Kirkwood A, Bear M F
Brown University Department of Neuroscience, Providence, Rhode Island 02912.
J Neurosci. 1994 Mar;14(3 Pt 2):1634-45. doi: 10.1523/JNEUROSCI.14-03-01634.1994.
We discovered in slices of rat visual cortex that reliable long-term potentiation (LTP) of synaptic responses in layer III could be elicited by theta burst stimulation delivered to a site in the middle of the cortical thickness, corresponding mainly to layer IV. This synaptic plasticity was reflected in the extracellular field potentials and intracellular EPSPs in layer III, but was not observed in the intracellular responses of layer V neurons, suggesting a preferential involvement of synapses on layer III neurons. Tetanus-induced LTP in this preparation was input specific, and was blocked by application of an NMDA receptor antagonist (but not by an antagonist of nitric oxide synthase). In addition, LTP of layer IV-evoked responses could also be produced reliably by pairing low-frequency synaptic stimulation (approximately 100 pulses at 1 Hz) with strong intracellular depolarization of layer III neurons. Thus, LTP in this circuit satisfies the definition of a "Hebbian" modification. Tetanic stimulation of the white matter, in sharp contrast, consistently failed to elicit LTP in layer III unless a GABAA receptor antagonist was applied to the slice. Analysis indicated that the critical difference between layer IV and white matter stimulation was not the magnitude of the responses to single stimuli delivered to the two sites, but that it might lie in the postsynaptic response during high-frequency stimulation. Consistent with this idea, "associative" LTP could be elicited from white matter when converging but independent inputs from the white matter and layer IV simultaneously received tetanic conditioning stimulation. A hypothetical model is presented to account for the differences between layer IV and white matter stimulation. According to this "plasticity gate hypothesis," inhibitory circuitry in layer IV normally acts as a sort of band-pass filter that constrains the types of activity patterns that can gain access to the modifiable synapses in layer III. By stimulating in layer IV, we have bypassed this filter and therefore do not need to block GABAA receptors to achieve the threshold for LTP in layer III.
我们在大鼠视觉皮层切片中发现，通过向皮层厚度中部的一个位点（主要对应于第IV层）施加θ波爆发刺激，可在第III层诱发可靠的突触反应长期增强（LTP）。这种突触可塑性反映在第III层的细胞外场电位和细胞内兴奋性突触后电位（EPSP）中，但在第V层神经元的细胞内反应中未观察到，这表明第III层神经元上的突触优先参与其中。在该制备中，强直刺激诱导的LTP具有输入特异性，并且可通过应用NMDA受体拮抗剂来阻断（但不能被一氧化氮合酶拮抗剂阻断）。此外，通过将低频突触刺激（约100个1Hz的脉冲）与第III层神经元的强细胞内去极化配对，也可可靠地产生第IV层诱发反应的LTP。因此，该回路中的LTP满足“赫布”修饰的定义。与之形成鲜明对比的是，除非向切片施加GABAA受体拮抗剂，否则对白质的强直刺激始终无法在第III层诱发LTP。分析表明，第IV层和白质刺激之间的关键差异不是对施加到这两个位点的单个刺激的反应幅度，而是可能在于高频刺激期间的突触后反应。与此观点一致，当来自白质和第IV层的汇聚但独立的输入同时接受强直条件刺激时，可从白质诱发“联合”LTP。提出了一个假设模型来解释第IV层和白质刺激之间的差异。根据这个“可塑性门控假说”，第IV层中的抑制性回路通常起到一种带通滤波器的作用，它限制了能够进入第III层可修饰突触的活动模式类型。通过在第IV层进行刺激，我们绕过了这个滤波器，因此无需阻断GABAA受体就能达到第III层LTP的阈值。
