Optogenetics enables functional analysis of human embryonic stem cell–derived grafts in a Parkinson's disease model

Steinbeck, Julius A.; Choi, Se Joon; Mrejeru, Ana; Ganat, Yosif; Deisseroth, Karl; Sulzer, David; Mosharov, Eugene V.; Studer, Lorenz

doi:10.1038/nbt.3124

Cited by 264 publications

(237 citation statements)

References 48 publications

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“…In addition, they are capable of innervating distant target structures (Grealish et al, 2014) and modulating the glutamatergic input to striatal medium spiny neurons (Steinbeck et al, 2015). This has been made possible because of an improved understanding of mDA neuron development and a focus on studying human cells, overcoming species differences and allowing the preclinical development of stem cellbased cell replacement therapy for PD.…”

Section: Towards Cell Replacement Therapies For Pd With Pscsmentioning

confidence: 99%

How to make a midbrain dopaminergic neuron

2015

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Midbrain dopaminergic (mDA) neuron development has been an intense area of research during recent years. This is due in part to a growing interest in regenerative medicine and the hope that treatment for diseases affecting mDA neurons, such as Parkinson's disease (PD), might be facilitated by a better understanding of how these neurons are specified, differentiated and maintained in vivo. This knowledge might help to instruct efforts to generate mDA neurons in vitro, which holds promise not only for cell replacement therapy, but also for disease modeling and drug discovery. In this Primer, we will focus on recent developments in understanding the molecular mechanisms that regulate the development of mDA neurons in vivo, and how they have been used to generate human mDA neurons in vitro from pluripotent stem cells or from somatic cells via direct reprogramming. Current challenges and future avenues in the development of a regenerative medicine for PD will be identified and discussed.

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Section: Towards Cell Replacement Therapies For Pd With Pscsmentioning

confidence: 99%

How to make a midbrain dopaminergic neuron

2015

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“…Optogenetics thus allows for the noninvasive activation or inhibition of specific cells with light, a method that can be leveraged to combat a wide range of neurological conditions. Already, the potential of optogenetic techniques has been demonstrated in sciatic nerve injury [2], Parkinson's disease [3], epilepsy [4], depression [5,6], and retinal degeneration [7,8]. In this work, we describe a new method of using optogenetic techniques to study retinal circuit interactions between neurons and vascular cells, and show how this general approach can be potentially applied to treat neurological diseases.…”

Section: Introductionmentioning

confidence: 99%

Leveraging Optogenetic-Based Neurovascular Circuit Characterization for Repair

2016

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Optogenetic techniques are a powerful tool for determining the role of individual functional components within complex neural circuits. By genetically targeting specific cell types, neural mechanisms can be actively manipulated to gain a better understanding of their origin and function, both in health and disease. The potential of optogenetics is not limited to answering biological questions, as it is also a promising therapeutic approach for neurological diseases. An important prerequisite for this approach is to have an identified target with a uniquely defined role within a given neural circuit. Here, we examine the retinal neurovascular unit, a circuit that incorporates neurons and vascular cells to control blood flow in the retina. We highlight the role of a specific cell type, the cholinergic amacrine cell, in modulating vascular cells, and demonstrate how this can be targeted and controlled with optogenetics. A better understanding of these mechanisms will not only extend our understanding of neurovascular interactions in the brain, but ultimately may also provide new targets to treat vision loss in a variety of retinal diseases.

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“…To probe the mechanisms underlying the efficacy of this effect, Steinbeck et al optogenetically inhibited engrafted DA stem cells after motor recovery. They reported that inhibiting DA neurons resulted in the reappearance of motor deficits, indicating the essential role of DA neurons at the lesion site (Steinbeck et al, 2015).…”

Section: Parkinson's Diseasementioning

confidence: 99%

Optogenetics: Applications in neurobiology

Mikhailova

Deal

Budygin

et al. 2017

BioComm

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Commonly used neuromodulation techniques such as electrical stimulation or pharmacologic intervention have some technical limitations that preclude dissecting particular cell-or pathway-specific functions in the brain, which is composed of billions of neurons. An advancement of molecular genetics techniques has provided a novel method in neuroscience called optogenetics. Optogenetics uses a combination of genetic and optical methods that provide a means to, with great temporal precision, experimentally control the activation or suppression of specific neuronal sub-populations in heterogeneous brain regions where multiple neuronal subtypes exist; this approach can be performed even on freely moving animals. Thus, this tool can uniquely assist in establishing causality between the disorder and the underlying pathology. Ongoing exploration of pathological mechanisms in various animal models of neuropsychiatric disorders with precise tools such as optogenetics can provide significant advances in the development of more focused approaches to treatment of these disorders. Here, we selectively highlight the major advancements gained by the use of optogenetic tools to uncover at circuit levels mechanisms relevant to neuropsychiatric disorders.

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Optogenetics enables functional analysis of human embryonic stem cell–derived grafts in a Parkinson's disease model

Cited by 264 publications

References 48 publications

How to make a midbrain dopaminergic neuron

How to make a midbrain dopaminergic neuron

Leveraging Optogenetic-Based Neurovascular Circuit Characterization for Repair

Optogenetics: Applications in neurobiology

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