Sarro Emma C, Kotak Vibhakar C, Sanes Dan H, Aoki Chiye
Center for Neural Science, New York University, New York, NY 10003, USA.
Cereb Cortex. 2008 Dec;18(12):2855-67. doi: 10.1093/cercor/bhn044. Epub 2008 Apr 9.
We have shown previously that auditory experience regulates the maturation of excitatory synapses in the auditory cortex (ACx). In this study, we used electron microscopic immunocytochemistry to determine whether the heightened excitability of the ACx following neonatal sensorineural hearing loss (SNHL) also involves pre- or postsynaptic alterations of GABAergic synapses. SNHL was induced in gerbils just prior to the onset of hearing (postnatal day 10). At P17, the gamma-aminobutyri acid type A (GABA(A)) receptor's beta2/3-subunit (GABA(A)beta2/3) clusters residing at plasma membranes in layers 2/3 of ACx was reduced significantly in size (P < 0.05) and number (P < 0.005), whereas the overall number of immunoreactive puncta (intracellular + plasmalemmal) remained unchanged. The reduction of GABA(A)beta2/3 was observed along perikaryal plasma membranes of excitatory neurons but not of GABAergic interneurons. This cell-specific change can contribute to the enhanced excitability of SNHL ACx. Presynaptically, GABAergic axon terminals were significantly larger but less numerous and contained 47% greater density of glutamic acid decarboxylase immunoreactivity (P < 0.05). This suggests that GABA synthesis may be upregulated by a retrograde signal arising from lowered levels of postsynaptic GABA(A)R. Thus, both, the pre- and postsynaptic sides of inhibitory synapses that form upon pyramidal neurons of the ACx are regulated by neonatal auditory experience.
我们之前已经表明，听觉经验会调节听觉皮层（ACx）中兴奋性突触的成熟。在本研究中，我们使用电子显微镜免疫细胞化学方法来确定新生期感音神经性听力损失（SNHL）后ACx兴奋性增强是否也涉及GABA能突触的突触前或突触后改变。在沙鼠听力开始前（出生后第10天）诱导其发生SNHL。在出生后第17天，位于ACx第2/3层质膜上的γ-氨基丁酸A型（GABA(A)）受体的β2/3亚基（GABA(A)β2/3）簇的大小（P < 0.05）和数量（P < 0.005）显著减少，而免疫反应性斑点（细胞内+质膜）的总数保持不变。在兴奋性神经元的胞周质膜上观察到GABA(A)β2/3的减少，但在GABA能中间神经元上未观察到。这种细胞特异性变化可能导致SNHL ACx兴奋性增强。在突触前，GABA能轴突终末明显更大但数量更少，谷氨酸脱羧酶免疫反应性密度增加47%（P < 0.05）。这表明GABA合成可能由突触后GABA(A)R水平降低产生的逆行信号上调。因此，在ACx锥体神经元上形成的抑制性突触的突触前和突触后两侧均受新生期听觉经验的调节。
