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Identification of two classes of somatosensory neurons that display resistance to retrograde infection by rabies virus


Albisetti, Gioele W; Ghanem, Alexander; Foster, Edmund; Conzelmann, Karl-Klaus; Zeilhofer, Hanns Ulrich; Wildner, Hendrik (2017). Identification of two classes of somatosensory neurons that display resistance to retrograde infection by rabies virus. Journal of Neuroscience:Epub ahead of print.

Abstract

Glycoprotein-deleted (ΔG) rabies virus-mediated monosynaptic tracing has become a standard method for neuronal circuit mapping, and is applied to virtually all parts of the rodent nervous system including the spinal cord and primary sensory neurons. Here we identified two classes of unmyelinated sensory neurons (non-peptidergic/NP- and C-LTMR/TH neurons) that are resistant to direct and transsynaptic infection from the spinal cord with rabies viruses carrying glycoproteins in their envelopes that are routinely used for infection of CNS neurons (SAD-G or N2C-G). However, the same neurons were susceptible to infection with EnvA-pseudotyped rabies virus in TVA transgenic mice, indicating that resistance to retrograde infection was due to impaired virus adsorption rather than to deficits in subsequent steps of infection. These results demonstrate an important limitation of rabies virus-based retrograde tracing of sensory neurons in adult mice, and may help to better understand the molecular machinery required for rabies virus spread in the nervous system. In this study mice of both sexes were used.SIGNIFICANCE STATEMENTIn order to understand the neuronal bases of behavior it is important to identify the underlying neural circuitry. Rabies virus based monosynaptic tracing has been used to identify neuronal circuits in various parts of the nervous system. This has included connections between peripheral sensory neurons and their spinal targets, which form the first synapse in the somatosensory pathway. Here we demonstrate that two classes of unmyelinated sensory neurons, which account for more than 40% of DRG neurons, display resistance to rabies infection. Our results are therefore critical for interpreting monosynaptic rabies-based tracing in the sensory system. In addition, identification of rabies resistant neurons might provide a means for future studies addressing rabies pathobiology.

Abstract

Glycoprotein-deleted (ΔG) rabies virus-mediated monosynaptic tracing has become a standard method for neuronal circuit mapping, and is applied to virtually all parts of the rodent nervous system including the spinal cord and primary sensory neurons. Here we identified two classes of unmyelinated sensory neurons (non-peptidergic/NP- and C-LTMR/TH neurons) that are resistant to direct and transsynaptic infection from the spinal cord with rabies viruses carrying glycoproteins in their envelopes that are routinely used for infection of CNS neurons (SAD-G or N2C-G). However, the same neurons were susceptible to infection with EnvA-pseudotyped rabies virus in TVA transgenic mice, indicating that resistance to retrograde infection was due to impaired virus adsorption rather than to deficits in subsequent steps of infection. These results demonstrate an important limitation of rabies virus-based retrograde tracing of sensory neurons in adult mice, and may help to better understand the molecular machinery required for rabies virus spread in the nervous system. In this study mice of both sexes were used.SIGNIFICANCE STATEMENTIn order to understand the neuronal bases of behavior it is important to identify the underlying neural circuitry. Rabies virus based monosynaptic tracing has been used to identify neuronal circuits in various parts of the nervous system. This has included connections between peripheral sensory neurons and their spinal targets, which form the first synapse in the somatosensory pathway. Here we demonstrate that two classes of unmyelinated sensory neurons, which account for more than 40% of DRG neurons, display resistance to rabies infection. Our results are therefore critical for interpreting monosynaptic rabies-based tracing in the sensory system. In addition, identification of rabies resistant neurons might provide a means for future studies addressing rabies pathobiology.

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Additional indexing

Item Type:Journal Article, refereed, original work
Communities & Collections:04 Faculty of Medicine > Institute of Pharmacology and Toxicology
07 Faculty of Science > Institute of Pharmacology and Toxicology
Dewey Decimal Classification:570 Life sciences; biology
610 Medicine & health
Language:English
Date:26 September 2017
Deposited On:05 Oct 2017 08:14
Last Modified:05 Oct 2017 08:19
Publisher:Society for Neuroscience
ISSN:0270-6474
Free access at:Publisher DOI. An embargo period may apply.
Publisher DOI:https://doi.org/10.1523/JNEUROSCI.1277-17.2017
PubMed ID:28951448

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