Microglia contribute to neuronal synchrony despite endogenous ATP-related phenotypic transformation in acute mouse brain slices.

Acute brain slices represent a workhorse model for studying the central nervous system (CNS) from nanoscale events to complex circuits. While slice preparation inherently involves tissue damage, it is unclear how microglia, the main immune cells and damage sensors of the CNS react to this injury and shape neuronal activity ex vivo. To this end, we investigated microglial phenotypes and contribution to network organization and functioning in acute brain slices. We reveal time-dependent microglial phenotype changes influenced by complex extracellular ATP dynamics through P2Y12R and CX3CR1 signalling, which is sustained for hours in ex vivo mouse brain slices. Downregulation of P2Y12R and changes of microglia-neuron interactions occur in line with alterations in the number of excitatory and inhibitory synapses over time. Importantly, functional microglia modulate synapse sprouting, while microglial dysfunction results in markedly impaired ripple activity both ex vivo and in vivo. Collectively, our data suggest that microglia are modulators of complex neuronal networks with important roles to maintain neuronal network integrity and activity. We suggest that slice preparation can be used to model time-dependent changes of microglia-neuron interactions to reveal how microglia shape neuronal circuits in physiological and pathological conditions.

Synaptic and dendritic architecture of different types of hippocampal somatostatin interneurons.

GABAergic inhibitory neurons fundamentally shape the activity and plasticity of cortical circuits. A major subset of these neurons contains somatostatin (SOM); these cells play crucial roles in neuroplasticity, learning, and memory in many brain areas including the hippocampus, and are implicated in several neuropsychiatric diseases and neurodegenerative disorders. Two main types of SOM-containing cells in area CA1 of the hippocampus are oriens-lacunosum-moleculare (OLM) cells and hippocampo-septal (HS) cells. These cell types show many similarities in their soma-dendritic architecture, but they have different axonal targets, display different activity patterns in vivo, and are thought to have distinct network functions. However, a complete understanding of the functional roles of these interneurons requires a precise description of their intrinsic computational properties and their synaptic interactions. In the current study we generated, analyzed, and make available several key data sets that enable a quantitative comparison of various anatomical and physiological properties of OLM and HS cells in mouse. The data set includes detailed scanning electron microscopy (SEM)-based 3D reconstructions of OLM and HS cells along with their excitatory and inhibitory synaptic inputs. Combining this core data set with other anatomical data, patch-clamp electrophysiology, and compartmental modeling, we examined the precise morphological structure, inputs, outputs, and basic physiological properties of these cells. Our results highlight key differences between OLM and HS cells, particularly regarding the density and distribution of their synaptic inputs and mitochondria. For example, we estimated that an OLM cell receives about 8,400, whereas an HS cell about 15,600 synaptic inputs, about 16% of which are GABAergic. Our data and models provide insight into the possible basis of the different functionality of OLM and HS cell types and supply essential information for more detailed functional models of these neurons and the hippocampal network.

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-1ß (IL-1ß), 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.

Synthesis and investigation of SiO2-MgO coated MWCNTs and their potential application.

In the present publication, multiwalled carbon nanotubes (MWCNT) coated with SiO2-MgO nanoparticles were successfully fabricated via sol-gel method to facilitate their incorporation into polymer matrices. Magnesium acetate tetrahydrate and tetraethyl orthosilicate were used as precursors. The coated MWCNTs were characterized by transmission electron microscopy (TEM), X-ray diffraction (XRD) and Raman spectroscopy methods. These investigation techniques verified the presence of the inorganic nanoparticles on the surface of MWCNTs. Surface coated MWCNTs were incorporated into polyamide (PA), polyethylene (PE) and polypropylene (PP) matrices via melt blending. Tensile test and differential scanning calorimetry (DSC) investigations were performed on SiO2-MgO/MWCNT polymer composites to study the reinforcement effect on the mechanical and thermal properties of the products. The obtained results indicate that depending on the type of polymer, the nanoparticles differently influenced the Young's modulus of polymers. Generally, the results demonstrated that polymers treated with SiO2-MgO/MWCNT nanoparticles have higher modulus than neat polymers. DSC results showed that nanoparticles do not change the melting and crystallization behavior of PP significantly. According to the obtained results, coated MWCNTs are promising fillers to enhance mechanical properties of polymers.

Preparing SnO2/MWCNT Nanocomposite Catalysts via High Energy Ball Milling.

Ball milling method was used to fabricate successfully tin dioxide (SnO2)/multi-walled carbon nanotubes nanocomposite materials using SnCl2 ×2H2O as precursor together with soda and salt as admixture. The as-prepared materials were characterized by transmission electron microscopy, scanning electron microscopy with energy-dispersive X-ray spectroscopy, Raman microscopy, and X-ray diffraction techniques. Observations revealed that applying both soda and salt are advantageous for increasing dispersity of tin dioxide nanoparticles on the surface of carbon nanotubes. These multi-walled carbon nanotube-based composites are promising candidates as thick film gas sensors or catalysts. Results indicate that SnO2/MWCNT composites can be achieved under solvent free dry conditions, too.