Elektrofizjologiczne badania neuronalnych mechanizmów plastyczności kory baryłkowej myszy wywołanych uczeniem się

Awersyjne warunkowanie klasyczne, polegające na skojarzeniu stymulacji dotykowej jednego z rzędów wibrys, jako bodźca warunkowego (CS), z szokiem elektrycznym w ogon, jako bodźcem bezwarunkowym (UCS), wywołuje powiększenie rozmiarów funkcjonalnych reprezentacji stym ulowanych wibrys w korze somatosensorycznej myszy, co wykazano przy zastosowaniu pomiarów aktywności metabolicznej tkanki nerwowej [13]. Efekt ten ma charakter uczenia asocjacyjnego. Dane literaturowe wskazują, źe po zakończeniu treningu, w obszarach stanowiących reprezentacje stymulowanych wibrys dochodzi do wzrostu poziomu markerów GABAergicznego przekaźnictwa synaptycznego. Jak dotąd, brak jednak danych na temat modyfikacji funkcji neuronów korowych i ich połączeń, które mogą być efektem zmian plastycznych. Celem wykonanych badań było określenie, które elementy sieci neuronalnej kory somatosensorycznej ulegają modyfikacjom w efekcie awersyjnego warunkowania klasycznego. Badania prowadzone były metodami rejestracji elektrofizjologicznej ex vivo z pojedynczych neuronów whole-cell patch-clamp w skrawkach kory somatosensorycznej myszy, poddanych wcześniej warunkowaniu awersyjnemu. W pierwszym etapie badań przeprowadzono charakterystykę elektrofizjologiczną glutaminianergicznych neuronów pobudzających i GABAergicznych neuronów hamujących. Następnie rejestrowano postsynaptyczne prądy hamujące i pobudzające, powstające spontanicznie. Uzyskane wyniki wykazały, że warunkowanie awersyjne nie spowodowało zmian podstawowych parametrów elektrofizjologicznych komórek GABAergicznych i glutaminianergicznych. w skrawkach kory pochodzących z mózgów zwierząt poddanych uprzednio procedurze warunkowania klasycznego. Wykazano, że warunkowanie klasyczne nasiliło częstotliwość spontanicznych postsynaptycznych prądów hamujących (sIPSC) rejestrowanych w komórkach glutaminianergicznych w skrawkach kory pochodzących z mózgów zwierząt poddanych procedurze warunkowania klasycznego. W przeciwieństwie do tego, nie stwierdzono istotnych zmian w częstotliwości spontanicznych postsynaptycznych prądów pobudzających (sEPSC) rejestrowanych w komórkach GABA i glutaminianergicznych. Wyniki te potwierdzają hipotezę o nasileniu przekaźnictwa synaptycznego w połączeniach pomiędzy interneuronami GABAergicznymi a neuronami pobudzającymi, powstającym w efekcie treningu. Zaobserwowane nasilenie przekaźnictwa GABAergicznego stanowi, prawdopodobnie, wyraz adaptacyjnej modyfikacji sieci neuronalnej połączeń pomiędzy neuronami baryłki, której sens polega na zapewnieniu niezbędnej równowagi pomiędzy przekaźnictwem pobudzającym a hamującym w zmienionych warunkach, związanych z awersyjnym warunkowaniem klasycznym. Mechanizm zaobserwowanych zmian nie jest znany i wymaga dalszych badań.Zadanie pt. „Digitalizacja i udostępnienie w Cyfrowym Repozytorium Uniwersytetu Łódzkiego kolekcji czasopism naukowych wydawanych przez Uniwersytet Łódzki” nr 885/P-DUN/2014 dofinansowane zostało ze środków MNiSW w ramach działalności upowszechniającej naukę

5-HT_{7} receptor modulates GABAergic transmission in the rat dorsal raphe nucleus and controls cortical release of serotonin

The 5-HT7 receptor is one of the several serotonin (5-HT) receptor subtypes that are expressed in the dorsal raphe nucleus (DRN). Some earlier findings suggested that 5-HT7 receptors in the DRN were localized on GABAergic interneurons modulating the activity of 5-HT projection neurons. The aim of the present study was to find out how the 5-HT7 receptor modulates the GABAergic synaptic input to putative 5-HT DRN neurons, and whether blockade of the 5-HT7 receptor would affect the release of 5-HT in the target structure. Male Wistar rats with microdialysis probes implanted in the prefrontal cortex (PFC) received injections of the 5-HT7 receptor antagonist (2R)-1-[(3-hydroxyphenyl)sulfonyl]-2-[2-(4-methyl-1-piperidinyl)ethyl]pyrrolidine hydrochloride (SB 269970), which induced an increase in the levels of 5-HT and its metabolite, 5-hydroxyindoleacetic acid (5-HIAA) in the PFC. In another set of experiments whole-cell recordings from presumed projection neurons were carried out using DRN slices. SB 269970 application resulted in depolarization and in an increase in the firing frequency of the cells. In order to activate 5-HT7 receptors, 5-carboxamidotryptamine (5-CT) was applied in the presence of N-[2-[4-(2-methoxyphenyl)-1piperazinyl]ethyl]-N-2-pyridinylcyclohexanecarboxamide (WAY100635). Hyperpolarization of cells and a decrease in the firing frequency were observed after activation of the 5-HT7 receptor. Blockade of 5-HT7 receptors caused a decrease in the mean frequency of spontaneous inhibitory postsynaptic currents (sIPSCs), while its activation induced an increase. The mechanism of these effects appears to involve tonically-active 5-HT7 receptors modulating firing and/or GABA release from inhibitory interneurons which regulate the activity of DRN serotonergic projection neurons

Nitric oxide synthase inhibitor attenuates the effects of repeated restraint stress on synaptic transmission in the paraventricular nucleus of the rat hypothalamus

Corticotropin-releasing hormone (CRH)-synthesizing parvocellular neuroendocrine cells (PNCs) of the hypothalamic paraventricular nucleus (PVN) play a key role in the activation of the hypothalamic-pituitary-adrenocortical (HPA) axis. Several studies have demonstrated that synaptic inputs to these cells may undergo stress-related enhancement but, on the other hand, it has been reported that exposition to the same stressor for prolonged time periods may induce a progressive reduction in the response of the HPA axis to homotypic stressors. In the present study rats were subjected to 10 min restraint sessions, repeated twice daily for 3 or 7 days. Miniature excitatory and inhibitory postsynaptic currents (mEPSCs and mIPSCs) were then recorded from PNCs in ex vivo hypothalamic slice preparations obtained 24 h after the last restraint. Restraint stress repeated over 3 days resulted in increased mean frequency and decreased rise time and decay time constant of mEPSCs, accompanied by a decrease in the excitability of PNCs, however, no such changes were evident in slices obtained from rats subjected to restraint over 7 days. There were no changes in mIPSCs after repeated restraint. Administration of the unspecific nitric oxide synthase (NOS) blocker Nω-Nitro-L-arginine (L-NNA) before each restraint, repeated over 3 days, prevented the occurrence of an increase in mEPSC frequency. However, animals receiving L-NNA and subjected to repeated restraint had similar changes in PNCs membrane excitability and mEPSC kinetics as stressed rats not receiving L-NNA. Comparison of the effects of a single 10 min restraint session followed by either an immediate or delayed (24 h) decapitation revealed an increase in the mean mEPSC frequency and a decrease in the mean mIPSC frequency in slices prepared immediately after restraint, with no apparent effects when slice preparation was delayed by 24 h. These results demonstrate that restraint, lasting 10 min and repeated twice daily for 3 days, induces a selective and long-lasting enhancement of excitatory synaptic input onto PNCs, partially by a NOS-dependent mechanism, and reduces PNC excitability, whereas prolongation of repeated stress for up to 7 days results in an adaptation

ELECTROCHEMICAL CODEPOSITION OF MOLYBDENUM AND SELENIUM

The electrodeposition of the Mo-Se thin films from sulfate solution containing Na2MoO4 and H2SeO3 was studied. The process of deposition were conducted under potentiostatic condition on copper electrode. The effect of different potential, pH and time of deposition were examined. The deposits were characterized by X-ray diffraction, X-ray fluorescence and scanning electron microscopy

Hyperforin Potentiates Antidepressant-Like Activity of Lanicemine in Mice

N-methyl-D-aspartate receptor (NMDAR) modulators induce rapid and sustained antidepressant like-activity in rodents through a molecular mechanism of action that involves the activation of Ca2+ dependent signaling pathways. Moreover, ketamine, a global NMDAR antagonist is a potent, novel, and atypical drug that has been successfully used to treat major depressive disorder (MDD). However, because ketamine evokes unwanted side effects, alternative strategies have been developed for the treatment of depression. The objective of the present study was to determine the antidepressant effects of either a single dose of hyperforin or lanicemine vs. their combined effects in mice. Hyperforin modulates intracellular Ca2+ levels by activating Ca2+-conducting non-selective canonical transient receptor potential 6 channel (TRPC6) channels. Lanicemine, on the other hand, blocks NMDARs and regulates Ca2+ dependent processes. To evaluate the antidepressant-like activity of hyperforin and lanicemine, a set of in vivo (behavioral) and in vitro methods (western blotting, Ca2+ imaging studies, electrophysiological, and radioligand binding assays) was employed. Combined administration of hyperforin and lanicemine evoked long-lasting antidepressant-like effects in both naïve and chronic corticosterone-treated mice while also enhancing the expression of the synapsin I, GluA1 subunit, and brain derived neurotrophic factor (BDNF) proteins in the frontal cortex. In Ca2+ imaging studies, lanicemine enhanced Ca2+ influx induced by hyperforin. Moreover, compound such as MK-2206 (Akt kinase inhibitor) inhibited the antidepressant-like activity of hyperforin in the tail suspension test (TST). Hyperforin reversed disturbances induced by MK-801 in the novel object recognition (NOR) test and had no effects on NMDA currents and binding to NMDAR. Our results suggest that co-administration of hyperforin and lanicemine induces long-lasting antidepressant effects in mice and that both substances may have different molecular targets

Characteristics of natural background radiation in the Polkowice-Sieroszowice mine, Poland

Natural radioactivity in underground locations is the main parameter for the safety of work (occupational hazards) and for the success of experiments in physics or biology requiring unique conditions. The characterization of natural prominence was carried out in the Conceptual Lab development in one of KGHM deep copper mines co‐ordinated by KGHM Cuprum R&D. Natural radioactivity studies were performed and included in situ gamma spectrometry, neutron flux measurements, radon concentration, and alpha and gamma laboratory spectrometry measurements of rock samples. At a depth of 1014.4 m (2941.8 m w.e.) within the anhydrite layer, a neutron flux of 2.0 ± 0.2 × 10−6 cm−2 s−1, a gamma‐ray dose of 0.008 ± 0.001 μSv/h, a photon flux density of 0.64 ± 0.20 cm−2 s−1, and a radon concentration of 6.6 Bq/m3 were determined. Laboratory analyses of 226,228Ra, 40K, and 238,234U concentrations in collected rock samples showed low values. The exceptionally low level of natural radioactivity in the Polkowice‐Sieroszowice mine makes this location a unique place for scientific research