Kotak Vibhakar C, Breithaupt Andrew D, Sanes Dan H
Center for Neural Science and Department of Biology, New York University, New York, NY 10003, USA.
Proc Natl Acad Sci U S A. 2007 Feb 27;104(9):3550-5. doi: 10.1073/pnas.0607177104. Epub 2007 Feb 20.
Severe hearing loss during early development is associated with deficits in speech and language acquisition. Although functional studies have shown a deafness-induced alteration of synaptic strength, it is not known whether long-term synaptic plasticity depends on auditory experience. In this study, sensorineural hearing loss (SNHL) was induced surgically in developing gerbils at postnatal day 10, and excitatory synaptic plasticity was examined subsequently in a brain slice preparation that preserves the thalamorecipient auditory cortex. Extracellular stimuli were applied at layer 6 (L6), whereas evoked excitatory synaptic potentials (EPSPs) were recorded from L5 neurons by using a whole-cell current clamp configuration. In control neurons, the conditioning stimulation of L6 significantly altered EPSP amplitude for at least 1 h. Approximately half of neurons displayed long-term potentiation (LTP), whereas the other half displayed long-term depression (LTD). In contrast, SNHL neurons displayed only LTD after the conditioning stimulation of L6. Finally, the vast majority of neurons recorded from control prehearing animals (postnatal days 9-11) displayed LTD after L6 stimulation. Thus, normal auditory experience may be essential for the maturation of synaptic plasticity mechanisms.
早期发育过程中的严重听力损失与言语和语言习得缺陷有关。尽管功能研究表明耳聋会导致突触强度改变，但长期突触可塑性是否依赖听觉经验尚不清楚。在本研究中，在出生后第10天对发育中的沙鼠进行手术诱导感音神经性听力损失（SNHL），随后在保留丘脑接受性听觉皮层的脑片标本中检测兴奋性突触可塑性。在第6层（L6）施加细胞外刺激，同时使用全细胞电流钳配置从第5层（L5）神经元记录诱发的兴奋性突触后电位（EPSP）。在对照神经元中，L6的条件刺激至少1小时内显著改变了EPSP幅度。约一半的神经元表现出长时程增强（LTP），而另一半表现出长时程抑制（LTD）。相比之下，SNHL神经元在L6条件刺激后仅表现出LTD。最后，从对照听力前动物（出生后第9 - 11天）记录的绝大多数神经元在L6刺激后表现出LTD。因此，正常的听觉经验可能对突触可塑性机制的成熟至关重要。
