Walsh M A, Graham B A, Brichta A M, Callister R J
School of Biomedical Sciences, Faculty of Health, The University of Newcastle, Callaghan, NSW 2308, Australia.
J Neurophysiol. 2009 Apr;101(4):1800-12. doi: 10.1152/jn.90755.2008. Epub 2009 Jan 28.
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.
浅表背角(SDH;I-II层)神经元的输出对于处理伤害性、热和触觉信息至关重要。与其他神经元一样,突触输入和内在膜特性的综合作用决定了它们的输出。众所周知,SDH神经元的外周突触输入在产前和产后发育过程中会发生广泛的重组。然而,在此期间,塑造SDH神经元输出的膜特性或阈下全细胞电流如何变化尚不清楚。在这里,我们评估了胚胎晚期和出生后早期发育阶段(E15-P25)小鼠SDH神经元的内在膜特性和全细胞电流。从腰脊髓制备横向切片,并在32℃下进行全细胞记录。在这个发育阶段,静息膜电位(RMP)变得更加超极化(约10 mV,E15-E17与P21-P25相比),输入电阻降低(1074±78与420±27 MΩ)。此外,动作电位(AP)幅度和AP后超极化增加,而AP半宽度减小。出生前后(E15-P10),在许多神经元中(>41%),细胞内电流注入诱发的AP放电在去极化开始时仅限于单个AP。在年龄较大的动物(P11-P25)中,这种情况发生了变化,AP放电在电流开始时由短暂的爆发组成(约46%的神经元)。对主要阈下全细胞电流的研究表明,快速A型钾电流(I(Ar))在所有检测年龄中占主导地位(E15-E17时90%的神经元,P10后降至>50%)。基于峰值电流幅度,I(Ar)表达水平在发育过程中增加。在接近RMP(-55 mV)的电位下,E15-E17神经元与P21-P25神经元相比,I(Ar)的稳态失活和激活作用略弱。总之,我们的数据表明,在发育过程中,SDH神经元的内在特性和I(Ar)表达发生了显著变化,最大的变化发生在关键期P6-P10的两侧。