177,027 research outputs found

    Functional expression of the GABA A receptor α2 and α3 subunits at synapses between intercalated medial paracapsular neurons of mouse amygdala

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    In the amygdala, GABAergic neurons in the intercalated medial paracapsular cluster (Imp) have been suggested to play a key role in fear learning and extinction. These neurons project to the central (CE) amygdaloid nucleus and to other areas within and outside the amygdala. In addition, they give rise to local collaterals that innervate other neurons in the Imp. Several drugs, including benzodiazepines (BZ), are allosteric modulators of GABA A receptors. BZ has both anxiolytic and sedative actions, which are mediated through GABA A receptors containing α2/α3 and α1 subunits, respectively. To establish whether α1 or α2/α3 subunits are expressed at Imp cell synapses, we used paired recordings of anatomically identified Imp neurons and high resolution immunocytochemistry in the mouse. We observed that a selective α3 subunit agonist, TP003 (100 nM), significantly increased the decay time constant of the unitary IPSCs. A similar effect was also induced by zolpidem (10 μM) or by diazepam (1 μM). In contrast, lower doses of zolpidem (0.1-1 μM) did not significantly alter the kinetics of the unitary IPSCs. Accordingly, immunocytochemical experiments established that the α2 and α3, but not the α1 subunits of the GABA A receptors, were present at Imp cell synapses of the mouse amygdala. These results define, for the first time, some of the functional GABA A receptor subunits expressed at synapses of Imp cells. The data also provide an additional rationale to prompt the search of GABA A receptor α3 selective ligands as improved anxiolytic drugs. © 2012 Geracitano, Fischer, Kasugai, Ferraguti and Capogna

    On the effects of psychostimulants, antidepressants, and the antiparkinsonian drug levodopa on dopamine neurons

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    The dopaminergic system constitutes the principal target of many psychostimulants, antidepressant, and antiparkinsonian drugs. The effects caused by these compounds are partly associated with an increased dopamine (DA) levels within the terminal areas of DA neurons and in the ventral midbrain. Therefore, several substances of abuse, antidepressants, and endogenous compounds (levodopa and trace amines [TAs]) regulate the activity of DA cells by activating D2 autoreceptors located on the terminals, soma, and dendrites. Considering our past and recent experimental studies on this issue, here we will briefly reexamine the mechanisms of action of several psychoactive drugs on DA neurons. In particular, we propose three different modalities by which the mesencephalic DA neurons can be regulated by drugs: amphetamine/TAs-like, cocaine-like, and levodopa-like. We, therefore, discuss the potential therapeutic and addictive properties of the psychoactive substances

    Appropriate Similarity Measures for Author Cocitation Analysis

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    We provide a number of new insights into the methodological discussion about author cocitation analysis. We first argue that the use of the Pearson correlation for measuring the similarity between authors’ cocitation profiles is not very satisfactory. We then discuss what kind of similarity measures may be used as an alternative to the Pearson correlation. We consider three similarity measures in particular. One is the well-known cosine. The other two similarity measures have not been used before in the bibliometric literature. Finally, we show by means of an example that our findings have a high practical relevance.information science;Pearson correlation;cosine;similarity measure;author cocitation analysis

    Dopamine-containing neurons are silenced by energy deprivation: a defensive response or beginning of cell death?

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    Metabolic stress associated to mitochondrial dysfunction has been put forward as an important factor causing degeneration of mesencephalic dopamine-containing neurons in Parkinson’s disease (PD). Here we overview how these neurons react to acute hypoxia or hypoglycemia, that are conditions of energy deprivation causing a reduced production of ATP by mitochondria. These neurons, which show a tonic firing discharge under normal condition, undergo into membrane hyperpolarization during hypoxia or hypoglycemia that silence their spontaneous activity. We outline the cellular mechanisms causing membrane hyperpolarization and the accompanied disturbances of intracellular calcium and sodium homeostasis. A better understanding of the changes occurring during transient energy deprivation might contribute to understand the physiopathology of these neurons that derives from mitochondrial dysfunction. # 2005 Elsevier Inc. All rights reserved

    "Closing the R&D Gap, Evaluating the Sources of R&D Spending"

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    Both spending and tax policies have been implemented in the United States with the goal of stimulating private sector research and development (R&D). Karier questions whether current R&D policy, especially the research and experimentation tax credit, can contribute to closing the gap between nondefense expenditures on R&D in the United States and such expenditures in other countries, such as Japan and Germany. He also explores possible changes to our current R&D policy to make it more effective.

    Synaptic heterogeneity between mouse paracapsular intercalated neurons of the amygdala

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    GABAergic medial paracapsular intercalated (Imp) neurons of amygdala are thought of as playing a central role in fear learning and extinction. We report here that the synaptic network formed by these neurons exhibits distinct short-term plastic synaptic responses. The success rate of synaptic events evoked at a frequency range of 0.1-10 Hz varied dramatically between different connected cell pairs. Upon enhancing the frequency of stimulation, the success rate increased, decreased or remained constant, in a similar number of cell pairs. Such synaptic heterogeneity resulted in inhibition of the firing of the postsynaptic neurons with different efficacies. Moreover, we found that the different synaptic weights were mainly determined by diversity in presynaptic release probabilities rather than postsynaptic changes. Sequential paired recording experiments demonstrated that the same presynaptic neuron established the same type of synaptic connections with different postsynaptic neurons, suggesting the absence of target-cell specificity. Conversely, the same postsynaptic neuron was contacted by different types of synaptic connections formed by different presynaptic neurons. A detailed anatomical analysis of the recorded neurons revealed discrete and unexpected peculiarities in the dendritic and axonal patterns of different cell pairs. In contrast, several intrinsic electrophysiological responses were homogeneous among neurons, and synaptic failure counts were not affected by presynaptic cannabinoid 1 or GABAB receptors. We propose that the heterogeneous functional connectivity of Imp neurons, demonstrated by this study, is required to maintain the stability of firing patterns which is critical for the computational role of the amygdala in fear learning and extinction. © 2007 The Authors. Journal compilation © 2007 The Physiological Society

    Going Beyond Counting First Authors in Author Co-citation Analysis

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    The present study examines one of the fundamental aspects of author co-citation analysis (ACA) - the way co-citation counts are defined. Co-citation counting provides the data on which all subsequent statistical analyses and mappings are based, and we compare ACA results based on two different types of co-citation counting - the traditional type that only counts the first one among a cited work's authors on the one hand and a non-traditional type that takes into account the first 5 authors of a cited work on the other hand. Results indicate that the picture produced through this non-traditional author co-citation counting contains more coherent author groups and is therefore considerably clearer. However, this picture represents fewer specialties in the research field being studied than that produced through the traditional first-author co-citation counting when the same number of top-ranked authors is selected and analyzed. Reasons for these effects are discussed

    Letter from R. R. Zellick, Assistant Trust Officer, Anglo California National Bank of San Francisco, to Joseph R. Goodman, October 2, 1942

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    Letter from R. R. Zellick, Assistant Trust Officer at The Anglo California National Bank of San Francisco, to Joseph R. Goodman, regarding property owned by Dave Tatsuno. Zellick mentions a dispute between current tenants and Tatsuno, and that Tatsuno has asked Goodman to help locate trustworthy tenants.Personal correspondence, organizational records, government documents, publications, and other papers created or collected by Joseph R. Goodman documenting the forced removal and incarceration of Japanese Americans during World War II, as well as organized resistance to incarceration. Included in the collection are records of the Japanese Young Men's Christian Association and the Japanese American Citizens' League in San Francisco, including papers of the Japanese YMCA's executive secretary Lincoln Kanai; Sakai family papers; Goodman's correspondence to and from Japanese American incarcerees, organizations opposing forced removal and incarceration of Japanese Americans, the War Relocation Authority, and others; publications, photographs, and ephemera from the Topaz Relocation Center, where Goodman taught high school; War Relocation Authority records and publications; and newspaper clippings, pamphlets, and reports about forced removal and incarceration created by various government, religious, and civic organizations, in California and nationwide
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