title: Subpopulations of PKCγ interneurons within the medullary dorsal horn revealed by electrophysiologic and morphologic approach.
abstract: Mechanical allodynia, a cardinal symptom of persistent pain, is associated with the unmasking of usually blocked local circuits within the superficial spinal or medullary dorsal horn (MDH) through which low-threshold mechanical inputs can gain access to the lamina I nociceptive output neurons. Specific interneurons located within inner lamina II (IIi) and expressing the gamma isoform of protein kinase C (PKCγ⁺) have been shown to be key elements for such circuits. However, their morphologic and electrophysiologic features are still unknown. Using whole-cell patch-clamp recordings and immunohistochemical techniques in slices of adult rat MDH, we characterized such lamina IIi PKCγ⁺ interneurons and compared them with neighboring PKCγ⁻ interneurons. Our results reveal that PKCγ⁺ interneurons display very specific activity and response properties. Compared with PKCγ⁻ interneurons, they exhibit a smaller membrane input resistance and rheobase, leading to a lower threshold for action potentials. Consistently, more than half of PKCγ⁺ interneurons respond with tonic firing to step current. They also receive a weaker excitatory synaptic drive. Most PKCγ⁺ interneurons express Ih currents. The neurites of PKCγ⁺ interneurons arborize extensively within lamina IIi, can spread dorsally into lamina IIo, but never reach lamina I. In addition, at least 2 morphologically and functionally different subpopulations of PKCγ⁺ interneurons can be identified: central and radial PKCγ⁺ interneurons. The former exhibit a lower membrane input resistance, rheobase and, thus, action potential threshold, and less PKCγ⁺ immunoreactivity than the latter. These 2 subpopulations might thus differently contribute to the gating of dorsally directed circuits within the MDH underlying mechanical allodynia.
authors.affiliation: Inserm/UdA U1107, Neuro-Dol: Trigeminal Pain and Migraine, Université d'Auvergne, Faculté de Chirurgie Dentaire, Clermont-Ferrand, France CHU Clermont-Ferrand, Service d'Odontologie, Clermont-Ferrand, France.
authors.forename: Cristina
authors.initials: C
authors.lastname: Alba-Delgado
authors.forename: Corinne
authors.initials: C
authors.lastname: El Khoueiry
authors.forename: Cédric
authors.initials: C
authors.lastname: Peirs
authors.forename: Radhouane
authors.initials: R
authors.lastname: Dallel
authors.forename: Alain
authors.initials: A
authors.lastname: Artola
authors.forename: Myriam
authors.initials: M
authors.lastname: Antri
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D004558:Electric Stimulation; D019706:Excitatory Postsynaptic Potentials; D021621:Imaging, Three-Dimensional; D066298:In Vitro Techniques; D007395:Interneurons / Q000145:classification / Q000502:physiology*; D008297:Male; D008526:Medulla Oblongata / Q000166:cytology*; D008564:Membrane Potentials / Q000502:physiology*; D016501:Neurites; D018408:Patch-Clamp Techniques; D011493:Protein Kinase C / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D066148:Spinal Cord Dorsal Horn / Q000166:cytology*
chemical_list: C087857:protein kinase C gamma; D011493:Protein Kinase C