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Dev Neurobiol. 2017 Jan;77(1):102-119. doi: 10.1002/dneu.22414. Epub 2016 Jun 30.

Lamina specific postnatal development of PKCγ interneurons within the rat medullary dorsal horn.

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Neuro-Dol, Clermont Université, Université D'Auvergne, BP 10448, F-63000, Clermont-Ferrand & Inserm U1107, Clermont-Ferrand, F-63100, France.
Biostatistics Unit (DRCI), CHU Clermont-Ferrand, Clermont-Ferrand, F-63100, France.
Service D'Odontologie, CHU Clermont-Ferrand, Clermont-Ferrand, F-63000, France.


Protein kinase C gamma (PKCγ) interneurons, located in the superficial spinal (SDH) and medullary dorsal horns (MDH), have been shown to play a critical role in cutaneous mechanical hypersensitivity. However, a thorough characterization of their development in the MDH is lacking. Here, it is shown that the number of PKCγ-ir interneurons changes from postnatal day 3 (P3) to P60 (adult) and such developmental changes differ according to laminae. PKCγ-ir interneurons are already present at P3-5 in laminae I, IIo, and III. In lamina III, they then decrease from P11-P15 to P60. Interestingly, PKCγ-ir interneurons appear only at P6 in lamina IIi, and they conversely increase to reach adult levels at P11-15. Analysis of neurogenesis using bromodeoxyuridine (BrdU) does not detect any PKCγ-BrdU double-labeling in lamina IIi. Quantification of the neuronal marker, NeuN, reveals a sharp neuronal decline (∼50%) within all superficial MDH laminae during early development (P3-15), suggesting that developmental changes in PKCγ-ir interneurons are independent from those of other neurons. Finally, neonatal capsaicin treatment, which produces a permanent loss of most unmyelinated afferent fibers, has no effect on the development of PKCγ-ir interneurons. Together, the results show that: (i) the expression of PKCγ-ir interneurons in MDH is developmentally regulated with a critical period at P11-P15, (ii) PKCγ-ir interneurons are developmentally heterogeneous, (iii) lamina IIi PKCγ-ir interneurons appear less vulnerable to cell death, and (iv) postnatal maturation of PKCγ-ir interneurons is due to neither neurogenesis, nor neuronal migration, and is independent of C-fiber development.


BrdU; C-fiber; PKC gamma; medullary dorsal horn; pain

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