36 research outputs found

    Conserved properties of dendritic trees in four cortical interneuron subtypes

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    Dendritic trees influence synaptic integration and neuronal excitability, yet appear to develop in rather arbitrary patterns. Using electron microscopy and serial reconstructions, we analyzed the dendritic trees of four morphologically distinct neocortical interneuron subtypes to reveal two underlying organizational principles common to all. First, cross-sectional areas at any given point within a dendrite were proportional to the summed length of all dendritic segments distal to that point. Consistent with this observation, total cross-sectional area was almost perfectly conserved at bifurcation points. Second, dendritic cross-sections became progressively more elliptical at more proximal, larger diameter, dendritic locations. Finally, computer simulations revealed that these conserved morphological features limit distance dependent filtering of somatic EPSPs and facilitate distribution of somatic depolarization into all dendritic compartments. Because these features were shared by all interneurons studied, they may represent common organizational principles underlying the otherwise diverse morphology of dendritic trees

    Exploration of Shared Genetic Architecture Between Subcortical Brain Volumes and Anorexia Nervosa

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    In MRI scans of patients with anorexia nervosa (AN), reductions in brain volume are often apparent. However, it is unknown whether such brain abnormalities are influenced by genetic determinants that partially overlap with those underlying AN. Here, we used a battery of methods (LD score regression, genetic risk scores, sign test, SNP effect concordance analysis, and Mendelian randomization) to investigate the genetic covariation between subcortical brain volumes and risk for AN based on summary measures retrieved from genome-wide association studies of regional brain volumes (ENIGMA consortium, n = 13,170) and genetic risk for AN (PGC-ED consortium, n = 14,477). Genetic correlations ranged from − 0.10 to 0.23 (all p > 0.05). There were some signs of an inverse concordance between greater thalamus volume and risk for AN (permuted p = 0.009, 95% CI: [0.005, 0.017]). A genetic variant in the vicinity of ZW10, a gene involved in cell division, and neurotransmitter and immune system relevant genes, in particular DRD2, was significantly associated with AN only after conditioning on its association with caudate volume (pFDR = 0.025). Another genetic variant linked to LRRC4C, important in axonal and synaptic development, reached significance after conditioning on hippocampal volume (pFDR = 0.021). In this comprehensive set of analyses and based on the largest available sample sizes to date, there was weak evidence for associations between risk for AN and risk for abnormal subcortical brain volumes at a global level (that is, common variant genetic architecture), but suggestive evidence for effects of single genetic markers. Highly powered multimodal brain- and disorder-related genome-wide studies are needed to further dissect the shared genetic influences on brain structure and risk for AN

    Intrinsic programs regulating dendrites and synapses in the upper layer neurons of the cortex

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    Dendrites and spines are key regulators of neuronal function often affected in cognitive disorders. Neuronal subclasses are characterized by a wide range of dendritic morphologies that aid their specific functions. However, how subclass-specific dendritic trees arise during vertebrate development remains largely unknown. We have recently reported that the restricted expression of Cux1 and Cux2 genes in the upper layers of the cerebral cortex determines the specific morphology of dendrites and spines and the function of these neurons. Since Cux genes are the vertebrate homologs of Drosophila Cut, which specifies the dendritic morphologies of certain sensory neuron populations, our findings suggest that mechanisms of dendrite differentiation are conserved between Drosophila and mammals, which had yet to be demonstrated. Importantly, we found that Cux genes not only modulate dendritic branching, but also dendritic spine morphogenesis, the functional synapse and cognition. Dendritic spine stabilization was partly mediated by direct repression of genes of the Xlr family, previously implicated in cognitive defects in a model of Turner syndrome. Hence, our work indicates that neuronal subclass specific determinants may intrinsically affect synaptic activity beyond expected. The functions of Cux1 and Cux2 were additive and complement each other to establish the final pattern of the dendritic tree and the number and strength of the synapses. This work unravels novel mechanisms of dendritogenesis and synaptogenesis and illustrates how regulating dendritic structures contributes to the specialization of upper layer neurons. It will be interesting to dissect how these mechanisms regulate cortical activity, area specialization and cognitive functions

    Potential evidence of fossilised Neoproterozoic deep life: SEM observations on calcite veins from Oppaminda Creek, Arkaroola, South Australia

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    Scanning electron microscopy revealed micronsized globular and coccoid objects, associated with filaments and mucus-like patches in antitaxial fibrous calcite veins from Oppaminda Creek, Northern Flinders Ranges, South Australia. Chemically the objects only differ from their calcite (CaCO3) matrix by a higher sulphur content. The similar to 585 Ma veins formed at about 3-6 km below the surface. Fluid inclusions indicate a temperature of formation of about 60-80 degrees C, and not exceeding 100 degrees C. A nonbiogenic origin of the objects is discussed, but considered unlikely. Instead, morphology, chemistry and size distribution all indicate that the objects are fossilised microbes that lived in the veins at the time and depth of vein formation

    Lactoferrin induces concentration-dependent functional modulation of intestinal proliferation and differentation

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    Human milk stimulates intestinal development through the effects of various moieties. Lactoferrin (LF) is a glycoprotein of human milk whose concentration is highest in colostrum decreasing in mature milk. LF promotes enterocyte growth in intestinal cell lines. We tested the hypothesis that LF induces a distinct effect on enterocyte proliferation and differentiation, depending on its concentration. We examined the dose-related effects by human-native LF (N-LF) in Caco-2 (human colon adenocarcinoma) cells. At high concentrations, N-LF stimulated cell proliferation in immature Caco-2 cells, as judged by 3H-thymidine incorporation. In contrast, sucrase and lactase activities were increased at low but not high LF concentrations and their mRNA were also increased, indicating a transcriptional effect. Because iron binds specific LF sites, we compared the potency of N-LF and iron-saturated LF (I-LF) and found the native form more potent. Finally, we tested the effects by bovine LF (bLF) in the same system and found the latter more potent than the human isoform in inducing cell growth and lactase expression. These results suggest that LF directly induces enterocyte growth and proliferation, depending on its concentration, thereby regulating the earlyx postnatal intestinal development. bLF could be added to infant formula as a growth factor in selected intestinal diseases
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