Combination of Neural Loop Tracing and Tissue Transparency Technology Enables Neuroscience Research

The human brain contains approximately one hundred billion neurons, which are interconnected by approximately one hundred trillion synaptic connections, forming an almost infinite number of neural loops. These loops are the structural foundation that supports a variety of basic and advanced brain functions. A deeper understanding of neural loops is essential for understanding the principles of brain function and the pathogenesis of neurological diseases.

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Neural Circuit Tracing Tools

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Virus Vector Tools for Neural Cell Manipulation

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Neurons receive information from upstream neurons via dendritic ridges (postsynaptic structures) and send signals to downstream neurons via axon terminals (presynaptic structures). The number of direct upstream and downstream partners per neuron varies widely, from a few hundred to 100,000, and neuronal information can be transmitted through confluent or differentiated neural pathways with monosynaptic or polysynaptic connections.

Neural tracer techniques can map how these neurons are connected to each other. Typically, a paracrine tracer will travel from the cell body to the downstream region of the projection via paraxoplasmic transport, whereas a retrograde tracer can move from the axon terminal to the cell body via retrograde axoplasmic transport. Taking advantage of the natural properties of viral propagation, more and more viruses are being adapted for tracing neural circuits, thus greatly facilitating the study of neural circuits and specific neural projection networks in the brain.

Fig. 1 Schematic illustrations of transneuronal or trans-synaptic viral tracing.¹

We present an article that describes specific viral vectors for neuroscience research and details advances in the application of viral vectors for axonal tracing and trans-synaptic tracing. As a partner, Creative Biolabs provides cis- and retrograde tracers for neural loop studies and offers the following related services to help accelerate the progress of your program.

Viruses as Tools for Neural Loop Tracing

Viral tools in neuroscience provide more precise tracing and mapping, and viruses can be localized to specific cell types through genetic strategies to improve transduction efficiency and extend or limit their virulophilicity.

Viruses used in neuroscience research are typically genetically modified or recombinant strains of wild-type viruses, including:

A number of tracer products are important tools commonly used in research. You can browse the table below to see a list of our recommended products.

Application Cases of Tissue Transparency Techniques in Neural Loop Studies

Choosing the right tracer/tracer virus to accomplish neural labeling efficiently is the basis for probing neural loop studies. Next, optical imaging techniques are needed to detect the projections of the entire loop. Traditional tissue slicing methods allow precise brain localization of neuronal signals in the projection area, but the information at the level of two-dimensional slices does not provide a complete picture of the transmission and projection of nerve fibers. In recent years, tissue transparency techniques have been rapidly developed to reduce light attenuation in biological tissues by equalizing the refractive indices between different cellular components and removing pigments to improve the imaging depth, providing an effective tool for 3D imaging of thick tissues or even whole organisms.

• 3D Visualization of Peripheral Nerve Circuits - The researchers first injected fluorescently labeled AAV virus at the dorsal root ganglion (DRG) of the mouse spinal cord, where the virus delivered a tracer labeling the downstream nerves in passing, and combined it with tissue transparency and light-sheet micrographic imaging to better trace the pathways of sensory neurons that extend into adipose tissue.
• 3D Visualization of Central Nervous Circuits - Using viral tracer technology, scientists injected AAV-eGFP and AAV-tdtomato viruses in the sweet-taste-responsive cortex (GCsw) and bitter-taste-responsive cortex (GCbt), respectively, and, in conjunction with tissue-transparency and light-sheet micrographic imaging systems, found that neurons in the sweet-taste-responsive and bitter-taste-responsive cortices projected to different regions in the amygdala.
• 3D Visualization of Peripheral-Central Neural Circuits - Investigators meta-injected pseudorabies virus PRV152-EGFP into the superficial flexor digitorum profundus muscle, where the virus was retrogradely delivered from within the peripheral skeletal muscle to the lower motor neurons in the spinal cord and completed trans-synaptic transmission to illuminate the upper motor neurons in the brain, and then subsequently, using the FDISCO Transparencies method and light-sheet microscopy, the functional connectivity of functional connections that regulate the motor function of skeletal muscle in the brain were neurons were imaged.

Creative Biolabs provides various types of neural tracer markers as well as a number of leading-edge technologies to solve the challenges encountered in neural tracer loop research, and help research in the field of brain science and neuroscience.

Reference

1. Xu, Xiangmin, et al. "Viral vectors for neural circuit mapping and recent advances in trans-synaptic anterograde tracers." Neuron 107.6 (2020): 1029-1047.

Related Scientific Resources

Viral Vectors in the Central Nervous System (CNS)

Neural Circuit Function Research Technology