Optogenetics and the Circuit Dynamics of Psychiatric Disease

Deisseroth, Karl; Etkin, Amit; Malenka, Robert C.

doi:10.1001/jama.2015.2544

Cited by 39 publications

(11 citation statements)

References 9 publications

(8 reference statements)

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“…4a). Using a combination of recently developed technologies such as optogenetics, chemogenetics, trans-synaptic tracers and single-cell sequencing in both animal models and human cells [76][77][78][79] , we now have the ability to determine the effect of genetic variants on specific cells and networks with unprecedented detail.…”

Section: Identifying the Circuitsmentioning

confidence: 99%

A framework for the investigation of rare genetic disorders in neuropsychiatry

Sanders

Şahin

Hostyk

et al. 2019

Nat Med

101

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Section: Identifying the Circuitsmentioning

confidence: 99%

A framework for the investigation of rare genetic disorders in neuropsychiatry

Sanders

Şahin

Hostyk

et al. 2019

Nat Med

101

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“…The recent development and implementation of powerful new experimental techniques including DREADDs 4 , CLARITY 5 , optogenetics 6,7 , and many others has finally opened the door to circuit-level investigations of psychiatric disease in the animal model. These methods, respectively, enable the researcher to chemically modify neuronal activity, visualize long-range projections in intact brains, and control neuronal activity with light.…”

Section: Limitations Of Animal Modelsmentioning

confidence: 99%

Animal Models in Psychiatric Disease: A Circuit-Search Approach

Theyel

2018

Harv Rev Psychiatry

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Our collective desire to understand how the “normal” vs. “diseased” brain works drives our ongoing need for nonhuman animal research. Our current understanding of circuits within the brain, and the techniques required to investigate neural activity, stem from animal work. These techniques often require invasive methods, which necessitate animal models. Unfortunately, this means that our investigative approaches are subject to the same limitations that animal models had before these new techniques were developed. In this article I briefly overview these limitations, then outline a relatively new strategy that enables us to establish a causal relationship between a specific neurocircuit abnormality and disease. This approach utilizes novel techniques designed to selectively target mutations to specific brain circuits in the mouse. Such a strategy allows the researcher to “home in” on how a gene affects a single brain circuit. This is powerful because it avoids an often-cited problem that plagues traditional animal models: non-targeted mutations disrupt a myriad of circuits. Rather than mutating all brain cells, targeting a gene known to be highly penetrant for human disease to an individual, relatively conserved, circuit element helps us determine whether that circuit is involved in generating an abnormal behavioral phenotype. This will provide invaluable clues about where and how psychiatric disease originates in humans. Finally, I briefly discuss how computational neuroscience-based techniques and noninvasive, low-risk neuromodulation techniques could be employed to test hypotheses generated by these animal models in humans, leading to both greater understanding of neurocircuits underlying psychiatric disease and possibly new treatments.

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“…In particular, it is important to identify circuits underlying the different domains of AUD and how they are altered during the development of AUD (Luthi and Luscher, 2014). Methods include high angular resolution diffusion imaging (HARDI) with magnetic resonance, resting state functional magnetic resonance imaging (R-fMRI), electrophysiological or magnetoencephalographical recording combined with fMRI (E/M-fMRI), optogenetics, and CLARITY, a method that makes brain tissue more transparent, enabling us to observe real-time activity of specific neurons and their projections (Acheson et al, 2014; Chung and Deisseroth, 2013; Deisseroth et al, 2015; Zhu et al, 2015;). Each technique provides different information about the brain’s connectivity, so combining techniques offers significant additional information concerning the structure and function of individual circuits.…”

Section: Phases Of Medications Developmentmentioning

confidence: 99%

Discovery, Development, and Adoption of Medications to Treat Alcohol Use Disorder: Goals for the Phases of Medications Development

Litten

Falk

Ryan

et al. 2016

Alcohol Clin Exp Res

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For more than 25 years, advances have been made in developing medications to treat alcohol use disorder (AUD), highlighted by the U.S. Food and Drug Administration’s (FDA’s) approval of naltrexone (oral and long-acting) and acamprosate. Despite this progress, more work remains to be done in this area because these medications, though effective for some people, do not work for everyone. A high priority for the National Institute on Alcohol Abuse and Alcohol (NIAAA) is to put into place a solid infrastructure to aid in the development of medications that are more effective than those currently available, and with few side effects. Medication development, especially for a disorder as complex as AUD, is challenging and involves multiple phases, including discovery of “druggable” targets, preclinical studies, human clinical trials, and the adoption and implementation of the new medication into mainstream medicine. A successful medications development program requires clearly established goals for each phase to ensure that a candidate compound is not trapped in one particular phase, a condition known as “the valley of death.” In this article, the phases of medication development are described as they apply to AUD, and specific goals of each phase are identified for the next decade. In addition, several important crosscutting themes are outlined for each phase, all of which are essential for advancing medications development. These include identifying and validating screening models and druggable targets, making use of precision medicine, and establishing partnerships among key stakeholders. Our goal in writing this article is to provide a guide on medications development that will aid the alcohol research community in planning, testing, and developing medications for AUD.

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Optogenetics and the Circuit Dynamics of Psychiatric Disease

Cited by 39 publications

References 9 publications

A framework for the investigation of rare genetic disorders in neuropsychiatry

A framework for the investigation of rare genetic disorders in neuropsychiatry

Animal Models in Psychiatric Disease: A Circuit-Search Approach

Discovery, Development, and Adoption of Medications to Treat Alcohol Use Disorder: Goals for the Phases of Medications Development

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