesis of dideoxy-epigallocatechin gallate (DO-EGCG) and evaluation of its anti-influenza virus activity.

Dideoxy-epigallocatechin gallate (DO-EGCG) (2), a simplified analog of naturally occurring EGCG (1), was efficiently prepared by directly introducing a ketone group at C3 and successive reduction to the sec-alcohol with 2,3-cis stereochemistry. Compound 2 showed potent anti-influenza virus activity, indicating that the hydroxyl substituents on the A-ring are not crucial for anti-influenza virus activity.

Study on enteric parasitosis and nutritional status of school children in remote hilly areas in Nepal.

We examined the effect of enteric parasitosis on nutritional status of school children in remote hilly areas in Nepal. A total of 325 school children aged 6 to 19 years (boys: 214; girls: 111) who provided both blood and stool samples were included. The height (Ht) (cm), weight (Wt) (kg), age, sex, ethnic of each child were recorded. Fecal samples were examined by direct smear method in duplicate. The blood hemoglobin (Hb) was estimated by Sahli's method in the field (Nepal) whereas the serum protein (Prot), albumin (Alb), Alb/globulin ratio (A/G), serum glutamate pyruvate transaminase (SGPT), cholesterol (Chol), triglycerides (Trig), and serum iron (SI) were measured in Japan. Of the total, 201 (61.8%) had enteric parasites, predominantly the soil transmitted helminths. Ascaris lumbricoides was the most common parasite detected (72.6%) followed by hookworm (16.2%) and others. Protozoan infections were very low (<6.0%). Of the total 201 parasite positive children, 15.4% had multiple infections. No significant differences in Ht and Wt in parasite positive and negative boys and girls of both age groups (< 11 and 11-19 years) were observed (P>0.05). Overall, no significant differences in levels of Hb, Prot, A/G, SGPT, Chol, Trig and SI in the parasite positive and negative children were observed (P>0. 05) but in Alb level (P<0.05). When, the levels of these parameters were compared in the age groups of <11 and 11-19 years, similar findings were observed in both the age groups. But, in the age group of 11-19 years, a significant difference was observed in Trig level (P<0.05). No differences were found in the levels of these parameters in the parasitic positive and negative children belonging to Dalits and different ethnic namely, Indo-Aryan and Tibeto-Burman, respectively.