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The mammalian nervous system consists of a seemingly infinitely complex network of specialized synaptic connections that coordinate the flow of information. In the past few decades, neuroscience research has focused primarily on molecules, genes, and cells at the microscopic level, or structural/functional networks based on magnetic resonance imaging and behavior at the macroscopic level. However, the human brain contains approximately 100 billion neurons, which are connected by approximately 10 quadrillion synapses to form a virtually infinite number of neural circuits at the mesoscopic level. These circuits are the structural basis for coordinating and executing a wide range of basic and higher-level brain functions. Elucidating neural circuits is a prerequisite for understanding the principles of brain function and the pathogenesis of neurological diseases.
Currently, viral tools are widely used in neural circuit research. They are modified from natural strains of neurotropic viruses, such as herpes simplex virus (HSV), pseudorabies virus (PRV), rabies virus (RV), vesicular stomatitis virus (VSV), and Sindbis virus (SINV). In addition, some non-transsynaptic recombinant viral vectors can be used as auxiliary vectors for exogenous gene expression, such as lentivirus (LV) and adeno-associated virus (AAV), or efficiently label the fine structure of neurons, such as Semliki Forest virus (SFV), or show upstream projections in local brain areas, such as AAV2-retro and canine adenovirus type 2 (CAV-2), or efficiently cross the mouse blood-brain barrier (BBB), such as AAV9-PHP.eB, and retrogradely infect projection neurons after crossing the whole brain BBB, such as AAV9-retro.
Figure 1. Schematics of the anterograde or retrograde transmission of non-transsynaptic (static) and transsynaptic (trans-multisynaptic or monosynaptic) viral tools. (Liu Q, et al., 2022)
To comprehend the intricate systems of the brain, it is necessary to understand how neurons are connected, to describe the fine structure of neural circuits, and to recognize their functions. With the advent of viral vector technology, new methods have been developed to study neuronal connectivity. These methods are less neurotoxic and better compatible with other neuroscience methods such as electrophysiological recordings. Creative Biogene developed a series of novel neurotropic virus which can infect neuronal cells, duplicate and transmit along neuronal tract pathways. These neuronal tracing tools can specifically label cell types and visualize conduction directions with controllable directionality to enable precise understanding and research of neural circuit networks.
Explore Our Neuronal Tracing Tools
HSV-1 has the properties of neuronal tropism and efficient infection of the central nervous system (CNS), making it a neuron-specific marker and gene delivery vector.
Vesicular stomatitis virus (VSV) is known for its rapid replication and assembly, high infection efficiency, and foreign gene expression, and has been shown to be delivered anterogradely between neurons.
Rabies viruses (RABVs) are ideal viruses for mapping neuronal connectivity due to their transsynaptic spreading properties, allowing even attenuated forms of RABV to enter axonal transport pathways.
Due to the nature of polysynaptic transmission, Pseudorabies virus (PRV) is an excellent tool for short-term retrograde tracing of multilevel neural circuits that terminate in the periphery.
For markers, we have EGFP, dsRed, mCherry, mRFP, tdTomato inserted in the RV, VSV, PRV backbones.
Recombinant neural viruses have become the most effective and common tools in modern neuroscience research, whether it is neuronal morphology depiction or neural circuit tracing. Since its first discovery and application, each virus has been rapidly developed and has made many amazing advances in the past few decades. The following are some applications of recombinant viruses in neural circuit tracing.
Our viral vector products are designed to facilitate groundbreaking discoveries in neuroscience research, allowing researchers to explore the complexity of the brain and generate new insights into the mechanisms underlying neural function and dysfunction. Creative Biogene can also provide customized neuron tracing viral vectors to customers around the world. If you are interested in our services and products, please feel free to contact us for more details.
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