| 1. |
- Adori, Csaba, et al.
(författare)
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Neuropeptide S- and Neuropeptide S receptor-expressing neuron populations in the human pons
- 2015
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Ingår i: Frontiers in Neuroanatomy. - : Frontiers Media SA. - 1662-5129. ; 9
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Tidskriftsartikel (refereegranskat)abstract
- Neuropeptide S (NPS) is a regulatory peptide with potent pharmacological effects. In rodents, NPS is expressed in a few pontine cell clusters. Its receptor (NPSR1) is, however, widely distributed in the brain. The anxiolytic and arousal promoting effects of NPS make the NPS NPSR1 system an interesting potential drug target in mood-related disorders. However, so far possible disease-related mechanisms involving NPS have only been studied in rodents. To validate the relevance of these animal studies for i.a. drug development, we have explored the distribution of NPS-expressing neurons in the human pons using in situ hybridization and stereological methods and we compared the distribution of NPS mRNA expressing neurons in the human and rat brain. The calculation revealed a total number of 22,317 +/- 2411 NPS mRNA-positive neurons in human, bilaterally. The majority of cells (84%) were located in the parabrachial area in human: in the extension of the medial and lateral parabrachial nuclei, in the Kolliker-Fuse nucleus and around the adjacent lateral lemniscus. In human, in sharp contrast to the rodents, only very few NPS-positive cells (5%) were found close to the locus coeruleus. In addition, we identified a smaller cell cluster (11% of all NPS cells) in the pontine central gray matter both in human and rat, which has not been described previously even in rodents. We also examined the distribution of NPSR1 mRNA-expressing neurons in the human pons. These cells were mainly located in the rostral laterodorsal tegmental nucleus, the cuneiform nucleus, the microcellular tegmental nucleus region and in the periaqueductal gray. Our results show that both NPS and NPSR1 in the human pons are preferentially localized in regions of importance for integration of visceral autonomic information and emotional behavior. The reported interspecies differences must, however, be considered when looking for targets for new pharmacotherapeutical interventions.
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| 4. |
- Arganda-Carreras, Ignacio, et al.
(författare)
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Crowdsourcing the creation of image segmentation algorithms for connectomics
- 2015
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Ingår i: Frontiers in Neuroanatomy. - : Frontiers Media S.A.. - 1662-5129. ; 9:142
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Tidskriftsartikel (refereegranskat)abstract
- To stimulate progress in automating the reconstruction of neural circuits, we organized the first international challenge on 2D segmentation of electron microscopic (EM) images of the brain. Participants submitted boundary maps predicted for a test set of images, and were scored based on their agreement with a consensus of human expert annotations. The winning team had no prior experience with EM images, and employed a convolutional network. This "deep learning" approach has since become accepted as a standard for segmentation of FM images. The challenge has continued to accept submissions, and the best so far has resulted from cooperation between two teams. The challenge has probably saturated, as algorithms cannot progress beyond limits set by ambiguities inherent in 2D scoring and the size of the test dataset. Retrospective evaluation of the challenge scoring system reveals that it was not sufficiently robust to variations in the widths of neurite borders. We propose a solution to this problem, which should be useful for a future 3D segmentation challenge.
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| 5. |
- Barros Da Cunha, Felipe, et al.
(författare)
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Neuronal and non-neuronal scaling across brain regions within an intercross of domestic and wild chickens
- 2022
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Ingår i: Frontiers in Neuroanatomy. - : Frontiers Media SA. - 1662-5129. ; 16
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Tidskriftsartikel (refereegranskat)abstract
- The allometric scaling of the brain size and neuron number across species has been extensively studied in recent years. With the exception of primates, parrots, and songbirds, larger brains have more neurons but relatively lower neuronal densities than smaller brains. Conversely, when considering within-population variability, it has been shown that mice with larger brains do not necessarily have more neurons but rather more neurons in the brain reflect higher neuronal density. To what extent this intraspecific allometric scaling pattern of the brain applies to individuals from other species remains to be explored. Here, we investigate the allometric relationships among the sizes of the body, brain, telencephalon, cerebellum, and optic tectum, and the numbers of neurons and non-neuronal cells of the telencephalon, cerebellum, and optic tectum across 66 individuals originated from an intercross between wild and domestic chickens. Our intercross of chickens generates a population with high variation in brain size, making it an excellent model to determine the allometric scaling of the brain within population. Our results show that larger chickens have larger brains with moderately more neurons and non-neuronal cells. Yet, absolute number of neurons and non-neuronal cells correlated strongly and positively with the density of neurons and non-neuronal cells, respectively. As previously shown in mice, this scaling pattern is in stark contrast with what has been found across different species. Our findings suggest that neuronal scaling rules across species are not a simple extension of the neuronal scaling rules that apply within a species, with important implications for the evolutionary developmental origins of brain diversity.
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| 6. |
- Bekkouche, Bo M.B., et al.
(författare)
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Comparison of Transparency and Shrinkage During Clearing of Insect Brains Using Media With Tunable Refractive Index
- 2020
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Ingår i: Frontiers in Neuroanatomy. - : Frontiers Media SA. - 1662-5129. ; 14
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Tidskriftsartikel (refereegranskat)abstract
- Improvement of imaging quality has the potential to visualize previously unseen building blocks of the brain and is therefore one of the great challenges in neuroscience. Rapid development of new tissue clearing techniques in recent years have attempted to solve imaging compromises in thick brain samples, particularly for high resolution optical microscopy, where the clearing medium needs to match the high refractive index of the objective immersion medium. These problems are exacerbated in insect tissue, where numerous (initially air-filled) tracheal tubes branching throughout the brain increase the scattering of light. To date, surprisingly few studies have systematically quantified the benefits of such clearing methods using objective transparency and tissue shrinkage measurements. In this study we compare a traditional and widely used insect clearing medium, methyl salicylate combined with permanent mounting in Permount (“MS/P”) with several more recently applied clearing media that offer tunable refractive index (n): 2,2′-thiodiethanol (TDE), “SeeDB2” (in variants SeeDB2S and SeeDB2G matched to oil and glycerol immersion, n = 1.52 and 1.47, respectively) and Rapiclear (also with n = 1.52 and 1.47). We measured transparency and tissue shrinkage by comparing freshly dissected brains with cleared brains from dipteran flies, with or without addition of vacuum or ethanol pre-treatments (dehydration and rehydration) to evacuate air from the tracheal system. The results show that ethanol pre-treatment is very effective for improving transparency, regardless of the subsequent clearing medium, while vacuum treatment offers little measurable benefit. Ethanol pre-treated SeeDB2G and Rapiclear brains show much less shrinkage than using the traditional MS/P method. Furthermore, at lower refractive index, closer to that of glycerol immersion, these recently developed media offer outstanding transparency compared to TDE and MS/P. Rapiclear protocols were less laborious compared to SeeDB2, but both offer sufficient transparency and refractive index tunability to permit super-resolution imaging of local volumes in whole mount brains from large insects, and even light-sheet microscopy. Although long-term permanency of Rapiclear stored samples remains to be established, our samples still showed good preservation of fluorescence after storage for more than a year at room temperature.
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| 7. |
- Boije, Henrik, et al.
(författare)
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Horizontal Cells, the Odd Ones Out in the Retina, Give Insights into Development and Disease
- 2016
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Ingår i: Frontiers in Neuroanatomy. - : Frontiers Media SA. - 1662-5129. ; 10
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Forskningsöversikt (refereegranskat)abstract
- Thorough investigation of a neuronal population can help reveal key aspects regarding the nervous system and its development. The retinal horizontal cells have several extraordinary features making them particularly interesting for addressing questions regarding fate assignment and subtype specification. In this review we discuss and summarize data concerning the formation and diversity of horizontal cells, how morphology is correlated to molecular markers, and how fate assignment separates the horizontal lineage from the lineages of other retinal cell types. We discuss the novel and unique features of the final cell cycle of horizontal cell progenitors and how they may relate to retinoblastoma carcinogenesis.
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| 9. |
- Correia, Sofia, et al.
(författare)
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Fibroblast growth factor-20 increases the yield of midbrain dopaminergic neurons derived from human embryonic stem cells.
- 2007
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Ingår i: Frontiers in Neuroanatomy. - : Frontiers Media SA. - 1662-5129. ; 1:Dec 30
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Tidskriftsartikel (refereegranskat)abstract
- In the central nervous system, fibroblast growth factor (FGF)-20 has been reported to act preferentially on midbrain dopaminergic neurons. It also promotes the dopaminergic differentiation of stem cells. We have analyzed the effects of FGF-20 on human embryonic stem cells (hESCs) differentiation into dopaminergic neurons. We induced neuronal differentiation of hESCs by co-culturing those with PA6 mouse stromal cells for 3 weeks. When we supplemented the culture medium with FGF-20, the number of tyrosine hydroxylase (TH)-expressing neurons increased fivefold, from 3% to 15% of the hESC-derived cells. The cultured cells also expressed other midbrain dopaminergic markers (PITX3, En1, Msx1, and Aldh1), suggesting that some had differentiated into midbrain dopaminergic neurons. We observed no effect of FGF-20 on the size of the soma area or neurite length of the TH-immunopositive neurons. Regardless of whether FGF-20 had been added or not, 17% of the hESC-derived cells expressed the pan-neuronal marker b-III-Tubulin. The proportion of proliferating cells positive for Ki-67 was also not affected by FGF-20 (7% of the hESC-derived cells). By contrast, after 3 weeks in culture FGF-20 significantly reduced the proportion of cells undergoing cell death, as revealed by immunoreactivity for cleaved caspase-8, Bcl-2 associated X protein (BAX) and cleaved caspase-3 (2.5% to 1.2% of cleaved caspase-3-positive cells out of the hESC-derived cells). Taken together, our results indicate that FGF-20 specifically increases the yield of dopaminergic neurons from hESCs grown on PA6 feeder cells and at least part of this effect is due to a reduction in cell death.
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| 10. |
- Eilertsen, Mariann, et al.
(författare)
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An EvoDevo Study of Salmonid Visual Opsin Dynamics and Photopigment Spectral Sensitivity
- 2022
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Ingår i: Frontiers in Neuroanatomy. - : Frontiers Media S.A.. - 1662-5129. ; 16
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Tidskriftsartikel (refereegranskat)abstract
- Salmonids are ideal models as many species follow a distinct developmental program from demersal eggs and a large yolk sac to hatching at an advanced developmental stage. Further, these economically important teleosts inhabit both marine- and freshwaters and experience diverse light environments during their life histories. At a genome level, salmonids have undergone a salmonid-specific fourth whole genome duplication event (Ss4R) compared to other teleosts that are already more genetically diverse compared to many non-teleost vertebrates. Thus, salmonids display phenotypically plastic visual systems that appear to be closely related to their anadromous migration patterns. This is most likely due to a complex interplay between their larger, more gene-rich genomes and broad spectrally enriched habitats; however, the molecular basis and functional consequences for such diversity is not fully understood. This study used advances in genome sequencing to identify the repertoire and genome organization of visual opsin genes (those primarily expressed in retinal photoreceptors) from six different salmonids [Atlantic salmon (Salmo salar), brown trout (Salmo trutta), Chinook salmon (Oncorhynchus tshawytcha), coho salmon (Oncorhynchus kisutch), rainbow trout (Oncorhynchus mykiss), and sockeye salmon (Oncorhynchus nerka)] compared to the northern pike (Esox lucius), a closely related non-salmonid species. Results identified multiple orthologues for all five visual opsin classes, except for presence of a single short-wavelength-sensitive-2 opsin gene. Several visual opsin genes were not retained after the Ss4R duplication event, which is consistent with the concept of salmonid rediploidization. Developmentally, transcriptomic analyzes of Atlantic salmon revealed differential expression within each opsin class, with two of the long-wavelength-sensitive opsins not being expressed before first feeding. Also, early opsin expression in the retina was located centrally, expanding dorsally and ventrally as eye development progressed, with rod opsin being the dominant visual opsin post-hatching. Modeling by spectral tuning analysis and atomistic molecular simulation, predicted the greatest variation in the spectral peak of absorbance to be within the Rh2 class, with a ∼40 nm difference in λmax values between the four medium-wavelength-sensitive photopigments. Overall, it appears that opsin duplication and expression, and their respective spectral tuning profiles, evolved to maximize specialist color vision throughout an anadromous lifecycle, with some visual opsin genes being lost to tailor marine-based vision.
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