Gruart Agnès, Muñoz María Dolores, Delgado-García José M
División de Neurociencias, Universidad Pablo de Olavide, 41013 Sevilla, Spain.
J Neurosci. 2006 Jan 25;26(4):1077-87. doi: 10.1523/JNEUROSCI.2834-05.2006.
One of the brain sites more directly related with learning and memory processes is the hippocampus. We recorded, in conscious mice, the activity-dependent changes taking place at the hippocampal CA3-CA1 synapse during the acquisition, extinction, recall, and reconditioning of an associative task. Mice were classically conditioned to evoke eyelid responses using a trace [conditioned stimuli (CS), tone; unconditioned stimuli (US), shock] paradigm. A single electrical pulse presented to the Schaffer collateral-commissural pathway during the CS-US interval evoked a monosynaptic field EPSP (fEPSP) at ipsilateral CA1 pyramidal cells. The slope of evoked fEPSPs increased across conditioning sessions and decreased during extinction, being linearly related to learning evolution. In contrast, fEPSPs were not modified when evoked in control mice in the absence of a conditioning protocol. Long-term potentiation (LTP) evoked by high-frequency stimulation of Schaffer collaterals prevented acquisition, extinction, recall, or reconditioning, depending on the moment when it was triggered. Learning and memory impairments evoked by LTP induction resulted probably from the functional saturation of the CA3-CA1 synapse, although an additional disturbance of the subsequent information transfer toward postsynaptic circuits cannot be discarded. CGP 39551 [(E)-(+/-)-2-amino-4-methyl-5-phosphono-3-pentenoic acid ethyl ester] (an NMDA antagonist) prevented LTP induction in behaving mice, as well as the acquisition of an eyelid learned response, and the synaptic changes taking place at the CA3-CA1 synapse across conditioning. In conclusion, the responsivity of the CA3-CA1 synapse seems to be modulated during associative learning, and both processes are prevented by experimental LTP or NMDA-receptor inactivation. Our results provide evidence of a relationship between activity-dependent synaptic plasticity and associative learning in behaving mice.
大脑中与学习和记忆过程更直接相关的部位之一是海马体。我们在清醒小鼠中记录了在关联任务的习得、消退、回忆和重新训练过程中，海马体CA3-CA1突触处发生的活动依赖性变化。使用痕迹[条件刺激（CS），音调；非条件刺激（US），电击]范式对小鼠进行经典条件反射以诱发眼睑反应。在CS-US间隔期间向Schaffer侧支-连合通路施加单个电脉冲，可在同侧CA1锥体细胞诱发单突触场兴奋性突触后电位（fEPSP）。诱发的fEPSP斜率在条件反射过程中增加，在消退过程中降低，与学习进程呈线性相关。相比之下，在没有条件反射方案的对照小鼠中诱发fEPSP时，其并未改变。Schaffer侧支的高频刺激诱发的长时程增强（LTP）会根据其触发时间阻止习得、消退、回忆或重新训练。LTP诱导引起的学习和记忆损伤可能是由于CA3-CA1突触的功能饱和所致，尽管不能排除随后向突触后回路的信息传递受到额外干扰的可能性。CGP 39551[（E）-（±）-2-氨基-4-甲基-5-膦酰基-3-戊烯酸乙酯]（一种NMDA拮抗剂）可阻止行为小鼠中的LTP诱导，以及眼睑学习反应的习得，以及在整个条件反射过程中CA3-CA1突触处发生 的突触变化。总之，CA3-CA1突触的反应性在关联学习过程中似乎受到调节，并且实验性LTP或NMDA受体失活会阻止这两个过程。我们的结果提供了行为小鼠中活动依赖性突触可塑性与关联学习之间关系的证据。
