scholarly journals In vivo assay of cortical microcircuitry in frontotemporal dementia: a platform for experimental medicine studies

2018 ◽  
Author(s):  
Alexander D Shaw ◽  
Laura E Hughes ◽  
Rosalyn Moran ◽  
Ian Coyle-Gilchrist ◽  
Tim Rittman ◽  
...  
Keyword(s):  
Frontotemporal Dementia ◽  
Neural Circuits ◽  
Case Control ◽  
Experimental Medicine ◽  
Non Invasive ◽  
Cortical Responses ◽  
Sensory Predictions ◽  
Local Coupling ◽  
Laminar Specificity

AbstractThe analysis of neural circuits can provide critical insights into the mechanisms of neurodegeneration and dementias, and offer potential quantitative biological tools to assess novel therapeutics. Here we use behavioural variant frontotemporal dementia (bvFTD) as a model disease. We demonstrate that inversion of canonical microcircuit models to non-invasive human magnetoecphalography can identify the regional- and laminar-specificity of bvFTD pathophysiology, and their parameters can accurately differentiate patients from matched healthy controls. Using such models, we show that changes in local coupling in frontotemporal dementia underlie the failure to adequately establish sensory predictions, leading to altered prediction error responses in a cortical information-processing hierarchy. Using machine learning, this model-based approach provided greater case-control classification accuracy than conventional evoked cortical responses. We suggest that this approach provides an in vivo platform for testing mechanistic hypotheses about disease progression and pharmacotherapeutics.

scholarly journals Optogenetic Manipulation of Olfactory Responses in Transgenic Zebrafish: A Neurobiological and Behavioral Study

2021 ◽  
Vol 22 (13) ◽  
pp. 7191
Author(s):  
Yun-Mi Jeong ◽  
Tae-Ik Choi ◽  
Kyu-Seok Hwang ◽  
Jeong-Soo Lee ◽  
Robert Gerlai ◽  
...  
Keyword(s):  
Olfactory System ◽  
Neural Circuits ◽  
Transgenic Fish ◽  
Neural System ◽  
Transgenic Zebrafish ◽  
Olfactory Responses ◽  
Non Invasive ◽  
Zebrafish Larvae ◽  
Calcium Indicator

Olfaction is an important neural system for survival and fundamental behaviors such as predator avoidance, food finding, memory formation, reproduction, and social communication. However, the neural circuits and pathways associated with the olfactory system in various behaviors are not fully understood. Recent advances in optogenetics, high-resolution in vivo imaging, and reconstructions of neuronal circuits have created new opportunities to understand such neural circuits. Here, we generated a transgenic zebrafish to manipulate olfactory signal optically, expressing the Channelrhodopsin (ChR2) under the control of the olfactory specific promoter, omp. We observed light-induced neuronal activity of olfactory system in the transgenic fish by examining c-fos expression, and a calcium indicator suggesting that blue light stimulation caused activation of olfactory neurons in a non-invasive manner. To examine whether the photo-activation of olfactory sensory neurons affect behavior of zebrafish larvae, we devised a behavioral choice paradigm and tested how zebrafish larvae choose between two conflicting sensory cues, an aversive odor or the naturally preferred phototaxis. We found that when the conflicting cues (the preferred light and aversive odor) were presented together simultaneously, zebrafish larvae swam away from the aversive odor. However, the transgenic fish with photo-activation were insensitive to the aversive odor and exhibited olfactory desensitization upon optical stimulation of ChR2. These results show that an aversive olfactory stimulus can override phototaxis, and that olfaction is important in decision making in zebrafish. This new transgenic model will be useful for the analysis of olfaction related behaviors and for the dissection of underlying neural circuits.

Current and Future Magnetic Resonance Technologies for Assessing Liver Disease in Clinical and Experimental Medicine

2017 ◽  
Vol 35 (4) ◽  
pp. 314-322 ◽  
Author(s):  
Stephen J. Bawden ◽  
R.A. Scott ◽  
Guruprasad P. Aithal
Keyword(s):  
Magnetic Resonance ◽  
Mr Spectroscopy ◽  
Experimental Studies ◽  
Organ Specificity ◽  
Experimental Medicine ◽  
Sampling Errors ◽  
Non Invasive ◽  
Quantitative Mr ◽  
Underlying Mechanisms

Background: In the past decades, a number of non-invasive methods have emerged for detecting and estimating liver fibrosis; these include both serum-based panels and imaging-based technology. Some of these methods are now being incorporated in clinical practice. However, the limitations of the current techniques include lack of organ specificity, sampling errors and limited ability to reflect the efficacy of interventions. Key Messages: Novel magnetic resonance (MR)-based techniques provide an opportunity to bring about further changes in the investigations and management of patients with liver diseases. Multimodal quantitative MR techniques enable the estimation of fat, iron accumulation, degree of liver injury/inflammation and fibrosis within the whole liver without the need for administering contrast agents. Architectural changes within the liver can be evaluated concurrently with portal haemodynamic changes allowing non-invasive assessment of portal hypertension and effects of interventions. A combination ultra-high field (7T) provides greater sensitivity with a potential to distinguish inflammation from fibrosis on imaging and determine specific types of fats (saturated vs. unsaturated) present within the liver using MR spectroscopy. 13C MR spectroscopy can estimate glutathione flux and rate of beta oxidation in-vivo providing novel tools for experimental studies that evaluate the efficacy of interventions as well as underlying mechanisms. Conclusions: Translational research should focus on converting the potentials of these innovative methodologies into clinical applications for the benefit of patients.

scholarly journals In Vivo Assay of Cortical Microcircuitry in Frontotemporal Dementia: A Platform for Experimental Medicine Studies

2019 ◽  
Author(s):  
Alexander D Shaw ◽  
Laura E Hughes ◽  
Rosalyn Moran ◽  
Ian Coyle-Gilchrist ◽  
Tim Rittman ◽  
...  
Keyword(s):  
Frontotemporal Dementia ◽  
Experimental Medicine ◽  
In Vivo Assay

scholarly journals Sub-second multi-channel magnetic control of select neural circuits in behaving flies

2021 ◽  
Author(s):  
Charles Sebesta ◽  
Daniel Torres ◽  
Boshuo Wang ◽  
Zhongxi Li ◽  
Guillaume Duret ◽  
...  
Keyword(s):  
Magnetic Nanoparticles ◽  
Neural Circuits ◽  
Cell Activity ◽  
Temperature Sensitive ◽  
Magnetic Control ◽  
Deep Tissue ◽  
Minimal Invasiveness ◽  
Non Invasive ◽  
Freely Behaving

Abstract Precisely timed activation of genetically targeted cells is a powerful tool for studying neural circuits and controlling cell-based therapies. Magnetic control of cell activity or “magnetogenetics” using magnetic nanoparticle heating of temperature-sensitive ion channels enables remote, non-invasive activation of neurons for deep-tissue applications and studies of freely behaving animals. However, the in vivo response time of thermal magnetogenetics is currently tens of seconds, which prevents the precise temporal modulation of neural activity similar to light-based optogenetics. Moreover, magnetogenetics has not provided a means to selectively activate multiple channels to drive behavior. Here we demonstrate that by combining magnetic nanoparticles with a rate-sensitive thermoreceptor (TRPA1-A) it is possible to achieve sub-second behavioral responses in Drosophila melanogaster. Furthermore, by tuning the properties of magnetic nanoparticles to respond to different magnetic field strengths and frequencies, we can achieve fast, multi-channel stimulation, analogous to optogenetic stimulation with different wavelengths of light. These results bring magnetogenetics closer to the temporal resolution and multiplexed stimulation possible with optogenetics while maintaining the minimal invasiveness and deep-tissue stimulation only possible by magnetic control.

scholarly journals Sub-second multi-channel magnetic control of select neural circuits in behaving flies

2021 ◽  
Author(s):  
Charles Sebesta ◽  
Daniel Torres ◽  
Boshuo Wang ◽  
Zhongxi Li ◽  
Guillaume Duret ◽  
...  
Keyword(s):  
Magnetic Nanoparticles ◽  
Neural Circuits ◽  
Cell Activity ◽  
Temperature Sensitive ◽  
Magnetic Control ◽  
Deep Tissue ◽  
Minimal Invasiveness ◽  
Non Invasive ◽  
Freely Behaving

Precisely timed activation of genetically targeted cells is a powerful tool for studying neural circuits and controlling cell-based therapies. Magnetic control of cell activity or "magnetogenetics" using magnetic nanoparticle heating of temperature-sensitive ion channels enables remote, non-invasive activation of neurons for deep-tissue applications and studies of freely behaving animals. However, the in vivo response time of thermal magnetogenetics is currently tens of seconds, which prevents the precise temporal modulation of neural activity similar to light-based optogenetics. Moreover, magnetogenetics has not provided a means to selectively activate multiple channels to drive behavior. Here we demonstrate that by combining magnetic nanoparticles with a rate-sensitive thermoreceptor (TRPA1-A) it is possible to achieve sub-second behavioral responses in Drosophila melanogaster. Furthermore, by tuning the properties of magnetic nanoparticles to respond to different magnetic field strengths and frequencies, we can achieve fast, multi-channel stimulation, analogous to optogenetic stimulation with different wavelengths of light. These results bring magnetogenetics closer to the temporal resolution and multiplexed stimulation possible with optogenetics while maintaining the minimal invasiveness and deep-tissue stimulation only possible by magnetic control.

Clinical Trials in Thrombosis: Secondary Prevention of Myocardial Infarction

1976 ◽  
Vol 35 (01) ◽  
pp. 049-056 ◽  
Author(s):  
Christian R Klimt ◽  
P. H Doub ◽  
Nancy H Doub
Keyword(s):  
Myocardial Infarction ◽  
Secondary Prevention ◽  
Case Control ◽  
Therapeutic Effects ◽  
Case Control Studies ◽  
Definitive Answer ◽  
Inhibition Of Platelet Aggregation ◽  
Prospective Trials

SummaryNumerous in vivo and in vitro experiments, investigating the inhibition of platelet aggregation and the prevention of experimentally-induced thrombosis, suggest that anti-platelet drugs, such as aspirin or the combination of aspirin and dipyridamole or sulfinpyrazone, may be effective anti-thrombotic agents in man. Since 1971, seven randomized prospective trials and two case-control studies have been referenced in the literature or are currently being conducted, which evaluate the effects of aspirin, sulfinpyrazone, or dipyridamole in combination with aspirin in the secondary prevention of myocardial infarction. A critical review of these trials indicates a range of evidence from no difference to a favorable trend that antiplatelet drugs may serve as anti-thrombotic agents in man. To date, a definitive answer concerning the therapeutic effects of these drugs in the secondary prevention of coronary heart disease is not available.

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