School of Biological Sciences, College of Natural Sciences, Seoul National University, Seoul, Korea.
PLoS One. 2011;6(9):e24260. doi: 10.1371/journal.pone.0024260. Epub 2011 Sep 19.
It is generally believed that after memory consolidation, memory-encoding synaptic circuits are persistently modified and become less plastic. This, however, may hinder the remaining capacity of information storage in a given neural circuit. Here we consider the hypothesis that memory-encoding synaptic circuits still retain reversible plasticity even after memory consolidation. To test this, we employed a protocol of auditory fear conditioning which recruited the vast majority of the thalamic input synaptic circuit to the lateral amygdala (T-LA synaptic circuit; a storage site for fear memory) with fear conditioning-induced synaptic plasticity. Subsequently the fear memory-encoding synaptic circuits were challenged with fear extinction and re-conditioning to determine whether these circuits exhibit reversible plasticity. We found that fear memory-encoding T-LA synaptic circuit exhibited dynamic efficacy changes in tight correlation with fear memory strength even after fear memory consolidation. Initial conditioning or re-conditioning brought T-LA synaptic circuit near the ceiling of their modification range (occluding LTP and enhancing depotentiation in brain slices prepared from conditioned or re-conditioned rats), while extinction reversed this change (reinstating LTP and occluding depotentiation in brain slices prepared from extinguished rats). Consistently, fear conditioning-induced synaptic potentiation at T-LA synapses was functionally reversed by extinction and reinstated by subsequent re-conditioning. These results suggest reversible plasticity of fear memory-encoding circuits even after fear memory consolidation. This reversible plasticity of memory-encoding synapses may be involved in updating the contents of original memory even after memory consolidation.
人们普遍认为，在记忆巩固后，记忆编码的突触回路会持续发生改变，从而变得不那么具有可塑性。然而，这可能会限制特定神经回路中剩余的信息存储能力。在这里，我们提出了一个假设，即在记忆巩固后，记忆编码的突触回路仍然具有可逆可塑性。为了验证这一假设，我们采用了听觉恐惧条件反射协议，该协议招募了绝大多数丘脑输入突触回路到外侧杏仁核（T-LA 突触回路；恐惧记忆的存储部位），并诱导了恐惧条件反射引起的突触可塑性。随后，我们对恐惧记忆编码的 T-LA 突触回路进行了恐惧消退和重新条件反射的挑战，以确定这些回路是否表现出可逆的可塑性。我们发现，即使在恐惧记忆巩固后，恐惧记忆编码的 T-LA 突触回路仍表现出与恐惧记忆强度紧密相关的动态效能变化。最初的条件反射或重新条件反射使 T-LA 突触回路接近其修饰范围的上限（在从条件反射或重新条件反射的大鼠中制备的脑片中阻断 LTP 并增强 depotentiation），而消退则逆转了这种变化（在从消退的大鼠中制备的脑片中恢复 LTP 并阻断 depotentiation）。一致地，恐惧条件反射引起的 T-LA 突触的突触增强作用可通过消退而功能性逆转，并可通过随后的重新条件反射而恢复。这些结果表明，即使在恐惧记忆巩固后，恐惧记忆编码回路也具有可逆的可塑性。这种记忆编码突触的可逆可塑性可能参与了在记忆巩固后更新原始记忆的内容。
