The Age of Enlightenment: Evolving Opportunities in Brain Research Through Optical Manipulation of Neuronal Activity

Jerome, Jason; Heck, Detlef

doi:10.3389/fnsys.2011.00095

Cited by 6 publications

(9 citation statements)

References 132 publications

(149 reference statements)

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“…Two-photon (2P) microscopy is now widely used in neuroscience [1]. Its applications include structural and functional imaging [2–4], and neuronal stimulation by photolysis of caged chemical compounds and activation of light-gated ion channels [5, 6]. For example, the non-linear 2P excitation process allows highly localized photolysis of caged neurotransmitters, thereby enabling targeted activation of single spines and effectively mimicking synaptic inputs onto a neuron.…”

Section: Introductionmentioning

confidence: 99%

A compact holographic projector module for high-resolution 3D multi-site two-photon photostimulation

Mueller

Castañares

et al. 2019

PLoS ONE

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Patterned two-photon (2P) photolysis via holographic illumination is a powerful method to investigate neuronal function because of its capability to emulate multiple synaptic inputs in three dimensions (3D) simultaneously. However, like any optical system, holographic projectors have a finite space-bandwidth product that restricts the spatial range of patterned illumination or field-of-view (FOV) for a desired resolution. Such trade-off between holographic FOV and resolution restricts the coverage within a limited domain of the neuron’s dendritic tree to perform highly resolved patterned 2P photolysis on individual spines. Here, we integrate a holographic projector into a commercial 2P galvanometer-based 2D scanning microscope with an uncaging unit and extend the accessible holographic FOV by using the galvanometer scanning mirrors to reposition the holographic FOV arbitrarily across the imaging FOV. The projector system utilizes the microscope’s built-in imaging functions. Stimulation positions can be selected from within an acquired 3D image stack (the volume-of-interest, VOI) and the holographic projector then generates 3D illumination patterns with multiple uncaging foci. The imaging FOV of our system is 800×800 μm2 within which a holographic VOI of 70×70×70 μm3 can be chosen at arbitrary positions and also moved during experiments without moving the sample. We describe the design and alignment protocol as well as the custom software plugin that controls the 3D positioning of stimulation sites. We demonstrate the neurobiological application of the system by simultaneously uncaging glutamate at multiple spines within dendritic domains and consequently observing summation of postsynaptic potentials at the soma, eventually resulting in action potentials. At the same time, it is possible to perform two-photon Ca2+ imaging in 2D in the dendrite and thus to monitor synaptic Ca2+ entry in selected spines and also local regenerative events such as dendritic action potentials.

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Section: Introductionmentioning

confidence: 99%

A compact holographic projector module for high-resolution 3D multi-site two-photon photostimulation

Mueller

Castañares

et al. 2019

PLoS ONE

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“…Furthermore, difficulties in manipulating the functions of the neurons because of the elaboration and size of their interconnections lead to the demand for more spatiotemporally accurate physiological research tools, because the neurons respond to an external exciter within a few milliseconds. [31]…”

Section: Introductionmentioning

confidence: 99%

Optogenetics, Tools and Applications in Neurobiology

2017

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Comprehension of the brain function can be helpful for therapy of neurodegenerative diseases. The brain consists of various types of neuron sets, which organize in three-dimensional complex networks and form neural circuits underlying different behaviors. The circuits act based on the patterns that encode the brain functions. Recognition of the neural patterns requires methods to manipulate the neurons. Electrical stimulation may be the most common method. However, it has significant drawbacks including failure to identify specific neurons in experiments. As an alternative, optical stimulation is a new method that acts in combination with genetic approaches. The novel, optogenetic technology makes it feasible to manipulate either the specific cell types or the neural circuits. This is associated with minimum tissue damages as well as side effects. In this study, a new technology has been introduced, and then its optical and genetical tools have been investigated.

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“…Light is an excellent source of excitation as the strength, shape, wavelength and duration of the light beam can be tightly controlled by the experimenter (Callaway & Yuste, ; Jerome & Heck, ). Moreover, for circuit mapping applications a focused light beam can be rapidly shifted between different sites in the tissue.…”

Section: Introductionmentioning

confidence: 99%

“…If performed correctly, experimental resolutions in the order of ∼50 μm are readily achievable (Shepherd et al . ; Jerome & Heck, ; Anastasiades & Butt, ), activating somewhere in the region of 30–60 presynaptic neurons with each light pulse (Shepherd et al . ).…”

Section: Introductionmentioning

confidence: 99%

“…2‐P uncaging utilises a mode‐locked laser light source which drastically increases the probability of coincident multi‐photon excitation at the focal point of the objective (Denk et al . ; Denk & Svoboda, ; Jerome & Heck, ). This provides much greater axial resolution compared to single‐photon techniques, allowing stimulation of single neurons in a defined plane (Furuta et al .…”

Section: Introductionmentioning

confidence: 99%

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Studies of cortical connectivity using optical circuit mapping methods

Anastasiades

Marques-Smith

Butt

2017

The Journal of Physiology

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An important consideration when probing the function of any neuron is to uncover the source of synaptic input onto the cell, its intrinsic physiology and efferent targets. Over the years, electrophysiological approaches have generated considerable insight into these properties in a variety of cortical neuronal subtypes and circuits. However, as researchers explore neuronal function in greater detail, they are increasingly turning to optical techniques to bridge the gap between local network interactions and behaviour. The application of optical methods has increased dramatically over the past decade, spurred on by the optogenetic revolution. In this review, we provide an account of recent innovations, providing researchers with a primer detailing circuit mapping strategies in the cerebral cortex. We will focus on technical aspects of performing neurotransmitter uncaging and channelrhodopsin-assisted circuit mapping, with the aim of identifying common pitfalls that can negatively influence the collection of reliable data.

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The Age of Enlightenment: Evolving Opportunities in Brain Research Through Optical Manipulation of Neuronal Activity

Cited by 6 publications

References 132 publications

A compact holographic projector module for high-resolution 3D multi-site two-photon photostimulation

A compact holographic projector module for high-resolution 3D multi-site two-photon photostimulation

Optogenetics, Tools and Applications in Neurobiology

Studies of cortical connectivity using optical circuit mapping methods

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