scholarly journals Advances in Engineering and Application of Optogenetic Indicators for Neuroscience

2019 ◽  
Vol 9 (3) ◽  
pp. 562 ◽  
Author(s):  
Kiryl D. Piatkevich ◽  
Mitchell H. Murdock ◽  
Fedor V. Subach
Keyword(s):  
Molecular Design ◽  
Optical Recording ◽  
Model Organisms ◽  
Biological Processes ◽  
Spatiotemporal Resolution ◽  
Systems Neuroscience ◽  
Physiological Processes ◽  
Neuroscience Research ◽  
The Brain

Our ability to investigate the brain is limited by available technologies that can record biological processes in vivo with suitable spatiotemporal resolution. Advances in optogenetics now enable optical recording and perturbation of central physiological processes within the intact brains of model organisms. By monitoring key signaling molecules noninvasively, we can better appreciate how information is processed and integrated within intact circuits. In this review, we describe recent efforts engineering genetically-encoded fluorescence indicators to monitor neuronal activity. We summarize recent advances of sensors for calcium, potassium, voltage, and select neurotransmitters, focusing on their molecular design, properties, and current limitations. We also highlight impressive applications of these sensors in neuroscience research. We adopt the view that advances in sensor engineering will yield enduring insights on systems neuroscience. Neuroscientists are eager to adopt suitable tools for imaging neural activity in vivo, making this a golden age for engineering optogenetic indicators.

scholarly journals Development of Optically-Controlled “Living Electrodes” with Long-Projecting Axon Tracts for a Synaptic Brain-Machine Interface

2018 ◽  
Author(s):  
Dayo O. Adewole ◽  
Laura A. Struzyna ◽  
James P. Harris ◽  
Ashley D. Nemes ◽  
Justin C. Burrell ◽  
...  
Keyword(s):  
Brain Activity ◽  
Optical Recording ◽  
Neural Interfaces ◽  
New Class ◽  
Brain Surface ◽  
Long Term Performance ◽  
Term Performance ◽  
The Brain

AbstractAchievements in intracortical neural interfaces are compromised by limitations in specificity and long-term performance. A biological intermediary between devices and the brain may offer improved specificity and longevity through natural synaptic integration with deep neural circuitry, while being accessible on the brain surface for optical read-out/control. Accordingly, we have developed the first “living electrodes” comprised of implantable axonal tracts protected within soft hydrogel cylinders for the biologically-mediated monitoring/modulation of brain activity. Here we demonstrate the controlled fabrication, rapid axonal outgrowth, reproducible cytoarchitecture, and simultaneous optical stimulation and recording of neuronal activity within these engineered constructs in vitro. We also present their transplantation, survival, integration, and optical recording in rat cortex in vivo as a proof-of-concept for this neural interface paradigm. The creation and functional validation of these preformed, axon-based “living electrodes” is a critical step towards developing a new class of biohybrid neural interfaces to probe and modulate native circuitry.

scholarly journals Sonogenetic stimulation of the brain at a spatiotemporal resolution suitable for vision restoration

2021 ◽  
Author(s):  
Sara Cadoni ◽  
Charlie Demene ◽  
Matthieu Provansal ◽  
Diep Nguyen ◽  
Dasha Nelidova ◽  
...  
Keyword(s):  
Visual Cortex ◽  
Neurological Disorders ◽  
Real Life ◽  
Spatiotemporal Resolution ◽  
Brain Machine Interfaces ◽  
Ultrasound Stimulation ◽  
Wide Range ◽  
The Brain ◽  
Stimulation Of

Remote, precisely controlled activation of the brain is a fundamental challenge in the development of brain machine interfaces providing feasible rehabilitation strategies for neurological disorders. Low-frequency ultrasound stimulation can be used to modulate neuronal activity deep in the brain, but this approach lacks spatial resolution and cellular selectivity and loads the brain with high levels of acoustic energy. The combination of the expression of ultrasound-sensitive proteins with ultrasound stimulation (sonogenetic stimulation) can provide cellular selectivity and higher sensitivity, but such strategies have been subject to severe limitations in terms of spatiotemporal resolution in vivo, precluding their use for real-life applications. We used the expression of large-conductance mechanosensitive ion channels (MscL) with high-frequency ultrasonic stimulation for a duration of milliseconds to activate neurons selectively at a relatively high spatiotemporal resolution in the rat retina ex vivo and the primary visual cortex of rodents in vivo. This spatiotemporal resolution was achieved at low energy levels associated with negligible tissue heating and far below those leading to complications in ultrasound neuromodulation. We showed, in an associative learning test, that sonogenetic stimulation of the visual cortex generated light perception. Our findings demonstrate that sonogenetic stimulation is compatible with millisecond pattern presentation for visual restoration at the cortical level. They represent a step towards the precise transfer of information over large distances to the cortical and subcortical regions of the brain via an approach less invasive than that associated with current brain machine interfaces and with a wide range of applications in neurological disorders.

Organoids, Assembloids, and Novel Biotechnology: Steps Forward in Developmental and Disease-Related Neuroscience

2020 ◽  
pp. 107385842096011
Author(s):  
Alexios A. Panoutsopoulos
Keyword(s):  
Pluripotent Stem Cells ◽  
State Of The Art ◽  
Model Organisms ◽  
Microfluidic Chips ◽  
3 Dimensional ◽  
Neuroscience Research ◽  
Primary Cell Lines ◽  
Approaches To Study ◽  
Induced Pluripotent

In neuroscience research, the efforts to find the model through which we can mimic the in vivo microenvironment of a developing or defective brain have been everlasting. While model organisms are used for over a hundred years, many more methods have been introduced with immortalized or primary cell lines and later induced pluripotent stem cells and organoids to be some of these. As the use of organoids becomes more and more common by many laboratories in biology and neuroscience in particular, it is crucial to deeper understand the challenges and possible pitfalls of their application in research, many of which can be surpassed with the support of state-of-the art bioengineering solutions. In this review, after a brief chronicle of the path to the discovery of organoids, we focus on the latest approaches to study neuroscience related topics with organoids, such as the use of assembloids, CRISPR technology, patch-clamp and optogenetics techniques and discuss how modern 3-dimensional biomaterials, miniaturized bioreactors and microfluidic chips can help to overcome the disadvantages of their use.

scholarly journals Exaggerated inflammation, impaired host defense, and neuropathology in progranulin-deficient mice

2009 ◽  
Vol 207 (1) ◽  
pp. 117-128 ◽  
Author(s):  
Fangfang Yin ◽  
Rebecca Banerjee ◽  
Bobby Thomas ◽  
Ping Zhou ◽  
Liping Qian ◽  
...  
Keyword(s):  
Host Defense ◽  
Hippocampal Slices ◽  
Interleukin 10 ◽  
Biological Processes ◽  
Listeria Monocytogenes Infection ◽  
The Brain ◽  
Deficient Mice

Progranulin (PGRN) is a widely expressed protein involved in diverse biological processes. Haploinsufficiency of PGRN in the human causes tau-negative, ubiquitin-positive frontotemporal dementia (FTD). However, the mechanisms are unknown. To explore the role of PGRN in vivo, we generated PGRN-deficient mice. Macrophages from these mice released less interleukin-10 and more inflammatory cytokines than wild type (WT) when exposed to bacterial lipopolysaccharide. PGRN-deficient mice failed to clear Listeria monocytogenes infection as quickly as WT and allowed bacteria to proliferate in the brain, with correspondingly greater inflammation than in WT. PGRN-deficient macrophages and microglia were cytotoxic to hippocampal cells in vitro, and PGRN-deficient hippocampal slices were hypersusceptible to deprivation of oxygen and glucose. With age, brains of PGRN-deficient mice displayed greater activation of microglia and astrocytes than WT, and their hippocampal and thalamic neurons accumulated cytosolic phosphorylated transactivation response element DNA binding protein–43. Thus, PGRN is a key regulator of inflammation and plays critical roles in both host defense and neuronal integrity. FTD associated with PGRN insufficiency may result from many years of reduced neutrotrophic support together with cumulative damage in association with dysregulated inflammation.

scholarly journals Development of optically controlled “living electrodes” with long-projecting axon tracts for a synaptic brain-machine interface

2021 ◽  
Vol 7 (4) ◽  
pp. eaay5347
Author(s):  
Dayo O. Adewole ◽  
Laura A. Struzyna ◽  
Justin C. Burrell ◽  
James P. Harris ◽  
Ashley D. Nemes ◽  
...  
Keyword(s):  
Cortical Neurons ◽  
Brain Activity ◽  
Optical Recording ◽  
New Class ◽  
Brain Surface ◽  
Machine Interface ◽  
The Brain

For implantable neural interfaces, functional/clinical outcomes are challenged by limitations in specificity and stability of inorganic microelectrodes. A biological intermediary between microelectrical devices and the brain may improve specificity and longevity through (i) natural synaptic integration with deep neural circuitry, (ii) accessibility on the brain surface, and (iii) optogenetic manipulation for targeted, light-based readout/control. Accordingly, we have developed implantable “living electrodes,” living cortical neurons, and axonal tracts protected within soft hydrogel cylinders, for optobiological monitoring/modulation of brain activity. Here, we demonstrate fabrication, rapid axonal outgrowth, reproducible cytoarchitecture, and simultaneous optical stimulation and recording of these tissue engineered constructs in vitro. We also present their transplantation, survival, integration, and optical recording in rat cortex as an in vivo proof of concept for this neural interface paradigm. The creation and characterization of these functional, optically controllable living electrodes are critical steps in developing a new class of optobiological tools for neural interfacing.

scholarly journals PARIS, an optogenetic method for functionally mapping gap junctions

2018 ◽  
Author(s):  
Ling Wu ◽  
Ao Dong ◽  
Liting Dong ◽  
Shi-Qiang Wang ◽  
Yulong Li
Keyword(s):  
Gap Junctions ◽  
Cell Communication ◽  
Cell Type Specificity ◽  
Spatiotemporal Resolution ◽  
Physiological Processes ◽  
Wide Range ◽  
Junctional Coupling ◽  
Chemical Coupling ◽  
And Function

ABSTRACTCell-cell communication via gap junctions regulates a wide range of physiological processes by enabling the direct intercellular electrical and chemical coupling. However, the in vivo distribution and function of gap junctions remain poorly understood, partly due to the lack of non-invasive tools with both cell-type specificity and high spatiotemporal resolution. Here we developed PARIS (pairing actuators and receivers to optically isolate gap junctions), a new fully genetically encoded tool for measuring the cell-specific gap junctional coupling (GJC). PARIS successfully enabled monitoring of GJC in several cultured cell lines under physiologically relevant conditions and in distinct genetically defined neurons in Drosophila brain, with ~10-sec temporal resolution and sub-cellular spatial resolution. These results demonstrate that PARIS is a robust, highly sensitive tool for mapping functional gap junctions and study their regulation in both health and disease.

scholarly journals Controlling gene expression with light: a multidisciplinary endeavour

2020 ◽  
Vol 48 (4) ◽  
pp. 1645-1659
Author(s):  
Denis Hartmann ◽  
Jefferson M. Smith ◽  
Giacomo Mazzotti ◽  
Razia Chowdhry ◽  
Michael J. Booth
Keyword(s):  
Gene Expression ◽  
Small Molecules ◽  
Cellular Damage ◽  
Biological Processes ◽  
Tissue Penetration ◽  
Spatiotemporal Resolution ◽  
Control Gene Expression ◽  
Diverse Field ◽  
Biological Methods

The expression of a gene to a protein is one of the most vital biological processes. The use of light to control biology offers unparalleled spatiotemporal resolution from an external, orthogonal signal. A variety of methods have been developed that use light to control the steps of transcription and translation of specific genes into proteins, for cell-free to in vivo biotechnology applications. These methods employ techniques ranging from the modification of small molecules, nucleic acids and proteins with photocages, to the engineering of proteins involved in gene expression using naturally light-sensitive proteins. Although the majority of currently available technologies employ ultraviolet light, there has been a recent increase in the use of functionalities that work at longer wavelengths of light, to minimise cellular damage and increase tissue penetration. Here, we discuss the different chemical and biological methods employed to control gene expression, while also highlighting the central themes and the most exciting applications within this diverse field.

scholarly journals Targeted Deletion of the Mitogen-Activated Protein Kinase Kinase 4 Gene in the Nervous System Causes Severe Brain Developmental Defects and Premature Death

2007 ◽  
Vol 27 (22) ◽  
pp. 7935-7946 ◽  
Author(s):  
Xin Wang ◽  
Bagirathy Nadarajah ◽  
Andrew C. Robinson ◽  
Barry W. McColl ◽  
Jia-Wei Jin ◽  
...  
Keyword(s):  
Protein Kinase ◽  
Physiological Role ◽  
Premature Death ◽  
Mitogen Activated Protein Kinase ◽  
Developmental Defects ◽  
Physiological Processes ◽  
Mitogen Activated Protein ◽  
Altered Gene ◽  
The Brain

ABSTRACT The c-Jun NH2-terminal protein kinase (JNK) is a mitogen-activated protein kinase (MAPK) involved in the regulation of various physiological processes. Its activity is increased upon phosphorylation by the MAPK kinases MKK4 and MKK7. The early embryonic death of mice lacking an mkk4 or mkk7 gene has provided genetic evidence that MKK4 and MKK7 have nonredundant functions in vivo. To elucidate the physiological role of MKK4, we generated a novel mouse model in which the mkk4 gene could be specifically deleted in the brain. At birth, the mutant mice were indistinguishable from their control littermates, but they stopped growing a few days later and died prematurely, displaying severe neurological defects. Decreased JNK activity in the absence of MKK4 correlated with impaired phosphorylation of a subset of physiologically relevant JNK substrates and with altered gene expression. These defects resulted in the misalignment of the Purkinje cells in the cerebellum and delayed radial migration in the cerebral cortex. Together, our data demonstrate for the first time that MKK4 is an essential activator of JNK required for the normal development of the brain.

Nature, Nurture, and Their Interplay

2016 ◽  
Vol 48 (1) ◽  
pp. 4-22 ◽  
Author(s):  
Joni Y. Sasaki ◽  
Heejung S. Kim
Keyword(s):  
Neural Activation ◽  
Biological Processes ◽  
Psychological Processes ◽  
Cultural Neuroscience ◽  
Biological Factors ◽  
Methodological Issues ◽  
Physiological Processes ◽  
Neuroscience Research ◽  
The Social ◽  
Different Cultures

Cultural neuroscience research examines how psychological processes are affected by the interplay between culture and biological factors, including genetic influences, patterns of neural activation, and physiological processes. In this review, we present foundational and current empirical research in this area, and we also discuss theories that aim to explain how various aspects of the social environment are interpreted as meaningful in different cultures and interact with a cascade of biological processes to ultimately influence thoughts and behaviors. This review highlights theoretical and methodological issues, potential solutions, and future implications for a field that aspires to integrate the complexities of human biology with the richness of culture.

scholarly journals The Role of Metal Regulatory Proteins in Brain Oxidative Stress: A Tutorial

2012 ◽  
Vol 2012 ◽  
pp. 1-9 ◽  
Author(s):  
Wayne Briner
Keyword(s):  
Oxidative Stress ◽  
Redox Activity ◽  
Biological Processes ◽  
Physiological Processes ◽  
Pharmacological Targets ◽  
Wide Range ◽  
Brain Oxidative Stress ◽  
The Brain ◽  
And Oxidative Stress

The proteins that regulate the metabolism of a metal must also play a role in regulating the redox activity of the metal. Metals are intrinsic to a substantial number of biological processes and the proteins that regulate those activities are also considerable in number. The role these proteins play in a wide range of physiological processes involves them directly and indirectly in a variety of disease processes. Similarly, it may be therapeutically advantageous to pharmacologically alter the activity of these metal containing proteins to influence disease processes. This paper will introduce the reader to a number of important proteins in both metal metabolism and oxidative stress, with an emphasis on the brain. Potential pharmacological targets will be considered.

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