Neuronal carbonic anhydrase VII provides GABAergic excitatory drive to exacerbate febrile seizures

Peer reviewe

The NKCC1 ion transporter modulates microglial phenotype and inflammatory response to brain injury in a cell-autonomous manner

The NKCC1 ion transporter contributes to the pathophysiology of common neurological disorders, but its function in microglia, the main inflammatory cells of the brain, has remained unclear to date. Therefore, we generated a novel transgenic mouse line in which microglial NKCC1 was deleted. We show that microglial NKCC1 shapes both baseline and reactive microglia morphology, process recruitment to the site of injury, and adaptation to changes in cellular volume in a cell-autonomous manner via regulating membrane conductance. In addition, microglial NKCC1 deficiency results in NLRP3 inflammasome priming and increased production of interleukin-1 beta (IL-1 beta), rendering microglia prone to exaggerated inflammatory responses. In line with this, central (intracortical) administration of the NKCC1 blocker, bumetanide, potentiated intracortical lipopolysaccharide (LPS)-induced cytokine levels. In contrast, systemic bumetanide application decreased inflammation in the brain. Microglial NKCC1 KO animals exposed to experimental stroke showed significantly increased brain injury, inflammation, cerebral edema, and, worse, neurological outcome. Thus, NKCC1 emerges as an important player in controlling microglial ion homeostasis and inflammatory responses through which microglia modulate brain injury. The contribution of microglia to central NKCC1 actions is likely to be relevant for common neurological disorders.Peer reviewe

SLC4A10 mutation causes a neurological disorder associated with impaired GABAergic transmission

SLC4A10 is a plasma-membrane bound transporter which utilizes the Na+ gradient to drive cellular HCO3- uptake, thus mediating acid extrusion. In the mammalian brain, SLC4A10 is expressed in principal neurons and interneurons, as well as in epithelial cells of the choroid plexus, the organ regulating the production of cerebrospinal fluid. Using next generation sequencing on samples from five unrelated families encompassing ten affected individuals, we show that biallelic SLC4A10 loss-of-function variants cause a clinically recognizable neurodevelopmental disorder in humans. The cardinal clinical features of the condition include hypotonia in infancy, delayed psychomotor development across all domains and typically severe intellectual impairment. Affected individuals commonly display traits associated with autistic spectrum disorders including anxiety, hyperactivity and stereotyped movements. In two cases isolated episodes of seizures were reported in the first few years of life, and a further affected child displayed bitemporal epileptogenic discharges on EEG without overt clinical seizures. While occipitofrontal circumference was reported to be normal at birth, progressive postnatal microcephaly evolved in 7 out of 10 affected individuals. Neuroradiological features included a relative preservation of brain volume compared to occipitofrontal circumference, characteristic narrow sometimes 'slit-like' lateral ventricles and corpus callosum abnormalities. Slc4a10 -/- mice, deficient for SLC4A10, also display small lateral brain ventricles and mild behavioral abnormalities including delayed habituation and alterations in the 2-object novel object recognition task. Collapsed brain ventricles in both Slc4a10-/- mice and affected individuals suggests an important role of SLC4A10 in the production of the cerebrospinal fluid. However, it is notable that despite diverse roles of the cerebrospinal fluid in the developing and adult brain, the cortex of Slc4a10-/- mice appears grossly intact. Co-staining with synaptic markers revealed that in neurons, SLC4A10 localizes to inhibitory, but not excitatory, presynapses. These findings are supported by our functional studies which show the release of the inhibitory neurotransmitter GABA is compromised in Slc4a10-/- mice, while the release of the excitatory neurotransmitter glutamate is preserved. Manipulation of intracellular pH partially rescues GABA release. Together our studies define a novel characteristic neurodevelopmental disorder associated with biallelic pathogenic variants in SLC4A10 and highlight the importance of further analyses of the consequences of SLC4A10 loss-of-function for brain development, synaptic transmission and network properties

Object Description and Decomposition by Symmetry Hierarchies

Symmetry is an important feature of visual scene exploration and interpretation. Similarly, hierarchical structures figure an important aspect of symmetry. Visual symmetries describe image regions that might naturally overlap or enclose smaller symmetries. For this reason, objects and scenes can be described in their overall shape as also in their decomposition into more detailed subordinate structures by symmetry hierarchies. Most hierarchical approaches in this area are based on structural, multi-scalar or multi-resolution hierarchies. In this paper, we propose a symmetry-oriented hierarchy with a related, but more cognitive meaning by describing a hierarchy of symmetry itself based on a range-based symmetry detector. We motivate and present an approach for symmetry hierarchy representation and show experiments towards object description and decomposition by symmetry hierarchies

German Airport Noise Surcharges – Method of Calculation and Effects

Over the last decade, nearly all major German airports have switched to noise surcharges based on measured sound levels at take-off and landing of aircrafts even though the impact of noise surcharges on airline fleet decisions is not yet proven. Noise surcharges represent about 1% of a network airline’s operating costs, which reduces the probability of a steering effect of noise surcharges to a minimum. Thus an analysis of the level and structure of airport charges identifies a monetary incentive to operate noise-reduced aircrafts. An empirical study at five German international airports over a 10-year period analyzing the development of the fleet mix at the airports shows the fraction of movements of quiet aircrafts did increase. However, the study could not prove this development was caused by noise charges rather than a general fleet modernization process. In fact, there are many other factors, e.g. fuel consumption or range, on the decision of which aircraft type is operated at certain airports. Nevertheless, the study does indicate some marginal impact of noise charges. Recommendations for an optimization of noise charges could be drawn and are presented