The Picower Institute for Learning and Memory, Howard Hughes Medical Institute, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, USA.
J Neurosci. 2010 Dec 1;30(48):16304-13. doi: 10.1523/JNEUROSCI.4333-10.2010.
Stimulus-specific response potentiation (SRP) is a robust form of experience-dependent plasticity that occurs in primary visual cortex. In awake mice, visual evoked potentials (VEPs) recorded in layer 4 of binocular visual cortex undergo increases in amplitude with repeated presentation of a sinusoidal grating stimulus over days. This effect is highly specific to the experienced stimulus. Here, we test whether the mechanisms of thalamocortical long-term potentiation (LTP), induced with a theta burst electrical stimulation (TBS) of the dorsal lateral geniculate nucleus, are sufficient to account for SRP. First, we demonstrate that LTP similarly enhances the amplitude of VEPs, but in a way that generalizes across multiple stimuli, spatial frequencies, and contrasts. Second, we show that LTP occludes the subsequent expression of SRP. Third, we reveal that previous SRP occludes TBS-induced LTP of the VEP evoked by the experienced stimulus, but not by unfamiliar stimuli. Finally, we show that SRP is rapidly and selectively reversed by local cortical infusion of a peptide that inhibits PKMζ, a constitutively active kinase known to maintain NMDA receptor-dependent LTP and memory. Thus, SRP is expressed by the same core mechanisms as LTP. SRP therefore provides a simple assay to assess the integrity of LTP in the intact nervous system. Moreover, the results suggest that LTP of visual cortex, like SRP, can potentially be exploited to improve vision.
刺激特异性反应增强（SRP）是一种在初级视觉皮层中发生的强大的经验依赖性可塑性形式。在清醒的小鼠中，双眼视觉皮层第 4 层记录的视觉诱发电位（VEPs）在数天内随着正弦光栅刺激的重复呈现而振幅增加。这种效应高度特异于所经历的刺激。在这里，我们测试了用背外侧膝状体的 theta 爆发电刺激（TBS）诱导的丘脑皮质长时程增强（LTP）的机制是否足以解释 SRP。首先，我们证明 LTP 同样增强了 VEP 的振幅，但以一种跨多种刺激、空间频率和对比度的方式进行。其次，我们表明 LTP 会阻碍随后的 SRP 表达。第三，我们揭示了先前的 SRP 会阻碍由经验刺激引起的 TBS 诱导的 VEP 的 LTP，但不会阻碍不熟悉的刺激。最后，我们表明，通过局部皮质输注抑制 PKMζ 的肽可以快速和选择性地逆转 SRP，PKMζ 是一种已知维持 NMDA 受体依赖性 LTP 和记忆的组成型活性激酶。因此，SRP 是由与 LTP 相同的核心机制表达的。因此，SRP 为评估完整神经系统中 LTP 的完整性提供了一种简单的测定方法。此外，结果表明，像 SRP 一样，视觉皮层的 LTP 可以潜在地被利用来改善视力。
