scholarly journals Brain-wide genetic mapping identifies the indusium griseum as a prenatal target of pharmacologically unrelated psychostimulants

2019 ◽  
Vol 116 (51) ◽  
pp. 25958-25967
Author(s):  
Janos Fuzik ◽  
Sabah Rehman ◽  
Fatima Girach ◽  
Andras G. Miklosi ◽  
Solomiia Korchynska ◽  
...  
Keyword(s):  
Granule Cells ◽  
Light Sheet ◽  
Pregnant Mouse ◽  
Tissue Imaging ◽  
Drug Induced ◽  
Genetic Ablation ◽  
Glutamatergic Neurons ◽  
Light Sheet Microscopy ◽  
Adult Mice ◽  
Dramatic Rise

Psychostimulant use is an ever-increasing socioeconomic burden, including a dramatic rise during pregnancy. Nevertheless, brain-wide effects of psychostimulant exposure are incompletely understood. Here, we performed Fos-CreERT2–based activity mapping, correlated for pregnant mouse dams and their fetuses with amphetamine, nicotine, and caffeine applied acutely during midgestation. While light-sheet microscopy-assisted intact tissue imaging revealed drug- and age-specific neuronal activation, the indusium griseum (IG) appeared indiscriminately affected. By using GAD67gfp/+mice we subdivided the IG into a dorsolateral domain populated by γ-aminobutyric acidergic interneurons and a ventromedial segment containing glutamatergic neurons, many showing drug-induced activation and sequentially expressing Pou3f3/Brn1 and secretagogin (Scgn) during differentiation. We then combined Patch-seq and circuit mapping to show that the ventromedial IG is a quasi-continuum of glutamatergic neurons (IG-Vglut1+) reminiscent of dentate granule cells in both rodents and humans, whose dendrites emanate perpendicularly toward while their axons course parallel with the superior longitudinal fissure. IG-Vglut1+neurons receive VGLUT1+and VGLUT2+excitatory afferents that topologically segregate along their somatodendritic axis. In turn, their efferents terminate in the olfactory bulb, thus being integral to a multisynaptic circuit that could feed information antiparallel to the olfactory–cortical pathway. In IG-Vglut1+neurons, prenatal psychostimulant exposure delayed the onset of Scgn expression. Genetic ablation ofScgnwas then found to sensitize adult mice toward methamphetamine-induced epilepsy. Overall, our study identifies brain-wide targets of the most common psychostimulants, among whichScgn+/Vglut1+neurons of the IG link limbic and olfactory circuits.

scholarly journals Brain-wide genetic mapping identifies the indusium griseum as a prenatal and shared target of pharmacologically-unrelated psychostimulants

2019 ◽  
Author(s):  
Janos Fuzik ◽  
Sabah Rehman ◽  
Fatima Girach ◽  
Andras G. Miklosi ◽  
Solomiia Korchynska ◽  
...  
Keyword(s):  
Brain Area ◽  
Fetal Brain ◽  
Mouse Genetics ◽  
Tissue Imaging ◽  
Neuronal Activation ◽  
Drug Induced ◽  
Genetic Ablation ◽  
Glutamatergic Neurons ◽  
Light Sheet Microscopy ◽  
Epileptiform Discharges

AbstractPsychostimulant use is an ever-increasing socioeconomic burden, including a dramatic rise during pregnancy. Nevertheless, brain-wide effects of psychostimulant exposure are incompletely understood. Here, we performed Fos-CreERT2-based activity mapping, correlated for pregnant mouse dams and their fetuses with amphetamine, nicotine and caffeine applied acutely during mid-gestation. While light-sheet microscopy-assisted intact tissue imaging revealed drug- and age-specific neuronal activation, the indusium griseum (IG) appeared indiscriminately affected. By using GAD67gfp/+ mice we subdivided the IG into a dorsolateral domain populated by GABA interneurons and a ventromedial segment containing glutamatergic neurons, many showing drug-induced activation and sequentially expressing Pou3f3/Brn1 and secretagogin (Scgn) during differentiation. We then combined Patch-seq and circuit mapping to show that the ventromedial IG is a quasi-continuum of glutamatergic neurons (IG-Vglut1+) reminiscent to dentate granule cells in both rodents and humans, whose dendrites emanate perpendicularly towards, while their axons course parallel with the superior longitudinal fissure. IG-Vglut1+ neurons receive Vglut1+ and Vglut2+ excitatory afferents that topologically segregate along their somatodendritic axis. In turn, their efferents terminate in the olfactory bulb, thus being integral to a multi-synaptic circuit that could feed information antiparallel to the olfactory-cortical pathway. In IG-Vglut1+ neurons, prenatal psychostimulant exposure delayed the onset of Scgn expression. Genetic ablation of Scgn was then found to sensitize adult mice towards methamphetamine-induced epilepsy, suggesting a role for this Ca2+-binding protein in scaling IG-Vglut1+ neuronal excitability. Overall, our study identifies brain-wide targets of the most common psychostimulants, among which Scgn+/Vglut1+ neurons of the IG link limbic and olfactory circuits.Significance statementDrug abuse during pregnancy is a significant socioeconomic problem. The use of psychostimulants is particularly common during pregnancy even though a risk to the developing fetus is significant. Here, we show that short-lived exposure to amphetamine, nicotine and caffeine during pregnancy induces neuronal activation in the fetal brain with the indusium griseum (IG), a brain area situated parallel to the central surface of the cortical hemispheres, becoming indiscriminately activated. By using mouse genetics, we find that psychostimulants preferentially target glutamatergic IG neurons, and delay their differentiation postnatally. Notably, the expressional onset of secretagogin, a Ca2+-sensor amenable for synaptic integration, is deregulated. This is significant because these neurons are integral to a multi-synaptic neuronal pathway that links limbic and olfactory circuits. As such, genetic deletion of secretagogin brings about heightened sensitivity to psychostimulants, manifesting as epileptiform discharges. Cumulatively, we describe a novel psychostimulant-sensitive neuronal subtype and its circuit arrangement whose developmental delay seems critical for behavioral abnormalities in offspring prenatally exposed to the most common psychostimulants.

scholarly journals Balancing signal and photoperturbation in multiphoton light-sheet microscopy by optimizing laser pulse frequency

2020 ◽  
Author(s):  
Vincent Maioli ◽  
Antoine Boniface ◽  
Pierre Mahou ◽  
Júlia Ferrer Ortas ◽  
Lamiae Abdeladim ◽  
...  
Keyword(s):  
Laser Pulse ◽  
Multiphoton Microscopy ◽  
Light Sheet ◽  
Pulse Frequency ◽  
Heart Beat ◽  
Research Field ◽  
Tissue Imaging ◽  
Power Pulse ◽  
Light Sheet Microscopy

AbstractImproving the imaging speed of multiphoton microscopy is an active research field. Among recent strategies, light-sheet illumination holds distinctive advantages for achieving fast imaging in vivo. However, photoperturbation in multiphoton light-sheet microscopy remains poorly investigated. We show here that the heart beat rate of zebrafish embryos is a sensitive probe of linear and nonlinear photoperturbations. By analyzing its behavior with respect to laser power, pulse frequency and wavelength, we derive guidelines to balance signal and photoperturbation. We then demonstrate one order-of-magnitude signal enhancement over previous implementations by optimizing the laser pulse frequency. These results open new opportunities for fast live tissue imaging.

scholarly journals Visualization and Analysis of Whole Depot Adipose Tissue Innervation

2019 ◽  
Author(s):  
Jake W. Willows ◽  
Magdalena Blaszkiewicz ◽  
Amy Lamore ◽  
Samuel Borer ◽  
Amanda L. Dubois ◽  
...  
Keyword(s):  
Adipose Tissue ◽  
Second Harmonic ◽  
Imaging Techniques ◽  
Three Dimensional ◽  
Light Sheet ◽  
Tissue Imaging ◽  
Label Free ◽  
Adipose Tissues ◽  
Light Sheet Microscopy ◽  
Neurite Density

AbstractAdipose tissue requires neural innervation in order to regulate important metabolic functions. Though seminal work on adipose denervation has underscored the importance of adipose-nerve interactions in both white (energy storing) and brown (energy expending) adipose tissues, much remains a mystery. This is due, in part, to the inability to effectively visualize the various nerve subtypes residing within these tissues and to gain a comprehensive quantitation of neurite density in an entire depot. With the recent surge of advanced imaging techniques such as light sheet microscopy and optical clearing procedures, adipose tissue imaging has been reinvigorated with a focus on three-dimensional analysis of tissue innervation. However, clearing techniques are time consuming, often require solvents caustic to objective lenses, alter tissue morphology, and greatly reduce fluorophore lifespan. Not only are current methods of imaging wholemount adipose tissues inconvenient, but often attempts to quantify neurite density across physiological or pathophysiological conditions have been limited to representative section sampling. We have developed a new method of adipose tissue neurite imaging and quantitation that is faster than current clearing-based methods, does not require caustic chemicals, and leaves the tissue fully intact. Maintenance of a fully intact depot allowed for tiling z-stacks and producing maximum intensity projections of the entire adipose depot, which were then used to quantify neurite density across the tissue. With this processing method we were able to characterize the nerves, nerve-subtypes, and neurovascular interactions within the inguinal subcutaneous white adipose tissue in mice using up to five fluorescent channels at high resolution. We also utilized second harmonic generation, which provides label-free imaging, to investigate collagen fiber abundance in adipose of obese mice.

scholarly journals Congenital hypothyroidism impairs spine growth of dentate granule cells by downregulation of CaMKIV

2021 ◽  
Vol 7 (1) ◽  
Author(s):  
Qingying Tang ◽  
Shuxia Chen ◽  
Hui Wu ◽  
Honghua Song ◽  
Yongjun Wang ◽  
...  
Keyword(s):  
Congenital Hypothyroidism ◽  
Granule Cells ◽  
Spine Density ◽  
Drug Induced ◽  
Distinct Cell Type ◽  
Cognitive Behaviors ◽  
Dentate Granule Cells ◽  
Rat Pups ◽  
Cognitive Deficiency ◽  
Underlying Mechanisms

AbstractCongenital hypothyroidism (CH), a common neonatal endocrine disorder, can result in cognitive deficits if delay in diagnose and treatment. Dentate gyrus (DG) is the severely affected subregion of the hippocampus by the CH, where the dentate granule cells (DGCs) reside in. However, how CH impairs the cognitive function via affecting DGCs and the underlying mechanisms are not fully elucidated. In the present study, the CH model of rat pups was successfully established, and the aberrant dendrite growth of the DGCs and the impaired cognitive behaviors were observed in the offspring. Transcriptome analysis of hippocampal tissues following rat CH successfully identified that calcium/calmodulin-dependent protein kinase IV (CaMKIV) was the prominent regulator involved in mediating deficient growth of DGC dendrites. CaMKIV was shown to be dynamically regulated in the DG subregion of the rats following drug-induced CH. Interference of CaMKIV expression in the primary DGCs significantly reduced the spine density of dendrites, while addition of T3 to the primary DGCs isolated from CH pups could facilitate the spine growth of dendrites. Insights into relevant mechanisms revealed that CH-mediated CaMKIV deficiency resulted in the significant decrease of phosphorylated CREB in DGCs, in association with the abnormality of dendrites. Our results have provided a distinct cell type in hippocampus that is affected by CH, which would be beneficial for the treatment of CH-induced cognitive deficiency.

scholarly journals Achromatic terahertz Airy beam generation with dielectric metasurfaces

Nanophotonics ◽  
2020 ◽  
Vol 0 (0) ◽  
Author(s):  
Qingqing Cheng ◽  
Juncheng Wang ◽  
Ling Ma ◽  
Zhixiong Shen ◽  
Jing Zhang ◽  
...  
Keyword(s):  
Biomedical Imaging ◽  
Frequency Dispersion ◽  
Light Sheet ◽  
Photonic Devices ◽  
Self Healing ◽  
Beam Focusing ◽  
Light Sheet Microscopy ◽  
Airy Beam ◽  
Potential Applications ◽  
Airy Beams

AbstractAiry beams exhibit intriguing properties such as nonspreading, self-bending, and self-healing and have attracted considerable recent interest because of their many potential applications in photonics, such as to beam focusing, light-sheet microscopy, and biomedical imaging. However, previous approaches to generate Airy beams using photonic structures have suffered from severe chromatic problems arising from strong frequency dispersion of the scatterers. Here, we design and fabricate a metasurface composed of silicon posts for the frequency range 0.4–0.8 THz in transmission mode, and we experimentally demonstrate achromatic Airy beams exhibiting autofocusing properties. We further show numerically that a generated achromatic Airy-beam-based metalens exhibits self-healing properties that are immune to scattering by particles and that it also possesses a larger depth of focus than a traditional metalens. Our results pave the way to the realization of flat photonic devices for applications to noninvasive biomedical imaging and light-sheet microscopy, and we provide a numerical demonstration of a device protocol.

scholarly journals Single-Molecule Light-Sheet Microscopy with Local Nanopipette Delivery

2021 ◽  
Vol 93 (8) ◽  
pp. 4092-4099
Author(s):  
Bing Li ◽  
Aleks Ponjavic ◽  
Wei-Hsin Chen ◽  
Lee Hopkins ◽  
Craig Hughes ◽  
...  
Keyword(s):  
Single Molecule ◽  
Light Sheet ◽  
Light Sheet Microscopy

scholarly journals Effect of captopril on post-infarction remodelling visualized by light sheet microscopy and echocardiography

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Urmas Roostalu ◽  
Louise Thisted ◽  
Jacob Lercke Skytte ◽  
Casper Gravesen Salinas ◽  
Philip Juhl Pedersen ◽  
...  
Keyword(s):  
Morphological Changes ◽  
Light Sheet ◽  
Automated Image Analysis ◽  
Border Zone ◽  
Vascular Density ◽  
Mouse Heart ◽  
Imaging Method ◽  
Light Sheet Microscopy ◽  
Post Surgery ◽  
Captopril Treatment

AbstractAngiotensin converting enzyme inhibitors, among them captopril, improve survival following myocardial infarction (MI). The mechanisms of captopril action remain inadequately understood due to its diverse effects on multiple signalling pathways at different time periods following MI. Here we aimed to establish the role of captopril in late-stage post-MI remodelling. Left anterior descending artery (LAD) ligation or sham surgery was carried out in male C57BL/6J mice. Seven days post-surgery LAD ligated mice were allocated to daily vehicle or captopril treatment continued over four weeks. To provide comprehensive characterization of the changes in mouse heart following MI a 3D light sheet imaging method was established together with automated image analysis workflow. The combination of echocardiography and light sheet imaging enabled to assess cardiac function and the underlying morphological changes. We show that delayed captopril treatment does not affect infarct size but prevents left ventricle dilation and hypertrophy, resulting in improved ejection fraction. Quantification of lectin perfused blood vessels showed improved vascular density in the infarct border zone in captopril treated mice in comparison to vehicle dosed control mice. These results validate the applicability of combined echocardiographic and light sheet assessment of drug mode of action in preclinical cardiovascular research.

The Light-Sheet Microscopy

2021 ◽  
Author(s):  
Rolf Theodor Borlinghaus
Keyword(s):  
Light Sheet ◽  
Light Sheet Microscopy
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