title: Evidence for a critical period in the development of excitability and potassium currents in mouse lumbar superficial dorsal horn neurons.
abstract: The output of superficial dorsal horn (SDH; laminae I-II) neurons is critical for processing nociceptive, thermal, and tactile information. Like other neurons, the combined effects of synaptic inputs and intrinsic membrane properties determine their output. It is well established that peripheral synaptic inputs to SDH neurons undergo extensive reorganization during pre- and postnatal development. It is unclear, however, how membrane properties or the subthreshold whole cell currents that shape SDH neuron output change during this period. Here we assess the intrinsic membrane properties and whole cell currents in mouse SDH neurons during late embryonic and early postnatal development (E15-P25). Transverse slices were prepared from lumbar spinal cord and whole cell recordings were obtained at 32 degrees C. During this developmental period resting membrane potential (RMP) became more hyperpolarized (by approximately 10 mV, E15-E17 vs. P21-P25) and input resistance decreased (1,074 +/- 78 vs. 420 +/- 27 MOmega). In addition, action potential (AP) amplitude and AP afterhyperpolarization increased, whereas AP half-width decreased. Before and after birth (E15-P10), AP discharge evoked by intracellular current injection was limited to a single AP at depolarization onset in many neurons (>41%). In older animals (P11-P25) this changed, with AP discharge consisting of brief bursts at current onset ( approximately 46% of neurons). Investigation of major subthreshold whole cell currents showed the rapid A-type potassium current (I(Ar)) dominated at all ages examined (90% of neurons at E15-E17, decreasing to >50% after P10). I(Ar) expression levels, based on peak current amplitude, increased during development. Steady-state inactivation and activation for I(Ar) were slightly less potent in E15-E17 versus P21-P25 neurons at potentials near RMP (-55 mV). Together, our data indicate that intrinsic properties and I(Ar) expression change dramatically in SDH neurons during development, with the greatest alterations occurring on either side of a critical period, P6-P10.
authors.affiliation: School of Biomedical Sciences, Faculty of Health, The University of Newcastle, Callaghan, NSW 2308, Australia.
authors.forename: M A
authors.initials: MA
authors.lastname: Walsh
authors.forename: B A
authors.initials: BA
authors.lastname: Graham
authors.forename: A M
authors.initials: AM
authors.lastname: Brichta
authors.forename: R J
authors.initials: RJ
authors.lastname: Callister
mesh_terms: D015761:4-Aminopyridine / Q000494:pharmacology; D000200:Action Potentials / Q000187:drug effects / Q000502:physiology; D000367:Age Factors; D000818:Animals; D000831:Animals, Newborn; D055592:Biophysical Phenomena / Q000187:drug effects / Q000502:physiology*; D001703:Biophysics; D004558:Electric Stimulation / Q000379:methods; D004622:Embryo, Mammalian; D066298:In Vitro Techniques; D008161:Lumbosacral Region; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018408:Patch-Clamp Techniques / Q000379:methods; D020671:Posterior Horn Cells / Q000187:drug effects / Q000502:physiology*; D026902:Potassium Channel Blockers / Q000494:pharmacology; D015221:Potassium Channels / Q000502:physiology*; D013116:Spinal Cord / Q000166:cytology / Q000196:embryology / Q000254:growth & development
chemical_list: D026902:Potassium Channel Blockers; D015221:Potassium Channels; D015761:4-Aminopyridine