The antennal lobe of the sphinx moth
Manduca sexta serves as a model for the development of the olfactory system. Here, the establishment of the glomerular synaptic network formed by the olfactory ...receptor axons and antennal lobe neurons at pupal stage P12 was followed by transection of the right antenna and – within 24
h – by injection of MnCl
2 into the hemolymph. In vivo 3D MRI at 100 and 60
μm isotropic resolution was then performed at P13 to P17. Whereas the left antennal lobe revealed a pronounced increase of the signal-to-noise ratio (SNR) reflecting normal synaptic activity, the observation of only a small SNR increase within the right antennal lobe indicated the disruption of pertinent activity after antennal transection. The accumulation of manganese in the intact antennal system became observable within 3
h and lasted for at least 2 days after injection. Intra-individual comparisons between the right and left side yielded a statistically significant differential SNR increase in the left antennal lobe. Because such an effect was not observed in younger animals studied at pupal stages P10/P11, the MRI findings confirm the development of functional synapses in the antennal lobe of
Manduca sexta by P13.
Oligodendrocytes, the myelin-forming glial cells of the central nervous system, maintain long-term axonal integrity. However, the underlying support mechanisms are not understood. Here we identify a ...metabolic component of axon-glia interactions by generating conditional Cox10 (protoheme IX farnesyltransferase) mutant mice, in which oligodendrocytes and Schwann cells fail to assemble stable mitochondrial cytochrome c oxidase (COX, also known as mitochondrial complex IV). In the peripheral nervous system, Cox10 conditional mutants exhibit severe neuropathy with dysmyelination, abnormal Remak bundles, muscle atrophy and paralysis. Notably, perturbing mitochondrial respiration did not cause glial cell death. In the adult central nervous system, we found no signs of demyelination, axonal degeneration or secondary inflammation. Unlike cultured oligodendrocytes, which are sensitive to COX inhibitors, post-myelination oligodendrocytes survive well in the absence of COX activity. More importantly, by in vivo magnetic resonance spectroscopy, brain lactate concentrations in mutants were increased compared with controls, but were detectable only in mice exposed to volatile anaesthetics. This indicates that aerobic glycolysis products derived from oligodendrocytes are rapidly metabolized within white matter tracts. Because myelinated axons can use lactate when energy-deprived, our findings suggest a model in which axon-glia metabolic coupling serves a physiological function.
Neurons and glial cells exchange energy-rich metabolites and it has been suggested, originally based on
data, that astrocytes provide lactate to glutamatergic synapses ("lactate shuttle"). Here, we ...have studied astrocytes that lack mitochondrial respiration
and
A novel mouse mutant (
::
) was generated, in which the administration of tamoxifen causes mutant astrocytes to fail in the assembly of mitochondrial cytochrome
oxidase (COX). Focusing on cerebellar Bergmann glia (BG) cells, which exhibit the highest rate of Cre-mediated recombination, we found a normal density of viable astrocytes even 1 year after tamoxifen-induced
gene targeting. Our data show that BG cells, and presumably all astrocytes, can survive by aerobic glycolysis for an extended period of time in the absence of glial pathology or unspecific signs of neurodegeneration.
When astrocytes are placed into culture, they import glucose and release lactate, an energy-rich metabolite readily metabolized by neurons. This observation led to the "glia-to-neuron lactate shuttle hypothesis," but
evidence for this hypothesis is weak. To study astroglial energy metabolism and the directionality of lactate flux, we generated conditional
mouse mutants lacking mitochondrial respiration in astrocytes, which forces these cells to survive by aerobic glycolysis. Here, we report that these mice are fully viable in the absence of any signs of glial or neuronal loss, suggesting that astrocytes are naturally glycolytic cells.
In the developing nervous system, constitutive activation of the AKT/mTOR (mammalian target of rapamycin) pathway in myelinating glial cells is associated with hypermyelination of the brain, but is ...reportedly insufficient to drive myelination by Schwann cells. We have hypothesized that it requires additional mechanisms downstream of NRG1/ErbB signaling to trigger myelination in the peripheral nervous system. Here, we demonstrate that elevated levels of phosphatidylinositol 3,4,5-trisphosphate (PIP3) have developmental effects on both oligodendrocytes and Schwann cells. By generating conditional mouse mutants, we found that Pten-deficient Schwann cells are enhanced in number and can sort and myelinate axons with calibers well below 1 microm. Unexpectedly, mutant glial cells also spirally enwrap C-fiber axons within Remak bundles and even collagen fibrils, which lack any membrane surface. Importantly, PIP3-dependent hypermyelination of central axons, which is observed when targeting Pten in oligodendrocytes, can also be induced after tamoxifen-mediated Cre recombination in adult mice. We conclude that it requires distinct PIP3 effector mechanisms to trigger axonal wrapping. That myelin synthesis is not restricted to early development but can occur later in life is relevant to developmental disorders and myelin disease.
Nonhuman primate neuroimaging is on the cusp of a transformation, much in the same way its human counterpart was in 2010, when the Human Connectome Project was launched to accelerate progress. ...Inspired by an open data-sharing initiative, the global community recently met and, in this article, breaks through obstacles to define its ambitions.
This magnetic resonance imaging (MRI) study describes mapping of the habenulo-interpeduncular pathway in living mice based on manganese-induced contrast. Six hours after intracerebroventricular ...microinjection of MnCl
2, T1-weighted 3D MRI (2.35 T) at 117 μm isotropic resolution revealed a continuous pattern of anterograde labeling from the habenula via the fasciculus retroflexus to the interpeduncular nucleus. Alternatively, the less invasive systemic administration of MnCl
2 allowed for monitoring of the dynamic uptake pattern of respective neural components with even higher reproducibility across animals. Time courses covered the range from 42 min to 24 h after injection. In conclusion, manganese-enhanced MRI may open new ways for functional assessments of the habenulo-interpeduncular system in animal models with cognitive impairment.
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