Two-photon optogenetics of dendritic spines and neural circuits

Packer, Adam M.; Peterka, Darcy S.; Hirtz, Jan J.; Prakash, Rohit; Deisseroth, Karl; Yuste, Rafael

doi:10.1038/nmeth.2249

Cited by 266 publications

(274 citation statements)

References 22 publications

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“…Because shift-averaging removes speckle deterministically 28 , and the display's projection rate is 2,000 frames per second, effective patch de-speckling requires only a few milliseconds (2-12 ms in these experiments), allowing for very high effective temporal resolution, which would practically probably be limited by other factors (for example, video processing, hologram computation and optogenetic probe response times). Holographic speckle has emerged as an important issue in the implementation of diffractive photostimulation systems 31 , and it is important to note several alternative designs for circumventing this issue including the use of Generalized Phase Contrast 26 , hybrid holographicmechanical projection systems (that is, rotating diffusers 32 or mechanically vibrated smearing of point patterns 33 ). Other possibilities for speckle reduction are the use of temporally and/ or spatially incoherent light sources.…”

Section: Resultsmentioning

confidence: 99%

Holographic optogenetic stimulation of patterned neuronal activity for vision restoration

et al. 2013

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When natural photoreception is disrupted, as in outer-retinal degenerative diseases, artificial stimulation of surviving nerve cells offers a potential strategy for bypassing compromised neural circuits. Recently, light-sensitive proteins that photosensitize quiescent neurons have generated unprecedented opportunities for optogenetic neuronal control, inspiring early development of optical retinal prostheses. Selectively exciting large neural populations are essential for eliciting meaningful perceptions in the brain. Here we provide the first demonstration of holographic photo-stimulation strategies for bionic vision restoration. In blind retinas, we demonstrate reliable holographically patterned optogenetic stimulation of retinal ganglion cells with millisecond temporal precision and cellular resolution. Holographic excitation strategies could enable flexible control over distributed neuronal circuits, potentially paving the way towards high-acuity vision restoration devices and additional medical and scientific neuro-photonics applications.

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Section: Resultsmentioning

confidence: 99%

Holographic optogenetic stimulation of patterned neuronal activity for vision restoration

et al. 2013

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“…By contrast, mammalian cells contain ATR (Fenno et al, 2011), preventing application of a similar control. Future studies could use direct focal illumination of neuronal subcompartments (Packer et al, 2012) to assay effects of even more targeted depolarization or hyperpolarization on neural circuit morphogenesis. In addition, it will be particularly interesting to use optogenetics to test the altered E/I synaptic balance hypothesis in the FXS disease state (Gatto and Broadie, 2011;Gatto et al, 2014), including both hyperexcitation and hypoinhibition (Selby et al, 2007;Gibson et al, 2008), by hyperpolarizing MB circuit excitatory neurons or depolarizing MB circuit inhibitory neurons to assay restoration of circuit architecture and learning and memory behavioral outputs.…”

Section: Discussionmentioning

confidence: 99%

Activity-dependent FMRP requirements in development of the neural circuitry of learning and memory

2015

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The activity-dependent refinement of neural circuit connectivity during critical periods of brain development is essential for optimized behavioral performance. We hypothesize that this mechanism is defective in fragile X syndrome (FXS), the leading heritable cause of intellectual disability and autism spectrum disorders. Here, we use optogenetic tools in the Drosophila FXS disease model to test activitydependent dendritogenesis in two extrinsic neurons of the mushroom body (MB) learning and memory brain center: (1) the input projection neuron (PN) innervating Kenyon cells (KCs) in the MB calyx microglomeruli and (2) the output MVP2 neuron innervated by KCs in the MB peduncle. Both input and output neuron classes exhibit distinctive activity-dependent critical period dendritic remodeling. MVP2 arbors expand in Drosophila mutants null for fragile X mental retardation 1 (dfmr1), as well as following channelrhodopsin-driven depolarization during critical period development, but are reduced by halorhodopsin-driven hyperpolarization. Optogenetic manipulation of PNs causes the opposite outcome -reduced dendritic arbors following channelrhodopsin depolarization and expanded arbors following halorhodopsin hyperpolarization during development. Importantly, activity-dependent dendritogenesis in both neuron classes absolutely requires dfmr1 during one developmental window. These results show that dfmr1 acts in a neuron type-specific activity-dependent manner for sculpting dendritic arbors during early-use, critical period development of learning and memory circuitry in the Drosophila brain.

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“…In addition, optogenetic manipulations that are even more precise, from opsins that target specific cell compartments to light delivery systems that drive more naturalistic patterns of activity, may both reduce unintended network side effects and reveal how more specific or complex patterns of activity alter the network. For instance, two-photon holographic excitation of opsin-expressing neurons may support manipulation of activity with near-single cell resolution (Andrasfalvy et al 2010;Papagiakoumou et al 2010;Packer et al 2012Packer et al , 2015. In sum, while optogenetic tools allow for the temporally and spatially precise recruitment of well-defined sets of cells, these tools may lead to potential confounds due to protein expression, ions conducted, heat and light, and network effects.…”

Section: Network-level Side Effectsmentioning

confidence: 99%

Principles of designing interpretable optogenetic behavior experiments

2015

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Over the last decade, there has been much excitement about the use of optogenetic tools to test whether specific cells, regions, and projection pathways are necessary or sufficient for initiating, sustaining, or altering behavior. However, the use of such tools can result in side effects that can complicate experimental design or interpretation. The presence of optogenetic proteins in cells, the effects of heat and light, and the activity of specific ions conducted by optogenetic proteins can result in cellular side effects. At the network level, activation or silencing of defined neural populations can alter the physiology of local or distant circuits, sometimes in undesired ways. We discuss how, in order to design interpretable behavioral experiments using optogenetics, one can understand, and control for, these potential confounds.

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Two-photon optogenetics of dendritic spines and neural circuits

Cited by 266 publications

References 22 publications

Holographic optogenetic stimulation of patterned neuronal activity for vision restoration

Holographic optogenetic stimulation of patterned neuronal activity for vision restoration

Activity-dependent FMRP requirements in development of the neural circuitry of learning and memory

Principles of designing interpretable optogenetic behavior experiments

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