https://ogma.newcastle.edu.au/vital/access/ /manager/Index ${session.getAttribute("locale")} 5 Evidence for a critical period in the development of excitability and potassium currents in mouse lumbar superficial dorsal horn neurons https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:6928 41%). In older animals (P11–P25) this changed, with AP discharge consisting of brief bursts at current onset (~46% of neurons). Investigation of major subthreshold whole cell currents showed the rapid A-type potassium current (IAr) dominated at all ages examined (90% of neurons at E15–E17, decreasing to >50% after P10). IAr expression levels, based on peak current amplitude, increased during development. Steady-state inactivation and activation for IAr 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 IAr expression change dramatically in SDH neurons during development, with the greatest alterations occurring on either side of a critical period, P6–P10.]]> Sat 24 Mar 2018 08:40:23 AEDT ]]> Altered nociceptive, endocrine, and dorsal horn neuron responses in rats following a neonatal immune challenge https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:21485 Salmonella enteritidis) or saline on postnatal days (PNDs) 3 and 5 and later subjected to the formalin test at PNDs 7, 13, and 22. One hour after formalin injection, blood was collected to assess corticosterone responses. Transverse spinal cord slices were also prepared for whole-cell patch clamp recording from lumbar superficial dorsal horn neurons (SDH). Brains were obtained at PND 22 and the hypothalamus was isolated to measure glucocorticoid (GR) and mineralocorticoid receptor (MR) transcript expression using qRT-PCR. Behavioural analyses indicate that at PND 7, no significant differences were observed between saline- or LPS-challenged rats. At PND 13, LPS-challenged rats exhibited enhanced licking (p < .01), and at PND 22, increased flinching in response to formalin injection (p < .05). LPS-challenged rats also displayed increased plasma corticosterone at PND 7 and PND 22 (p < .001) but not at PND 13 following formalin administration. Furthermore, at PND 22 neonatal LPS exposure induced decreased levels of GR mRNA and increased levels of MR mRNA in the hypothalamus. The intrinsic properties of SDH neurons were similar at PND 7 and PND 13. However, at PND 22, ipsilateral SDH neurons in LPS-challenged rats had a lower input resistance compared to their saline-challenged counterparts (p < .05). These data suggest neonatal LPS exposure produces developmentally regulated changes in formalin-induced behavioural responses, corticosterone levels, and dorsal horn neuron properties following noxious stimulation later in life. These findings highlight the importance of immune activation during the neonatal period in shaping pain sensitivity later in life. This programming involves both spinal cord neurons and the HPA axis.]]> Sat 24 Mar 2018 08:03:35 AEDT ]]> Are all spinal segments equal: intrinsic membrane properties of superficial dorsal horn neurons in the developing and mature mouse spinal cord https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:22273 IN), resting membrane potential, AP amplitude, half-width and AHP amplitude were similar across spinal cord regions in both neonates and adults (~100 neurons for each region and age). In contrast, these intrinsic membrane properties differed dramatically between neonates and adults. Five types of AP discharge were observed during depolarizing current injection. In neonates, single spiking dominated (~40%) and the proportions of each discharge category did not differ across spinal regions. In adults, initial bursting dominated in each spinal region, but was significantly more prevalent in rostral segments (49% of neurons in C2-4 vs. 29% in L3-5). During development the dominant AP discharge pattern changed from single spiking to initial bursting. The rapid A-type potassium current (IAr) dominated in neonates and adults, but its prevalence decreased (~80% vs. ~50% of neurons) in all regions during development. IAr steady state inactivation and activation also changed in upper cervical and lumbar regions during development. Together, our data show the intrinsic properties of SDH neurons are generally conserved in the three spinal cord regions examined in both neonate and adult mice. We propose the conserved intrinsic membrane properties of SDH neurons along the length of the spinal cord cannot explain the marked differences in pain experienced in the limbs, viscera, and head and neck.]]> Sat 24 Mar 2018 07:17:39 AEDT ]]>