An Ultra-Sensitive Step-Function Opsin for Minimally Invasive Optogenetic Stimulation in Mice and Macaques

Gong, Xiaolan; Mendoza-Halliday, Diego; Ting, Jonathan T.; Kaiser, Tobias; Sun, Xuyun; Bastos, André M.; Wimmer, Ralf; Guo, Baolin; Chen, Qian; Zhou, Yang; Pruner, Maxwell T.; Wu, Chin H.; Park, Demian; Deisseroth, Karl; Barak, Boaz; Boyden, Edward S.; Miller, Earl K.; Halassa, Michael M.; Fu, Zhanyan; Bi, Guoqiang; Desimone, Robert; Feng, Guoping

doi:10.1016/j.neuron.2020.03.032

Cited by 104 publications

(75 citation statements)

References 73 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Recently, an ultra-sensitive light-responsive molecule, SOUL, has been developed. Once engineered in the neurons inside the brain of mice and monkeys, the neurons can be turned on and off by illumination from outside of the head (Gong et al, 2020 ). Such non-invasive approaches hold promise for therapeutic optogenetics.…”

Section: Discussionmentioning

confidence: 99%

Bidirectional Dysregulation of AMPA Receptor-Mediated Synaptic Transmission and Plasticity in Brain Disorders

Zhang

Bramham

2020

Front. Synaptic Neurosci.

View full text Add to dashboard Cite

AMPA receptors (AMPARs) are glutamate-gated ion channels that mediate the majority of fast excitatory synaptic transmission throughout the brain. Changes in the properties and postsynaptic abundance of AMPARs are pivotal mechanisms in synaptic plasticity, such as long-term potentiation (LTP) and long-term depression (LTD) of synaptic transmission. A wide range of neurodegenerative, neurodevelopmental and neuropsychiatric disorders, despite their extremely diverse etiology, pathogenesis and symptoms, exhibit brain region-specific and AMPAR subunit-specific aberrations in synaptic transmission or plasticity. These include abnormally enhanced or reduced AMPAR-mediated synaptic transmission or plasticity. Bidirectional reversal of these changes by targeting AMPAR subunits or trafficking ameliorates drug-seeking behavior, chronic pain, epileptic seizures, or cognitive deficits. This indicates that bidirectional dysregulation of AMPAR-mediated synaptic transmission or plasticity may contribute to the expression of many brain disorders and therefore serve as a therapeutic target. Here, we provide a synopsis of bidirectional AMPAR dysregulation in animal models of brain disorders and review the preclinical evidence on the therapeutic targeting of AMPARs.

show abstract

Section: Discussionmentioning

confidence: 99%

Bidirectional Dysregulation of AMPA Receptor-Mediated Synaptic Transmission and Plasticity in Brain Disorders

Zhang

Bramham

2020

Front. Synaptic Neurosci.

View full text Add to dashboard Cite

show abstract

“…Due to the strong scattering and absorption of visible photons (400-750 nm) in the brain, skull, and scalp 9,30 , a chronic brain implant of an optical fiber 44 or a microLED 13 is usually required to deliver light to deep-brain regions, whereas transcranial red-light delivery can penetrate to a depth of 7 mm by mounting the optical fiber above the exposed skull of head-tethered animals 14,15,18,19 . In the latter example, optical fibers need to be fixed on the exposed skull after scalp removal, since only ~0.02% of the incident 635-nm light can penetrate to the 7 mm depth 18 , necessitating a high output power of ≥400 mW mm -2 from the fiber.…”

Section: Discussionmentioning

confidence: 99%

“…Furthermore, tethering the animal to an electrical wire or light source during behavioral studies leads to various deleterious consequences, especially for socially interacting animals ( Supplementary Table 1) 3,12 . To mitigate these challenges, several novel methods have been demonstrated, including wireless optogenetic interfaces 3,13 , red-shifted opsins [14][15][16][17][18] , ultrasensitive opsins [18][19][20] , optogenetic antennas based on upconversion nanoparticles 21 , and sono-optogenetics based on mechanoluminescent nanoparticles 22 . Despite these recent advances, none of the existing optogenetic interfaces are able to altogether eliminate both the head tethering/fixing and the brain implants for deep-brain neural modulation in freely moving animals 13,21 .…”

Section: Introductionmentioning

confidence: 99%

Through-scalp deep-brain stimulation in tether-free, naturally-behaving mice with widefield NIR-II illumination

Jiang

Rommelfanger

et al. 2020

Preprint

View full text Add to dashboard Cite

Neural modulation techniques with electricity, light and other forms of energy have enabled the deconstruction of neural circuitry. One major challenge of existing neural modulation techniques is the invasive brain implants and the permanent skull attachment of an optical fiber for modulating neural activity in the deep brain. Here we report an implant-free and tether-free optical neuromodulation technique in deep-brain regions through the intact scalp with brain-penetrant second near-infrared (NIR-II) illumination. Macromolecular infrared nanotransducers for deep-brain stimulation (MINDS) demonstrate exceptional photothermal conversion efficiency of 71% at 1064 nm, the wavelength that minimizes light attenuation by the brain in the entire 400-1700 nm spectrum. Upon widefield 1064-nm illumination >50 cm above the mouse head at a low incident power density of 10 mW/mm2, deep-brain neurons are activated by MINDS-sensitized TRPV1 channels with minimal thermal damage. Our approach could open opportunities for simultaneous neuromodulation of multiple socially interacting animals by remotely irradiating NIR-II light to stimulate each subject individually.

show abstract

“…The tetrodes in the DMCdrive design can be lowered up to 4 mm and the recording sites can, thus, be lowered beyond the range of light-induced activation of e.g., ChR2 expressing neurons 33 . Fortunately, novel opsins with increased light-sensitivity are regularly being developed, and recent additions can induce spiking activity > 3 mm from the optical fiber tip 34 , reducing both the need for, and benefits of, movable optical fibers.…”

Section: Discussionmentioning

confidence: 99%

The DMCdrive: practical 3D-printable micro-drive system for reliable chronic multi-tetrode recording and optogenetic application in freely behaving rodents

Kim

Brünner

Carlén

2020

Sci Rep

View full text Add to dashboard Cite

Electrophysiological recording and optogenetic control of neuronal activity in behaving animals have been integral to the elucidation of how neurons and circuits modulate network activity in the encoding and causation of behavior. However, most current electrophysiological methods require substantial economical investments and prior expertise. Further, the inclusion of optogenetics with electrophysiological recordings in freely moving animals adds complexity to the experimental design. Expansion of the technological repertoire across laboratories, research institutes, and countries, demands open access to high-quality devices that can be built with little prior expertise from easily accessible parts of low cost. We here present an affordable, truly easy-to-assemble micro-drive for electrophysiology in combination with optogenetics in freely moving rodents. The DMCdrive is particularly suited for reliable recordings of neurons and network activities over the course of weeks, and simplify optical tagging and manipulation of neurons in the recorded brain region. The highly functional and practical drive design has been optimized for accurate tetrode movement in brain tissue, and remarkably reduced build time. We provide a complete overview of the drive design, its assembly and use, and proof-of-principle demonstration of recordings paired with cell-type-specific optogenetic manipulations in the prefrontal cortex (PFC) of freely moving transgenic mice and rats. Tetrode-containing micro-drives have long been an important technique for recordings of extracellular neuronal signals in behaving mice 1 and rats 2. More recently developed techniques, such as neuronal population calcium imaging 3 and high-density silicon probes 4 are superior to micro-drive arrays in respect to the number of neurons that can be recorded simultaneously. Despite this, there is still a range of application areas where micro-drive arrays are the method of choice, particularly for chronic recordings of action potential and local field potential (LFP) activity in freely moving rodents, including in conjunction with optogenetics. We here present a lowcost, easy to assemble micro-drive for tetrode recordings in conjunction with optogenetics (the DMCdrive). The strategy for the design has been to construct a user-friendly low size-low weight drive that reliably provides a) single-unit recordings over time b) persistent precise and predictable movement of all tetrodes c) efficient opto-tagging and optical manipulation of neurons. The drive consists of a few lab-made parts, printed using a standard 3D printer, a custom-made electronic interface board (EIB), and parts available off-the-shelf, and the easy-to-assemble design makes the drive particularly suitable for researchers with no or little experience of drive building. The production cost of the 3D printed material is ~ 1$, and the total cost for one drive ~ 40$ (six 3D-printed parts, an EIB with an 18-pin Omnetics connector, eight screws and a screw nut).

show abstract

An Ultra-Sensitive Step-Function Opsin for Minimally Invasive Optogenetic Stimulation in Mice and Macaques

Cited by 104 publications

References 73 publications

Bidirectional Dysregulation of AMPA Receptor-Mediated Synaptic Transmission and Plasticity in Brain Disorders

Bidirectional Dysregulation of AMPA Receptor-Mediated Synaptic Transmission and Plasticity in Brain Disorders

Through-scalp deep-brain stimulation in tether-free, naturally-behaving mice with widefield NIR-II illumination

The DMCdrive: practical 3D-printable micro-drive system for reliable chronic multi-tetrode recording and optogenetic application in freely behaving rodents

Contact Info

Product

Resources

About