title: Integration time in a subset of spinal lamina I neurons is lengthened by sodium and calcium currents acting synergistically to prolong subthreshold depolarization.
abstract: Lamina I of the spinal dorsal horn plays an important role in processing and relaying nociceptive information to the brain. It comprises physiologically distinct cell types that process information in fundamentally different ways: tonic neurons fire repetitively during stimulation and display prolonged EPSPs, suggesting operation as integrators, whereas single-spike neurons act like coincidence detectors. Using whole-cell recordings from a rat spinal slice preparation, we set out to determine the basis for prolonged EPSPs in tonic cells and the implications for signal processing. Kinetics of synaptic currents could not explain differences in EPSP kinetics. Instead, tonic neurons were found to express a persistent sodium current, I(Na,P), that amplified and prolonged depolarization in response to brief stimulation. Tonic neurons also expressed a persistent calcium current, I(Ca,P), that contributed to prolongation but not to amplification. Simulations using NEURON software demonstrated that I(Na,P) was necessary and sufficient to explain amplification, whereas I(Na,P) and I(Ca,P) acted synergistically to prolong depolarization: initial activation of the slower current (I(Ca,P)) depended on the faster current (I(Na,P)) but maintained activation of the faster current likewise depended on the slower current. Additional investigation revealed that I(Na,P) and I(Ca,P) could dramatically increase integration time (>30x) and thereby encourage temporal summation but at the expense of spike time precision. Thus, by prolonging subthreshold depolarization, intrinsic inward currents allow tonic neurons in spinal lamina I to specialize as integrators that are optimally suited to encode stimulus intensity.
authors.affiliation: Division de Neurobiologie Cellulaire, Centre de Recherche Université Laval Robert-Giffard, Québec, Québec, Canada.
authors.forename: Steven A
authors.initials: SA
authors.lastname: Prescott
authors.forename: Yves
authors.initials: Y
authors.lastname: De Koninck
mesh_terms: D000818:Animals; D002118:Calcium / Q000378:metabolism*; D004307:Dose-Response Relationship, Radiation; D004347:Drug Interactions; D004558:Electric Stimulation / Q000379:methods; D019706:Excitatory Postsynaptic Potentials / Q000502:physiology / Q000528:radiation effects; D066298:In Vitro Techniques; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology* / Q000528:radiation effects; D008959:Models, Neurological; D009532:Nickel / Q000494:pharmacology; D018408:Patch-Clamp Techniques / Q000379:methods; D020671:Posterior Horn Cells / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012964:Sodium / Q000378:metabolism*; D026941:Sodium Channel Blockers / Q000494:pharmacology; D013116:Spinal Cord / Q000166:cytology*; D018709:Statistics, Nonparametric; D013779:Tetrodotoxin / Q000494:pharmacology; D013997:Time Factors
chemical_list: D026941:Sodium Channel Blockers; D013779:Tetrodotoxin; D009532:Nickel; D012964:Sodium; D002118:Calcium