Developmental changes in the fidelity and short-term plasticity of GABAergic synapses in the neonatal rat dorsal horn
Developmental changes in the fidelity and short-term plasticity of GABAergic synapses in the neonatal rat dorsal horn
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DOI：
10.1152/jn.01342.2007
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发表时间：
2008-06-01
影响因子：
2.5
通讯作者：
Baccei, Mark L.
中科院分区：
文献类型：
--
作者：
Ingram, Rachel A.;Fitzgerald, Maria;Baccei, Mark L.
新生大鼠背角神经元的阈值较低和兴奋性增加表明，未成熟脊髓中的抑制处理效率较低。这不太可能用功能性 GABA 能抑制的缺失来解释，因为从生命的第一天起，γ-氨基丁酸 (GABA) A 型受体的拮抗作用就会增强体内的神经元放电。然而，新生儿的 GABA 信号可能存在更微妙的缺陷，例如传输可靠性降低或重复刺激期间抑制程度更大，这两者都可能影响未成熟脊髓的相对兴奋性。为了解决这个问题，我们使用在一系列出生后年龄（P3、P10 和 P21）的脊髓切片中制作的全细胞膜片钳记录，检查了浅表背角神经元的单突触 GABA 能输入。在年轻动物中，诱发抑制性突触后电流 (IPSC) 的幅度显着较低，并且表现出更大的变异性，表明出生后早期 GABA 信号的保真度较低。在整个产后期间，成对脉冲比率相似，而刺激序列（1、5、10 和 20 Hz）显示所有年龄段的 IPSC 均存在频率依赖性短期抑制（STD）。尽管性病的严重程度在不同年龄之间没有差异，但未成熟的 GABA 能突触从抑郁症中恢复的速度明显较慢。这些特性可能会影响发育中的浅表背角神经元内突触输入的整合，从而有助于其更大的感受野和增强的后放电。
The lower thresholds and increased excitability of dorsal horn neurons in the neonatal rat suggest that inhibitory processing is less efficient in the immature spinal cord. This is unlikely to be explained by an absence of functional GABAergic inhibition because antagonism of gamma-aminobutyric acid (GABA) type A receptors augments neuronal firing in vivo from the first days of life. However, it is possible that more subtle deficits in GABAergic signaling exist in the neonate, such as decreased reliability of transmission or greater depression during repetitive stimulation, both of which could influence the relative excitability of the immature spinal cord. To address this issue we examined monosynaptic GABAergic inputs onto superficial dorsal horn neurons using whole cell patch-clamp recordings made in spinal cord slices at a range of postnatal ages (P3, P10, and P21). The amplitudes of evoked inhibitory postsynaptic currents (IPSCs) were significantly lower and showed greater variability in younger animals, suggesting a lower fidelity of GABAergic signaling at early postnatal ages. Paired-pulse ratios were similar throughout the postnatal period, whereas trains of stimuli (1, 5, 10, and 20 Hz) revealed frequency-dependent short-term depression (STD) of IPSCs at all ages. Although the magnitude of STD did not differ between ages, the recovery from depression was significantly slower at immature GABAergic synapses. These properties may affect the integration of synaptic inputs within developing superficial dorsal horn neurons and thus contribute to their larger receptive fields and enhanced after-discharge.