scholarly journals Altered hippocampal interneuron activity precedes ictal onset

2016 ◽  
Author(s):  
Mitra L. Miri ◽  
Martin Vinck ◽  
Rima Pant ◽  
Jessica A. Cardin
Keyword(s):  
Inhibitory Interneuron ◽  
Seizure Disorders ◽  
Hippocampal Interneuron ◽  
Ictal Activity ◽  
Cell Type Specific ◽  
Hippocampal Network ◽  
The Impact ◽  
Interneuron Activity ◽  
Rapid Shift

SummaryAlthough failure of GABAergic inhibition is a commonly hypothesized mechanism underlying seizure disorders, the series of events that precipitate a rapid shift from healthy to ictal activity remain unclear. Furthermore, the diversity of inhibitory interneuron populations poses a challenge for understanding local circuit interactions during seizure initiation. Using a combined optogenetic and electrophysiological approach, we examined the activity of two identified hippocampal interneuron classes during seizure induction in vivo. We identified cell type-specific differences in preictal firing patterns and input sensitivity of parvalbumin- and somatostatin-expressing interneurons. Surprisingly, the impact of both sources of inhibition remained intact throughout the preictal period and into the early ictal phase. Our findings suggest that the onset of ictal activity is not due to a failure of inhibition, but is instead associated with a decoupling of inhibitory cells from their normal relationship with the local hippocampal network.

scholarly journals Altered hippocampal interneuron activity precedes ictal onset

eLife ◽  
2018 ◽  
Vol 7 ◽  
Author(s):  
Mitra L Miri ◽  
Martin Vinck ◽  
Rima Pant ◽  
Jessica A Cardin
Keyword(s):  
Inhibitory Interneuron ◽  
Synaptic Inhibition ◽  
Cell Type ◽  
Seizure Disorders ◽  
Hippocampal Interneuron ◽  
Ictal Activity ◽  
Cell Type Specific ◽  
Interneuron Activity ◽  
Rapid Shift

Although failure of GABAergic inhibition is a commonly hypothesized mechanism underlying seizure disorders, the series of events that precipitate a rapid shift from healthy to ictal activity remain unclear. Furthermore, the diversity of inhibitory interneuron populations poses a challenge for understanding local circuit interactions during seizure initiation. Using a combined optogenetic and electrophysiological approach, we examined the activity of identified mouse hippocampal interneuron classes during chemoconvulsant seizure induction in vivo. Surprisingly, synaptic inhibition from parvalbumin- (PV) and somatostatin-expressing (SST) interneurons remained intact throughout the preictal period and early ictal phase. However, these two sources of inhibition exhibited cell-type-specific differences in their preictal firing patterns and sensitivity to input. Our findings suggest that the onset of ictal activity is not associated with loss of firing by these interneurons or a failure of synaptic inhibition but is instead linked with disruptions of the respective roles these interneurons play in the hippocampal circuit.

scholarly journals Btbd11 is an inhibitory interneuron specific synaptic scaffolding protein that supports excitatory synapse structure and function

2021 ◽  
Author(s):  
Alexei M. Bygrave ◽  
Ayesha Sengupta ◽  
Ella P. Jackert ◽  
Mehroz Ahmed ◽  
Beloved Adenuga ◽  
...  
Keyword(s):  
Inhibitory Interneuron ◽  
Nmda Receptor Antagonist ◽  
Specific Protein ◽  
Network Activity ◽  
Scaffolding Protein ◽  
Inhibitory Interneurons ◽  
Cell Type ◽  
Cell Type Specific

Synapses in the brain exhibit cell–type–specific differences in basal synaptic transmission and plasticity. Here, we evaluated cell–type–specific differences in the composition of glutamatergic synapses, identifying Btbd11, as an inhibitory interneuron–specific synapse–enriched protein. Btbd11 is highly conserved across species and binds to core postsynaptic proteins including Psd–95. Intriguingly, we show that Btbd11 can undergo liquid–liquid phase separation when expressed with Psd–95, supporting the idea that the glutamatergic post synaptic density in synapses in inhibitory and excitatory neurons exist in a phase separated state. Knockout of Btbd11 from inhibitory interneurons decreased glutamatergic signaling onto parvalbumin–positive interneurons. Further, both in vitro and in vivo, we find that Btbd11 knockout disrupts network activity. At the behavioral level, Btbd11 knockout from interneurons sensitizes mice to pharmacologically induced hyperactivity following NMDA receptor antagonist challenge. Our findings identify a cell–type–specific protein that supports glutamatergic synapse function in inhibitory interneurons–with implication for circuit function and animal behavior.

scholarly journals Cell Type-Specific Tuning of Hippocampal Interneuron Firing during Gamma Oscillations In Vivo

2007 ◽  
Vol 27 (31) ◽  
pp. 8184-8189 ◽  
Author(s):  
J. J. Tukker ◽  
P. Fuentealba ◽  
K. Hartwich ◽  
P. Somogyi ◽  
T. Klausberger
Keyword(s):  
Gamma Oscillations ◽  
Cell Type ◽  
Hippocampal Interneuron ◽  
Cell Type Specific

scholarly journals Functional anatomy of distant-acting mammalian enhancers

2013 ◽  
Vol 368 (1620) ◽  
pp. 20120359 ◽  
Author(s):  
D. E. Dickel ◽  
A. Visel ◽  
L. A. Pennacchio
Keyword(s):  
Cultured Cells ◽  
Functional Anatomy ◽  
Transcriptional Enhancers ◽  
Genome Wide ◽  
Multiple Transcription Factor ◽  
Cell Type Specific ◽  
Specific Regulation ◽  
Architectural Characteristics ◽  
The Impact

Transcriptional enhancers are a major class of functional element embedded in the vast non-coding portion of the human genome. Acting over large genomic distances, enhancers play critical roles in the tissue and cell type-specific regulation of genes, and there is mounting evidence that they contribute to the aetiology of many human diseases. Methods for genome-wide mapping of enhancer regions are now available, but the functional architecture contained within human enhancer elements remains unclear. Here, we review recent approaches aimed at understanding the functional anatomy of individual enhancer elements, using systematic qualitative and quantitative assessments of mammalian enhancer variants in cultured cells and in vivo . These studies provide direct insight into common architectural characteristics of enhancers including the presence of multiple transcription factor-binding sites and the mixture of both transcriptionally activating and repressing domains within the same enhancer. Despite such progress in understanding the functional composition of enhancers, the inherent complexities of enhancer anatomy continue to limit our ability to predict the impact of sequence changes on in vivo enhancer function. While providing an initial glimpse into the mutability of mammalian enhancers, these observations highlight the continued need for experimental enhancer assessment as genome sequencing becomes routine in the clinic.

scholarly journals Cell-type–specific, multicolor labeling of endogenous proteins with split fluorescent protein tags in Drosophila

2021 ◽  
Vol 118 (23) ◽  
pp. e2024690118
Author(s):  
Rie Kamiyama ◽  
Kota Banzai ◽  
Peiwei Liu ◽  
Abhijit Marar ◽  
Ryo Tamura ◽  
...  
Keyword(s):  
Tandem Repeats ◽  
Fluorescent Protein ◽  
Protein Localization ◽  
Fluorescence Signal ◽  
Cell Type ◽  
Genomic Locus ◽  
Cell Type Specific ◽  
Endogenous Proteins ◽  
The Impact

The impact of the Drosophila experimental system on studies of modern biology cannot be understated. The ability to tag endogenously expressed proteins is essential to maximize the use of this model organism. Here, we describe a method for labeling endogenous proteins with self-complementing split fluorescent proteins (split FPs) in a cell-type–specific manner in Drosophila. A short fragment of an FP coding sequence is inserted into a specific genomic locus while the remainder of the FP is expressed using an available GAL4 driver line. In consequence, complementation fluorescence allows examination of protein localization in particular cells. Besides, when inserting tandem repeats of the short FP fragment at the same genomic locus, we can substantially enhance the fluorescence signal. The enhanced signal is of great value in live-cell imaging at the subcellular level. We can also accomplish a multicolor labeling system with orthogonal split FPs. However, other orthogonal split FPs do not function for in vivo imaging besides split GFP. Through protein engineering and in vivo functional studies, we report a red split FP that we can use for duplexed visualization of endogenous proteins in intricate Drosophila tissues. Using the two orthogonal split FP systems, we have simultaneously imaged proteins that reside in distinct subsynaptic compartments. Our approach allows us to study the proximity between and localization of multiple proteins endogenously expressed in essentially any cell type in Drosophila.

scholarly journals A Cre-dependent massively parallel reporter assay allows for cell-type specific assessment of the functional effects of genetic variants in vivo

2021 ◽  
Author(s):  
Tomas Lagunas ◽  
Stephen P Plassmyer ◽  
Ryan Z Friedman ◽  
Michael A Rieger ◽  
Anthony D Fischer ◽  
...  
Keyword(s):  
Mouse Brain ◽  
Genetic Variants ◽  
Massively Parallel ◽  
Psychiatric Disease ◽  
Functional Screening ◽  
Cell Type ◽  
Cell Type Specific ◽  
The Impact

Human genetic studies have identified a large number of disease-associated de novo variants in presumptive regulatory regions of the genome that pose a challenge for interpretation of their effects: the impact of regulatory variants is highly dependent on the cellular context, and thus for psychiatric diseases these would ideally be studied in neurons in a living brain. Furthermore, for both common and rare variants, it is expected that only a subset fraction will affect gene expression. Massively Parallel Reporter Assays (MPRAs) are molecular genetic tools that enable functional screening of hundreds of predefined sequences in a single experiment. These assays have been used for functional screening of several different types of regulatory sequences in vitro. However, they have not yet been adapted to query specific cell types in vivo in a complex tissue like the mouse brain. Here, using a test-case 3′UTR MPRA library with variants from ASD patients, we sought to develop a method to achieve reproducible measurements of variant effects in vivo in a cell type-specific manner. We implemented a Cre-dependent design to control expression of our library and first validated our system in vitro. Next, we measured the effect of >500 3′UTR variants in excitatory neurons in the mouse brain. Finally, we report >40 variants with significant effects on transcript abundance in the context of the brain. This new technique should enable robust, functional annotation of genetic variants in the cellular contexts most relevant to psychiatric disease.

scholarly journals The Role of Activator Protein-1 (AP-1) Family Members in CD30-Positive Lymphomas

Cancers ◽  
2018 ◽  
Vol 10 (4) ◽  
pp. 93 ◽  
Author(s):  
Ines Garces de los Fayos Alonso ◽  
Huan-Chang Liang ◽  
Suzanne Turner ◽  
Sabine Lagger ◽  
Olaf Merkel ◽  
...  
Keyword(s):  
Transcriptional Response ◽  
Large Cell ◽  
In Vivo Studies ◽  
Activator Protein 1 ◽  
Activator Protein ◽  
Cell Type Specific ◽  
The Impact

The Activator Protein-1 (AP-1) transcription factor (TF) family, composed of a variety of members including c-JUN, c-FOS and ATF, is involved in mediating many biological processes such as proliferation, differentiation and cell death. Since their discovery, the role of AP-1 TFs in cancer development has been extensively analysed. Multiple in vitro and in vivo studies have highlighted the complexity of these TFs, mainly due to their cell-type specific homo- or hetero-dimerization resulting in diverse transcriptional response profiles. However, as a result of the increasing knowledge of the role of AP-1 TFs in disease, these TFs are being recognized as promising therapeutic targets for various malignancies. In this review, we focus on the impact of deregulated expression of AP-1 TFs in CD30-positive lymphomas including Classical Hodgkin Lymphoma and Anaplastic Large Cell Lymphoma.

Experimental Study of the Impact of Alisma plantago-aquatica Secretions on Pathogenic Bacteria

2014 ◽  
Vol 1 (3) ◽  
pp. 3-7
Author(s):  
O. Zhukorskyy ◽  
O. Hulay
Keyword(s):  
Pathogenic Bacteria ◽  
Initial Density ◽  
Biologically Active ◽  
Erysipelothrix Rhusiopathiae ◽  
Natural Focus ◽  
Test Species ◽  
Popula Tions ◽  
And Control ◽  
The Impact

Aim. To estimate the impact of in vivo secretions of water plantain (Alisma plantago-aquatica) on the popula- tions of pathogenic bacteria Erysipelothrix rhusiopathiae. Methods. The plants were isolated from their natural conditions, the roots were washed from the substrate residues and cultivated in laboratory conditions for 10 days to heal the damage. Then the water was changed; seven days later the selected samples were sterilized using fi lters with 0.2 μm pore diameter. The dilution of water plantain root diffusates in the experimental samples was 1:10–1:10,000. The initial density of E. rhusiopathiae bacteria populations was the same for both experimental and control samples. The estimation of the results was conducted 48 hours later. Results. When the dilution of root diffusates was 1:10, the density of erysipelothrixes in the experimental samples was 11.26 times higher than that of the control, on average, the dilution of 1:100 − 6.16 times higher, 1:1000 – 3.22 times higher, 1:10,000 – 1.81 times higher, respectively. Conclusions. The plants of A. plantago-aquatica species are capable of affecting the populations of E. rhusiopathiae pathogenic bacteria via the secretion of biologically active substances into the environment. The consequences of this interaction are positive for the abovementioned bacteria, which is demon- strated by the increase in the density of their populations in the experiment compared to the control. The intensity of the stimulating effect on the populations of E. rhusiopathiae in the root diffusates of A. plantago-aquatica is re- ciprocally dependent on the degree of their dilution. The investigated impact of water plantain on erysipelothrixes should be related to the topical type of biocenotic connections, the formation of which between the test species in the ecosystems might promote maintaining the potential of natural focus of rabies. Keywords: Alisma plantago-aquatica, in vivo secretions, Erysipelothrix rhusiopathiae, population density, topical type of connections.

ITag-RNA Allows in Vivo Cell-Type Specific Transcriptional Characterization and Tracking of Circulating Transcripts

2018 ◽  
Author(s):  
J. Darr ◽  
M. Lassi ◽  
R. Gerlini ◽  
F. Scheid ◽  
M. Hrabě de Angelis ◽  
...  
Keyword(s):  
Cell Type ◽  
Cell Type Specific
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