scholarly journals Cell-type–specific inhibition of the dendritic plateau potential in striatal spiny projection neurons

2017 ◽  
Vol 114 (36) ◽  
pp. E7612-E7621 ◽  
Author(s):  
Kai Du ◽  
Yu-Wei Wu ◽  
Robert Lindroos ◽  
Yu Liu ◽  
Balázs Rózsa ◽  
...  
Keyword(s):  
Computational Simulation ◽  
Synaptic Integration ◽  
Projection Neurons ◽  
Cell Type ◽  
Plateau Potentials ◽  
Synaptic Inputs ◽  
Plateau Potential ◽  
Dendritic Computation ◽  
A Cell ◽  
Cell Type Specific

Striatal spiny projection neurons (SPNs) receive convergent excitatory synaptic inputs from the cortex and thalamus. Activation of spatially clustered and temporally synchronized excitatory inputs at the distal dendrites could trigger plateau potentials in SPNs. Such supralinear synaptic integration is crucial for dendritic computation. However, how plateau potentials interact with subsequent excitatory and inhibitory synaptic inputs remains unknown. By combining computational simulation, two-photon imaging, optogenetics, and dual-color uncaging of glutamate and GABA, we demonstrate that plateau potentials can broaden the spatiotemporal window for integrating excitatory inputs and promote spiking. The temporal window of spiking can be delicately controlled by GABAergic inhibition in a cell-type–specific manner. This subtle inhibitory control of plateau potential depends on the location and kinetics of the GABAergic inputs and is achieved by the balance between relief and reestablishment of NMDA receptor Mg2+ block. These findings represent a mechanism for controlling spatiotemporal synaptic integration in SPNs.

IFIH1-deficiency results in a cell-type specific alteration of autophagic activity in response to S. typhimurium

2017 ◽  
Vol 55 (05) ◽  
pp. e28-e56
Author(s):  
S Macheiner ◽  
R Gerner ◽  
A Pfister ◽  
A Moschen ◽  
H Tilg
Keyword(s):  
Cell Type ◽  
A Cell ◽  
Cell Type Specific ◽  
Autophagic Activity ◽  
Specific Alteration

scholarly journals A cell type‐specific expression map of NCoR1 and SMRT transcriptional co‐repressors in the mouse brain

2020 ◽  
Vol 528 (13) ◽  
pp. 2218-2238 ◽  
Author(s):  
Attilio Iemolo ◽  
Patricia Montilla‐Perez ◽  
I‐Chi Lai ◽  
Yinuo Meng ◽  
Syreeta Nolan ◽  
...  
Keyword(s):  
Mouse Brain ◽  
Cell Type ◽  
Specific Expression ◽  
Cell Type Specific Expression ◽  
A Cell ◽  
Cell Type Specific

scholarly journals Connectivity characterization of the mouse basolateral amygdalar complex

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Houri Hintiryan ◽  
Ian Bowman ◽  
David L. Johnson ◽  
Laura Korobkova ◽  
Muye Zhu ◽  
...  
Keyword(s):  
Granular Cell ◽  
Cell Types ◽  
Projection Neurons ◽  
Cell Type ◽  
Connectivity Map ◽  
Analysis Techniques ◽  
Domain Specific ◽  
Cell Type Specific ◽  
Unique Domain

AbstractThe basolateral amygdalar complex (BLA) is implicated in behaviors ranging from fear acquisition to addiction. Optogenetic methods have enabled the association of circuit-specific functions to uniquely connected BLA cell types. Thus, a systematic and detailed connectivity profile of BLA projection neurons to inform granular, cell type-specific interrogations is warranted. Here, we apply machine-learning based computational and informatics analysis techniques to the results of circuit-tracing experiments to create a foundational, comprehensive BLA connectivity map. The analyses identify three distinct domains within the anterior BLA (BLAa) that house target-specific projection neurons with distinguishable morphological features. We identify brain-wide targets of projection neurons in the three BLAa domains, as well as in the posterior BLA, ventral BLA, posterior basomedial, and lateral amygdalar nuclei. Inputs to each nucleus also are identified via retrograde tracing. The data suggests that connectionally unique, domain-specific BLAa neurons are associated with distinct behavior networks.

Gene therapy can target mutations such as BRAF, which have been shown to make tumors more susceptible to autophagy suppression

2021 ◽  
Author(s):  
Moataz Dowaidar
Keyword(s):  
Signaling Pathways ◽  
Chemotherapy Resistance ◽  
Effective Strategy ◽  
Cell Type ◽  
Normal Cells ◽  
A Cell ◽  
Cell Type Specific ◽  
Catabolic Process ◽  
Specific Impact

Autophagy is a double-edged sword in cancer, and numerous aspects should be taken into account before deciding on the most effective strategy to target the process. The fact that several clinical studies are now ongoing does not mean that the patient group that may benefit from autophagy-targeting medicines has been identified. Autophagy inhibitors that are more potent and specialized, as well as autophagy indicators, are also desperately required. The fact that these inhibitors only work against tumors that rely on autophagy for survival (RAS mutants) makes it difficult to distinguish them from tumors that continue to develop even when autophagy is absent. Furthermore, mutations such as BRAF have been shown to make tumors more susceptible to autophagy suppression, suggesting that targeting such tumours may be a viable strategy for overcoming their chemotherapy resistance. In the meantime, we are unable to identify if autophagy regulation works in vivo or whether it selectively targets a disease while inflicting injury to other healthy organs and tissues. A cell-type-specific impact appears to be observed with such therapy. As a result, it is just as important to consider the differences between tumors that originate in different organs as it is to consider the signaling pathways that are similar across them. For a therapy or cure to be effective, the proposed intervention must be tailored to the specific needs of each patient.Over the last several years, a growing amount of data has implicated autophagy in a variety of disorders, including cancer. In normal cells, this catabolic process is also required for cell survival and homeostasis. Despite the fact that medications targeting intermediates in the autophagy signaling pathway are being created and evaluated at both the preclinical and clinical levels, given the complicated function of autophagy in cancer, we still have a long way to go in terms of establishing an effective therapeutic approach. This article discusses current tactics for exploiting cancer cells' autophagy dependency, as well as obstacles in the area. We believe that the unanswered concerns raised in this work will stimulate researchers to investigate previously unknown connections between autophagy and other signaling pathways, which might lead to the development of novel, highly specialized autophagy therapies.

Elements regulating an alternatively spliced exon of the rat fibronectin gene

1993 ◽  
Vol 13 (9) ◽  
pp. 5301-5314 ◽  
Author(s):  
G S Huh ◽  
R O Hynes
Keyword(s):  
Splice Sites ◽  
Cell Type ◽  
Long Distance ◽  
Sequence Elements ◽  
Alternatively Spliced ◽  
A Cell ◽  
Cell Type Specific ◽  
Alternatively Spliced Exons

We have investigated the regulation of splicing of one of the alternatively spliced exons in the rat fibronectin gene, the EIIIB exon. This 273-nucleotide exon is excluded by some cells and included to various degrees by others. We find that EIIIB is intrinsically poorly spliced and that both its exon sequences and its splice sites contribute to its poor recognition. Therefore, cells which recognize the EIIIB exon must have mechanisms for improving its splicing. Furthermore, in order for EIIB to be regulated, a balance must exist between the EIIIB splice sites and those of its flanking exons. Although the intron upstream of EIIIB does not appear to play a role in the recognition of EIIIB for splicing, the intron downstream contains sequence elements which can promote EIIIB recognition in a cell-type-specific fashion. These elements are located an unusually long distance from the exon that they regulate, more than 518 nucleotides downstream from EIIIB, and may represent a novel mode of exon regulation.

scholarly journals Rel Induces Interferon Regulatory Factor 4 (IRF-4) Expression in Lymphocytes

2000 ◽  
Vol 191 (8) ◽  
pp. 1281-1292 ◽  
Author(s):  
Raelene J. Grumont ◽  
Steve Gerondakis
Keyword(s):  
Gene Expression ◽  
Cell Proliferation ◽  
Nuclear Factor Κb ◽  
Wild Type ◽  
Cell Type ◽  
Regulatory Factor ◽  
Specific Manner ◽  
A Cell ◽  
Cell Type Specific ◽  
Interferon Regulatory Factor 4

In lymphocytes, the Rel transcription factor is essential in establishing a pattern of gene expression that promotes cell proliferation, survival, and differentiation. Here we show that mitogen-induced expression of interferon (IFN) regulatory factor 4 (IRF-4), a lymphoid-specific member of the IFN family of transcription factors, is Rel dependent. Consistent with IRF-4 functioning as a repressor of IFN-induced gene expression, the absence of IRF-4 expression in c-rel−/− B cells coincided with a greater sensitivity of these cells to the antiproliferative activity of IFNs. In turn, enforced expression of an IRF-4 transgene restored IFN modulated c-rel−/− B cell proliferation to that of wild-type cells. This cross-regulation between two different signaling pathways represents a novel mechanism that Rel/nuclear factor κB can repress the transcription of IFN-regulated genes in a cell type–specific manner.

Immunocytochemistry Based on a Cell-Type-Specific Aptamer for Rapid Immunostaining of Adenocarcinoma Cells in Clinical Serosal Fluids

2018 ◽  
Vol 25 (3) ◽  
pp. 1143-1152 ◽  
Author(s):  
Yunmei Zhang ◽  
Jieru Xu ◽  
Dairong Li ◽  
Tao Wan ◽  
Qianfang Hu
Keyword(s):  
Cell Type ◽  
Adenocarcinoma Cells ◽  
A Cell ◽  
Cell Type Specific

scholarly journals Periaqueductal efferents to dopamine and GABA neurons of the VTA

2017 ◽  
Author(s):  
Niels R. Ntamati ◽  
Meaghan Creed ◽  
Christian Lüscher
Keyword(s):  
Functional Analysis ◽  
Ventral Tegmental Area ◽  
Periaqueductal Gray ◽  
Retrograde Tracing ◽  
The Other ◽  
Projection Neurons ◽  
Cell Type ◽  
Gaba Neurons ◽  
Other Hand ◽  
Cell Type Specific

AbstractNeurons in the periaqueductal gray (PAG) modulate threat responses and nociception. Activity in the ventral tegmental area (VTA) on the other hand can cause reinforcement and aversion. While in many situations these behaviors are related, the anatomical substrate of a crosstalk between the PAG and VTA remains poorly understood. Here we describe the anatomical and electrophysiological organization of the VTA-projecting PAG neurons. Using rabies-based, cell type-specific retrograde tracing, we observed that PAG to VTA projection neurons are evenly distributed along the rostro-caudal axis of the PAG, but concentrated in its posterior and ventrolateral segments. Optogenetic projection targeting demonstrated that the PAG-to-VTA pathway is predominantly excitatory and targets similar proportions of Ih-expressing VTA DA and GABA neurons. Taken together, these results set the framework for functional analysis of the interplay between PAG and VTA in the regulation of reward and aversion.

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