Daniele Claire A, MacDermott Amy B
Department of Neuroscience, Columbia University, New York, NY 10032, USA.
J Neurosci. 2009 Jan 21;29(3):686-95. doi: 10.1523/JNEUROSCI.5120-08.2009.
Inhibition in the spinal cord dorsal horn is crucial for maintaining separation of touch and pain modalities. Disruption of this inhibition results in allodynia, allowing low-threshold drive onto pain and temperature-sensitive projection neurons. This low-threshold (LT) excitatory pathway is normally under strong inhibition. We hypothesized that superficial dorsal horn inhibitory neurons, which would be ideally located to suppress LT drive onto projection neurons in a feedforward manner, are driven by LT input. In addition, because disinhibition-induced allodynia shares some features with the immature dorsal horn such as elevated sensitivity to LT input, we also questioned whether LT drive onto inhibitory neurons changes during postnatal maturation. To investigate these questions, slices were made at different ages from transgenic mice with enhanced green fluorescent protein expression in GABAergic neurons and whole-cell recordings were made from these fluorescent neurons. Evoked synaptic activity was measured in response to electrical stimulation of the dorsal root. We demonstrate that Abeta fibers activate a significant proportion of superficial dorsal horn GABAergic neurons. This occurs with similar excitatory synaptic drive throughout postnatal maturation, but with a greater prevalence at younger ages. These GABAergic neurons are well situated to contribute to suppressing LT activation of output projection neurons. In addition, the majority of these GABAergic neurons also had convergent input from high-threshold fibers, suggesting that this novel subclass of GABAergic neurons is important for gating innocuous as well as noxious information.
脊髓背角的抑制作用对于维持触觉和痛觉模式的分离至关重要。这种抑制作用的破坏会导致异常性疼痛,使低阈值驱动作用于对疼痛和温度敏感的投射神经元。这条低阈值(LT)兴奋性通路通常受到强烈抑制。我们推测,浅表背角抑制性神经元,其位置理想,能够以前馈方式抑制投射神经元上的LT驱动,是由LT输入驱动的。此外,由于去抑制诱导的异常性疼痛与未成熟背角具有一些共同特征,如对LT输入的敏感性升高,我们还质疑LT对抑制性神经元的驱动在出生后成熟过程中是否会发生变化。为了研究这些问题,从在GABA能神经元中增强绿色荧光蛋白表达的转基因小鼠的不同年龄段制作切片,并从这些荧光神经元进行全细胞记录。响应于背根的电刺激测量诱发的突触活动。我们证明,Aβ纤维激活了相当一部分浅表背角GABA能神经元。这种情况在整个出生后成熟过程中以类似的兴奋性突触驱动发生,但在较年轻时更为普遍。这些GABA能神经元的位置有利于抑制输出投射神经元的LT激活。此外,这些GABA能神经元中的大多数也有来自高阈值纤维的汇聚输入,这表明这种新型的GABA能神经元亚类对于筛选无害以及有害信息很重要。