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 Revisiting the role of IRF3 in inflammation and immunity by conditional and specifically targeted gene ablation in mice

2018 ◽  
Vol 115 (20) ◽  
pp. 5253-5258 ◽  
Author(s):  
Hideyuki Yanai ◽  
Shiho Chiba ◽  
Sho Hangai ◽  
Kohei Kometani ◽  
Asuka Inoue ◽  
...  
Keyword(s):  
Immune Cell ◽  
Cell Types ◽  
Type I ◽  
Type I Ifn ◽  
Cell Type ◽  
Gene Ablation ◽  
Cell Type Specific

IFN regulatory factor 3 (IRF3) is a transcription regulator of cellular responses in many cell types that is known to be essential for innate immunity. To confirm IRF3’s broad role in immunity and to more fully discern its role in various cellular subsets, we engineered Irf3-floxed mice to allow for the cell type-specific ablation of Irf3. Analysis of these mice confirmed the general requirement of IRF3 for the evocation of type I IFN responses in vitro and in vivo. Furthermore, immune cell ontogeny and frequencies of immune cell types were unaffected when Irf3 was selectively inactivated in either T cells or B cells in the mice. Interestingly, in a model of lipopolysaccharide-induced septic shock, selective Irf3 deficiency in myeloid cells led to reduced levels of type I IFN in the sera and increased survival of these mice, indicating the myeloid-specific, pathogenic role of the Toll-like receptor 4–IRF3 type I IFN axis in this model of sepsis. Thus, Irf3-floxed mice can serve as useful tool for further exploring the cell type-specific functions of this transcription factor.

Deciphering how interneuron specific 3 cells control oriens lacunosum-moleculare cells to contribute to circuit function

2021 ◽  
Author(s):  
Alexandre Guet-McCreight ◽  
Frances K Skinner
Keyword(s):  
Pyramidal Cell ◽  
Inhibitory Interneuron ◽  
Cell Type ◽  
Cell Recruitment ◽  
External Modulation ◽  
Theta Frequency ◽  
Cell Firing ◽  
Circuit Function

The wide diversity of inhibitory cells across the brain makes them suitable to contribute to network dynamics in specialized fashions. However, the contributions of a particular inhibitory cell type in a behaving animal are challenging to untangle as one needs to both record cellular activities and identify the cell type being recorded. Thus, using computational modeling and theory to predict and hypothesize cell-specific contributions is desirable. Here, we examine potential contributions of interneuron-specific 3 (I-S3) cells - an inhibitory interneuron found in CA1 hippocampus that only targets other inhibitory interneurons - during simulated theta rhythms. We use previously developed multi-compartment models of oriens lacunosum-moleculare (OLM) cells, the main target of I-S3 cells, and explore how I-S3 cell inputs during in vitro and in vivo scenarios contribute to theta. We find that I-S3 cells suppress OLM cell spiking, rather than engender its spiking via post-inhibitory rebound mechanisms, and contribute to theta frequency spike resonance during simulated in vivo scenarios. To elicit recruitment similar to in vitro experiments, inclusion of disinhibited pyramidal cell inputs is necessary, implying that I-S3 cell firing broadens the window for pyramidal cell disinhibition. Using in vivo virtual networks, we show that I-S3 cells contribute to a sharpening of OLM cell recruitment at theta frequencies. Further, shifting the timing of I-S3 cell spiking due to external modulation shifts the timing of the OLM cell firing and thus disinhibitory windows. We propose a specialized contribution of I-S3 cells to create temporally precise coordination of modulation pathways.

scholarly journals The contribution of astrocyte and neuronal Panx1 to seizures is model and brain region dependent

2021 ◽  
Author(s):  
Price Obot ◽  
Libor Velíšek ◽  
Jana Velíšková ◽  
Eliana Scemes
Keyword(s):  
Brain Region ◽  
Power Spectra ◽  
Cortical Region ◽  
Cell Type ◽  
Epileptiform Discharges ◽  
Seizure Models ◽  
Cell Type Specific ◽  
Specific Deletion

AbstractPannexin1 (Panx1) is an ATP release channel expressed in neurons and astrocytes that plays important roles in CNS physiology and pathology. Evidence for the involvement of Panx1 in seizures includes the reduction of epileptiform activity and ictal discharges following Panx1 channel blockade or deletion. However, very little is known about the relative contribution of astrocyte and neuronal Panx1 channels to hyperexcitability. To this end, mice with global and cell type specific deletion of Panx1 were used in one in vivo and two in vitro seizure models. In the low-Mg2+in vitro model, global deletion but not cell-type specific deletion of Panx1 reduced the frequency of epileptiform discharges. This reduced frequency of discharges did not impact the overall power spectra obtained from local field potentials. In the in vitro KA model, in contrast, global or cell type specific deletion of Panx1 did not affect the frequency of discharges, but reduced the overall power spectra. EEG recordings following KA-injection in vivo revealed that although global deletion of Panx1 did not affect the onset of status epilepticus (SE), SE onset was delayed in mice lacking neuronal Panx1 and accelerated in mice lacking astrocyte Panx1. EEG power spectral analysis disclosed a Panx1-dependent cortical region effect; while in the occipital region, overall spectral power was reduced in all three Panx1 genotypes; in the frontal cortex, the overall power was not affected by deletion of Panx1. Together, our results show that the contribution of Panx1 to ictal activity is model, cell-type and brain region dependent.

scholarly journals DeepG4: A deep learning approach to predict cell-type specific active G-quadruplex regions

2021 ◽  
Vol 17 (8) ◽  
pp. e1009308
Author(s):  
Vincent Rocher ◽  
Matthieu Genais ◽  
Elissar Nassereddine ◽  
Raphael Mourad
Keyword(s):  
Deep Learning ◽  
Double Helix ◽  
Complex Molecule ◽  
Cell Types ◽  
Sequence Motif ◽  
Cell Type ◽  
G Quadruplex ◽  
Cell Type Specific

DNA is a complex molecule carrying the instructions an organism needs to develop, live and reproduce. In 1953, Watson and Crick discovered that DNA is composed of two chains forming a double-helix. Later on, other structures of DNA were discovered and shown to play important roles in the cell, in particular G-quadruplex (G4). Following genome sequencing, several bioinformatic algorithms were developed to map G4s in vitro based on a canonical sequence motif, G-richness and G-skewness or alternatively sequence features including k-mers, and more recently machine/deep learning. Recently, new sequencing techniques were developed to map G4s in vitro (G4-seq) and G4s in vivo (G4 ChIP-seq) at few hundred base resolution. Here, we propose a novel convolutional neural network (DeepG4) to map cell-type specific active G4 regions (e.g. regions within which G4s form both in vitro and in vivo). DeepG4 is very accurate to predict active G4 regions in different cell types. Moreover, DeepG4 identifies key DNA motifs that are predictive of G4 region activity. We found that such motifs do not follow a very flexible sequence pattern as current algorithms seek for. Instead, active G4 regions are determined by numerous specific motifs. Moreover, among those motifs, we identified known transcription factors (TFs) which could play important roles in G4 activity by contributing either directly to G4 structures themselves or indirectly by participating in G4 formation in the vicinity. In addition, we used DeepG4 to predict active G4 regions in a large number of tissues and cancers, thereby providing a comprehensive resource for researchers. Availability: https://github.com/morphos30/DeepG4.

scholarly journals Induction of Golli-MBP Expression in CNS Macrophages During Acute LPS-Induced CNS Inflammation and Experimental Autoimmune Encephalomyelitis (EAE)

2007 ◽  
Vol 7 ◽  
pp. 112-120 ◽  
Author(s):  
Tracey L. Papenfuss ◽  
J. Cameron Thrash ◽  
Patricia E. Danielson ◽  
Pamela E. Foye ◽  
Brian S. Hllbrush ◽  
...  
Keyword(s):  
Experimental Autoimmune Encephalomyelitis ◽  
Cell Type ◽  
Autoimmune Encephalomyelitis ◽  
Cns Inflammation ◽  
Cell Type Specific ◽  
Candidate Molecule ◽  
Experimental Autoimmune

Microglia are the tissue macrophages of the CNS. Microglial activation coupled with macrophage infiltration is a common feature of many classic neurodegenerative disorders. The absence of cell-type specific markers has confounded and complicated the analysis of cell-type specific contributions toward the onset, progression, and remission of neurodegeneration. Molecular screens comparing gene expression in cultured microglia and macrophages identified Golli-myelin basic protein (MBP) as a candidate molecule enriched in peripheral macrophages.In situhybridization analysis of LPS/IFNg and experimental autoimmune encephalomyelitis (EAE)–induced CNS inflammation revealed that only a subset of CNS macrophages express Golli-MBP. Interestingly, the location and morphology of Golli-MBP+ CNS macrophages differs between these two models of CNS inflammation. These data demonstrate the difficulties of extendingin vitroobservations toin vivobiology and concretely illustrate the complex heterogeneity of macrophage activation states present in region- and stage-specific phases of CNS inflammation. Taken altogether, these are consistent with the emerging picture that the phenotype of CNS macrophages is actively defined by their molecular interactions with the CNS microenvironment.

scholarly journals Interneuron Transplantation Creates New Network States and Rescues Social Behavior Deficits in a Mouse Model of Autism

Neurosurgery ◽  
2019 ◽  
Vol 66 (Supplement_1) ◽  
Author(s):  
Derek Southwell ◽  
Helia Seifikar ◽  
Ruchi Malik ◽  
Karen Lavi ◽  
Daniel Vogt ◽  
...  
Keyword(s):  
Social Behavior ◽  
Neuropsychiatric Disorders ◽  
Inhibitory Interneuron ◽  
Network Activity ◽  
Therapeutic Effects ◽  
Synaptic Inhibition ◽  
Behavioral State ◽  
Wild Type

Abstract INTRODUCTION Inhibitory interneuron transplantation is a prospective treatment for neuropsychiatric disorders, but it is unclear whether transplantation might elicit therapeutic effects by reversing preexisting abnormalities, nonspecifically increasing synaptic inhibition, or engaging mechanisms that vary depending on recipient background and behavioral state. METHODS We transplanted wild-type embryonic interneuron precursors into mice lacking an autism-associated gene, Pten, in inhibitory interneurons. Additionally, we performed transplantation into wild-type recipient mice, and then examined the recipient behavior, cellular physiology in Vitro, and network physiology in Vivo. RESULTS Transplantation rescued social behavior deficits in Pten mutants without normalizing excessive synaptic inhibition in Vitro or reduced baseline gamma oscillatory power in Vivo. However, transplantation altered recipient electroencephalography (EEG) responses observed specifically during periods of social interaction. When transplantation was performed into wild-type recipients, the subtype composition of the transplanted population varied from that observed in Pten mutants, and, moreover, recipients did not exhibit alterations to social behavior or related EEG responses. CONCLUSION Interneuron transplantation elicits recipient- and behavioral state-dependent effects, and normalizes behavior by creating new patterns of network activity, rather than restoring wild-type states. Interneuron transplantation may provide a novel therapeutic approach to the treatment of autism and related neuropsychiatric disorders.

scholarly journals In vivo FRET–FLIM reveals cell-type-specific protein interactions in Arabidopsis roots

Nature ◽  
2017 ◽  
Vol 548 (7665) ◽  
pp. 97-102 ◽  
Author(s):  
Yuchen Long ◽  
Yvonne Stahl ◽  
Stefanie Weidtkamp-Peters ◽  
Marten Postma ◽  
Wenkun Zhou ◽  
...  
Keyword(s):  
Protein Interactions ◽  
Specific Protein ◽  
Cell Type ◽  
Cell Type Specific

Glial fibrillary acidic protein - a cell type specific marker for Ito cells in vivo and in vitro

1996 ◽  
Vol 24 (6) ◽  
pp. 719-730 ◽  
Author(s):  
Katrin Neubauer ◽  
Thomas Knittel ◽  
Sabine Aurisch ◽  
Peter Fellmer ◽  
Giuliano Ramadori
Keyword(s):  
Glial Fibrillary Acidic Protein ◽  
Protein A ◽  
Acidic Protein ◽  
Specific Marker ◽  
Cell Type ◽  
Ito Cells ◽  
A Cell ◽  
Cell Type Specific

Liver cell type specific discrimination of TGF-beta signaling and outcome in vitro and in vivo

2019 ◽  
Author(s):  
M Han ◽  
ZC Nwosu ◽  
MP Ebert ◽  
S Hammad ◽  
S Dooley ◽  
...  
Keyword(s):  
Liver Cell ◽  
Tgf Beta ◽  
Cell Type ◽  
Cell Type Specific

Cell-Type Specific and Cytoplasmic Targeting of PEGylated Carbon Nanotube-Based Nanoassemblies

2008 ◽  
Vol 8 (5) ◽  
pp. 2259-2269 ◽  
Author(s):  
Matthew H. Cato ◽  
Federica D'Annibale ◽  
David M. Mills ◽  
Fabio Cerignoli ◽  
Marcia I. Dawson ◽  
...  
Keyword(s):  
Carbon Nanotubes ◽  
Average Length ◽  
Cell Receptor ◽  
Specific Cell ◽  
Cell Type ◽  
Cytoplasmic Delivery ◽  
Cell Type Specific ◽  
Walled Carbon Nanotubes

In this paper we report the fabrication of a multivalent, cell-type specific and cytoplasmic delivery system based on single-walled carbon nanotubes. The latter were functionalized through adsorption of phospholipids terminated by biotinylated PEG chains functionalized with fluorochrome-coupled neutravidin, and subsequently with antibodies (anti-CD3ε and anti-CD28) for T cell receptor post-signaling endocytosis and a synthetic fusogenic polymer for disruption of lysosomal compartments. The biomimetic nanoassemblies were composed by PEGylated individual/very small bundles of carbon nanotubes having an average length and a standard deviation of 176 nm and 77 nm, respectively. The nanoassemblies were stably dispersed under physiological conditions, visible by conventional optical and confocal microscopy and specifically targeted to T cells both in vitro and in living animals. The addition of a fusogenic polymer to the nanoassemblies did not affect the cellular uptake and allowed the release into the cytosol of the targeted cells both in vitro and in the animals. The present manuscript is the first report about the cytoplasmic delivery of carbon nanotubes in a specific cell type in intact animals and paves the way for their use as in vivo intracellular delivery systems.

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