| 1. |
- Alsiö, Johan, et al.
(författare)
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Enhanced Sucrose and Cocaine Self-Administration and Cue-Induced Drug Seeking after Loss of VGLUT2 in Midbrain Dopamine Neurons in Mice
- 2011
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Ingår i: Journal of Neuroscience. - 0270-6474 .- 1529-2401. ; 31:35, s. 12593-12603
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Tidskriftsartikel (refereegranskat)abstract
- The mesostriatal dopamine (DA) system contributes to several aspects of responses to rewarding substances and is implicated in conditions such as drug addiction and eating disorders. A subset of DA neurons has been shown to express the type 2 Vesicular glutamate transporter (Vglut2) and may therefore corelease glutamate. In the present study, we analyzed mice with a conditional deletion of Vglut2 in DA neurons (Vglut2(f/f;DAT-Cre)) to address the functional significance of the glutamate-DA cophenotype for responses to cocaine and food reinforcement. Biochemical parameters of striatal DA function were also examined by using DA receptor autoradiography, immediate-early gene quantitative in situ hybridization after cocaine challenge, and DA-selective in vivo chronoamperometry. Mice in which Vglut2 expression had been abrogated in DA neurons displayed enhanced operant self-administration of both high-sucrose food and intravenous cocaine. Furthermore, cocaine seeking maintained by drug-paired cues was increased by 76%, showing that reward-dependent plasticity is perturbed in these mice. In addition, several lines of evidence suggest that adaptive changes occurred in both the ventral and dorsal striatum in the absence of VGLUT2: DA receptor binding was increased, and basal mRNA levels of the DA-induced early genes Nur77 and c-fos were elevated as after cocaine induction. Furthermore, in vivo challenge of the DA system by potassium-evoked depolarization revealed less DA release in both striatal areas. This study demonstrates that absence of VGLUT2 in DA neurons leads to perturbations of reward consumption as well as reward-associated memory, features of particular relevance for addictive-like behavior.
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| 2. |
- Berube-Carriere, Noemie, et al.
(författare)
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Ultrastructural characterization of the mesostriatal dopamine innervation in mice, including two mouse lines of conditional VGLUT2 knockout in dopamine neurons
- 2012
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Ingår i: European Journal of Neuroscience. - : Wiley. - 0953-816X .- 1460-9568. ; 35:4, s. 527-538
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Tidskriftsartikel (refereegranskat)abstract
- Despite the increasing use of genetically modified mice to investigate the dopamine (DA) system, little is known about the ultrastructural features of the striatal DA innervation in the mouse. This issue is particularly relevant in view of recent evidence for expression of the vesicular glutamate transporter 2 (VGLUT2) by a subset of mesencephalic DA neurons in mouse as well as rat. We used immuno-electron microscopy to characterize tyrosine hydroxylase (TH)-labeled terminals in the core and shell of nucleus accumbens and the neostriatum of two mouse lines in which the Vglut2 gene was selectively disrupted in DA neurons (cKO), their control littermates, and C57BL/6/J wild-type mice, aged P15 or adult. The three regions were also examined in cKO mice and their controls of both ages after dual THVGLUT2 immunolabeling. Irrespective of the region, age and genotype, the TH-immunoreactive varicosities appeared similar in size, vesicular content, percentage with mitochondria, and exceedingly low frequency of synaptic membrane specialization. No dually labeled axon terminals were found at either age in control or in cKO mice. Unless TH and VGLUT2 are segregated in different axon terminals of the same neurons, these results favor the view that the glutamatergic cophenotype of mesencephalic DA neurons is more important during the early development of these neurons than for the establishment of their scarce synaptic connectivity. They also suggest that, in mouse even more than rat, the mesostriatal DA system operates mainly through non-targeted release of DA, diffuse transmission and the maintenance of an ambient DA level.
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| 3. |
- Brannon, A Rose, et al.
(författare)
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Molecular Stratification of Clear Cell Renal Cell Carcinoma by Consensus Clustering Reveals Distinct Subtypes and Survival Patterns.
- 2010
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Ingår i: Genes & cancer. - : Sage. - 1947-6027 .- 1947-6019. ; 1:2, s. 152-163
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Tidskriftsartikel (refereegranskat)abstract
- Clear cell renal cell carcinoma (ccRCC) is the predominant RCC subtype, but even within this classification, the natural history is heterogeneous and difficult to predict. A sophisticated understanding of the molecular features most discriminatory for the underlying tumor heterogeneity should be predicated on identifiable and biologically meaningful patterns of gene expression. Gene expression microarray data were analyzed using software that implements iterative unsupervised consensus clustering algorithms to identify the optimal molecular subclasses, without clinical or other classifying information. ConsensusCluster analysis identified two distinct subtypes of ccRCC within the training set, designated clear cell type A (ccA) and B (ccB). Based on the core tumors, or most well-defined arrays, in each subtype, logical analysis of data (LAD) defined a small, highly predictive gene set that could then be used to classify additional tumors individually. The subclasses were corroborated in a validation data set of 177 tumors and analyzed for clinical outcome. Based on individual tumor assignment, tumors designated ccA have markedly improved disease-specific survival compared to ccB (median survival of 8.6 vs 2.0 years, P = 0.002). Analyzed by both univariate and multivariate analysis, the classification schema was independently associated with survival. Using patterns of gene expression based on a defined gene set, ccRCC was classified into two robust subclasses based on inherent molecular features that ultimately correspond to marked differences in clinical outcome. This classification schema thus provides a molecular stratification applicable to individual tumors that has implications to influence treatment decisions, define biological mechanisms involved in ccRCC tumor progression, and direct future drug discovery.
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| 4. |
- El Mestikawy, Salah, et al.
(författare)
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From glutamate co-release to vesicular synergy : vesicular glutamate transporters
- 2011
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Ingår i: Nature Reviews Neuroscience. - : Springer Science and Business Media LLC. - 1471-003X .- 1471-0048. ; 12:4, s. 204-216
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Forskningsöversikt (refereegranskat)abstract
- Recent data indicate that 'classical' neurotransmitters can also act as co-transmitters. This notion has been strengthened by the demonstration that three vesicular glutamate transporters (vesicular glutamate transporter 1 (VGLUT1), VGLUT2 and VGLUT3) are present in central monoamine, acetylcholine and GABA neurons, as well as in primarily glutamatergic neurons. Thus, intriguing questions are raised about the morphological and functional organization of neuronal systems endowed with such a dual signalling capacity. In addition to glutamate co-release, vesicular synergy - a process leading to enhanced packaging of the 'primary' transmitter - is increasingly recognized as a major property of the glutamatergic co-phenotype. The behavioural relevance of this co-phenotype is presently the focus of considerable interest.
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| 5. |
- Kelber, Almut, et al.
(författare)
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Light intensity limits the foraging activity in nocturnal and crepuscular bees.
- 2006
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Ingår i: Behavioral Ecology. - : Oxford University Press (OUP). - 1045-2249 .- 1465-7279. ; 17:1, s. 63-72
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Tidskriftsartikel (refereegranskat)abstract
- A crepuscular or nocturnal lifestyle has evolved in bees several times independently, probably to explore rewarding pollen sources without competition and to minimize predation and nest parasites. Despite these obvious advantages, only few bee species are nocturnal. Here we show that the sensitivity of the bee apposition eye is a major factor limiting the ability to forage in dim light. We present data on eye size, foraging times, and light levels for Megalopta genalis (Augochlorini, Halictidae) in Panama, and Lasioglossum (Sphecodogastra) sp. (Halictini, Halictidae) in Utah, USA. M. genalis females forage exclusively during twilight, but as a result of dim light levels in the rain forest, they are adapted to extremely low intensities. The likely factor limiting their foraging activity is finding their nest entrance on return from a foraging trip. The lowest light intensity at which they can do this, both in the morning and the evening, is 0.0001 cd m–2. Therefore, they leave the nest at dimmer light levels in the morning than in the evening. Lasioglossum (Sphecodogastra) foraging is limited by light intensity in the evening, but probably by temperature in the morning in the temperate climate of Utah. We propose that the evolution of nocturnality in bees was favored by the large variance in the size of females.
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| 6. |
- Somanathan, Hema, et al.
(författare)
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Resolution and sensitivity of the eyes of the Asian honeybees Apis florea, Apis cerana and Apis dorsata.
- 2009
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Ingår i: Journal of Experimental Biology. - : The Company of Biologists. - 1477-9145 .- 0022-0949. ; 212:Pt 15, s. 2448-2453
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Tidskriftsartikel (refereegranskat)abstract
- Bees of the genus Apis are important foragers of nectar and pollen resources. Although the European honeybee, Apis mellifera, has been well studied with respect to its sensory abilities, learning behaviour and role as pollinators, much less is known about the other Apis species. We studied the anatomical spatial resolution and absolute sensitivity of the eyes of three sympatric species of Asian honeybees, Apis cerana, Apis florea and Apis dorsata and compared them with the eyes of A. mellifera. Of these four species, the giant honeybee A. dorsata (which forages during moonlit nights) has the lowest spatial resolution and the most sensitive eyes, followed by A. mellifera, A. cerana and the dwarf honeybee, A. florea (which has the smallest acceptance angles and the least sensitive eyes). Moreover, unlike the strictly diurnal A. cerana and A. florea, A. dorsata possess large ocelli, a feature that it shares with all dim-light bees. However, the eyes of the facultatively nocturnal A. dorsata are much less sensitive than those of known obligately nocturnal bees such as Megalopta genalis in Panama and Xylocopa tranquebarica in India. The differences in sensitivity between the eyes of A. dorsata and other strictly diurnal Apis species cannot alone explain why the former is able to fly, orient and forage at half-moon light levels. We assume that additional neuronal adaptations, as has been proposed for A. mellifera, M. genalis and X. tranquebarica, might exist in A. dorsata.
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| 7. |
- Stensmyr, M C, et al.
(författare)
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Insect-like olfactory adaptations in the terrestrial giant robber crab
- 2005
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Ingår i: Current Biology. - : Elsevier BV. - 1879-0445 .- 0960-9822. ; 15:2, s. 116-121
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Tidskriftsartikel (refereegranskat)abstract
- The robber crab (Birgus latro), also known as the coconut crab, is the world's largest land-living arthropod, with a weight reaching 4 kg and a length of over half a meter [1]. Apart from the marine larval stage [2, 3], this crab is fully terrestrial, and will actually drown if submerged in water [4]. A transition from sea to land raises dramatically new demands on the sensory equipment of an animal. In olfaction, the stimulus changes from hydrophilic molecules in aqueous solution to mainly hydrophobic in the gaseous phase [5]. The olfactory system of land crabs thus represents an excellent opportunity for investigating the effects of the transition from sea to land. Have land crabs come to the same solutions as other terrestrial animals, or is their olfactory sense characterized by unique innovations? Here, we show that the robber crab has evolved an olfactory sense with a high degree of resemblance to the insect system. The similarities extend to physiological, behavioral, and morphological characters. The insect nose of the robber crab is a striking example of convergent evolution and nicely illustrates how similar selection pressures result in similar adaptation.
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