The role of pannexin hemichannels in the anoxic depolarization of hippocampal pyramidal cells

Neuronal gap junctional hemichannels, composed of pannexin-1 subunits, have been suggested to play a crucial role in epilepsy and brain ischaemia. After a few minutes of anoxia or ischaemia, neurons in brain slices show a rapid depolarization to ∼−20 mV, called the anoxic depolarization. Glutamate receptor blockers can prevent the anoxic depolarization, suggesting that it is produced by a cation influx through glutamate-gated channels. However, in isolated hippocampal pyramidal cells, simulated ischaemia evokes a large inward current and an increase in permeability to large molecules, mediated by the opening of pannexin-1 hemichannels. N-methyl-d-aspartate is also reported to open these hemichannels, suggesting that the activation of N-methyl-d-aspartate receptors, which occurs when glutamate is released in ischaemia, might cause the anoxic depolarization by evoking a secondary ion flux through pannexin-1 hemichannels. We tested the contribution of pannexin hemichannels to the anoxic depolarization in CA1 pyramidal cells in the more physiological environment of hippocampal slices. Three independent inhibitors of hemichannels—carbenoxolone, lanthanum and mefloquine—had no significant effect on the current generating the anoxic depolarization, while a cocktail of glutamate and gamma-aminobutyric acid class A receptor blockers abolished it. We conclude that pannexin hemichannels do not generate the large inward current that underlies the anoxic depolarization. Glutamate receptor channels remain the main candidate for generating the large inward current that produces the anoxic depolarization

Compound Names as “Markers of Situation”: Replenishment of the Fund of Set Word Combinations of the Russian Language During a Period of Forced Self­Isolation

The article deals with the problems associated with the formation of new categories of Russian language — compound names, motivated by anti-COVID-19 measures. Based on the analysis of extensive factual material (texts of bylaws, media articles, messages from Internet forums), the authors make an attempt to create an up-to-date functional-thematic classification of compound names of the period of forced self-isolation to identify specific implementations of the semantics of set combinations, and to define the function of compound names as “markers of situation”. It is concluded that the observation of the formation and functioning of the compound names of the period of struggle with COVID-19 gives the linguist an exceptional opportunity to “in motio” consider each element of the mechanism of phraseologization of the meaning, to accurately identify the stages of “rebirth” of the features of phrasal components in combinations

Problems of teaching foreign students in mixed groups

The article analyzes the problems associated with teaching foreign students in mixed groups. A mixed group is a formally isolated part of the educational institution cohort that possesses such characteristics as: 1) a fixed heterogeneous ethno-cultural composition, 2) a different level of preparation of students for mastering the disciplines of the general educational program, 3) common cognitive interests and a single educational content in the current period of time; 4) joint educational activities under the guidance of the same teachers, 5) a single period of study. This article aims to highlight the range of language problems that hinder the development of general education programs by foreign students when studying as part of a mixed group. Since the structure of language difficulties varies for different categories of foreign citizens (foreigners with an initial level of proficiency in Russian, foreign speakers, bilinguals), it is important to have a differentiated approach to regulating the educational process and specially organized training taking into account the ethnic and linguistic needs of all members of the group. A differentiated approach to learning, building an individual way of each group member development allows mobilizing cognitive interests and motivating participants in the educational process. The development of specific recommendations to overcome the possible negative impact of a mixed group on the process of obtaining subject knowledge by foreign students is an important methodological task that requires further study

N-oleoyldopamine modulates activity of midbrain dopaminergic neurons through multiple mechanisms

N-oleoyl-dopamine (OLDA) is an amide of dopamine and oleic acid, synthesized in catecholaminergic neurons. The present study investigates OLDA targets in midbrain dopaminergic (DA) neurons. Substantia Nigra compacta (SNc) DA neurons recorded in brain slices were excited by OLDA in wild type mice. In transient receptor potential vanilloid 1 (TRPV1) knockout (KO) mice, however, SNc DA neurons displayed sustained inhibition of firing. In the presence of the dopamine type 2 receptor (D2R) antagonist sulpiride or the dopamine transporter blocker nomifensine no such inhibition was observed. Under sulpiride OLDA slightly excited SNc DA neurons, an action abolished upon combined application of the cannabinoid1 and 2 receptor antagonists AM251 and AM630. In ventral tegmental area (VTA) DA neurons from TRPV1 KO mice a transient inhibition of firing by OLDA was observed. Thus OLDA modulates the firing of nigrostriatal DA neurons through interactions with TRPV1, cannabinoid receptors and dopamine uptake. These findings suggest further development of OLDA-like tandem molecules for the treatment of movement disorders including Parkinson's disease

Long-lasting enhancement of synaptic excitability of CA1/subiculum neurons of the rat ventral hippocampus by vasopressin and vasopressin(4-8)

Vasopressin (VP) is axonally distributed in many brain structures, including the ventral hippocampus. Picogram quantities of VP injected into the hippocampus improve the passive avoidance response of rats, presumably by enhancing memory processes. Vasopressin is metabolized by the brain tissue into shorter peptides, such as [pGlu4r,Cyt6]VP(49[ and [pGIu4,Cyt6,]VP(48), which preserve the behavioral activity but lose the peripheral activities of the parent hormone. Using brain slices, we investigated whether VP or VP(48) affects excitatory postsynaptic potentials (EPSPs) and/or membrane responses to depolarization in neurons of the CA 1 /subiculum of the ventral hippocampus. The EPSPs were evoked by stimulating the stratum radiatum of the CAI field; the membrane responses were elicited by current injections. Exposure of slices for 15 min to 0.1 nM solution of these peptides resulted in an increase in the amplitude and slope of the EPSPs in 21 neurons (67%) tested. No consistent change in either the resting membrane potential or the input resistance of the neurons was observed. The peptide-induced increase in EPSPs reached a maximum 3045 min after peptide application. In 14 of these neurons (66%), the peptide-induced increase in EPSPs remained throughout the entire 60120 min washout period. In the remaining 7 neurons (33%), the initial increase in EPSPs amplitude was followed by a gradual decline to the pre-administration level. The increase in EPSP amplitude was often. but not always, associated with a decrease in the threshold and increase in the number of action potentials in response to depolarizing current injection. Suppression of GABAA receptor-mediated inhibition and N-methyl--aspartate (NMDA) receptor-mediated excitation did not prevent the effects of VP and VP(48[ on the EPSP amplitude or the threshold for action potentials. The results demonstrate that 0.1 nM concentrations of these neuropeptides can elicit a long-lasting enhancement of the excitability of CA1/subiculum neurons of the ventral hippocampus to excitatory, glutamatergic synaptic input. This novel action of VP and its metabolite in the ventral hippocampus may be the physiological action, mediating the memory-enhancing effect of these peptides

Guanidinoethyl sulphonate is a glycine receptor antagonist in striatum

1. Guanidinoethyl sulphonate (GES) is an analogue of taurine and an inhibitor of taurine transport. Interactions of GES with GABA(A) and glycine receptors are studied by whole cell recording and fast drug application in isolated striatal neurons of the mouse. 2. We confirm that GES is a weak agonist at GABA(A) receptors, and is able to antagonize GABA-evoked responses. GES did not gate GlyR. 3. GES antagonized glycine responses in a concentration-dependent and surmountable manner. Glycine dose–response curves were shifted to the right by GES (0.5 mM), yielding EC(50)s and Hill coefficients of 62 μM and 2.5 in control, 154 μM and 1.3 in the presence of GES. 4. GlyR-mediated taurine responses were competitively antagonized by GES. Taurine dose–response curves, in contrast to the glycine dose–response curves were shifted by GES to the right in a parallel manner. 5. The GlyR-block by GES was not voltage-dependent. 6. In contrast to our findings in the mouse, in rat striatal neurons which lack expression of the α3 GlyR subunit, GES shifted the glycine dose–response curve to the right in a parallel way without affecting the maximal response. Subtype-specificity of the GES action at GlyR must await further investigation in artificial expression systems. 7. We conclude that GES is a competitive antagonist at GlyR. The antagonistic action of GES at inhibitory ionotropic receptors can explain its epileptogenic action. Care must be taken with the interpretation of data on GES evoked taurine release

GABAA-receptor modification in taurine transporter knockout mice causes striatal disinhibition

The Striatum is involved in the regulation of movements and motor skills. We have shown previously, that the osmolyte and neuromodulator taurine plays a role in striatal plasticity. We demonstrate now that hereditary taurine deficiency in taurine-transporter knock-out (TAUT KO) mice results in disinhibition of striatal network activity, which can be corrected by taurine supplementation. Modification of GABAA but not glycine receptors (taurine is a ligand for both receptor types) underlies this disinhibition. Whole-cell recordings from acutely isolated as well as cultured striatal neurons revealed a decreased agonist sensitivity of the GABAA receptor in TAUT KO neurons in the absence of changes in the maximal GABA-evoked current amplitude. The striatal GABA level in TAUT KO mice was unchanged. The amplitude enhancement of spontaneous IPSCs by zolpidem was stronger in TAUT KO than in wild-type (WT) animals. Tonic inhibition was absent in striatal neurons under control conditions but was detected after incubation with the GABA-transaminase inhibitor vigabatrin: bicuculline induced a larger shift of baseline current in WT as compared to TAUT KO neurons. Lack of taurine leads to reduced sensitivity of synaptic and extrasynaptic GABAA receptors and consequently to disinhibition. These findings help in understanding neuropathologies accompanied by the loss of endogenous taurine, for instance in hepatic encephalopathy

Taurine-Induced Long-Lasting Enhancement of Synaptic Transmission in Mice: Role of Transporters

Taurine, a major osmolyte in the brain evokes a long-lasting enhancement (LLETAU) of synaptic transmission in hippocampal and cortico-striatal slices. Hippocampal LLETAU was abolished by the GABA uptake blocker nipecotic acid (NPA) but not by the taurine-uptake inhibitor guanidinoethyl sulphonate (GES). Striatal LLETAU was sensitive to GES but not to NPA. Semiquantitative PCR analysis and immunohistochemistry revealed that taurine transporter expression is significantly higher in the striatum than in the hippocampus. Taurine transporter-deficient mice displayed very low taurine levels in both structures and a low ability to develop LLETAU in the striatum, but not in the hippocampus. The different mechanisms of taurine-induced synaptic plasticity may reflect the different vulnerabilities of these brain regions under pathological conditions that are accompanied by osmotic changes such as hepatic encephalopathy