EDITORIAL published: 09 January 2013 doi: 10.3389/fncel.2012.00062 Building up the inhibitory synapse Enrico Cherubini * and Paola Zacchi Department of Neuroscience, Scuola Internazionale Superiore di Studi Avanzati, Trieste, Italy *Correspondence: cher@sissa.it Edited by: Egidio D’Angelo, University of Pavia, Italy Reviewed by: Egidio D’Angelo, University of Pavia, Italy “Building up the inhibitory synapse” is a complex phenomenon involving a variety of dynamically regulated molecular and cellular processes whose nature is still largely unknown. Understanding the role of different proteins in controlling synapses formation and stabilization may help elucidating, at the network level, the mechanisms by which inhibitory transmission controls network excitability and oscillatory behavior, crucial for information processing in the brain. Aim of this e-book is to highlight recent advances in these pro- cesses, bringing together leading experts in the field, who have made major contributions to our understanding of the cellular and molecular mechanisms regulating the appropriate assembly, location, and function of pre and postsynaptic specializations at inhibitory synapses. This e-book comprises nine reviews, one perspective and three research articles organized in a logic way following the informa- tion flow from the pre to the postsynaptic site. In the first article, Jovanovic and Thomson (2011) (School of Pharmacy, UCL) review the developmental processes determin- ing the tangential migration of GABAergic interneurons from the ganglionic eminence to the neocortex where the formation of appropriate synapses seems to be facilitated by cell–cell recogni- tion, most probably via protein–protein interactions across the synaptic cleft. Grantyn et al. (2011) (Institute of Neurophysiology Charité, Berlin) discuss how, during postnatal development, GABAergic synapses are characterized by a high release probability, often multivesicular (ballistic) and asynchronous. The ballistic mode of operation of immature synaptic terminals might be instru- mental for recruiting and stabilizing receptors via postsynaptic calcium signals, triggered by the depolarizing action of GABA and activation of voltage-dependent calcium channels. Early in postnatal life, the depolarizing action of GABA is crucial for the construction of neuronal circuits. This process depends on intracellular chloride homeostasis which is under control of the cation-chloride co-transporter KCC2. In addition, by interacting with actin cytoskeleton, KCC2 exerts, indepen- dently of its role on chloride homeostasis, a crucial role on spines morphogenesis. Chamma et al. (2012) (INSERM UMR- 839, Paris), summarize the functional impact that structurally different forms of KCC2 have on inhibitory and excitatory trans- mission, highlighting the cellular and molecular mechanisms by which neuronal activity regulates its action via transcriptional and post-translational modifications. In the following research paper, Bhumbra et al. (2012) (Department of Neuroscience, Physiology and Pharmacology, UCL), convincingly demonstrate that, in contrast to neonates, in the spinal cord of juvenile animals inhibitory postsynaptic currents are entirely glycinergic, raising the possibility that the co-release of GABA and glycine is developmentally regulated. Once released from presynaptic terminals, GABA diffuses in the synaptic cleft and binds to postsynaptic receptors. This process is very fast and occurs in non-equilibrium conditions. Barberis et al. (2011) (Department of Neuroscience, IIT and Department of Biophysics, Wroclaw University) discuss how GABA transient in the cleft influences the shape of synaptic cur- rents. The authors describe the methods used to estimate the neurotransmitter transient using tools enabling to indirectly infer with its time course, including low affinity competitive GABA A receptor antagonists or gating modifiers. GABA transient may limit the activation of postsynaptic receptors and their binding reaction to mono-ligand state, promoting low probability channel opening and fast deactivation kinetics. The intriguing hypothesis that GABA transporters may exert a homeostatic control on GABA release is put forward in a perspec- tive article by Conti et al. (2011) (Department of Neuroscience, Università Politecnica delle Marche). On the basis of the litera- ture and recent findings the authors suggest that, in physiological conditions, vesicle filling is dominated by the GABA synthesizing enzyme GAD and by the GABA transporter GAT-1. This may be relevant for activity-dependent regulation of synaptic strength. In the following review, Mortensen et al. (2012) (Department of Neuroscience, Physiology and Pharmacology, UCL), compare the potency measured under the same experimental conditions, of a series of GABA A receptor isoforms, physiologically rele- vant to phasic and tonic inhibition. The highest potency would be compatible with extrasynaptic receptors, containing the α6 subunit and exposed, during spillover of GABA from synapses, to low agonist concentrations, while the lowest potency would be compatible with synaptic GABA A receptors containing the α2/α3βγ subunits, exposed, during vesicular release, to high agonist concentrations. Using a genetic approach, Janssen et al. (2011) (Department of Pharmacology and Physiology, Georgetown University) found that the conditional deletion of β3 subunits in D2-positive striato-pallidal medium spiny neurons led to a reduced network excitability due to a decrease in tonic GABA A -mediated conduc- tance. They suggest that the β3 subunit may be an important pharmacological target for the treatment of striatal disorders. Next, Shrivastava et al. (2011) (Department of Biochemistry and Molecular Biology, Vienna University and Institut de Biologie, Ecole Normale Superieure, Paris), provide an overview Frontiers in Cellular Neuroscience www.frontiersin.org January 2013 | Volume 6 | Article 62 | 1 CELLULAR NEUROSCIENCE
Este artigo apresenta os resultados da pesquisa que objetivou analisar o processo de fabricação do adobe na área de abrangência do eixo Itabuna – Ilhéus – Uruçuca, municípios localizados no Litoral Sul do Estado da Bahia, considerando os custos associados à sua manufatura (composição orçamentária). Foram escolhidas duas localidades rurais para coleta de dados, o Assentamento João Amazonas e o Projeto Sapê Ecológico. A metodologia compreendeu a observação participante para descrição e registro do processo de produção do adobe nas localidades selecionadas.
A composição orçamentária contemplou: 1 cálculo do volume de barro mínimo necessário para suprir a produção diária (que variou conforme a localidade analisada); 2 cálculo do custo para escavação (mecanizada ou
não mecanizada); 3 cálculo do custo de carga, transporte e descarga de material (manual ou mecanizado); 4 cálculo do custo de mistura, moldagem e desmoldagem do adobe e 5 cálculo do preço unitário do adobe. Os resultados mostraram que, em relação à fabricação do adobe, constatou-se que o processo se mantém vernáculo compreendendo
moldagem dos blocos de terra em estado plástico em formas de madeira, desforma e secagem ao ar. No que se refere ao custo final para produção do adobe, a coleta de dados permitiu encontrar dois valores unitários:
R$2,34 a unidade adobe no Assentamento João Amazonas e R$2,82 no Projeto Sapê Ecológico. Ambos podem ser considerados como parâmetro para precificação de venda do elemento construtivo, caso se mantenham as condições de produção, já que o custo para fabricação arca com os custos de materiais e honorários dos envolvidos na produção. Constituindo-se, dessa forma, fonte de renda para tais localidades.
1. Although economic deprivation and poverty are not synonymous, they carry similar connotations; people become poor due to continuous economic deprivation or lack of proper development over time.
2. Those who work to achieve people's democratic rights should be applauded.
3. Movement of own territory (or jurisdiction) and movement of separation are not the same; but, the same issue (declaration of independence) is called movement of liberation or movement of democracy by one side and movement of separation by the other.
4. There are examples that the 'liberationists’ declare and sign documents defending their movement of own territory (or jurisdiction); those who wage movement of separation usually not do have the same or similar planning, organization, goals, and objectives.
5. There is no doubt that both the Declaration of Independence of Bangladesh, 1971 and the Declaration of Independence, 1776' of the United States are 'documents of democracy.’
6. Generally, people consider movements of separation as rebellion or betrayal against integrity of the state; however, these days, many modern democratic methods of mediation have been developed where the issue of conflict is considered as the problem and dispute resolution rather than as rebellion or betrayal; In terms of fairness, the modern democratic system of mediation is the right one, no doubt.
7. Problems will exist in life, but democratic solutions, based on justifiable rights and fairness, are what people want to see in practice.
8. The new generation must study and research how Bangladesh became independent.
9. In the course of history, people have three countries today from one; however, concerned authorities have done little to improve the fortunes of common people and to make necessary structural changes to that end; Nonetheless, it is wholesome if it happens now, ‘better late than never.’
10. Everyone should work rapidly and relentlessly, based on democratic ideas, to bring about change in people's lives; the task is difficult, not impossible though.
11. If people are happy, the real goal of human life is achieved; with that in mind, it is best to work continuously avoiding skirmishes; it is expected that the quality of politics or geopolitics will improve as well.
12. Terrorism has a direct relationship with economic deprivation, which is called 'relative deprivation theory.’ According to this theory, the level of income inequality in a country is directly related to the level of terrorist activities that occur.
13. We need theory as de rigueur and theory is the first; reality is there and it will be; for calculation or to get an idea about something, we must start with the theory.
14. Reality is of two kinds; one is beyond human control or chance; the other is manmade or artificial.
15. Although international politics or geopolitics is not under the control of anyone specifically, it is, nonetheless, manmade and its democratic improvement is also possible.
هوازدگی سنگ در مناطق کوهستانی دوام و مقاومت آن را در طول زمان تحت تاثیر قرار میدهد. ارزیابی دوام و استحکام سنگها در اثر سیکلهای انجماد-ذوب فاکتور اساسی برای تحلیل پایداری سنگهای بستر پروژههای مهندسی از قبیل تونل، معدن و ... میباشد. در این مطالعه تأثیر سیکلهای انجماد-ذوب بر روی شاخص دوام سیکلهای دوم و پنجم، چگالی خشک و حجم سنگ شیست ارزیابی شده است. بدین منظور، 13 گمانه در دیواره غربی معدن انگوران حفر و نمونههای مورد نیاز تهیه و آمادهسازی شده است. در کل، 75 سیکل انجماد-ذوب روی نمونهها اعمال و در سیکلهای 0، 7، 15، 40 و 75، آزمایشهای آزمایشگاهی از قبیل شاخص دوام سیکلهای دوم و پنجم، چگالی خشک و اندازهگیری حجم نمونهها انجام شده است. بر این اساس، روابطی تجربی جهت محاسبه شاخص دوام و چگالی خشک نمونهها به ازای سیکل-های انجماد-ذوب مختلف ارائه شده است. نتایج حاصله نشان دهنده کاهش نمایی شاخص دوام سیکلهای دوم و پنجم و چگالی خشک می-باشد. همچنین، حجم نمونهها با افزایش تعداد سیکلهای انجماد-ذوب، افزایش یافته است. بعلاوه، مشخصات کانیشناسی سنگ شیست هم با استفاده از میکروسکوپ پلاریز...