scholarly journals Dynamic, Cell-Type-Specific Roles for GABAergic Interneurons in a Mouse Model of Optogenetically Inducible Seizures

Neuron ◽  
2017 ◽  
Vol 93 (2) ◽  
pp. 291-298 ◽  
Author(s):  
Sattar Khoshkhoo ◽  
Daniel Vogt ◽  
Vikaas S. Sohal
2019 ◽  
Vol 13 ◽  
Author(s):  
Corinna Höfling ◽  
Emira Shehabi ◽  
Peer-Hendrik Kuhn ◽  
Stefan F. Lichtenthaler ◽  
Maike Hartlage-Rübsamen ◽  
...  

eNeuro ◽  
2015 ◽  
Vol 2 (6) ◽  
pp. ENEURO.0114-15.2015 ◽  
Author(s):  
Brian E. Kalmbach ◽  
Daniel Johnston ◽  
Darrin H. Brager

Blood ◽  
2020 ◽  
Author(s):  
Qian Qi ◽  
Li Cheng ◽  
Xing Tang ◽  
Yanghua He ◽  
Yichao Li ◽  
...  

While constitutive CTCF-binding sites are needed to maintain relatively invariant chromatin structures, such as topologically associating domains, the precise roles of CTCF to control cell type-specific transcriptional regulation remain poorly explored. We examined CTCF occupancy in different types of primary blood cells derived from the same donor to elucidate a new role for CTCF in gene regulation during blood cell development. We identified dynamic, cell type-specific binding sites for CTCF that colocalize with lineage-specific transcription factors. These dynamic sites are enriched for single nucleotide polymorphisms that are associated with blood cell traits in different linages, and they coincide with the key regulatory elements governing hematopoiesis. CRISPR/Cas9-based perturbation experiments demonstrated that these dynamic CTCF-binding sites play a critical role in red blood cell development. Furthermore, precise deletion of CTCF-binding motifs in dynamic sites abolished interactions of erythroid genes, such as RBM38, with their associated enhancers and led to abnormal erythropoiesis. These results suggest a novel, cell type-specific function for CTCF in which it may serve to facilitate interaction of distal regulatory emblements with target promoters. Our study of the dynamic, cell type-specific binding and function of CTCF provides new insights into transcriptional regulation during hematopoiesis.


Cell Reports ◽  
2021 ◽  
Vol 34 (8) ◽  
pp. 108774
Author(s):  
Shovan Naskar ◽  
Jia Qi ◽  
Francisco Pereira ◽  
Charles R. Gerfen ◽  
Soohyun Lee

2021 ◽  
Author(s):  
Robert J. Fenster ◽  
Kenneth McCullough ◽  
Sergey Naumenko ◽  
Andrew Thompson ◽  
Claudia Klengel ◽  
...  

AbstractThe ability of the medial prefrontal cortex (mPFC) to exert top-down control of behavior is affected by stress. The molecular response of mPFC to stress is incompletely understood, however, in part because of the region’s cellular heterogeneity. Here we used single nucleus RNA sequencing (snRNAseq) to map specific molecular cell types within the mPFC and to detect cell-type specific transcriptional changes to foot-shock stress. We identified Ptgs2, encoding cyclo-oxygenase 2, as an important candidate that is upregulated in layer II/III excitatory neurons after stress. Specifically, Ptgs2 was transiently upregulated with shock-induced fear learning and fear expression, along with Bdnf, Nptx2, and Lingo1, in a layer II/III neuronal population marked by the neuronal excitatory gene Slc17a7 and cell-type specific neuropeptide Penk. These dynamic cell-type specific expression patterns identified with snRNAseq were validated with quantitative fluorescent in situ hybridization. Using a pharmacological approach, we found that systemic lumiracoxib, a selective Ptgs2-inhibitor, led to a significant reduction in fear expression. Furthermore, genetic ablation of Ptgs2 in excitatory Camk2a-expressing neurons led to reduced stress-induced anxiety-like behaviors. Together these findings suggest that Ptgs2 is expressed in a dynamic, cell-type specific way in Layer II/III Penk+ neurons in mPFC, and that its role in prostaglandin and /or endocannabinoid regulation within these neurons may be an important mediator of stress-related behavior.


2020 ◽  
Author(s):  
Julio D. Perez ◽  
Susanne tom Dieck ◽  
Beatriz Alvarez-Castelao ◽  
Ivy C.W. Chan ◽  
Erin M. Schuman

AbstractThe localization and translation of mRNAs to dendrites and axons maintains and modifies the local proteome of neurons, and is essential for synaptic plasticity. Although significant efforts have allowed the identification of localized mRNAs in excitatory neurons, it is still unclear whether interneurons also localize a large population of mRNAs. In addition, the variability in the population of localized mRNAs within and between cell-types is unknown. Here we developed a method for the transcriptomic characterization of a single neuron’s subcellular compartments, which combines laser capture microdissection with scRNA-seq. This allowed us to separately profile the dendritic and somatic transcriptomes of individual rat hippocampal neurons and investigate the relation in mRNA abundances between the soma and dendrites of single glutamatergic and GABAergic neurons. We identified two types of glutamatergic and three types of GABAergic interneurons and we found that, like their excitatory counterparts, interneurons contain a rich repertoire of ~4000 mRNAs. The individual somatic transcriptomes exhibited more cell type-specific features than their associated dendritic transcriptomes. The detection and abundance of dendritic mRNAs was not always simply predicted by their somatic counterparts. Finally, using cell-type specific metabolic labelling of isolated neurites, we demonstrated that the processes not only of Glutamatergic but also of GABAergic neurons are capable of local translation, suggesting mRNA localization and local translation is a general property of neurons.


2019 ◽  
Vol 50 (2) ◽  
pp. 1981-1993 ◽  
Author(s):  
Wenwen Dong ◽  
Yingfu Sun ◽  
Hao Cheng ◽  
Bei Yang ◽  
Linlin Wang ◽  
...  

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