Modal demultiplexing properties of tapered and nanostructured optical fibers for in vivo optogenetic control of neural activity

AbstractA major open challenge in neuroscience is the ability to measure and perturb neural activity in vivo from well-defined neural sub-populations at cellular resolution anywhere in the brain. However, limitations posed by scattering and absorption prohibit non-invasive (surface) multiphoton approaches1,2 for deep (>2mm) structures, while Gradient Refreactive Index (GRIN) endoscopes2–4 are thick and cause significant damage upon insertion. Here, we demonstrate a novel microendoscope to image neural activity at arbitrary depths via an ultrathin multimode optical fiber (MMF) probe that is 5-10X thinner than commercially available microendoscopes. We demonstrate micron-scale resolution, multispectral and volumetric imaging. In contrast to previous approaches1,5–8 we show that this method has an improved acquisition speed that is sufficient to capture rapid neuronal dynamics in-vivo in rodents expressing a genetically encoded calcium indicator. Our results emphasize the potential of this technology in neuroscience applications and open up possibilities for cellular resolution imaging in previously unreachable brain regions.

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Flexible and stretchable polymer optical fibers for chronic brain and vagus nerve optogenetic stimulations in free-behaving animals

BMC Biology ◽

10.1186/s12915-021-01187-x ◽

2021 ◽

Vol 19 (1) ◽

Author(s):

Yi Cao ◽

Suwan Pan ◽

Mengying Yan ◽

Chongyang Sun ◽

Jianyu Huang ◽

...

Keyword(s):

Vagus Nerve ◽

Optical Fibers ◽

Primary Motor Cortex ◽

Inhibitory Influence ◽

Therapeutic Effects ◽

Nervous Systems ◽

Optogenetic Stimulation ◽

Neuropsychiatric Diseases ◽

Polymer Optical Fibers

Abstract Background Although electrical stimulation of the peripheral and central nervous systems has attracted much attention owing to its potential therapeutic effects on neuropsychiatric diseases, its non-cell-type-specific activation characteristics may hinder its wide clinical application. Unlike electrical methodologies, optogenetics has more recently been applied as a cell-specific approach for precise modulation of neural functions in vivo, for instance on the vagus nerve. The commonly used implantable optical waveguides are silica optical fibers, which for brain optogenetic stimulation (BOS) are usually fixed on the skull bone. However, due to the huge mismatch of mechanical properties between the stiff optical implants and deformable vagal tissues, vagus nerve optogenetic stimulation (VNOS) in free-behaving animals continues to be a great challenge. Results To resolve this issue, we developed a simplified method for the fabrication of flexible and stretchable polymer optical fibers (POFs), which show significantly improved characteristics for in vivo optogenetic applications, specifically a low Young’s modulus, high stretchability, improved biocompatibility, and long-term stability. We implanted the POFs into the primary motor cortex of C57 mice after the expression of CaMKIIα-ChR2-mCherry detected frequency-dependent neuronal activity and the behavioral changes during light delivery. The viability of POFs as implantable waveguides for VNOS was verified by the increased firing rate of the fast-spiking GABAergic interneurons recorded in the left vagus nerve of VGAT-ChR2 transgenic mice. Furthermore, VNOS was carried out in free-moving rodents via chronically implanted POFs, and an inhibitory influence on the cardiac system and an anxiolytic effect on behaviors was shown. Conclusion Our results demonstrate the feasibility and advantages of the use of POFs in chronic optogenetic modulations in both of the central and peripheral nervous systems, providing new information for the development of novel therapeutic strategies for the treatment of neuropsychiatric disorders.

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Ex Vivo Brain Preparation to Analyze Vocal Pathways of Xenopus Frogs

Cold Spring Harbor Protocols ◽

10.1101/pdb.prot106872 ◽

2021 ◽

Vol 2021 (9) ◽

pp. pdb.prot106872

Author(s):

Ayako Yamaguchi

Keyword(s):

Neural Activity ◽

Ex Vivo ◽

Neural Circuitry ◽

Neural Basis ◽

Vocal Production ◽

Basic Principles ◽

Electrophysiological Recordings ◽

The Brain

Understanding the neural basis of behavior is a challenging task for technical reasons. Most methods of recording neural activity require animals to be immobilized, but neural activity associated with most behavior cannot be recorded from an anesthetized, immobilized animal. Using amphibians, however, there has been some success in developing in vitro brain preparations that can be used for electrophysiological and anatomical studies. Here, we describe an ex vivo frog brain preparation from which fictive vocalizations (the neural activity that would have produced vocalizations had the brain been attached to the muscle) can be elicited repeatedly. When serotonin is applied to the isolated brains of male and female African clawed frogs, Xenopus laevis, laryngeal nerve activity that is a facsimile of those that underlie sex-specific vocalizations in vivo can be readily recorded. Recently, this preparation was successfully used in other species within the genus including Xenopus tropicalis and Xenopus victorianus. This preparation allows a variety of techniques to be applied including extracellular and intracellular electrophysiological recordings and calcium imaging during vocal production, surgical and pharmacological manipulation of neurons to evaluate their impact on motor output, and tract tracing of the neural circuitry. Thus, the preparation is a powerful tool with which to understand the basic principles that govern the production of coherent and robust motor programs in vertebrates.

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Artifact‐Free 2D Mapping of Neural Activity In Vivo through Transparent Gold Nanonetwork Array

Advanced Functional Materials ◽

10.1002/adfm.202000896 ◽

2020 ◽

Vol 30 (34) ◽

pp. 2000896

Author(s):

Ji‐Won Seo ◽

Kiup Kim ◽

Ki‐Won Seo ◽

Mi Kyung Kim ◽

Sohyeon Jeong ◽

...

Keyword(s):

Neural Activity

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Forebrain NgR1 Overexpression Impairs DA Release Suggesting Synergy of Local and Global Synaptic Plasticity Mechanisms

Frontiers in Synaptic Neuroscience ◽

10.3389/fnsyn.2020.545854 ◽

2020 ◽

Vol 12 ◽

Author(s):

Emma Arvidsson ◽

Sarolta Gabulya ◽

Alvin Tore Brodin ◽

Tobias Erik Karlsson ◽

Lars Olson

Keyword(s):

Synaptic Plasticity ◽

Potassium Chloride ◽

Neural Activity ◽

Dorsal Striatum ◽

Inverse Correlation ◽

Long Term Memory ◽

The Status ◽

Global Systems ◽

Da Release

Structural synaptic reorganizations needed to permanently embed novel memories in the brain involve complex plasticity-enhancing and plasticity-inhibiting systems. Increased neural activity is linked to rapid downregulation of Nogo receptor 1 (NgR1), needed to allow local structural synaptic plasticity. This local regulation of plasticity is thought to be moderated by global systems, such as the ascending cholinergic and monoaminergic systems, adding significance to locally increased neural activity. Here we address the reverse possibility that the global systems may also be influenced by the status of local plasticity. Using NgR1-overexpressing mice, with impaired plasticity and long-term memory, we measured the ability to release dopamine (DA), implicated in regulating plasticity and memory. In vivo chronoamperometric recording with high temporal and spatial resolution revealed severe impairment of potassium chloride (KCl)-induced increase of extracellular DA in the dorsal striatum of mice overexpressing NgR1 in forebrain neurons. A similar, but lesser, impairment of DA release was seen following amphetamine delivery. In contrast, potassium chloride-evoked DA release in NgR1 knockout (KO) mice led to increased levels of extracellular DA. That NgR1 can impair DA signaling, thereby further dampening synaptic plasticity, suggests a new role for NgR1 signaling, acting in synergy with DA signaling to control synaptic plasticity.Significance Statement:The inverse correlation between local NgR1 levels and magnitude of KCl-inducible amounts of DA release in the striatum reinforces the rule of NgR1 as a regulator of structural synaptic plasticity and suggests synergy between local and global plasticity regulating systems.

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A high-speed, bright, red fluorescent voltage sensor to detect neural activity

Scientific Reports ◽

10.1038/s41598-019-52370-8 ◽

2019 ◽

Vol 9 (1) ◽

Cited By ~ 5

Author(s):

Connor Beck ◽

Yiyang Gong

Keyword(s):

Blue Light ◽

Neural Activity ◽

High Speed ◽

Fluorescent Protein ◽

Resonance Energy ◽

Fluorescent Sensors ◽

Fast Kinetics ◽

Spectral Separation ◽

Green Fluorescent

Abstract Genetically encoded voltage indicators (GEVIs) have emerged as a technology to optically record neural activity with genetic specificity and millisecond-scale temporal resolution using fluorescence microscopy. GEVIs have demonstrated ultra-fast kinetics and high spike detection fidelity in vivo, but existing red-fluorescent voltage indicators fall short of the response and brightness achieved by green fluorescent protein-based sensors. Furthermore, red-fluorescent GEVIs suffer from incomplete spectral separation from green sensors and blue-light-activated optogenetic actuators. We have developed Ace-mScarlet, a red fluorescent GEVI that fuses Ace2N, a voltage-sensitive inhibitory rhodopsin, with mScarlet, a bright red fluorescent protein (FP). Through fluorescence resonance energy transfer (FRET), our sensor detects changes in membrane voltage with high sensitivity and brightness and has kinetics comparable to the fastest green fluorescent sensors. Ace-mScarlet’s red-shifted absorption and emission spectra facilitate virtually complete spectral separation when used in combination with green-fluorescent sensors or with blue-light-sensitive sensors and rhodopsins. This spectral separation enables both simultaneous imaging in two separate wavelength channels and high-fidelity voltage recordings during simultaneous optogenetic perturbation.

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