Department of Molecular Neurobiology, Max Planck Institute for Medical Research, D-69120 Heidelberg, Germany.
J Neurosci. 2012 Jun 27;32(26):8952-68. doi: 10.1523/JNEUROSCI.6460-11.2012.
The GluA1 subunit of AMPA receptors (AMPARs) is critical for hippocampal synaptic transmission and plasticity. Here, we measured the activity of single units from the CA1 region of the hippocampus while GluA1 knock-out (GluA1⁻/⁻) and wild-type (WT) mice traversed a linear track. Although overall firing rates were similar, GluA1⁻/⁻ neurons were more likely to spike in bursts, but at lower burst frequencies, compared with WT neurons. GluA1⁻/⁻ neurons showed large reductions in all measures of spatial and directional selectivity compared with WT neurons. Consistent with these alterations of single-neuron properties, the accuracy of the population code for position was substantially reduced in GluA1⁻/⁻, yet it is predicted to approach the accuracy of WT with increasing population size. The absolute representation of space, independent of movement direction, was greatly diminished in GluA1⁻/⁻ mice and is predicted to remain reduced even for larger populations. Finally, we found that the rate maps of GluA1⁻/⁻ neurons showed increased trial-by-trial variability but reduced experiential plasticity compared with the WT. These results reveal the critical contribution of GluA1-containing AMPARs to individual place cells and the hippocampal population code for space, which could explain the selective behavioral impairments observed in these mice.
AMPA 受体（AMPARs）的 GluA1 亚基对于海马突触传递和可塑性至关重要。在这里，我们在 GluA1 敲除（GluA1⁻/⁻）和野生型（WT）小鼠穿越线性轨道时测量了海马 CA1 区的单个单位的活动。尽管总体放电率相似，但与 WT 神经元相比，GluA1⁻/⁻神经元更有可能爆发，但爆发频率较低。与 WT 神经元相比，GluA1⁻/⁻神经元的所有空间和方向选择性测量值均大幅降低。与这些单神经元特性的改变一致，GluA1⁻/⁻中的位置群体编码的准确性大大降低，但随着群体规模的增加，其准确性预计会接近 WT。GluA1⁻/⁻小鼠的空间绝对表示，与运动方向无关，大大降低，即使对于更大的群体，预计也会保持降低。最后，我们发现与 WT 相比，GluA1⁻/⁻神经元的速率图表现出更高的试验间变异性，但经验性可塑性降低。这些结果揭示了 GluA1 包含的 AMPARs 对单个位置细胞和海马体空间群体编码的关键贡献，这可以解释这些小鼠中观察到的选择性行为障碍。
