scholarly journals Disrupted-in-Schizophrenia-1 is required for proper pyramidal cell-interneuron communication and network dynamics in the prefrontal cortex

2021 ◽  
Author(s):  
Jonas-Frederic Sauer ◽  
Marlene Bartos
Keyword(s):  
Pyramidal Cell ◽  
Gamma Oscillations ◽  
Mutant Mice ◽  
Potential Mechanism ◽  
Excitatory Effect ◽  
Fast Spiking ◽  
Single Unit Recordings ◽  
Circuit Function

AbstractWe interrogated prefrontal circuit function in mice lacking Disrupted-in-schizophrenia-1 (Disc1-mutant mice), a risk factor for psychiatric disorders. Single-unit recordings in awake mice revealed reduced average firing rates of fast-spiking interneurons (INTs), including optogenetically identified parvalbumin-positive cells, and a lower proportion of INTs phase-coupled to ongoing gamma oscillations. Moreover, we observed decreased spike transmission efficacy at local pyramidal cell (PYR)-INT connections in vivo, suggesting a reduced excitatory effect of local glutamatergic inputs as a potential mechanism of lower INT rates. On the network level, impaired INT function resulted in altered activation of PYR assemblies: While assembly activations were observed equally often, the expression strength of individual assembly patterns was significantly higher in Disc1-mutant mice. Our data thus reveal a role of Disc1 in shaping the properties of prefrontal assembly patterns by setting prefrontal INT responsiveness to glutamatergic drive.

In vivo role of BDNF cleavage: Behavioral study of the mutant mice using test battery

2009 ◽  
Vol 65 ◽  
pp. S254
Author(s):  
Haruko Kumanogoh ◽  
Mitsuru Ohtsuka ◽  
Tomoko Hara ◽  
Yoshiko Urbanczyk ◽  
Keizo Takao ◽  
...  
Keyword(s):  
Test Battery ◽  
Mutant Mice ◽  
Behavioral Study

scholarly journals Garcinoic Acid Improves Cardiac Function and Enhances Angiogenesis Following Myocardial Infarction

2021 ◽  
Author(s):  
Hongyao Hu ◽  
Wei Li ◽  
Yanzhao Wei ◽  
Hui Zhao ◽  
Zhenzhong Wu ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Cardiac Function ◽  
Ventricular Remodeling ◽  
Vehicle Group ◽  
Potential Mechanism ◽  
Garcinia Kola ◽  
Angiogenic Proteins

Abstract Cardiac ischemia impairs angiogenesis in response to hypoxia, resulting in ventricular remodeling. Garcinoic acid (GA), the extraction from the plant garcinia kola, is validated to attenuate inflammatory response. However, the role of GA in heart failure (HF) and neovascularization after myocardial infarction (MI) is incompletely understood. The present study is striving to explore the role of GA and the potential mechanism of which in cardiac function after MI. SD rats were randomized into sham group, MI+vehicle group, and MI+GA group in vivo. Human umbilical endothelial cells (HUVECs) were cultured in vehicle or GA, and then additionally exposed to 2% hypoxia environment in vitro. MI rats displayed a dramatically reduced myocardial injury, cardiac function and vessel density in the peri-infarcted areas. GA delivery markedly improved cardiac performance and promoted angiogenesis. In addition, GA significantly enhanced tube formation in HUVECs under hypoxia condition. Furthermore, the expressions of pro-angiogenic factors HIF-1α, VEGF-A and bFGF, and pro-angiogenic proteins phospho-VEGFR2Tyr1175 and VEGFR2, as well as phosphorylation levels of Akt and eNOS were increased by GA treatment. In conclusion, GA preserved cardiac function after MI probably via promoting neovascularization. And the potential mechanism may be partially through upregulating the expressions of HIF-1α, VEGF-A, bFGF, phospho-VEGFR2Tyr1175 and VEGFR2 and activating the phosphorylations of Akt and eNOS.

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 Lunatic Fringe-mediated Notch signaling is required for lung alveogenesis

2010 ◽  
Vol 298 (1) ◽  
pp. L45-L56 ◽  
Author(s):  
Keli Xu ◽  
Erica Nieuwenhuis ◽  
Brenda L. Cohen ◽  
Wei Wang ◽  
Angelo J. Canty ◽  
...  
Keyword(s):  
Notch Signaling ◽  
Lung Development ◽  
Smooth Muscle Actin ◽  
Mutant Mice ◽  
Myofibroblast Differentiation ◽  
Lunatic Fringe ◽  
Notch Receptors ◽  
Distal Lung

Distal lung development occurs through coordinated induction of myofibroblasts, epithelial cells, and capillaries. Lunatic Fringe ( Lfng) is a β1–3 N-acetylglucosamine transferase that modifies Notch receptors to facilitate their activation by Delta-like (Dll1/4) ligands. Lfng is expressed in the distal lung during saccular development, and deletion of this gene impairs myofibroblast differentiation and alveogenesis in this context. A similar defect was observed in Notch2 β-geo/+ Notch3 β-geo/β-geo compound mutant mice but not in Notch2 β-geo/+ or Notch3 β-geo/β-geo single mutants. Finally, to directly test for the role of Notch signaling in myofibroblast differentiation in vivo, we used ROSA26-rtTA/+; tetO-CRE/+; RBPJκflox/flox inducible mutant mice to show that disruption of canonical Notch signaling during late embryonic development prevents induction of smooth muscle actin in mesenchymal cells of the distal lung. In sum, these results demonstrate that Lfng functions to enhance Notch signaling in myofibroblast precursor cells and thereby to coordinate differentiation and mobilization of myofibroblasts required for alveolar septation.

Identifying the Functional Role of Martinotti Cells in Cortical Sensory Processing

2009 ◽  
Vol 102 (1) ◽  
pp. 9-11 ◽  
Author(s):  
James C. H. Cottam
Keyword(s):  
Sensory Processing ◽  
Pyramidal Cell ◽  
Functional Significance ◽  
Functional Role ◽  
Neural Computation ◽  
Inhibitory Interneurons ◽  
Local Circuit ◽  
Processing Function

Inhibitory interneurons are highly diverse, although the functional significance of their diversity is not yet well understood. This presents a barrier to understanding neural computation at the local circuit level. This review focuses on a recent study by Murayama et al. who used a novel in vivo technique in neocortex to demonstrate a specific sensory processing function of dendritic-targeting Martinotti interneurons. The function of Martinotti cells arises from their interaction with layer 5 pyramidal cell dendrites.

Role of GATA-1 in Proliferation and Differentiation of Definitive Erythroid and Megakaryocytic Cells In Vivo

Blood ◽  
1998 ◽  
Vol 92 (2) ◽  
pp. 434-442 ◽  
Author(s):  
Satoru Takahashi ◽  
Takuya Komeno ◽  
Naruyoshi Suwabe ◽  
Keigyo Yoh ◽  
Osamu Nakajima ◽  
...  
Keyword(s):  
Es Cells ◽  
Early Adulthood ◽  
Mutant Mice ◽  
Selection Marker ◽  
Adult Mice ◽  
Proliferation And Differentiation ◽  
Neomycin Resistance ◽  
Definitive Hematopoiesis

To elucidate the contributions of GATA-1 to definitive hematopoiesis in vivo, we have examined adult mice that were rendered genetically defective in GATA-1 synthesis (Takahashi et al, J Biol Chem272:12611, 1997). Because the GATA-1 gene is located on the X chromosome, which is randomly inactivated in every cell, heterozygous females can bear either an active wild-type or mutant (referred to asGATA-1.05) GATA-1 allele, consequently leading to variable anemic severity. These heterozygous mutant mice usually developed normally, but they began to die after 5 months. These affected animals displayed marked splenomegaly, anemia, and thrombocytopenia. Proerythroblasts and megakaryocytes massively accumulated in the spleens of the heterozygotes, and we showed that the neomycin resistance gene (which is the positive selection marker in ES cells) was expressed profusely in the abnormally abundant cells generated in the GATA-1.05 mutant females. We also observed hematopoiesis outside of the bone marrow in the affected mutant mice. These data suggest that a small number of GATA-1.05 mutant hematopoietic progenitor cells begin to proliferate vigorously during early adulthood, but because the cells are unable to terminally differentiate, this leads to progenitor proliferation in the spleen and consequently death. Thus, GATA-1 plays important in vivo roles for directing definitive hematopoietic progenitors to differentiate along both the erythroid and megakaryocytic pathways. The GATA-1 heterozygous mutant mouse shows a phenotype that is analogous to human myelodysplastic syndrome and thus may serve as a useful model for this disorder.

scholarly journals Mild metabolic stress is sufficient to disturb the formation of pyramidal cell ensembles during gamma oscillations

2019 ◽  
Vol 40 (12) ◽  
pp. 2401-2415 ◽  
Author(s):  
Shehabeldin Elzoheiry ◽  
Andrea Lewen ◽  
Justus Schneider ◽  
Martin Both ◽  
Dimitri Hefter ◽  
...  
Keyword(s):  
Pyramidal Cell ◽  
Metabolic Stress ◽  
Pyramidal Cells ◽  
Gamma Oscillations ◽  
System Level ◽  
Attention And Memory ◽  
Neuronal Ensembles ◽  
Brain Functions ◽  
Fast Spiking ◽  
Underlying Mechanisms

Disturbances of cognitive functions occur rapidly during acute metabolic stress. However, the underlying mechanisms are not fully understood. Cortical gamma oscillations (30–100 Hz) emerging from precise synaptic transmission between excitatory principal neurons and inhibitory interneurons, such as fast-spiking GABAergic basket cells, are associated with higher brain functions, like sensory perception, selective attention and memory formation. We investigated the alterations of cholinergic gamma oscillations at the level of neuronal ensembles in the CA3 region of rat hippocampal slice cultures. We combined electrophysiology, calcium imaging (CamKII.GCaMP6f) and mild metabolic stress that was induced by rotenone, a lipophilic and highly selective inhibitor of complex I in the respiratory chain of mitochondria. The detected pyramidal cell ensembles showing repetitive patterns of activity were highly sensitive to mild metabolic stress. Whereas such synchronised multicellular activity diminished, the overall activity of individual pyramidal cells was unaffected. Additionally, mild metabolic stress had no effect on the rate of action potential generation in fast-spiking neural units. However, the partial disinhibition of slow-spiking neural units suggests that disturbances of ensemble formation likely result from alterations in synaptic inhibition. Our study bridges disturbances on the (multi-)cellular and network level to putative cognitive impairment on the system level.

scholarly journals Delayed liver regeneration in mice lacking liver serum response factor

2007 ◽  
Vol 292 (4) ◽  
pp. G996-G1001 ◽  
Author(s):  
M. Ujue Latasa ◽  
Dominique Couton ◽  
Claude Charvet ◽  
Aurélie Lafanechère ◽  
Jacques-Emmanuel Guidotti ◽  
...  
Keyword(s):  
Liver Regeneration ◽  
Partial Hepatectomy ◽  
Serum Response Factor ◽  
Early Response ◽  
Mutant Mice ◽  
Response Factor ◽  
Impaired Liver ◽  
Serum Response

Various immediate early genes (IEGs) upregulated during the early process of liver regeneration are transcriptional targets of the serum response factor (SRF). We show here that the expression of SRF is rapidly induced in rodent liver after partial hepatectomy. Because the inactivation of the SRF gene in mice is embryonic lethal, the in vivo role of SRF in liver regeneration after partial hepatectomy was analyzed in mutant mice conditionally deleted for SRF in the liver. We demonstrate that SRF is not an essential factor for liver ontogenesis. However, adult mutant mice show impaired liver regeneration after partial hepatectomy, associated with a blunted upregulation of various SRF target IEGs. In conclusion, our work suggests that SRF is an early response transcription factor that may contribute to the initial phases of liver regeneration through its activation of IEGs.

scholarly journals Reduced Granule Cell Proliferation and Molecular Dysregulation in the Cerebellum of Lysosomal Acid Phosphatase 2 (ACP2) Mutant Mice

2021 ◽  
Vol 22 (6) ◽  
pp. 2994
Author(s):  
Xiaodan Jiao ◽  
Maryam Rahimi Balaei ◽  
Ejlal Abu-El-Rub ◽  
Filippo Casoni ◽  
Hassan Pezeshgi Modarres ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Acid Phosphatase ◽  
Granule Cell ◽  
Granule Cells ◽  
Mutant Mice ◽  
Lysosomal Acid ◽  
Protein Synthesis Machinery

Lysosomal acid phosphatase 2 (Acp2) mutant mice (naked-ataxia, nax) have a severe cerebellar cortex defect with a striking reduction in the number of granule cells. Using a combination of in vivo and in vitro immunohistochemistry, Western blotting, BrdU assays, and RT-qPCR, we show downregulation of MYCN and dysregulation of the SHH signaling pathway in the nax cerebellum. MYCN protein expression is significantly reduced at P10, but not at the peak of proliferation at around P6 when the number of granule cells is strikingly reduced in the nax cerebellum. Despite the significant role of the SHH–MycN pathway in granule cell proliferation, our study suggests that a broader molecular pathway and additional mechanisms regulating granule cell development during the clonal expansion period are impaired in the nax cerebellum. In particular, our results indicate that downregulation of the protein synthesis machinery may contribute to the reduced number of granule cells in the nax cerebellum.

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