Jean-Xavier Céline, Pflieger Jean-François, Liabeuf Sylvie, Vinay Laurent
CNRS, P3M, 31 Chemin Joseph Aiguier, F-13402 Marseille cx 20, France.
J Neurophysiol. 2006 Nov;96(5):2274-81. doi: 10.1152/jn.00328.2006. Epub 2006 Jun 28.
GABA and glycine are excitatory in the immature spinal cord and become inhibitory during development. The shift from depolarizing to hyperpolarizing inhibitory postsynaptic potentials (IPSPs) occurs during the perinatal period in the rat, a time window during which the projections from the brain stem reach the lumbar enlargement. In this study, we investigated the effects of suppressing influences of the brain on lumbar motoneurons during this critical period for the negative shift of the reversal potential of IPSPs (E(IPSP)). The spinal cord was transected at the thoracic level on the day of birth [postnatal day 0 (P0)]. E(IPSP), at P4-P7, was significantly more depolarized in cord-transected than in cord-intact animals (E(IPSP) above and below resting potential, respectively). E(IPSP) at P4-P7 in cord-transected animals was close to E(IPSP) at P0-P2. K-Cl cotransporter KCC2 immunohistochemistry revealed a developmental increase of staining in the area of lumbar motoneurons between P0 and P7 in cord-intact animals; this increase was not observed after spinal cord transection. The motoneurons recorded from cord-transected animals were less sensitive to the experimental manipulations aimed at testing the functionality of the KCC2 system, which is sensitive to K(+) and blocked by bumetanide. Although bumetanide significantly depolarized E(IPSP), the shift was less pronounced than in cord-intact animals. In addition, a reduction of K(+) affected E(IPSP) significantly only in cord-intact animals. Therefore influences from the brain stem may play an essential role in the maturation of inhibitory synaptic transmission, possibly by upregulating KCC2 and its functionality.
γ-氨基丁酸（GABA）和甘氨酸在未成熟脊髓中具有兴奋性，而在发育过程中转变为抑制性。从去极化抑制性突触后电位（IPSP）向超极化抑制性突触后电位的转变发生在大鼠围产期，这是脑干投射到达腰膨大的时间窗。在本研究中，我们调查了在这个IPSP逆转电位（E(IPSP)）负向转变的关键时期，抑制大脑对腰运动神经元影响的作用。在出生当天（出生后第0天，P0）于胸段水平横断脊髓。在P4 - P7时，脊髓横断动物的E(IPSP)比脊髓完整动物的显著更去极化（分别高于和低于静息电位）。脊髓横断动物在P4 - P7时的E(IPSP)接近P0 - P2时的E(IPSP)。K-Cl共转运体KCC2免疫组化显示，脊髓完整动物在P0到P7期间腰运动神经元区域的染色呈发育性增加；脊髓横断后未观察到这种增加。从脊髓横断动物记录的运动神经元对旨在测试KCC2系统功能的实验操作敏感性较低，该系统对细胞外钾离子浓度（K⁺）敏感并被布美他尼阻断。虽然布美他尼使E(IPSP)显著去极化，但这种转变不如脊髓完整动物明显。此外，降低K⁺仅对脊髓完整动物的E(IPSP)有显著影响。因此，脑干的影响可能在抑制性突触传递的成熟中起重要作用，可能是通过上调KCC2及其功能来实现的。
