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新生大鼠背角GABA能突触的保真度和短期可塑性的发育变化。

Developmental changes in the fidelity and short-term plasticity of GABAergic synapses in the neonatal rat dorsal horn.

作者信息

Ingram Rachel A, Fitzgerald Maria, Baccei Mark L

机构信息

Department of Anatomy and Developmental Biology, University College London, London, WC1E 6BT, UK.

出版信息

J Neurophysiol. 2008 Jun;99(6):3144-50. doi: 10.1152/jn.01342.2007. Epub 2008 Apr 9.

Abstract

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 afterdischarge.

摘要

新生大鼠背角神经元的阈值较低且兴奋性增加,这表明在未成熟的脊髓中抑制性处理效率较低。这不太可能是由于缺乏功能性GABA能抑制来解释,因为从出生后的第一天起,体内A型γ-氨基丁酸(GABA)受体的拮抗作用就会增强神经元的放电。然而,新生儿的GABA能信号可能存在更细微的缺陷,例如传递可靠性降低或重复刺激时更大的抑制,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,我们使用全细胞膜片钳记录,在一系列出生后年龄(P3、P10和P21)的脊髓切片中,研究了对浅背角神经元的单突触GABA能输入。在较年幼的动物中,诱发的抑制性突触后电流(IPSCs)的幅度显著较低且变异性更大,这表明在出生后早期GABA能信号的保真度较低。在整个出生后时期,配对脉冲比率相似,而一系列刺激(1、5、10和20 Hz)显示,在所有年龄,IPSCs都存在频率依赖性短期抑制(STD)。尽管不同年龄的STD幅度没有差异,但未成熟GABA能突触的抑制恢复明显较慢。这些特性可能会影响发育中的浅背角神经元内突触输入的整合,从而导致它们具有更大的感受野和增强的后放电。

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