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Featured Research Papers

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The cover from this month's paper.

Featured Paper Archives
Featured paper of the Month!

April's Featured Paper!

An in vitro model of human neocortical development using pluripotent stem cells: cocaine-induced cytoarchitectural alterations

DMM 2014 vol. 7 no. 12 1397-1405

Abigail A. Kindberg, Raphael M. Bendriem, Charles E. Spivak, Jia Chen, Annelie Handreck, Carl R. Lupica, Jinny Liu, William J. Freed, and Chun-Ting Lee

Neocortical development involves ordered specification of forebrain cortical progenitors to various neuronal subtypes, ultimately forming the layered cortical structure. Modeling of this process using human pluripotent stem cells (hPSCs) would enable mechanistic studies of human neocortical development, while providing new avenues for exploration of developmental neocortical abnormalities. Here, we show that preserving hPSCs aggregates – allowing embryoid body formation – while adding basic fibroblast growth factor (bFGF) during neuroepithelial development generates neural rosettes showing dorsal forebrain identity, including Mash1+ dorsal telencephalic GABAergic progenitors. Structures that mirrored the organization of the cerebral cortex formed after rosettes were seeded and cultured for 3 weeks in the presence of FGF18, BDNF and NT3. Neurons migrated along radial glia scaffolding, with deep-layer CTIP2+ cortical neurons appearing after 1 week and upper-layer SATB2+ cortical neurons forming during the second and third weeks. At the end of differentiation, these structures contained both glutamatergic and GABAergic neurons, with glutamatergic neurons being most abundant. Thus, this differentiation protocol generated an hPSCbased model that exhibits temporal patterning and a neuronal subtype ratio similar to that of the developing human neocortex. This model was used to examine the effects of cocaine during neocorticogenesis. Cocaine caused premature neuronal differentiation and enhanced neurogenesis of various cortical neuronal subtypes. These cocaine-induced changes were inhibited by the cytochrome P450 inhibitor cimetidine. This in vitro model enables mechanistic studies of neocorticogenesis, and can be used to examine the mechanisms through which cocaine alters the development of the human neocortex.

You can read more about this paper at the website for Disease Models & Mechanisms.

March's Featured Paper!

Functional selectivity of allosteric interactions within G protein-coupled receptor oligomers: the dopamine D1-D3 receptor heterotetramer.

Mol Pharmacol. 2014 Oct;86(4):417-29.

Xavier Guitart, Gemma Navarro, Estefania Moreno, Hideaki Yano, Ning-Sheng Cai, Marta Sánchez-Soto, Sandeep Kumar-Barodia, Yamini T. Naidu, Josefa Mallol, Antoni Cortés, Carme Lluís, Enric I. Canela, Vicent Casadó, Peter J. McCormick, and Sergi Ferré

You can read more about this paper at the website for PubMed.

February's Featured Paper!

Synthesis and immunological effects of heroin vaccines

Org Biomol Chem. 2014 Oct 7;12(37):7211-32.

Li F, Cheng K, Antoline JF, Iyer MR, Matyas GR, Torres OB, Jalah R, Beck Z, Alving CR, Parrish DA, Deschamps JR, Jacobson AE, Rice KC

You can read more about this paper at the website for PubMed.

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Hot off the Press Archives
Featured paper of the Month!

Mesopontine median raphe regulates hippocampal ripple oscillation and memory consolidation

Nat Neurosci. 2015 Apr 13. doi: 10.1038/nn.3998. [Epub ahead of print]

Dong V Wang, Hau-Jie Yau, Carl J Broker, Jen-Hui Tsou, Antonello Bonci, and Satoshi Ikemoto

Sharp wave-associated field oscillations (~200 Hz) of the hippocampus, referred to as ripples, are believed to be important for consolidation of explicit memory. Little is known about how ripples are regulated by other brain regions. We found that the median raphe region (MnR) is important for regulating hippocampal ripple activity and memory consolidation. We performed in vivo simultaneous recording in the MnR and hippocampus of mice and found that, when a group of MnR neurons was active, ripples were absent. Consistently, optogenetic stimulation of MnR neurons suppressed ripple activity and inhibition of these neurons increased ripple activity. Notably, using a fear conditioning procedure, we found that photostimulation of MnR neurons interfered with memory consolidation. Our results demonstrate a critical role of the MnR in regulating ripples and memory consolidation.

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Clonidine Maintenance Prolongs Opioid Abstinence and Decouples Stress From Craving in Daily Life: A Randomized Controlled Trial With Ecological Momentary Assessment

Am J Psychiatry. 2015 Mar 17:appiajp201414081014. [Epub ahead of print]

Kowalczyk WJ, Phillips KA, Jobes ML, Kennedy AP, Ghitza UE, Agage DA, Schmittner JP, Epstein DH, Preston KL.

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Dopaminergic and glutamatergic microdomains in a subset of rodent mesoaccumbens axons

Nature Neuroscience Published online 09 February 2015

Shiliang Zhang, Jia Qi, Xueping Li, Hui-Ling Wang, Jonathan P Britt, Alexander F Hoffman, Antonello Bonci, Carl R Lupica & Marisela Morales

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The National Institute on Drug Abuse (NIDA), is part of the National Institutes of Health (NIH), the principal biomedical and behavioral research agency of the United States Government. NIH is a component of the U.S. Department of Health and Human Services.

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