Expression of AMPA/kainate receptors during development of chick embryo retina cells: in vitro versus in vivo studies

The activity and the subunit expression of [alpha]-amino-3-hydroxy-5-methylisoxazole-4-propionate (AMPA)/kainate ionotropic glutamate receptors were studied in retina cells developing in chick embryos and in retina cells cultured as retinospheroids, at the same stages of development. In the retinospheroids, the activity of the AMPA/kainate receptors was monitored by following the changes in the intracellular free calcium concentration ([Ca2+]i), in response to AMPA, kainate or to -glutamate, and the expression of the receptor subunits GluR1, GluR2/3, GluR4 and GluR6/7 was determined in the retinospheroids and in chick retinas by immunodetection using polyclonal antibodies. The changes in [Ca2+]i in response to 400 [mu]M kainate increased from 5 h in vitro to 3 days, and remained constant until day 14, whereas the [Ca2+]i in response to 500 [mu]M -glutamate or 400 [mu]M AMPA increased from 5 h in vitro to 3 days, and thereafter decreased slightly until day 14. The [Ca2+]i responses to kainate are mainly due to AMPA receptor stimulation, since the signals were abolished by LY303070, the AMPA receptor antagonist, and were not affected by MK-801, the NMDA receptor antagonist. In retinospheroids, the levels of expression of GluR1 subunit increased from 5 h in vitro until day 7, then decreased until day 14. The levels of expression of GluR2/3 and GluR4 subunits increased from 5 h in vitro until day 10, and remained constant until day 14. The levels of kainate receptor subunits GluR6/7 increased from 5 h in vitro until day 3, and thereafter decreased slightly until day 14. In the retinas, the expression of GluR1 and GluR6/7 subunits increased from day 8 until day 15, and then decreased until day 22 (post-natal 1). The subunits GluR2/3 and GluR4 increased from day 8 until day 18, and remained constant until day 22. The results suggest that AMPA/kainate receptors are expressed at early embryonic stages, although at low levels and before synapse formation (E12). However, the AMPA receptors are not completely functional at the first stage studied since they do not respond to the agonist AMPA. Also, the patterns of AMPA/kainate receptor subunit expression in retinospheroids of chick embryo retina cells cultured in vitro and in retina cells developing in the embryo (in vivo) were similar, indicating that the AMPA/kainate receptor subunits expression in these primary cultures mimics their expression in the developing chick retina.http://www.sciencedirect.com/science/article/B6T01-45CW0B3-1/1/a35858f1d7808b1301de428de93fa9e

Ketamine can reduce harmful drinking by pharmacologically rewriting drinking memories

Maladaptive reward memories (MRMs) are involved in the development and maintenance of acquired overconsumption disorders, such as harmful alcohol and drug use. The process of memory reconsolidation - where stored memories become briefly labile upon retrieval - may offer a means to disrupt MRMs and prevent relapse. However, reliable means for pharmacologically weakening MRMs in humans remain elusive. Here we demonstrate that the N-methyl D-aspartate (NMDA) antagonist ketamine is able to disrupt MRMs in hazardous drinkers when administered immediately after their retrieval. MRM retrieval + ketamine (RET + KET) effectively reduced the reinforcing effects of alcohol and long-term drinking levels, compared to ketamine or retrieval alone. Blood concentrations of ketamine and its metabolites during the critical ‘reconsolidation window’ predicted beneficial changes only following MRM reactivation. Pharmacological reconsolidation interference may provide a means to rapidly rewrite maladaptive memory and should be further pursued in alcohol and drug use disorders

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Not AvailableIn the most productive area of the Indo - Gangetic Plains in Northwest India where high yields of rice and wheat are commonplace, a medium - term cropping system trial was conducted in Haryana State. The goal of the study was to identify integrated management options for further improving productivity and profitability while rationalizing resource use and reducing environmental externalities (i.e., “sustainable intensification”, SI) by drawing on the principles of diversification, precision management, and conservation agriculture. Four scenarios were evaluated: Scenario 1 - “business - as - usual” [conventional puddled transplanted rice (PTR) followed by (fb) conventional - till wheat]; Scenario 2 - reduced tillage with opportunistic diversification and precision resource management [PTR fb zero - till (ZT) wheat fb ZT mungbean]; Scenario 3 - ZT for all crops with opportunistic diversification and precision resource management [ZT direct - seeded rice (ZT - DSR) fb ZT wheat fb ZT mungbean]; and Scenario 4 - ZT for all crops with strategic diversification and precision resource management [ZT maize fb ZT wheat fb ZT mungbean]. Results of this five - year study strongly suggest that, compared with business - as - usual practices, SI strategies that incorporate multi - objective yield, economic, and environmental criteria can be more productive when used in these production environments. For Scenarios 2, 3, and 4, system level increases in productivity (10 - 17%) and profitability (24 - 50%) were observed while using less irrigation water (15 - 71% reduction) and energy (17 - 47% reduction), leading to 15 - 30% lower global warming potential (GWP), with the ranges reflecting the implications of specific innovations. Scenario 3, where early wheat sowing was combined with ZT along with no puddling during the rice phase, resulted in a 13% gain in wheat yield compared with Scenario 2. A similar gain in wheat yield was observed in Scenario 4 vis - à - vis Scenario 2. Compared to Scenario 1, wheat yields in Scenarios 3 and 4 were 15 - 17% higher, whereas, in Scenario 2, yield was either similar in normal years or higher in warmer years. During the rainy (kharif) season, ZT - DSR provided yields similar to or higher than those of PTR in the first three years and lower (11 - 30%) in Years 4 and 5, a result that provides a note of caution for interpreting technology performance through short - term trials or simply averaging results over several years. The resource use and economic and environmental advantages of DSR were more stable through time, including reductions in irrigation water (22 - 40%), production cost (11 - 17%), energy inputs (13 - 34%), and total GWP (14 - 32%). The integration of “best practices” in PTR in Scenario 2 resulted in reductions of 24% in irrigation water and 21% in GWP, with a positive impact on yield (0.9 t/ha) and profitability compared to conventional PTR, demonstrating the power of simple management changes to generate improved SI outcomes. When ZT maize was used as a diversification option instead of rice in Scenario 4, reductions in resource use jumped to 82 - 89% for irrigation water and 49 - 66% for energy inputs, with 13 - 40% lower GWP, similar or higher rice equivalent yield, and higher profitability (27 - 73%) in comparison to the rice based scenarios. Despite these advantages, maize value chains are not robust in this part of India and public procurement is absent. Results do demonstrate that transformative opportunities exist to break the cycle of stagnating yields and inefficient resource use in the most productive cereal - based cropping systems of South Asia. However, these SI entry points need to be placed in the context of the major drivers of change in the region, including market conditions, risks, and declining labor availability, and matching with the needs and interests of different types of farmers.Not Availabl

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