Pain MechanismResearch PaperTriggering genetically-expressed transneuronal tracers by peripheral axotomy reveals convergent and segregated sensory neuron-spinal cord connectivity
Section snippets
Animals
All experiments were reviewed and approved by the Institutional Care and Animal Use Committee at the University of California, San Francisco. The ZWX mice were generated as previously described (Braz et al., 2002). To construct the pCZW-GFP-TTC (fusion protein of the green fluorescent protein and the C fragment of tetanus toxin) expression vector, we inserted the cDNA coding sequence for the fusion protein GFP-TTC (kindly provided by Philippe Brûlet, Institut Pasteur, Paris, France) into the
Results
Our initial objective was to generate new transgenic mouse lines that express two transneuronal tracers after Cre recombination: the anterograde tracer WGA and the retrograde tracer GFP-TTC (a fusion protein composed of green fluorescent protein (GFP) and the C-terminal fragment of tetanus toxin (TTC); Kissa et al 2002, Maskos et al 2002). By following transneuronal transport of the two tracers in vivo, we expected that it would be possible to label anterogradely the circuits (red neurons, Fig.
Discussion
Taking advantage of the unusual properties of the ZWX transgenic mouse, we designed a simple strategy that uses peripheral nerve injury to induce expression of an anterograde transneuronal tracer in neurochemically-defined subpopulations of primary sensory neurons so as to delineate the circuits that they engage. The patterns revealed in these animals elaborate significantly on those described in more traditional tracing studies that examined the central projections of the entire population of
Acknowledgments
This work was supported by NIH grants NS14627 and 48499. We are particularly grateful to Dr. John Wood at University College London, UK, for providing the Nav1.8-Cre mice; to Dr. Jeffrey Friedman at Rockefeller University, NY, for providing the NPY-Cre mice; and to Dr. Philippe Brûlet at Institut Pasteur, France, for providing the GFP-TTC cDNA.
References (35)
- et al.
Diversity of expression of the sensory neuron-specific TTX-resistant voltage-gated sodium ion channels SNS and SNS2
Mol Cell Neurosci
(2000) - et al.
Parallel “pain” pathways arise from subpopulations of primary afferent nociceptor
Neuron
(2005) - et al.
The receptive part of the primary afferent axon is most vulnerable to systemic capsaicin in adult rats
Brain Res
(1990) - et al.
In vivo neuronal tracing with GFP-TTC gene delivery
Mol Cell Neurosci
(2002) - et al.
Subpopulations of GABAergic neurons in laminae I–III of rat spinal dorsal horn defined by coexistence with classical transmitters, peptides, nitric oxide synthase or parvalbumin
Neuroscience
(1994) - et al.
Substance P and enkephalin immunoreactivities in axonal boutons presynaptic to physiologically identified dorsal horn neuronsAn ultrastructural multiple-labelling study in the cat
Neuroscience
(1997) - et al.
The types of neuron which contain protein kinase C gamma in rat spinal cord
Brain Res
(1999) - et al.
Characterization of neurons that express preprotachykinin B in the dorsal horn of the rat spinal cord
Neuroscience
(2006) - et al.
Nociceptor-specific gene deletion using heterozygous NaV18-Cre recombinase mice
Pain
(2005) - et al.
Activating transcription factor 3 (ATF3) induction by axotomy in sensory and motoneurons: a novel neuronal marker of nerve injury
Mol Cell Neurosci
(2000)