Networking and special educational institutions for the purpose of socialization of children with disabilities

© 2016 Fedotova.The relevance to the article topic due to the fact that the network character of interaction of educational institutions aims at the implementation of accessible education of children with disabilities as a strategic objective of educational policy of Russian Federation. The purpose of the article is to analyze the existing models of network interaction between special (correctional) and general education institutions, institutions of additional in the Chuvash Republic and administration of educational networks. Leading method to the study of these problems is the analyses of theoretical literature, statistical data and work experience of educational institutions of the Republic in the field of networking, which allowed to reveal mechanisms of effective management of network interaction of educational institutions on the basis of cooperation and competition, and to describe existing models of educational networks of the Chuvash Republic. Results overview of network interaction in education Chuvash Republic, identifying effective models and management mechanisms educational networks in practical terms allows to formulate and solve educational networks for the task of structural optimization, distribution of educational resources and motivational management

Mechanisms of long-term plasticity of hippocampal GABAergic synapses

© 2017, Pleiades Publishing, Ltd.Long-term potentiation and depression of synaptic transmission have been considered as cellular mechanisms of memory in studies conducted in recent decades. These studies were predominantly focused on mechanisms underlying plasticity at excitatory synapses. Nevertheless, normal central nervous system functioning requires maintenance of a balance between inhibition and excitation, suggesting existence of similar modulation of glutamatergic and GABAergic synapses. Here we review the involvement of G-protein-coupled receptors in the generation of long-term changes in synaptic transmission of inhibitory synapses. We considered the role of endocannabinoid and glutamate systems, GABAB and opioid receptors in the induction of long-term potentiation and long-term depression in inhibitory synapses. The preand postsynaptic effects of activation of these receptors are also discussed

Stimulation Pattern-Dependent Plasticity at Hippocampal CCK-Positive Interneuron to Pyramidal Cell Perisomatic Inhibitory Synapses

© 2016, Springer Science+Business Media New York.Long-term plasticity plays an important role in the functional construction of neuronal networks. While anatomical wiring provides essential hardware for brain function, activity-dependent plasticity works as an adjustable software interface allowing sensory induced modification of transmission efficacy at given synaptic connections. In contrast to the vast majority of excitatory synapses, at distinct types of inhibitory GABAergic connections, the link between the pattern of activity and the subsequent change of synaptic strength has not been well characterized. Here, we examined frequency and stimulation pattern dependence in long-term synaptic depression at CCK+/CB1R inhibitory perisomatic synapses in the hippocampal CA1 region, and we found that successful LTD induction depends on the pattern of stimulation rather than the number of stimuli

The role of polyamine-dependent facilitation of calcium permeable ampars in short-term synaptic enhancement

© 2018 Rozov, Zakharova, Vazetdinova and Valiullina-Rakhmatullina. Depending on subunit composition AMPA receptor channels can be subdivided into two groups: GluA2-containing calcium impermeable AMPARs, and GluA2-lacking calcium permeable, AMPARs. These two groups differ in a number of biophysical properties and, most likely, in their functional role at glutamatergic synapses. GluA2-lacking channels have received a lot of attention over the last two decades mainly due to high calcium permeability, which was suggested to play a significant role in the induction of long-term synaptic plasticity in healthy tissue and neuronal death under neuropathological conditions. However, calcium permeable AMPARs possess another property that can contribute substantially to frequency dependent dynamics of synaptic efficacy. In the closed state calcium permeable AMPARs are blocked by endogenous polyamines, however, repetitive activation leads to progressive relief from the block and to the facilitation of ion flux through these channels. Polyamine-dependent facilitation of AMPARs can contribute to short-term plasticity at synapses that have high initial release probability and express calcium permeable AMPARs. During synaptic transmission activity-dependent relief from polyamine block of postsynaptic calcium-permeable AMPARs either counteracts presynaptic short-term depression in a frequency-dependent manner or, under specific stimulation conditions, induces facilitation of a synaptic response. Taking into account the fact that expression of calcium permeable AMPARs is developmentally regulated, depends on network activity and increases in diseased brain states, polyamine-dependent facilitation of calcium permeable AMPARs is an important, entirely postsynaptic mechanism of synaptic gain regulation

GABABR-dependent long-term depression at hippocampal synapses between CB1-positive interneurons and CA1 pyramidal cells

© 2016 Jappy, Valiullina, Draguhn and Rozov. Activity induced long lasting modifications of synaptic efficacy have been extensively studied in excitatory synapses, however, long term plasticity is also a property of inhibitory synapses. Inhibitory neurons in the hippocampal CA1 region can be subdivided according to the compartment they target on the pyramidal cell. Some interneurons preferentially innervate the perisomatic area and axon hillock of the pyramidal cells while others preferentially target dendritic branches and spines. Another characteristic feature allowing functional classification of interneurons is cell type specific expression of different neurochemical markers and receptors. In the hippocampal CA1 region, nearly 90% of the interneurons expressing cannabinoid type 1 receptors (CB1R) also express cholecystokinin (CCK). Therefore, the functional presence of CB1 receptors can be used for identification of the inhibitory input from CCK positive (CCK+) interneurons to CA1 pyramidal cells. The goal of this study was to explore the nature of long term plasticity at the synapses between interneurons expressing CB1 Rs (putative CCK+) and pyramidal neurons in the CA1 region of the hippocampus in vitro. We found that theta burst stimulation triggered robust long-term depression (LTD) at this synapse. The locus of LTD induction was postsynaptic and required activation of GABAb receptors. We also showed that LTD at this synaptic connection involves GABAbR- dependent suppression of adenylyl cyclase and consequent reduction of PKA activity. In this respect. CB1+ to pyramidal cell synapses differ from the majority of the other hippocampal inhibitory connections where theta burst stimulation results in long-term potentiation

Promising new therapeutic targets for regulation of inflammation and immunity: RING-type E3 ubiquitin ligases

© 2018 European Federation of Immunological Societies Ubiquitin–proteasome system (UPS) is a primary signaling pathway for regulation of protein turnover and removal of misfolded proteins in eukaryotic cells. Enzymes of the UPS pathway - E1 activating, E2 conjugating, E3 ligating - act together to covalently tag substrate proteins with a chain of ubiquitins, small regulatory proteins. The poly-ubiquitin chain then serves as a recognition motif for 26S proteasome to recognize and degrade the substrate. In recent years UPS has emerged as attractive enzymatic cascade for development of novel therapeutics against various human diseases. Building on the previous success of targeting this pathway in cancer – the broader scientific community is currently looking for ways to elucidate functions of E3 ligases, substrate-specific members of the UPS. RING-type E3 ubiquitin ligases, the largest class of E3s, represent prospective targets for small molecule modulation and their importance is reinforced by ever growing evidence of playing role in non-cancer diseases, primarily associated with inflammatory and immune disorders. In this review, we aim to briefly cover the current knowledge of biological functions of RING-type E3 ligases in inflammation and immunity

Selective Extracellular Stimulation of Pharmacologically Distinct CCK/CB1R Positive Interneuron to Pyramidal Cell Perisomatic Inhibitory Synapses

© 2016, Springer Science+Business Media New York.During prolonged whole cell recording, the intracellular contents are progressively dialyzed with the pipette solution; this often leads to significant changes in synaptic efficacy. To overcome this problem, we developed an approach allowing reliable extracellular stimulation of perisomatic synapses formed by CCK+/CB1+ interneurons onto CA1 pyramidal cells. Functional identification of this input was based on the unique features of CCK+/CB1+ terminals: long-lasting asynchronous transmitter release following high-frequency stimulation and exclusive expression of CB1R. Asynchronous release was used as an indication of proper positioning of the theta glass stimulation pipettes. We found that all extracellularly stimulated inputs with characteristic asynchronous release undergo robust DSI in response to 5-s depolarization and could also be almost entirely blocked by application of the CB1R agonist CP55940, which were similar to the data obtained with paired recordings from connected CB1+ and CA1 pyramidal cells. Thus, we have developed an approach allowing the selective and reliable extracellular stimulation of a subtype of hippocampal perisomatic inhibitory synapses

GABA<inf>B</inf>R-dependent long-term depression at hippocampal synapses between CB1-positive interneurons and CA1 pyramidal cells

© 2016 Jappy, Valiullina, Draguhn and Rozov.Activity induced long lasting modifications of synaptic efficacy have been extensively studied in excitatory synapses, however, long term plasticity is also a property of inhibitory synapses. Inhibitory neurons in the hippocampal CA1 region can be subdivided according to the compartment they target on the pyramidal cell. Some interneurons preferentially innervate the perisomatic area and axon hillock of the pyramidal cells while others preferentially target dendritic branches and spines. Another characteristic feature allowing functional classification of interneurons is cell type specific expression of different neurochemical markers and receptors. In the hippocampal CA1 region, nearly 90% of the interneurons expressing cannabinoid type 1 receptors (CB1R) also express cholecystokinin (CCK). Therefore, the functional presence of CB1 receptors can be used for identification of the inhibitory input from CCK positive (CCK+) interneurons to CA1 pyramidal cells. The goal of this study was to explore the nature of long term plasticity at the synapses between interneurons expressing CB1 Rs (putative CCK+) and pyramidal neurons in the CA1 region of the hippocampus in vitro. We found that theta burst stimulation triggered robust long-term depression (LTD) at this synapse. The locus of LTD induction was postsynaptic and required activation of GABAb receptors. We also showed that LTD at this synaptic connection involves GABAbR- dependent suppression of adenylyl cyclase and consequent reduction of PKA activity. In this respect. CB1+ to pyramidal cell synapses differ from the majority of the other hippocampal inhibitory connections where theta burst stimulation results in long-term potentiation

Urinary clusterin is upregulated in nephropathia epidemica

© 2018 Ekaterina V. Martynova et al. Kidney insufficiency is a hallmark of nephropathia epidemica (NE). Little is known about the mechanisms of the NE kidney pathology, with current knowledge mainly based on findings in postmortem tissue. We have analyzed kidney damage biomarkers in urine collected from early- and late-phase NE using Bio-Plex kidney toxicity panels 1 and 2. To determine the disease specificity, kidney damage biomarkers were also analyzed in urine samples from patients diagnosed with gout, type 2 diabetes, systemic lupus erythematosus, and chronic kidney insufficiency. Analysis of 12 biomarkers suggests damage to the kidney proximal tubule at the onset of NE. Also, upregulation of biomarkers of inflammation and leukocyte chemotaxis were detected in NE urine. Furthermore, increased clusterin levels were found in early- and late-phase NE urine. Comparative analysis revealed that clusterin is a biomarker, upregulated in NE urine

Resting membrane potential of the rat ventroposteriomedial thalamic neurons during postnatal development

Resting membrane potential is a critical parameter determining tonic or bursting mode of the thalamic neurons function. Previous developmental studies using whole-cell recordings revealed strongly depolarized values ofthe resting membrane potential (near -50 mV) in the immature VPM and LGN thalamic neurons. Yet, whole-cell recordings are associated with an introduction of the shunting conductance via the gigaseal that may lead to neuronal depolarization in small neurons with high, in the gigaohm range, membrane resistance. Therefore, we have performed measurements of the resting potential of VPM neurons in slices obtained from neonatal rats of postnatal days P2-P7 using cell-attached recordings of NMDA channels as voltage sensors. Because the currents through NM DA channels reverse near 0 mV, we assumed that the resting membrane potential should equal the reversal potential of currents through NMDA channels in cell-attached recordings. Analysis of the current-voltage relationships of NMDA currents revealed that the resting membrane potential in the immature VPM neurons is around -74 mV and that it does not change during the first postnatal week. This suggests that VPM neurons may operate in the bursting mode during the early postnatal period and support the oscillatory activity (spindle-like bursts) in the developing thalamocortical networks